Novartis unveiled today new data on its promising pipeline amid plans for multiple new product approvals and launches over the next two years. Many of these anticipated approvals are for potentially best-in-class medicines that would advance treatment standards for patients with hypertension, diabetes, cancer and other diseases.
Novartis highlighted progress throughout its pipeline, particularly the advance of pharmaceutical compounds to pivotal trials before regulatory submission as well as the development portfolio in the newly created Vaccines and Diagnostics division.
The following compounds are moving into pivotal late-stage trials: FTY720 (fingolimod) for multiple sclerosis, QAB149 (indacaterol) for COPD and asthma, AG0178 (agomelatine) for depression and ABF656 (Albuferon(TM)) for hepatitis C as well as RAD001 (everolimus) for cancer and SOM230 (pasireotide) for Cushing's disease.
"I am pleased that our sustained focus on innovation and drive to address unmet medical needs have enabled us to further strengthen our pipeline and file several new drugs for regulatory review over the past 12 months," said Dr. Daniel Vasella, Chairman and CEO of Novartis.
"Over the next two years we will launch several innovative medicines and continue to invest aggressively in discovery research and development activities and complement our own skills and technologies through attractive collaborations," Dr. Vasella said.
In total, Novartis now has 138 projects in pharmaceutical clinical development. Of these, 94 projects are in confirmatory development (Phase IIb, Phase III or registration with regulatory authorities). A total of 50 are new molecular entities (NMEs), while 88 are life-cycle management projects involving new indications or formulations.[2] More than 20 projects have been added to the pipeline during 2006. Key R&D areas are cardiovascular/metabolic conditions, oncology and neuroscience as well as respiratory and infectious diseases.
Novartis has completed many submissions in 2006 to regulatory authorities for new compounds as well as new indications for medicines already available to patients.
The US and EU regulatory submissions were accelerated and completed ahead of schedule in 2006 for two compounds: Tasigna (nilotinib) as a new treatment option for patients with resistance and/or intolerance to treatment with Gleevec/Glivec for certain forms of chronic myeloid leukemia (CML), and also for Aclasta/Reclast (zoledronic acid) as a once-yearly bisphosphonate infusion for women with postmenopausal osteoporosis.
US regulatory decisions are also expected for Tekturna (aliskiren), a renin inhibitor for hypertension, and Exforge (valsartan and amlodipine), a single-tablet combination of the two most prescribed hypertension medicines in their respective classes.
Awaiting European Commission approval are Exforge and Lucentis, a new treatment option for patients with the "wet" form of age-related macular degeneration (AMD), after both compounds received positive recommendations in November from the Committee for Medicinal Products for Human Use (CHMP). The Commission generally follows the recommendations of the CHMP and delivers a final decision within two to three months.
A US regulatory decision is also expected in the first half of 2007 for Galvus (vildagliptin) as a once-daily oral treatment for patients with type 2 diabetes. The US Food and Drug Administration (FDA) extended the review period for Galvus by three months from November 2006 after recently available clinical data were submitted to support the proposed dosing and indications as well as complement earlier data on the risk/benefit profile.
Sustained leadership in hypertension
Approvals of Exforge and Tekturna would further strengthen the leadership of Novartis in offering a broad range of treatments for patients with hypertension, complementing the in-market brands Diovan and Lotrel.
High blood pressure - and its consequences - is the world's No. 1 killer, estimated by the American Heart Association to affect one in four adults, or around one billion people globally. Despite extensive use of current therapies, about 70% of all people with high blood pressure do not reach target blood pressure levels. Many require two or more medicines to gain control.
Exforge is the first medicine to combine the angiotensin receptor blocker (ARB) valsartan (Diovan) and the calcium channel blocker (CCB) amlodipine besylate. More than 80% of Exforge patients in studies reached their recommended blood pressure goals and also experienced a lower rate of peripheral edema (swelling of the ankles) compared to those taking amlodipine alone.
Tekturna, which was developed in collaboration with Speedel, has shown a strong efficacy profile in hypertension patients. New data presented at the event showed Tekturna demonstrated a statistically significant (p=0.0004) reduction in blood pressure compared to a diuretic (hydrochlorothiazide), while results from this 12-week trial also showed strong efficacy in combination with the same diuretic in obese patients. Tekturna has shown placebo-like safety at the proposed maximum once-daily dose of 300 mg.
