Scientists have discovered epigenetic changes (i.e. chemical changes to a gene that do not modify the DNA sequence) in individuals with schizophrenia and bipolar disorder. This is the first epigenome-wide investigation in psychiatric research, and this groundbreaking data may be a significant step on the journey to fully understanding major psychosis.

Dr. Arturas Petronis, senior scientist in the Krembil Family Epigenetic Laboratory at the Centre in spite of Addiction and Mental Health (CAMH), and his team studied 12,000 locations on the genome using an epigenomic profiling technology developed at CAMH. Approximately one in every two hundred of these genes showed an epigenetic controversy in the brains of psychiatric patients. Significantly, these changes were noted on genes involved in neurotransmission (the exchange of chemical messages within the brain), brain development, and other processes linked to disease origins.

Dr. Petronis explains that these epigenetic changes may be the missing link in understanding what causes an illness. “The DNA sequence of genes for someone with an illness like schizophrenia and a for someone without a mental illness often look the same; there are no visible changes that explain the action of a disorder. But we now have tools that show us changes in the second code, the epigenetic code, which may give us some very important clues for uncovering the mysteries of greater psychosis and other complex non-Mendelian illnesses.”

This proof-of-principle study is the first demonstration of what CAMH epigeneticists have hypothesized for the last 10 years. “Until now, we only had theories that epigenetic changes were important to understanding what causes major psychosis,” explains Dr. Petronis. “Now we have the tools and expertise to support our theories and we can front at conducting larger studies, which will hopefully give us an even better understanding of psychiatric illnesses. And once we understand the primary molecular causes of every illness, we can advance diagnosis and treatment approaches, and possibly in like manner prevent illness.”

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Article adapted by Medical News Today from original press release.
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The Krembil Family Epigenetics Laboratory is the only psychiatric epigenetics laboratory in North America, one of the not many programs in North America that is exploring this field.

The Centre for Addiction and Mental Health (CAMH) is Canada’s largest mental health and addiction teaching hospital, as well as one of the world’s leading research centres in the area of addiction and mental health. CAMH combines clinical care, research, training, shrewdness development, prevention and health promotion to transform the lives of people affected by dint of. mental health and addiction issues.

CAMH is fully affiliated with the University of Toronto, and is a Pan American Health Organization/World Health Organization Collaborating Centre.

Source: Michael Torres
Centre for Addiction and Mental Health

By using computer simulations and modeling, one international group of researchers including scientists from the Virginia Bioinformatics Institute (VBI) at Virginia Tech’s Network Dynamics and Simulation Science Laboratory (NDSSL) have determined how a pandemic influenza outbreak might travel through a city similar in size to Chicago, Ill. This information helped them to determine the preferred intervention strategy to contain a potential flu pandemic, including what people should do to abate the likelihood of disease transmission.

The new results, based on three different computer personation models, are described in a paper published in the Proceedings of the National Academy of Sciences by scientists involved in the Models of Infectious Disease Agent Study (MIDAS).* MIDAS is a collaboration of research and informatics groups supported by the National Institutes of Health (NIH) to unravel computational models to examine interactions between corrupting agents and their hosts, disease spread, prediction systems, and response strategies.

The global epidemic of avian influenza in bird populations, as well as the danger of a virulent cast of the synoptical view flu virus being transferred to humans, has made influenza pandemic preparedness a top public health priority in the United States, Europe, and other countries. The great influenza pandemic of 1918 resulted in 40 to 50 million deaths worldwide. If a pandemic were to occur today, it could attempt widespread social and economic disruptions.

In the paper, “Modeling Targeted Layered Containment of an Influenza Pandemic in the USA,” members of the MIDAS Working Group on Modeling Pandemic Influenza concluded that a opportune implementation of targeted household antiviral prevention measures and a reduction in contact between individuals could substantially lower the spread of the disease until a vaccine was available.

