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  • August 18, 2014
  • 10:16 AM
  • 212 views

Guidelines for Treatment of Problem Gambling

by William Yates, M.D. in Brain Posts

Despite the prevalence and impact of problem gambling, few summaries or guidelines address treatment.Searching the guideline.gov website shows no recent additions to the guideline literature.A guideline was published by the Singapore Ministry of Health in 2011. This guideline is still relevant and highlights some of the key elements of a problem gambling treatment program.I will summarize some of these key elements from this source titled: "Management of gambling disorders".  In their summary they highlight the level of evidence and research for each element. I will focus on those with the highest level of research support.Screening: Screening for problem gambling is not recommended for all the general primary care population.  However, screening for problem gambling is recommended for patients at high risk including those with "frequent physical or psychological complaints, or who have a history of substance/alcohol use problems". Additionally screening for problem gambling is recommended as part of psychiatric assessments for mental health evaluation.Assessing elements of gambling history:Initiation, progression and frequency information (days per week, hours per day)Severity in money lost compared to income Factors promoting maintenance of gambling behaviorFeatures of dependence similar to other addictive disordersGambling consequences: Review of list of potential gambling-related behaviors: Financial (credit card debt, neglect of payment of essential items such as utilities, rent, car payments)Social/interpersonal: marital conflict, neglect of usual social support activities, conflict with family members or friendsVocational: absence from work, neglect of work activities due to time spent gamblingLegal: Legal consequence of being in debt, stealing from family or work to finance gamblingPsychological Treatments:Cognitive behavioral therapy is the primary recommended psychological interventionMotivational enhancement therapy may be helpful for some individualsAdditionally, mindfulness therapy may be used as an adjunct therapySelf-help support groups are not recommended as a primary source of treatment and should only be used in conjunction with individual professional treatmentFinancial counseling may be needed to address gambling-related debt issuesPsychopharmacological Interventions: The Singapore guidelines do note some evidence-based support for opioid antagonists drugs naltrexone and nalmefene. Unfortunately, since 2011 additional evidence-based support for the opioid antagonists is sparse. Use of selective serotonin receptor inhibitor drugs such as fluvoxamine and paroxetine are also noted in the guideline. These may be helpful in problem gamblers with a comorbid depression or anxiety disorder.The Singapore guidelines do note the need for comprehensive assessment of axis I and II (personality disorder) issues in problem gamblers. I will take a look at the comorbidity topic in more depth in a future post.Readers with more interest in the Singapore Ministry of Health problem gambling treatment guidelines can access the summary here.Photo of green heron is from the author's files.Follow the author on Twitter at WRY999.Lee KM, Chan HN, Cheah B, Gentica GF, Guo S, Lim HK, Lim YC, Noorul F, Tan HS, Teo P, & Yeo HN (2011). Ministry of Health clinical practice guidelines: management of gambling disorders. Singapore medical journal, 52 (6) PMID: 21732000... Read more »

Lee KM, Chan HN, Cheah B, Gentica GF, Guo S, Lim HK, Lim YC, Noorul F, Tan HS, Teo P.... (2011) Ministry of Health clinical practice guidelines: management of gambling disorders. Singapore medical journal, 52(6), 456. PMID: 21732000  

  • August 18, 2014
  • 04:10 AM
  • 153 views

ADHD in the prison population: a micropost

by Paul Whiteley in Questioning Answers

"Compared with published general population prevalence, there is a fivefold increase in prevalence of ADHD in youth prison populations (30.1%) and a 10-fold increase in adult prison populations (26.2%)"."Mianly dry" apparently @ Paul WhiteleyThat was the primary conclusion reached in the meta-analysis by Young and colleagues [1] looking at the collected peer-reviewed literature on "the variable prevalence of attention deficit hyperactivity disorder (ADHD) in incarcerated populations".There is little more for me to say on this topic aside from the fact that as per the paper by Usher and colleagues [2], the presence of ADHD (including sub-threshold signs and symptoms) might have quite a few implications for things like comorbid mental health features [3] and issues like substance abuse [4]. That also: "ADHD symptoms were also found to predict institutional misconduct" is an important point to make without trying to make any sweeping generalisations.Screening of the prison population for ADHD sounds like it might be a good idea on the basis of the collected data in this area, leading on to further discussions about possible management options. That being said, intervention might not necessarily just include the more traditional pharmacotherapy but as per the important work by Bernard Gesch and colleagues [5] overlapping with the studies from Julia Rucklidge and colleagues (see here), on how good nutrition might also be on the menu. In fact...To close, the Foo Fighters and Learn to Fly.----------[1] Young S. et al. A meta-analysis of the prevalence of attention deficit hyperactivity disorder in incarcerated populations. Psychol Med. 2014 Apr 7:1-12.[2] Usher AM. et al. Attention deficit hyperactivity disorder in a Canadian prison population. Int J Law Psychiatry. 2013 May-Aug;36(3-4):311-5.[3] Kessler RC. et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006 Apr;163(4):716-23.[4] Harstad E. et al. Attention-deficit/hyperactivity disorder and substance abuse. Pediatrics. 2014 Jul;134(1):e293-301.[5] Gesch CB. et al. Influence of supplementary vitamins, minerals and essential fatty acids on the antisocial behaviour of young adult prisoners. Randomised, placebo-controlled trial. Br J Psychiatry. 2002 Jul;181:22-8.----------Young S, Moss D, Sedgwick O, Fridman M, & Hodgkins P (2014). A meta-analysis of the prevalence of attention deficit hyperactivity disorder in incarcerated populations. Psychological medicine, 1-12 PMID: 25066071... Read more »