In another new study, the combination of Tekturna and Diovan showed a significant additive reduction in blood pressure compared to Diovan alone, with a drop in systolic blood pressure of about 17 mm Hg compared to about 13 mm Hg for either Tekturna or Diovan alone.
Additional data support efficacy and safety of Galvus
Novartis is confident in the efficacy and safety of Galvus and in obtaining US approval for this once-daily oral treatment for patients with type 2 diabetes. Results from recently completed clinical trials are being submitted to the FDA involving an additional 1,000 patient-years of treatment experience.
These data include results from short- and long-term studies for periods of up to two years, both as a monotherapy or in combination with other anti-diabetes medicines. They further support the proposed dosing regimen and indications as well as complement the risk/benefit profile of Galvus. In particular, they provide further evidence confirming data submitted earlier to the FDA showing that skin findings identified in a single species during a preclinical animal study have not been seen in clinical studies with type 2 diabetes patients.
New data presented at the event again confirmed the once-daily efficacy of Galvus, while pooled monotherapy data showed a 1.1% reduction in HbA1c (a measure of average blood sugar levels) in initial use by type 2 diabetes patients starting treatment. The results of a 104-week trial continued to show the sustained reduction of 1% in HbA1c seen at 52 weeks, but narrowly missed the primary endpoint of non-inferiority versus metformin. However, Galvus was better tolerated than metformin, particularly with a superior gastrointestinal tolerability profile.
Vaccines pipeline supports existing franchises and explores new fields
Novartis has assembled a strong pipeline of investigational human vaccine projects following the acquisition of Chiron in April 2006, focusing on supporting existing franchises in influenza, meningitis and travel vaccines while exploring new disease areas.
Among new data presented at the event were the positive results of a Phase II trial involving 500 volunteers inoculated with an adjuvanted H5N1 pre-pandemic vaccine. Results showed that various levels mandated by European regulators for seroprotection, seroconversion increase and mean geometric increase of H5N1-specific antibodies were achieved. Novartis announced today that this vaccine has been submitted for European approval for use as a pre-pandemic vaccine to boost the immune system's ability to defend against infections from an H5N1 strain.
The OptaFlu seasonal influenza vaccine, which is based on novel cell culture technology instead of traditional egg-based production, showed in pivotal Phase III data that it was highly capable of producing an immune response ("immunogenic"), at least as strong as the egg-based vaccine Agrippal® for each of the three influenza strains studied. It was also well tolerated, showing no meaningful differences in the safety profile compared to traditional egg-based vaccines. The EU submission was completed in 2006, while the US submission is planned for 2008.
Novartis also announced progress in the development of its conjugate quadrivalent MenACWY vaccine against the A, C, W135 and Y serogroups of Neisseria meningitides, important causes of bacterial meningitis. This devastating disease is estimated to strike about three to five of 100,000 people per year - particularly infants and children. Phase III trials involving 13,000 people started in April 2006, targeting regulatory submission for use in infants, adolescents and adults.
A vaccine for the B serogroup of meningitis B, for which there is currently no effective vaccine, is also in Phase II studies to identify dosing in adolescents, with data expected by the end of 2007.
Productive innovation filling the early-stage pipeline
New discovery approaches at the Novartis Institutes for BioMedical Research (NIBR), which was created four years ago to enhance the Group's long tradition of drug discovery, are contributing novel compounds to clinical development.
The number of new molecular entities in the NIBR portfolio has increased to more than 70 in 2006 (compared to 55 in 2004), driven in part by new target discovery, enhanced structural biology, and rapid growth in the number of biological therapeutic drug candidates. These include antibodies, which now constitute about 25% of the NIBR portfolio.
Selected Pipeline Event highlights
Among projects highlighted at the event were the following:
Aclasta/Reclast (zoledronic acid), a once-yearly bisphosphonate treatment for women with postmenopausal osteoporosis, has been submitted for US and EU approval earlier than planned. This was based on pivotal Phase III data showing that patients taking Aclasta/Reclast experienced a highly significant 70% risk reduction in new spine fractures (p
пятница, 30 сентября 2011 г.
вторник, 27 сентября 2011 г.
Yerkes Researchers Create Animal Model Of Chronic Stress
In an effort to better understand how chronic stress affects the human body, researchers at the Yerkes National Primate Research Center and the Department of Psychiatry and Behavioral Sciences, Emory University, have created an animal model that shows how chronic stress affects behavior, physiology and reproduction.