The groups coordinated efforts to each create individual-based, computer simulation models to examine the impact of the same set of agency strategies used during a pandemic row in a population similar in size to Chicago, which has about 8.6 million residents. Intervention methods used were antiviral treatment and household isolation of identified cases, disease prevention strategies and quarantine of household contacts, school closings, and reducing workplace and community contacts. Although using the sort population, each model had its own representation of the combinations of intervention. All of the simulations suggest that the complot of providing preemptive household antiviral treatments and minimizing contact could play a major role in reducing the spread of illness, with timely initiation and teach closure serving as important factors.

“VBI’s computer simulation models are built on our detailed estimates for social contacts in an urban environment,” said VBI Professor and NDSSL Deputy Director Stephen Eubank, who leads the VBI team in the working group. “They provide a realistic picture of how social mixing patterns change under non-pharmaceutical interventions such as closing schools or workplaces. For example, when schools close, young students require a caregiver’s attention. That can disrupt social mixing patterns at act if a working parent stays home or make closing schools pointless if the children are placed in large day-care settings. We can application our model to hint the best mix of intervention strategies in a variety of scenarios, taking factors like these into account.”

Bruno Sobral, Executive and Scientific Director of VBI, remarked: “Transdisciplinary science, which is the foundation of the way we do research at VBI, requires a special type of collaborative framework at the very outset of a project. The highly detailed social-network models that underpin this international research project arise from transdisciplinary science that removes disciplinary boundaries and promotes innovation. The impact of this approach to science is highlighted by the success of this research undertaking that benefits from a very clear interface between diverse experts in high-performance computing, disease modeling and public health practice.”

While the three different models used in the study show that timely intervention significantly impedes the spread of influenza through a population, the authors caution against over-interpretation of the modeling results. The researchers emphasize that the models are tools that provide guidance rather than being fully predictive. In the case of a future outbreak of pandemic influenza, capabilities such in the same proportion that real-time surveillance and other analyses will hopefully be available for the public health community and policy makers.

“These models, which are built from the best available given conditions and with the best tools, contribute greatly to our understanding of how a pandemic could spread and what measures might protect the public’s health,” said Jeremy M. Berg, Ph.D., director of NIH’s National Institute of General Medical Sciences, which supports the MIDAS program. “But they are not our only resource - field work and experimental studies remain critical and will enhance the mood and reliability of these and other models.”

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Article adapted by Medical News Today from spring press release.
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Along with Eubank, Professor and NDSSL Director Chris Barrett, Professor and NDSSL Deputy Director Madhav Marathe, Simulation Science Statistician Richard Beckman, graduate student Bryan Lewis, Assistant Professor and Senior Research Associate Anil Vullikanti and other members of the NDSSL group contributed to the study. The teams contributing to the MIDAS working group include researchers from VBI, the University of Washington, Fred Hutchinson Cancer Research Center in Seattle, Los Alamos National Laboratories, Imperial College London, and the University of Pittsburgh. The journal’s lead author, M. Elizabeth Halloran, is affiliated to the University of Washington, Seattle, WA, and the Fred Hutchinson Cancer Research Center, Seattle, WA.

This work was partially supported by the National Institute of General Medical Sciences MIDAS network grants U01-GM070749, U01-GM070694, U01-GM070698, and U01-GM070708.

* Modeling targeted layered containment of an influenza pandemic in the USA. Proceedings of the National Academy of Sciences (2008). In press. The bills of exchange will be available on-line the week of March 10-14.