  • August 17, 2014
  • 02:36 PM
  • 182 views

Schizophrenia and the Twilight Zone

by Gabriel in Lunatic Laboratories

You are now entering the Twilight Zone. You may remember the television show, with it’s odd twists and turns, but for people with schizophrenia it means something just a little […]... Read more »

  • August 17, 2014
  • 11:26 AM
  • 297 views

A mosaic vaccine that could potentially protect from different ebola strains

by EE Giorgi in CHIMERAS

Disclaimer: The mosaic vaccine paper discussed in this article is from my own group and overlaps with some of the research I do. I'm sure you've been following the latest news about the Ebola virus outbreak in Africa."The Ebola outbreak in West Africa is the world's deadliest to date and the World Health Organization has declared an international health emergency as more than 1,000 people have died of the virus in Guinea, Liberia, Sierra Leone and Nigeria this year." [Source: BBC News]The ebola virus was first described in 1976, with outbreaks reported starting from 1967 [3]. It's part of the Filovirus family and its natural reservoir is believed to be fruit bats, though there is evidence that it could be wider than we think. In fact, ebola can infect other animals like monkeys and pigs. Because the virus is transmitted through bodily fluids and it can survive for a few days after the host's death, it can be easily spread through the butchering and consumption of bushmeat. You've probably heard from the news that two infected Americans were treated with "serum". Some headlines even dubbed it a "secret serum." The serum is actually no secret and has been used not just for ebola but also for other viruses like RSV [1]. The treatment, called passive transfer of antibodies (or antibody serum), is based on the transfer of antibody serum from one organism to another. The idea behind it is that the immune system of a person previously exposed to the virus has developed antibodies that can help other immunologically naive patients fight the infection. For the ebola virus, the therapy is still in the experimental phase and, up to these two patients, had only been tested in animals.There are several vaccines currently being tested, each one at various experimental phases. Friedrich et al. [1] list a nice summary of all the current testing in their review. The one they do not mention in their review is a mosaic vaccine being developed by my group, which is based on ideas originally designed for an HIV vaccine.What is a mosaic vaccine?A vaccine is an attenuated form of a virus. Even though unable to start a full infection, when injected into the body, the attenuated virus is detected by the immune system, which can then mount the appropriate response and "create" neutralizing antibodies. Typically, the attenuated virus is created from the natural virus found in organisms.And then came HIV and baffled everyone.The problem with HIV is that every single HIV-infected person has a different virus. In order to protect from every possible infection, one would need to put into a vaccine the over half a million genetically distinct circulating strains. Clearly, that's not possible. How do you protect people from a viral population that's so diverse? Natural strains are no longer sufficient. You have to come up with clever ways to 'summarize' the whole population of viruses with just 2-3 viral strains. That's when computers come in handy: the mosaic vaccine is a vaccine created in silico. Suppose you want to create one genetic sequence that "summarizes" all the genetic variants found in a population of 100 strains. The algorithm that creates the mosaic starts from the 100 strains and it literally reshuffles them bit by bit. The "bits" are not cut out randomly but in a way that, when reassembled in a full genome, the proteins are still functional and working. In other words, you want to make sure that after the reshuffling you still have functioning viruses. You repeat the reshuffling for a few times and at the end of the iterations you pick the one strain that best represents the original pool of 100 genomes.HIV-1 mosaic vaccines have given great results in guinea pigs and monkeys. But what would be the advantage of using them for ebola?If you are familiar with phylogenetics, you will certainly object that the two viruses (HIV and ebola) are quite different: while HIV spreads out in a star-like fashion (which translates into the fact that no two individuals have the same virus), ebola evolves more like the flu, with new emerging viruses causing new outbreaks. So, why would the mosaic vaccine help with ebola?"While the techniques used here are very similar to those used for HIV-1 mosaic vaccine design, a pattern of repeated introductions of the filoviruses into humans (and primates generally) gives a crucial difference from HIV-1. HIV-1 shows great diversity within the pandemic, but that diversity has developed continuously, leaving intermediate isolates in its wake. In contrast, known filovirus diversity has episodically increased as new outbreaks are found to result from novel viruses, lacking intermediates." [3]The fact that the ebola virus "lacks intermediates" seems to indicate that there are reservoirs that we don't know of where the virus accumulates diversity. This is worrisome: we not only need to protect from the current outbreaks, but also be prepared for new viruses that might emerge in the future. In [3], Fenimore et al show how the mosaic algorithm can be readapted from HIV to ebola, accounting for the evolutionary differences between the two viruses.A mosaic vaccine would protect from all ebola subspecies and also against new strains that could potentially develop from the current outbreaks. The problem with ebola is that its reservoir could be wider than we think. The viral diversity found in bats has not matched the diversity of the ebola strains found in humans. So, where are the new viruses coming from? There are likely pockets of diversity that come from reservoirs we don't know of."The implication is that a vaccine against the filoviruses should strive for good coverage of common epitopes from the maximum number of types and strains currently available, in the hope that future outbreaks will retain these elements, so the vaccine will still be effective when challenged by a novel strain in a new outbreak." [3]The authors tested the ebola mosaic vaccine on a mouse model and compared it with a vaccine created with a single natural strain from Zaire. All vaccinated mice in either group (mosaic or natural) survived the challenge. The natural strain vaccine provided 82.8% coverage of other Zaire strains, but only 14.0% coverage of non-Zaire strains. On the other hand, the single mosaic vaccine provided 54.7% coverage of other Zaire strains (still sufficient to protect the mice from infection) and 23.2% coverage of non-Zaire ebola virus strains, proving that a mosaic can indeed improve protection against different subtypes. Furthermore, comparing a cocktail of a two-mosaic vaccine with a two-protein natural cocktail and a vaccine that was previously tested in macaques (Hensley et al., 2010), the mosaic cocktail achieved the highest coverage.[1] Friedrich BM, Trefry JC, Biggins JE, Hensley LE, Honko AN, Smith DR, & Olinger GG (2012). Potential vaccines and post-exposure treatments for filovirus infections. Viruses, 4 (9), 1619-50 PMID: 23170176[2] ... Read more »