Developing the animal model better positions the researchers to understand the neurohormonal causes of such stress and the body reaction in order to develop more effective treatment options for humans. The study is available in the current online edition of Molecular Psychiatry.
According to lead researcher Mark Wilson, PhD, chief of the Division of Psychobiology at Yerkes, "Chronic stress can lead to a number of behavioral changes and physical health problems, including anxiety, depression and infertility."
Via the animal model, the researchers found corticotropin releasing factor (CRF) is a key neurohormone involved in stress response. Wilson explains, "CRF is located in several different brain regions, serving different functions. Its release is important for our ability to adapt to every day stressors and to maintain our physical and emotional health."
In response to stress, CRF levels rise; CRF levels decrease when the stressor no longer is present. Chronic stress, however, increases the length and volume of expression of CRF in areas of the brain associated with fear and emotion, including the amygdala. Such chronic stress changes the body's response, and the resulting increased expression of CRF is thought to be the cause of such health-related stress problems including anxiety, depression and infertility.
To study the importance of CRF, the research team used a viral vector to increase the production of CRF in the amygdala of female rats.
"In our study, rats that continuously were exposed to CRF from this area of the brain experienced anxious and depressive behavior, decreased libido and disrupted ovarian cycles suggesting that persistent release of CRF such as occurs in chronic stress clearly affects multiple body systems," says Wilson. "These behavioral changes are similar to what we see in human females who are exposed to stressors on a daily basis."
Dr. Wilson and his research team next will attempt to learn more about the negative effects of increased CRF by examining actual molecular and cellular changes in specific brain areas targeted by the neurohormone. Knowing how CRF affects the brain positions the researchers to develop better treatment options.
For more than seven decades, the Yerkes National Primate Research Center, Emory University, has been dedicated to conducting essential basic science and translational research to advance scientific understanding and to improve the health and well-being of humans and nonhuman primates. Today, the center, as one of only eight National Institutes of Health-funded national primate research centers, provides leadership, training and resources to foster scientific creativity, collaboration and discoveries. Yerkes-based research is grounded in scientific integrity, expert knowledge, respect for colleagues, an open exchange of ideas and compassionate, quality animal care.
Within the fields of microbiology and immunology, neuroscience, psychobiology and sensory-motor systems, the center's research programs are seeking ways to: develop vaccines for infectious and noninfectious diseases, such as AIDS and Alzheimer's disease; treat cocaine addiction; interpret brain activity through imaging; increase understanding of progressive illnesses such as Parkinson's and Alzheimer's; unlock the secrets of memory; determine behavioral effects of hormone replacement therapy; address vision disorders; and advance knowledge about the evolutionary links between biology and behavior.
Developing the animal model better positions the researchers to understand the neurohormonal causes of such stress and the body reaction in order to develop more effective treatment options for humans. The study is available in the current online edition of Molecular Psychiatry.
According to lead researcher Mark Wilson, PhD, chief of the Division of Psychobiology at Yerkes, "Chronic stress can lead to a number of behavioral changes and physical health problems, including anxiety, depression and infertility."
Via the animal model, the researchers found corticotropin releasing factor (CRF) is a key neurohormone involved in stress response. Wilson explains, "CRF is located in several different brain regions, serving different functions. Its release is important for our ability to adapt to every day stressors and to maintain our physical and emotional health."
In response to stress, CRF levels rise; CRF levels decrease when the stressor no longer is present. Chronic stress, however, increases the length and volume of expression of CRF in areas of the brain associated with fear and emotion, including the amygdala. Such chronic stress changes the body's response, and the resulting increased expression of CRF is thought to be the cause of such health-related stress problems including anxiety, depression and infertility.
To study the importance of CRF, the research team used a viral vector to increase the production of CRF in the amygdala of female rats.
"In our study, rats that continuously were exposed to CRF from this area of the brain experienced anxious and depressive behavior, decreased libido and disrupted ovarian cycles suggesting that persistent release of CRF such as occurs in chronic stress clearly affects multiple body systems," says Wilson. "These behavioral changes are similar to what we see in human females who are exposed to stressors on a daily basis."
Dr. Wilson and his research team next will attempt to learn more about the negative effects of increased CRF by examining actual molecular and cellular changes in specific brain areas targeted by the neurohormone. Knowing how CRF affects the brain positions the researchers to develop better treatment options.