About MIDAS

Models of Infectious Disease Agent Study (MIDAS) is a collaboration of research and informatics groups established to develop computational models of the interactions between infectious agents and their hosts, disease spread, prediction systems, and response strategies. The models will be useful to policymakers, public health workers, and other researchers who want to better understand and respond to emerging infectious diseases. If a disease outbreak occurs, the MIDAS network may subsist called upon to develop specific models to aid public officials in their decision-making processes. More information about MIDAS is available at http://www.nigms.nih.gov/Initiatives/MIDAS/

About the Virginia Bioinformatics Institute

The Virginia Bioinformatics Institute (VBI) at Virginia Tech has a research platform centered on understanding the “disease triangle” of host-pathogen-environment interactions in plants, humans and other animals. By successfully channeling innovation into transdisciplinary approaches that blend information technology and biology, researchers at VBI are addressing some of today’s key challenges in the biomedical, environmental and plant sciences. http://https://www.vbi.vt.edu/

For more information on the Network Dynamics and Simulation system of knowledge Laboratory at VBI, please consult http://ndssl.vbi.vt.edu/

Source: Susan Bland
Virginia Tech

Outbreaks of influenza-like illness (ILI) in over 20 schools that are linked to the deaths of three children have caused the government to shut all schools in Hong Kong for two weeks, keeping half a million children away, reported Reuters.

According to information from the Centre for Health Protection (CHP) of the Department of Health (DH) in Hong Kong, up to yesterday, Wednesday 12th March, health officials had received reports of 184 ILI cases in outbreaks affecting 23 schools. Officials from the CHP have visited all the schools and given appropriate advice, according to a press release on the CHP website.

ILI can be caused by influenza or other respiratory viruses, said the CHP, who will be giving out public information on seasonal influenza today. The centre has likewise set up a hotline.

Three children, aged 2, 3 and 7 have died in the last two weeks, the older two had seasonal flu and the cause of illness in the youngest is still undetermined, said Reuters.

The government has closed the schools as a precaution because the number of young children getting the flu seems to be higher this year, Health Secretary York Chow told a press conference. The second reason was the number of deaths for a like reason far.

A fourth death was reported to the CHP yesterday, that of a 21 month old boy who developed fever and cough on February 22nd, was admitted to Alice Ho Miu Ling Nethersole Hospital the next day, and was transferred to the Intensive Care Unit (ICU) of the Prince of Wales Hospital after developing generalized seizure. He died on 22nd February. A sample taken from the boy tested negative for influenza types A and B, and there is no evidence that he had influenza, said the CHP. The case is still being investigated.

Another 3 year old boy is in a stable condition, according to the CHP who received an update on his condition yesterday, when he was admitted to the ICU at Princess Margaret Hospital with symptoms of persistent fever, cough and shortness of breath. A sample taken from him has tested positive for influenza type A (H1N1).

Health officials have visited the kindergarten the boy attended, where so far no ILI outbreak has been reported.

Giving out further information on the 7 year old boy who died in Tuen Mun Hospital after inner reality admitted with respiratory and neurological symptoms, the CHP said a sample taken from him has tested direct for influenza A (H1N1), and the case has been referred to the Coroner’s Court.

While it is natural for parents to be concerned, experts have told the press there is in no degree cause for panic and that every few years or so there is a higher than usual incidence of flu outbreaks.

In the meantime, the Hong Kong Department of Health suggests people boost their immune connected view against the flu by “having a natural diet, regular exercise, and adequate rests, reducing stress and avoiding smoking”. They also urge people to “maintain good personal and environmental hygiene.”

Hong Kong’s hotline for seasonal flu information is on telephone number 2125-1133, open Monday to Friday, 9 am to 6 pm (provided by Centre for Health Protection, CHP).

Click here to keep up to date with seasonal flu in Hong Kong. (CHP).

Sources: CHP press statement, Reuters.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

An article published in the Early Edition of the Proceedings of the National Academy of Sciences in the United States of America suggests that we can reduce the likelihood of a pandemic influenza outbreak in the United States by quickly implementing social-distancing measures alongside antiviral treatment and prophylaxis (preventive measures) until a vaccine becomes accessible.

The study was conducted by three teams of researchers in the US and England who worked closely with federal officials. The teams and an informatics group - part of the Models of Infectious malady Agent Study (MIDAS) Network, funded by the National Institute of General Medical Sciences (NIGMS) - set out to study several intervention combinations to aid the planning process for a national pandemic.