Friedrich BM, Trefry JC, Biggins JE, Hensley LE, Honko AN, Smith DR, & Olinger GG. (2012) Potential vaccines and post-exposure treatments for filovirus infections. Viruses, 4(9), 1619-50. PMID: 23170176  

Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, Kuiken C, Haynes B, Letvin NL, Walker BD.... (2007) Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nature medicine, 13(1), 100-6. PMID: 17187074  

  • August 16, 2014
  • 01:00 PM
  • 223 views

Is your Stomach… Controlling your Mind?

by Gabriel in Lunatic Laboratories

Close the blinds, lock the doors, and find a safe place to hide. Are you alone? No, no you aren’t and you may not even be in control of your […]... Read more »

  • August 16, 2014
  • 09:14 AM
  • 123 views

High Sugar & Plants

by Viputheshwar Sitaraman in Draw Science

Activating PPARy can cure high blood sugar, but the problem is that current treatment has serious side effects. Accordingly, we turn to plants and natural medicine to provide new chemical formulas for PPARy agonists to help cure hyperglycemia.... Read more »

Wang L, Waltenberger B, Pferschy-Wenzig EM, Blunder M, Liu X, Malainer C, Blazevic T, Schwaiger S, Rollinger JM, Heiss EH.... (2014) Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review. Biochemical pharmacology. PMID: 25083916  

  • August 16, 2014
  • 03:21 AM
  • 191 views

The epidemiology of autism spectrum disorders

by Paul Whiteley in Questioning Answers

A very short post for readers to ponder based on the paper by Amanda Baxter and colleagues [1] who talked about the global epidemiology of the autism spectrum disorders (ASDs)."In 2010 there were an estimated 52 million cases of ASDs, equating to a prevalence of 7.6 per 1000 or one in 132 persons".Aside from emphasising the word 'estimated' (I highlighted that), be prepared to see the Baxter paper and that quote cited quite a bit in the peer-reviewed literature in times to come.----------[1] Baxter AJ. et al. The epidemiology and global burden of autism spectrum disorders. Psychological Medicine. 2014. August 11.----------A. J. Baxter, T. S. Brugha, H. E. Erskine, R. W. Scheurer, T. Vos, & J. G. Scott (2014). The epidemiology and global burden of autism spectrum disorders Psychological Medicine : http://dx.doi.org/10.1017/S003329171400172X... Read more »

A. J. Baxter, T. S. Brugha, H. E. Erskine, R. W. Scheurer, T. Vos, & J. G. Scott. (2014) The epidemiology and global burden of autism spectrum disorders. Psychological Medicine. info:/http://dx.doi.org/10.1017/S003329171400172X

  • August 15, 2014
  • 03:20 PM
  • 359 views

In Defense of Eating Junk Food in Eating Disorder Treatment

by Shirley in Science of Eating Disorders


Should eating disorder patients be introduced to “junk food” or “hyper-palatable” foods during treatment? A few days ago, I stumbled across a blog post where Dr. Julie O’Toole, Founder and Director of the Kartini Clinic for Disordered Eating, argues against introducing “junk food” during ED treatment. The crux of the argument is that “hyperpalatable foods”—e.g., chips and Cheetos—are not real food and should never be forced or encouraged for anyone, regardless of the presence of an eating disorder:
A lot of ink has been spilled on teaching Americans in general and children in particular to make good food choices. Just because you have anorexia nervosa as a child, and desperately need to gain and maintain adequate weight, does not mean that you will be immune from the health effects of bad eating as you get older. This is true whether or not you get fat later on. You can be thin and unhealthy; you can destroy a lot of things by ingesting a chemical cuisine in the place of real food.
While I don’t disagree that some foods have more …