For more than seven decades, the Yerkes National Primate Research Center, Emory University, has been dedicated to conducting essential basic science and translational research to advance scientific understanding and to improve the health and well-being of humans and nonhuman primates. Today, the center, as one of only eight National Institutes of Health-funded national primate research centers, provides leadership, training and resources to foster scientific creativity, collaboration and discoveries. Yerkes-based research is grounded in scientific integrity, expert knowledge, respect for colleagues, an open exchange of ideas and compassionate, quality animal care.
Within the fields of microbiology and immunology, neuroscience, psychobiology and sensory-motor systems, the center's research programs are seeking ways to: develop vaccines for infectious and noninfectious diseases, such as AIDS and Alzheimer's disease; treat cocaine addiction; interpret brain activity through imaging; increase understanding of progressive illnesses such as Parkinson's and Alzheimer's; unlock the secrets of memory; determine behavioral effects of hormone replacement therapy; address vision disorders; and advance knowledge about the evolutionary links between biology and behavior.
суббота, 24 сентября 2011 г.
Study Of Twins Connects Smoking Addiction With Major Depression
Ever wonder why smoking and depression seem to go together? A Saint Louis University School of Public Health researcher finds the connection is genetic.
"Some people with a history of depression may become smokers as a way of self-medicating," said Qiang John Fu, M.D., Ph.D., assistant professor of community health in biostatistics at Saint Louis University School of Public Health. "Some people who are smokers might become depressed when they try to give up cigarettes and can't.
"When I tried to find something to explain this correlation, I discovered the answer lay partly in a person's genes that are associated with conduct disorder, which is extreme rebellious behavior of teens and children," Dr. Fu continued. "My findings are an alternate explanation about why nicotine dependence and major depression go together."
Dr. Fu also found that the genes that increased a person's risk of developing major depression and nicotine addiction are found in those who have conduct disorder, such as stealing, vandalizing, running away from home and fighting. These people are likely to become addicted to other drugs and behave impulsively, he said.
Dr. Fu and his team analyzed 3,360 pairs of middle-aged, predominantly Caucasian twins who served in the military during the Vietnam War.
Slightly more than half were identical twins who had a 100-percent genetic match and about 45 percent were fraternal twins who shared half their genes. Researchers compared the answers from the twins, and used a mathematical model to estimate the genetic and environmental influences on nicotine addiction and major depression.
"Our data showed that both major depression and nicotine dependence were highly genetically correlated with conduct disorder," Dr. Fu said.
The research also helps to explain why smoking seems to run in some families, Dr. Fu said.
"Maybe Dad and Mom have a certain personality, which is why they may be more likely to smoke or to be depressed. That personality trait may be based in their genes," he said.
The research points geneticists in a new direction to determine the influences of a personality trait, Dr. Fu said. In addition, clinicians could use his findings to identify those who are at risk of developing major depression or nicotine addiction.
"When they see people with a history of conduct disorder, they may be able to predict those people who could develop major depression or nicotine dependence," Dr. Fu said.
The research was funded by grants from the National Institutes of Health. It appeared in Twin Research and Human Genetics.
Saint Louis University School of Public Health is one of only 37 fully accredited schools of public health in the United States and the nation's only School of Public Health sponsored by a Jesuit university. It offers master's degrees and doctoral programs in six public health disciplines and a number of joint degrees involving business, law, medicine, nursing and social work. It is home to 12 nationally recognized research centers and draws students from across the United States and from 21 foreign countries.
"Some people with a history of depression may become smokers as a way of self-medicating," said Qiang John Fu, M.D., Ph.D., assistant professor of community health in biostatistics at Saint Louis University School of Public Health. "Some people who are smokers might become depressed when they try to give up cigarettes and can't.
"When I tried to find something to explain this correlation, I discovered the answer lay partly in a person's genes that are associated with conduct disorder, which is extreme rebellious behavior of teens and children," Dr. Fu continued. "My findings are an alternate explanation about why nicotine dependence and major depression go together."
Dr. Fu also found that the genes that increased a person's risk of developing major depression and nicotine addiction are found in those who have conduct disorder, such as stealing, vandalizing, running away from home and fighting. These people are likely to become addicted to other drugs and behave impulsively, he said.
Dr. Fu and his team analyzed 3,360 pairs of middle-aged, predominantly Caucasian twins who served in the military during the Vietnam War.
Slightly more than half were identical twins who had a 100-percent genetic match and about 45 percent were fraternal twins who shared half their genes. Researchers compared the answers from the twins, and used a mathematical model to estimate the genetic and environmental influences on nicotine addiction and major depression.