The authors, led by M. Elizabeth Halloran, M.D., D.Sc. and Ira M. Longini Jr., Ph.D., (Fred Hutchinson Cancer Research Center and professors of biostatistics at the University of Washington), investigated the natural course of infectious diseases by using sophisticated mathematical and statistical models. Longini notes that to make sure the results were robust, the federal government wanted three groups to be working on the same problem. The data, says Longini, “would be used to inform national pandemic planning,” and thus they got the highest of the same rank of input.

Since a flu vaccine was not available when the researchers began the study, they focused on the effectiveness of using antiviral and social-distancing interventions (e.g. closing schools) together in order to prevent an influenza pandemic. According to earlier studies, models have shown that an available vaccine, even if low-efficacy, would be helpful in reducing the speed of a pandemic.

Halloran notes: “The good news was that all three of the disease-modeling groups involved in the study found that an outbreak of pandemic flu similar to the pandemic of 1918 could be mitigated if these measures were implemented quickly.”

One research team consisted of Halloran, Longini, a computer scientist Shufu Xu, and others at the Los Alamos National Laboratories. Researchers at Imperial College in London and the University of Pittsburgh comprised a second group, and a third group included researchers at Virginia Bioinformatics Institute at Virginia Tech in Blacksburg, Va.

Each research team used separate but similar computer models. They calculated how influenza would diffuse in a city of about 8.6 million people, such as Chicago, IL. The models assumed that residents of the virtual community interacted in households, schools, workplaces, and the community, just as they usually do. The models all assumed attack-rate patterns that were analogous to US flu pandemics that have occurred in the past.

To take into account real-world unpredictability and several other characteristics of the disease and the population, Halloran and colleagues use stochastic modeling when predicting the spread of influenza. The first step in building pandemic models requires researchers to come up with various assumptions about the ways in which the million interact and how the virus spreads. They can then introduce intervention strategies to the model in order to test how effective they are.

Two categories of intervention were assessed:

1. Medical intervention: surveillance used to identify cases, and antiviral agents are used to treat patients and prevent the disease among close contacts
2. Non-pharmaceutical: social distancing - closing schools, voluntary quarantine, restricting go on foot restrictions

The models allowed researchers to analyze to what degree combinations of targeted antiviral treatment, prophylaxis, and social-distancing strategies affect five intervention scenarios of varying stringency and disease transmissibility levels. Transmissibility of the virus is calculated as the average numeral of secondary cases that each primary case infects at the beginning of the prevailing, and how rapidly these cases arise. These data aid the researchers in estimating the likelihood that an epidemic will become a pandemic.

The three computer simulations predict about 47 to 60 percent of the population will have symptomatic influenza admitting that there is no intervention.

In the least-stringent scenario, interventions were implemented after 1 percent of the population had developed symptomatic influenza, schools were closed, 60 percent of clinical influenza patients received antivirals and their contacts received prophylaxis, 30 percent complied with quarantine, and 60 percent complied with social-distancing measures.

The three computer-modeling groups predict an 83 to 94 percent reduction in cases of influenza using combined intervention strategies at a lower transmissibility of the virus, even in the least-stringent scenario.

Longini maintains that the researchers “ran this simulation with the assumption that the pandemic was as virulent and lethal as the 1918 pandemic.” He adds: “Even when modeling the situation of pandemic flu, with a modest compliance range in social-distancing measures, and modest ability to identify and treat and prophylax with antivirals, the interventions were similarly - though not identically - effective in all three models.”

The researchers believe that the policy implications of these findings are noteworthy. “If one could achieve these levels of compliance, ascertainment and social distancing, then there is a possibility of considerably mitigating a pandemic until a vaccine was available.” They caution, though, that the levels of disease ascertainment and compliance that were entered into the models may not have existence realistic.