You May Also Like:
Bingeing Because Food is Yummy: A Stepping Stone Toward Recovery from Anorexia and Bulimia?
Maintaining Change Following Intensive Eating Disorder Treatment
The Research-Practice Gap in Eating Disorder Treatment



... Read more »

  • August 15, 2014
  • 04:07 AM
  • 182 views

Psychotic experience following childhood neurodevelopmental diagnosis

by Paul Whiteley in Questioning Answers

The paper by Golam Khandaker and colleagues [1] suggesting a higher risk of psychotic episodes (PEs) in early adolescence among those with a diagnosed childhood neurodevelopmental disorder (ND) makes for some interesting reading. Detailing several diagnoses as falling under the banner of neurodevelopmental disorder (autism spectrum, dyslexia, dyspraxia, dysgraphia, dysorthographia, dyscalculia), researchers concluded that: "The risk of PEs was higher in those with, compared with those without, NDs". IQ also seemed to show some connection to risk.The Flower Seller @ Wikipedia A few further details:Based on a cohort of over 8000 children, researchers reported that approximately 6% (487) were "reported to have NDs at age 9 years". By 'reported' they meant that parent's reported these via a questionnaire.PEs "were assessed by semi-structured interviews at age 13 years". IQ and a specific focus on working memory "were measured between ages 9 and 11 years".The authors suggested that the elevated risk of PEs accompanying a diagnosis of ND "is consistent with the neurodevelopmental hypothesis of schizophrenia".With specific focus on autism as one of the NDs mentioned in the Khandaker study, I was taken back to some interesting work looking at both the overlap between the autism and schizophrenia spectrums (see here) and the initial data talking about Asperger syndrome and first-episode psychosis (see here). Both these areas of work seem to tie into the neurodevelopmental hypothesis talked about by authors, accepting that I am not trying to promote any reunification of the conditions nor making any sweeping generalisations.I might also bring to your attention another piece of work by Khandaker and colleagues [2] which has been covered on this blog talking about the risk of psychotic episodes in cases of atopic disease such as asthma and eczema. Alongside other work by this group [3] talking about "Early-life exposure to EBV [Epstein-Barr virus]" and prenatal exposure to "a range of infections and inflammatory responses" [4] the emphasis is on how various somatic processes might be involved in bringing someone to a PE, particularly with the immune system as a potentially important player. Perhaps more evidence for a role for inflammation in psychiatry and possibly with overlapping issues [5]. As I've said before on this blog, autism and inflammation is a bit of a growth area in research terms.I'd like to think that the latest Khandaker findings might be further investigated with a view to looking at both potential mechanism(s) involved in that neurodevelopmental hypothesis of schizophrenia [6] (including genetic and non-genetic factors [7]) and also how prevalent the range of factors the authors have previously identified as being linked to PEs are in conditions such as autism and dyslexia for example. The additional question of whether targeting something like the immune system during 'inflammatory' phases might offset the risk of PEs is a tantalising one.And speaking of Khandaker, I'm minded to talk soon about even more recent findings from this group [8] on inflammation and psychiatry...Music then to close. The late Amy Winehouse and Back to Black.----------[1] Khandaker GM. et al. A population-based longitudinal study of childhood neurodevelopmental disorders, IQ and subsequent risk of psychotic experiences in adolescence. Psychol Med. 2014 Apr 25:1-10.[2] Khandaker GM. et al. A population-based study of atopic disorders and inflammatory markers in childhood before psychotic experiences in adolescence. Schizophr Res. 2014 Jan;152(1):139-45.[3] Khandaker GM. et al. Childhood Epstein-Barr Virus infection and subsequent risk of psychotic experiences in adolescence: A population-based prospective serological study. Schizophr Res. 2014 Jul 18. pii: S0920-9964(14)00251-5.[4] Khandaker GM. et al. Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies. Psychol Med. 2013 Feb;43(2):239-57.[5] Meyer U. et al. Schizophrenia and Autism: Both Shared and Disorder-Specific Pathogenesis Via Perinatal Inflammation? Pediatric Res. 2011; 69: 26R-33R.[6] Owen MJ. et al. Neurodevelopmental hypothesis of schizophrenia. Br J Psychiatry. 2011 Mar;198(3):173-5.[7] Zavos HMS. et al. Consistent Etiology of Severe, Frequent Psychotic Experiences and Milder, Less Frequent Manifestations. JAMA Psychiatry. 2014. 30 July.[8] Khandaker GM. et al. Association of Serum Interleukin 6 and C-Reactive Protein in Childhood With Depression and Psychosis in Young Adult Life. JAMA Psychiatry. 2014. August 13.----------Khandaker GM, Stochl J, Zammit S, Lewis G, & Jones PB (2014). A population-based longitudinal study of childhood neurodevelopmental disorders, IQ and subsequent risk of psychotic experiences in adolescence. Psychological medicine, 1-10 PMID: 25066026... Read more »