"Our data showed that both major depression and nicotine dependence were highly genetically correlated with conduct disorder," Dr. Fu said.
The research also helps to explain why smoking seems to run in some families, Dr. Fu said.
"Maybe Dad and Mom have a certain personality, which is why they may be more likely to smoke or to be depressed. That personality trait may be based in their genes," he said.
The research points geneticists in a new direction to determine the influences of a personality trait, Dr. Fu said. In addition, clinicians could use his findings to identify those who are at risk of developing major depression or nicotine addiction.
"When they see people with a history of conduct disorder, they may be able to predict those people who could develop major depression or nicotine dependence," Dr. Fu said.
The research was funded by grants from the National Institutes of Health. It appeared in Twin Research and Human Genetics.
Saint Louis University School of Public Health is one of only 37 fully accredited schools of public health in the United States and the nation's only School of Public Health sponsored by a Jesuit university. It offers master's degrees and doctoral programs in six public health disciplines and a number of joint degrees involving business, law, medicine, nursing and social work. It is home to 12 nationally recognized research centers and draws students from across the United States and from 21 foreign countries.
среда, 21 сентября 2011 г.
Depression Traced to Overactive Brain Circuit
A brain imaging study by the NIH's National Institute of Mental Health (NIMH) has found that an emotion-regulating brain circuit is overactive in people prone to depression - even when they are not depressed. Researchers discovered the abnormality in brains of those whose depressions relapsed when a key brain chemical messenger was experimentally reduced. Even when in remission, most subjects with a history of mood disorder experienced a temporary recurrence of symptoms when their brains were experimentally sapped of tryptophan, the chemical precursor of serotonin, the neurotransmitter that is boosted by antidepressants.
Neither a placebo procedure in patients nor tryptophan depletion in healthy volunteers triggered the mood and brain activity changes. Brain scans revealed that a key emotion-processing circuit was overactive only in patients in remission - whether or not they had re-experienced symptoms - and not in controls. Since the abnormal activity did not reflect mood state, the finding suggests that tryptophan depletion unmasks an inborn trait associated with depression.
Alexander Neumeister, M.D., Dennis Charney, M.D., Wayne Drevets, M.D., NIMH Mood and Anxiety Disorders Program, and colleagues, report on their positron emission tomography (PET) scan study in the August 2004 Archives of General Psychiatry.
The NIMH researchers and others had previously shown that omitting tryptophan from a cocktail of several other essential amino acids washes out the precursor chemical from the blood and brain, depleting serotonin and often triggering symptoms in people with a history of depression - and even in healthy people from depression-prone families. This added to evidence that a genetic predisposition that renders some people vulnerable to inadequate serotonin activity may be at the root of the mood disorder.
The researchers scanned subjects after their blood tryptophan levels were reduced by about three-fourths, using a radioactive tracer (a form of glucose, the brain's fuel) which reveals where the brain is active during a particular experimental condition.
They randomly gave 27 unmedicated depressed patients-in-remission and 19 controls either pills containing seven essential amino acids, such as lysine and valine, or identical-looking placebo pills. Subjects received either the active pills or placebos in repeated trials over several days in a blind, crossover design.
Sixteen (59 percent) of the patients experienced a transient return of symptoms under tryptophan depletion; their mood lifted to normal by the next day. Compared to controls, the patients showed increased brain activity in a circuit coursing through the front and center of the brain (orbitofrontal cortex, thalamus, anterior cingulate, and ventral striatum) - areas involved in regulating emotions and motivation that have been implicated in previous studies of depression. Whereas previous studies interpreted the circuit activation as a transient, mood-dependent phenomenon, the new evidence suggests that circuit over-activation is likely an underlying vulnerability trait, say the researchers.
Because of its ability to unmask what appears to be a trait marker for major depressive disorder, the researchers suggest that tryptophan depletion may be a useful tool for studying the genetic basis of depression.
"Since brain function appears to be disregulated even when patients are in remission, they need to continue long-term treatment beyond the symptomatic phase of their illness," noted Neumeister, who recently moved to the Yale University psychiatry department.
Also participating in the research were: Drs. Allison Nugent, Tracy Waldeck, Omer Bonne, Earl Bain and Marilla Geraci, David Luckenbaugh, NIMH; Dr. Markus Schwarz, Munich University Hospital of Psychiatry, Dr. Peter Herscovitch, NIH Clinical Center PET Department.
NIMH is part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.