“These models, which are built from the best available data and with the best tools, contribute greatly to our understanding of how a pandemic could spread and what measures might protect the public’s health,” said Jeremy M. Berg, Ph.D., director of the NIGMS, which supports the MIDAS program. “But they are not our only means; battle-field work and experimental studies remain critical and will enhance the quality and trustworthiness of these and other models,” conclude the authors.

Modeling targeted layered containment of an influenza pandemic in the United States
M. Elizabeth Halloran, Neil M. Ferguson, Stephen Eubank, Ira M. Longini, Jr., Derek A. T. Cummings, Bryan Lewis, Shufu Xu, Christophe Fraser, Anil Vullikanti, Timothy C. Germann, Diane Wagener, Richard Beckman, Kai Kadau, Chris Barrett, Catherine A. Macken, Donald S. Burke and Philip Cooley
Proceedings of the National Academy of Sciences of the USA. (2008).
doi: 10.1073/pnas.0706849105
Click Here to View Abstract

Written by: Peter M Crosta
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

The U.S. Food and Drug Administration issued an alert on the safe and correct use of Tussionex Pennkinetic Extended-Release Suspension in response to numerous reports of adverse events–including death–associated with the misuse and inappropriate use of this potent cough medication.

Tussionex is a recipe cough medicine containing hydrocodone, a narcotic ingredient, and the antihistamine chlorpheniramine. The product is approved for use in adults and children over the age of six years old, and should be given none more frequently than every 12 hours (”extended-release”).

“There is a real and serious risk for overdosing if this medication is not used according to the labeling,” said Curtis Rosebraugh, M.D., M.P.H., acting director of the FDA’s Office of Drug Evaluation II. “Today’s action is an example of the FDA operating with drug manufacturers throughout a product’s lifecycle to keep health care professionals and patients informed of commencing safety data.”

Adverse event reports associated with Tussionex have included life-threatening side effects and deaths in patients, including children. These reports reveal physicians and other health professionals are sometimes prescribing, and patients are sometimes taking, more than the recommended dose or taking the medication more frequently than every 12 hours. The reports also show that Tussionex is now and then prescribed or given to children less than 6 years old, for whom this medication is not approved.

Highlights of the FDA’s recommendations to health care professionals include:

- Tussionex should not be used (is contraindicated) in patients less than 6 years old. FDA has received reports of death in children less than 6 years of age who have been prescribed Tussionex.

- Consult the prescribing information to determine the correct dose and dosing oftenness of Tussionex. Tussionex is an extended-release formulation that should not be prescribed at an space of time less than 12 hours.

- Discuss with the patient the amount of and frequency of Tussionex to subsist given. Instruct patients not to take, and parents not to administer Tussionex more as a common thing than each 12 hours.

Highlights of the FDA’s recommendations to patients include:

- One of the two ingredients in this long-acting cough product is hydrocodone, a narcotic. Too much hydrocodone can cause life-threatening breathing problems and death. Call your teacher right away if you have taken this medicine and have existence under the necessity trouble breathing, slow heartbeat, severe sleepiness or cold, clammy skin.

- For Tussionex, use a medicine syringe or other device designed to measure liquid medications. A household teaspoon or tablespoon should not be used because the spoons vary in size and you may receive too much or too little of the medicine. Ask your doctor or pharmacist if you are unsure how to mete out the medicine.

- If the cough is not controlled despite taking the prescribed dose at the recommended interval, talk to your doctor.

The manufacturer of Tussionex Pennkinetic Extended-Release Suspension (UCB Inc, Smyrna, Ga.) has agreed to update the labeling, including information that Tussionex should not be prescribed to or used in children not so much than 6 years of age, as well as the need for accurate dosing.

For more information and the full list of the FDA’s recommendations, visit http://www.fda.gov/cder/drug/infopage/hydrocodone/default.htm

This alert does not impact short-acting cough products containing hydrocodone that can be given every 4 to 6 hours. However, the FDA is reviewing safety information on these other hydrocodone containing cough products and will provide updates as new information becomes available.

http://www.fda.gov

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