  • August 14, 2014
  • 03:35 PM
  • 224 views

Bringing the Fight to hidden HIV

by Gabriel in Lunatic Laboratories

We’ve got even more news for the HIV cure front. Yesterday we talked about broadly neutralizing antibodies, today we are going to be touching on that yet again,so if you […]... Read more »

Ariel Halper-Stromberg, Ching-Lan Lu, Florian Klein, Joshua A. Horwitz, Stylianos Bournazos, Lilian Nogueira, Thomas R. Eisenreich, Cassie Liu, Anna Gazumyan, Uwe Schaefer, Rebecca C. Furze, Michael S. Seaman.... (2014) Broadly Neutralizing Antibodies and Viral Inducers Decrease Rebound from HIV-1 Latent Reservoirs in Humanized Mice. Cell. info:/10.1016/j.cell.2014.07.043

  • August 14, 2014
  • 02:00 PM
  • 289 views

Dying To Make Us Laugh

by Mark E. Lasbury in The 'Scope

Robin William’s suicide was a tragic, but all too familiar happening amongst humorists of this period. New research is showing that comedians, performers in the arts, and even people with better senses of humor are prone to more health problems as adults. Depression , cardiovascular, pulmonary and stress related problem are not uncommon in comedians, and even children and adults that have better sense of humor are susceptible to obesity and cardiovascular disease.

The irony is that this occurs in the very people that are helping our health by making us laugh. Several recent studies and reviews indicate that mirthful laughter has health benefits, from increased immune function to improving vascular wall stiffness. Reduced cortisol and increased endorphin release improve both our mental and physical health, although no studies have directly linked laughing to increased longevity.
... Read more »

C.R. Epstein, R.J. Epstein. (2013) Death in The New York Times: the price of fame is a faster flame . QJM: monthly journal of the Association of Physicians, 106(6), 517-521. info:/

Greengross G. (2013) Humor and aging - a mini-review. Gerontology, 59(5), 448-53. PMID: 23689078  

Bennett MP, & Lengacher C. (2009) Humor and Laughter May Influence Health IV. Humor and Immune Function. Evidence-based complementary and alternative medicine : eCAM, 6(2), 159-64. PMID: 18955287  

  • August 14, 2014
  • 01:55 PM
  • 229 views

Getting High On Life

by Mark Lasbury in As Many Exceptions As Rules

Living organisms can survive and thrive in all kinds of rough environments. This would include the edges of space. There are bird species that can fly at almost 40,000 ft., as high as the highest clouds. New research is showing just how the bar headed goose is able to fly when the air is thin and the oxygen is scarce. But more impressive are the bacteria. They can actually live their whole lives in the air, dividing and growing nearly 25 miles (41 km) above the surface of the Earth. A study from India has now presented a draft genome for Janibacter hoylei, an organism found only in extremely high air. A 2009 paper presented evidence of two additional bacteria that have not been identified on Earth, only above it. These organisms could provide clues for astrobiologists looking to see how life might travel from planet to planet.... Read more »

Pawar SP, Dhotre DP, Shetty SA, Chowdhury SP, Chaudhari BL, & Shouche YS. (2012) Genome sequence of Janibacter hoylei MTCC8307, isolated from the stratospheric air. Journal of bacteriology, 194(23), 6629-30. PMID: 23144385  

Hawkes LA, Balachandran S, Batbayar N, Butler PJ, Chua B, Douglas DC, Frappell PB, Hou Y, Milsom WK, Newman SH.... (2013) The paradox of extreme high-altitude migration in bar-headed geese Anser indicus. Proceedings. Biological sciences / The Royal Society, 280(1750), 20122114. PMID: 23118436  

  • August 14, 2014
  • 12:10 PM
  • 181 views

HIV Vaccine One Step Closer to Reality

by Gabriel in Lunatic Laboratories

The war on HIV, that tricky little guy has avoided every thing we could throw at it in a broad sense. Sure a few people here and there get lucky, but we have yet to actually make any sort of we're going to kick your ass headway [don't worry it's the technical term for it]. That is hopefully going to change with a new scientific discovery that has enormous implications for HIV vaccine development. Researchers have uncovered novel properties of special HIV antibodies that promise to help eliminate HIV.[...]... Read more »

  • August 14, 2014
  • 11:17 AM
  • 233 views

FDA Approves Novel Insomnia Drug Suvorexant (Belsomra)

by William Yates, M.D. in Brain Posts

Regular readers of this blog had a heads up last year on the development of orexin receptor antagonists for the treatment of insomnia.I posted a review of an Italian clinical drug trial in humans with insomnia paired with polysomnography. This study used three different doses of a orexin receptor antagonist (10 mg 30 mg and 60 mg).In a second post, I reviewed a sleep lab study of the effects of an orexin antagonist drug compared to zolpidem (Ambien) on sleep architecture.This second study found superiority of the orexin antagonist drug at 30 mg versus 10 mg of zolpidem on total sleep time (increased 19 minutes).Yesterday, the FDA in the United States approved the orexin antagonist drug suvorexant (trade name Belsomra) for the treatment of insomnia.Four dosage strengths were approved including 5 mg, 10 mg, 15 mg and 20 mg. The FDA noted the importance of finding the lowest effective dose and not going above this dose for individual patients. Higher doses carry concern for impairment in morning psychomotor function including impaired driving ability. Two more recent studies are relevant to highlight.D Michelson and colleagues published a safety and efficacy study of suvorexant (40 mg for those less than 65 and 30 mg for those 65 years and older). This study found suvorexant "generally safe and well tolerated over 1 year of nightly treatment". Adverse effects in active drug were similar to placebo with the most notable exception somnolence (daytime) endorsed by 13% of the suvorexant group compared to only 3% of the placebo group.Tiffany Bennett and colleagues from the University of Georgia recently published a nice free full-text clinical summary of the orexin receptor antagonist drugs for insomnia.Their review noted this class of drug appears generally safe and may offer some advantage to persons needing to use a drug chronically for insomnia treatment. Benzodiazepines and nonbenzodiazepine drugs like lorazepam (Ativan) and zolpidem (Ambien) may have a more global cognition adverse effect profile including amnesia, daytime sedation and rebound insomnia. Bennett and colleagues recommend Pharmacy and Therapeutic (P&T) Committees consider the approval of suvorexant in addition to the currently available drugs for insomnia.A key issue for clinicians with be the challenge of finding the lowest effective dose for individual patients. This may take some time and be inconvenient. Additionally, individuals needing the higher doses of suvorexant may not experience all the orexin antagonist class benefits relative to benzodiazepines.Nevertheless, this novel drug may hold significant benefit for many individuals with chronic insomnia. It is good to see a new class of insomnia drugs available for clinicians and their patients. Readers with more interest in the cited manuscripts can access them by clicking on the PMID reference links below.Photo of tricolor heron is from the authors files.Follow the author on Twitter WRY999Michelson D, Snyder E, Paradis E, Chengan-Liu M, Snavely DB, Hutzelmann J, Walsh JK, Krystal AD, Benca RM, Cohn M, Lines C, Roth T, & Herring WJ (2014). Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet neurology, 13 (5), 461-71 PMID: 24680372Bennett T, Bray D, & Neville MW (2014). Suvorexant, a dual orexin receptor antagonist for the management of insomnia. P & T : a peer-reviewed journal for formulary management, 39 (4), 264-6 PMID: 24757363... Read more »

  • August 14, 2014
  • 04:09 AM
  • 171 views

Learning disability in autism: how prevalent is it?

by Paul Whiteley in Questioning Answers

"Results showed that 36.8 % of the children met the criteria for ID [intellectual disability], with 60.2 % of these in the mild range (IQ 50-69) and 39.8 % in the moderate range (IQ 35-49)".That was the finding reported by Mélina Rivard and colleagues [1] looking at the co-occurrence of intellectual disability (also called learning disability here in Blighty) and autism spectrum disorder (ASD) "in young children". Based on an analysis of over 200 children diagnosed with an ASD, researchers recorded various details before participants entry into an "early behavioral intervention program" including those relating to IQ and adaptive behaviours. Most of those children falling into the category of ID were in the 'mild' range (IQ 50-69) as opposed to the moderate range (IQ 35-49).Roses @ Wikipedia This is an important paper insofar as presenting some further details about how widespread ID is in cases of autism. Indeed, a figure hovering somewhere around 30-40% of all cases of autism (accepting the issue of variations in subtypes on the autism spectrum) presenting with ID is pretty much what many people have discussed on the basis of other research in this area [2]. That being said, the recent CDC prevalence estimates (yes, estimates) of autism (see here) kinda hinted that the rates of ID in autism might be on the move as per their reporting: "31% of children with ASD were classified as having IQ scores in the range of intellectual disability (IQ ≤70)" [3]. We'll have to wait and see how this goes alongside the introduction of the DSM-5 diagnostic criteria (see here).Having reliable data on the rate of ID in autism also goes beyond just knowing how many people fall into that category. When present alongside each other, one might assume that there may be shared factors at work in terms of aetiology as for example, discussed by Srivastava & Schwartz [4]. I've talked a few times on this blog about another triad of symptoms (autism, epilepsy & learning disability) appearing in some quite rare genetic conditions (see here) which provides some interesting details about possible onset and indeed intervention.That there may also be a greater risk of autism and ID in specific populations is another detail to bear in mind. Take for example the 2013 report on autism in the Somali population in Minneapolis (see here) and the finding: "Somali children with ASD were more likely to also have an intellectual disability than children with ASD in all other racial and ethnic groups in Minneapolis". I say this acknowledging that inferring causation from such epidemiology is not necessarily going to be straight forward.Perhaps also important is mention of the impact that comorbid ID can have on various other outcomes with autism in mind. Yes, we know that this probably means a greater requirement for service provision (see here) and inevitably this will have an economic cost attached to it (see here). But then there are issues like self-injurious behaviour (see here) and the topic no-one really likes to talk about, early mortality (see here) which might also be differentially affected by the presence of ID, or at least some behaviours which might place someone at greater risk of danger (see here). I personally see these as some of the more important effects of ID on autism.Eliza Doolittle to finish, and Pack Up.----------[1] Rivard M. et al. Indicators of Intellectual Disabilities in Young Children with Autism Spectrum Disorders. J Autism Dev Disord. 2014 Jul 29.[2] Chakrabarti S. & Fombonne E. Pervasive developmental disorders in preschool children: confirmation of high prevalence. Am J Psychiatry. 2005 Jun;162(6):1133-41.[3] Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators. Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2010. MMWR Surveill Summ. 2014 Mar 28;63(2):1-21.[4] Srivastava AK. & Schwartz CE. Intellectual disability and autism spectrum disorders: Causal genes and molecular mechanisms. Neurosci Biobehav Rev. 2014 Apr 4. pii: S0149-7634(14)00077-3.----------Rivard M, Terroux A, Mercier C, & Parent-Boursier C (2014). Indicators of Intellectual Disabilities in Young Children with Autism Spectrum Disorders. Journal of autism and developmental disorders PMID: 25070470... Read more »

  • August 13, 2014
  • 11:35 PM
  • 193 views

The Controversy of Admitting 'We Do Not Know What Works'

by Rogue Medic in Rogue Medic

There are several news articles today criticizing a study because the patients might be deprived of a drug that has not been adequately studied in humans. This criticism is coming from journalists – the people who publicized the fraudulent vaccines research by Andrew Wakefield, who was trying to sell his competing vaccine and was being paid to produce negative research by lawyers suing the vaccine companies.[1]

The real controversy is that this untested drug became the standard of care with no evidence that it improves outcomes that matter.

Is it controversial to give a placebo, rather than a drug not yet adequately tested in humans?... Read more »

Larabee TM, Liu KY, Campbell JA, & Little CM. (2012) Vasopressors in cardiac arrest: a systematic review. Resuscitation, 83(8), 932-9. PMID: 22425731  

Herlitz J, Ekström L, Wennerblom B, Axelsson A, Bång A, & Holmberg S. (1995) Adrenaline in out-of-hospital ventricular fibrillation. Does it make any difference?. Resuscitation, 29(3), 195-201. PMID: 7667549  

Olasveengen, T., Sunde, K., Brunborg, C., Thowsen, J., Steen, P., & Wik, L. (2009) Intravenous Drug Administration During Out-of-Hospital Cardiac Arrest: A Randomized Trial. JAMA: The Journal of the American Medical Association, 302(20), 2222-2229. DOI: 10.1001/jama.2009.1729  

Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, & Miyazaki S. (2012) Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. JAMA : the journal of the American Medical Association, 307(11), 1161-8. PMID: 22436956  

Hayashi Y, Iwami T, Kitamura T, Nishiuchi T, Kajino K, Sakai T, Nishiyama C, Nitta M, Hiraide A, & Kai T. (2012) Impact of early intravenous epinephrine administration on outcomes following out-of-hospital cardiac arrest. Circulation journal : official journal of the Japanese Circulation Society, 76(7), 1639-45. PMID: 22481099  

Glover BM, Brown SP, Morrison L, Davis D, Kudenchuk PJ, Van Ottingham L, Vaillancourt C, Cheskes S, Atkins DL, Dorian P.... (2012) Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium. Resuscitation. PMID: 22858552  

Stiell IG, Hebert PC, Weitzman BN, Wells GA, Raman S, Stark RM, Higginson LA, Ahuja J, & Dickinson GE. (1992) High-dose epinephrine in adult cardiac arrest. The New England journal of medicine, 327(15), 1045-50. PMID: 1522840  

Callaway, C. (2012) Questioning the Use of Epinephrine to Treat Cardiac Arrest. JAMA: The Journal of the American Medical Association, 307(11), 1198. DOI: 10.1001/jama.2012.313  

  • August 13, 2014
  • 08:00 AM
  • 220 views

Getting High On Life

by Mark Lasbury in As Many Exceptions As Rules

Living organisms can survive and thrive in all kinds of rough environments. This would include the edges of space. There are bird species that can fly at almost 40,000 ft., as high as the highest clouds. New research is showing just how the bar headed goose is able to fly when the air is thin and the oxygen is scarce. But more impressive are the bacteria. They can actually live their whole lives in the air, dividing and growing nearly 25 miles (41 km) above the surface of the Earth. A study from India has now presented a draft genome for Janibacter hoylei, an organism found only in extremely high air. A 2009 paper presented evidence of two additional bacteria that have not been identified on Earth, only above it. These organisms could provide clues for astrobiologists looking to see how life might travel from planet to planet.... Read more »

Pawar SP, Dhotre DP, Shetty SA, Chowdhury SP, Chaudhari BL, & Shouche YS. (2012) Genome sequence of Janibacter hoylei MTCC8307, isolated from the stratospheric air. Journal of bacteriology, 194(23), 6629-30. PMID: 23144385  

Hawkes LA, Balachandran S, Batbayar N, Butler PJ, Chua B, Douglas DC, Frappell PB, Hou Y, Milsom WK, Newman SH.... (2013) The paradox of extreme high-altitude migration in bar-headed geese Anser indicus. Proceedings. Biological sciences / The Royal Society, 280(1750), 20122114. PMID: 23118436  

  • August 13, 2014
  • 04:11 AM
  • 149 views

Neonatal intensive care unit (NICU) survivors and greater risk of autism?

by Paul Whiteley in Questioning Answers

"In term NICU [neonatal intensive care unit] survivors, ASD [autism spectrum disorder] occurs with a greater frequency than in the general population and often develops alongside comorbid conditions". That was the conclusion from the study by Alexander Winkler-Schwartz and colleagues [1] looking at term at-risk infants who survived NICU."You were only meant to blow the bloody doors off"'Surviving' their earliest days spent in NICU brings a bit of lump to my throat. As a parent, I can only imagine how worrying and daunting a prospect it must be to watch your child, your baby, spending what is meant to be the very happiest of occasions housed in an incubator with every aspect of their being monitored and controlled. I appreciate that with the technology and medical advances available these days, the prospects for many infants 'surviving' NICU are pretty good compared to even a few decades ago. But still, I imagine it can be an overwhelming prospect.The Winkler-Schwartz paper reported that out of 180 infants analysed as part of their study, 12 of them (6%) were later diagnosed with an ASD. This compared with ~40% diagnosed with global developmental delay and between 25-30% diagnosed with cerebral palsy (CP) and epilepsy. The authors also noted that: "Nine patients with ASD (75%) were diagnosed with at least one other adverse outcome", a point which ties in with their comorbidity finding.At least one of the authors on the Winkler-Schwartz paper has some interest in looking at the cognitive-behavioural profile of neonates under adverse conditions. A quick trawl of the peer-reviewed literature base confirms that Michael Shevell has some research form specifically focused in areas such as neurodevelopment associated with congenital heart defects for example [2]. The word 'autism' has also been discussed in some of his previous research investigations too [3].Aside from the primary conclusion included in the Winkler-Schwartz paper on NICU survivors and autism risk, the other important message is on how comorbidities might fit in with the presentation of autism. Autism and epilepsy has been an oft-discussed topic on this blog so I don't really need to say much more there. CP and autism is something of increasing interest (see here) particularly so when taking into account the findings from Christensen and colleagues [4] seemingly suggesting different autism risk profiles according to different types of CP.I close with another quote from the Winkler-Schwartz paper on: "the importance of screening term NICU survivors for ASD, particularly when comorbidities are present". Yes another group where screening for autism might be preferentially indicated...----------[1] Winkler-Schwartz A. et al. Autism spectrum disorder in a term birth neonatal intensive care unit population. Pediatric Neurology. 2014. July 16.[2] Limperopoulos C. et al. Neurologic status of newborns with congenital heart defects before open heart surgery. Pediatrics. 1999 Feb;103(2):402-8.[3] Webster RI. et al. The clinical spectrum of developmental language impairment in school-aged children: language, cognitive, and motor findings. Pediatrics. 2006 Nov;118(5):e1541-9.[4] Christensen D. et al. Prevalence of cerebral palsy, co-occurring autism spectrum disorders, and motor functioning - Autism and Developmental Disabilities Monitoring Network, USA, 2008. Dev Med Child Neurol. 2014 Jan;56(1):59-65.----------Winkler-Schwartz, A., Garfinkle, J., & Shevell, M. (2014). Autism spectrum disorder in a term birth neonatal intensive care unit population Pediatric Neurology DOI: 10.1016/j.pediatrneurol.2014.07.009... Read more »

  • August 13, 2014
  • 12:05 AM
  • 158 views

Make Sure You Charge That Phone Before Measuring Anterior Tibial Translation

by Kyle Harris in Sports Medicine Research (SMR): In the Lab & In the Field

A mobile phone arthrometer application may be a reliable alternative to the KT-1000 when measuring anterior tibial translation following an anterior cruciate ligament injury.... Read more »

Andrea, F., Luigi, V., Daniele, M., Luca, M., Paolo, I., Giovanni, G., Fabio, C., & Raffaele, I. (2014) Smartphone versus knee ligament arthrometer when size does not matter. International Orthopaedics. DOI: 10.1007/s00264-014-2432-9  

  • August 12, 2014
  • 02:07 PM
  • 174 views

Treatment and Prevention of PTSD

by Gabriel in Lunatic Laboratories

It’s no secret for anyone who follows me that I am a Marine veteran. It’s also no secret for anyone who follows me that I’ve had my own ups and downs in life because of my experiences. PTSD is a nightmare, one that you can’t quite shake no matter how hard you try. Then again, not everyone reacts the same way to the trauma that typically causes PTSD, not everyone walks away from war with it. The big question that scientists set out to answer was, why? And now they might just have an answer.[…]... Read more »

Nikolaos P. Daskalakis, Hagit Cohen, Guiqing Caia, Joseph D. Buxbaum, & Rachel Yehuda. (2014) Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes. Proceedings of the National Academy of Sciences of the United States of America, 111(32). info:/10.1073/pnas.1401660111

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