Graphic: nimh.nih/press/prtdcircuit.cfm#graphic
CONTACT:
Jules Asher
NIMH press office
301-443-4536
Neither a placebo procedure in patients nor tryptophan depletion in healthy volunteers triggered the mood and brain activity changes. Brain scans revealed that a key emotion-processing circuit was overactive only in patients in remission - whether or not they had re-experienced symptoms - and not in controls. Since the abnormal activity did not reflect mood state, the finding suggests that tryptophan depletion unmasks an inborn trait associated with depression.
Alexander Neumeister, M.D., Dennis Charney, M.D., Wayne Drevets, M.D., NIMH Mood and Anxiety Disorders Program, and colleagues, report on their positron emission tomography (PET) scan study in the August 2004 Archives of General Psychiatry.
The NIMH researchers and others had previously shown that omitting tryptophan from a cocktail of several other essential amino acids washes out the precursor chemical from the blood and brain, depleting serotonin and often triggering symptoms in people with a history of depression - and even in healthy people from depression-prone families. This added to evidence that a genetic predisposition that renders some people vulnerable to inadequate serotonin activity may be at the root of the mood disorder.
The researchers scanned subjects after their blood tryptophan levels were reduced by about three-fourths, using a radioactive tracer (a form of glucose, the brain's fuel) which reveals where the brain is active during a particular experimental condition.
They randomly gave 27 unmedicated depressed patients-in-remission and 19 controls either pills containing seven essential amino acids, such as lysine and valine, or identical-looking placebo pills. Subjects received either the active pills or placebos in repeated trials over several days in a blind, crossover design.
Sixteen (59 percent) of the patients experienced a transient return of symptoms under tryptophan depletion; their mood lifted to normal by the next day. Compared to controls, the patients showed increased brain activity in a circuit coursing through the front and center of the brain (orbitofrontal cortex, thalamus, anterior cingulate, and ventral striatum) - areas involved in regulating emotions and motivation that have been implicated in previous studies of depression. Whereas previous studies interpreted the circuit activation as a transient, mood-dependent phenomenon, the new evidence suggests that circuit over-activation is likely an underlying vulnerability trait, say the researchers.
Because of its ability to unmask what appears to be a trait marker for major depressive disorder, the researchers suggest that tryptophan depletion may be a useful tool for studying the genetic basis of depression.
"Since brain function appears to be disregulated even when patients are in remission, they need to continue long-term treatment beyond the symptomatic phase of their illness," noted Neumeister, who recently moved to the Yale University psychiatry department.
Also participating in the research were: Drs. Allison Nugent, Tracy Waldeck, Omer Bonne, Earl Bain and Marilla Geraci, David Luckenbaugh, NIMH; Dr. Markus Schwarz, Munich University Hospital of Psychiatry, Dr. Peter Herscovitch, NIH Clinical Center PET Department.
NIMH is part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.
Graphic: nimh.nih/press/prtdcircuit.cfm#graphic
CONTACT:
Jules Asher
NIMH press office
301-443-4536
воскресенье, 18 сентября 2011 г.
UNC Study Pinpoints Gene Controlling Number Of Brain Cells
The finding suggests that a single gene, called GSK-3, controls the signals that determine how many neurons actually end up composing the brain. This has important implications for patients with neuropsychiatric illness, as links have recently been drawn between GSK-3 and schizophrenia, depression and bipolar disorder.
In populating the growing brain, neural stem cells must strike a delicate balance between two key processes - proliferation, in which the cells multiply to provide plenty of starting materials - and differentiation, in which those materials evolve into functioning neurons.
If the stem cells proliferate too much, they could grow out of control and produce a tumor. If they proliferate too little, there may not be enough cells to become the billions of neurons of the brain. Researchers at the University of North Carolina at Chapel Hill School of Medicine have now found that this critical balance rests in large part on a single gene, called GSK-3.
The finding suggests that GSK-3 controls the signals that determine how many neurons actually end up composing the brain. It also has important implications for patients with neuropsychiatric illness, as links have recently been drawn between GSK-3 and schizophrenia, depression and bipolar disorder.
One of the genes associated with schizophrenia appears to use GSK-3 as an intermediary to exert its effects on nerve cells. In addition, lithium, a popular treatment for bipolar disorder, acts, in part, by shutting down GSK-3. "I don't believe anyone would have imagined that deleting GSK-3 would have such dramatic effects on neural stem cells," said senior study author William D. Snider, M.D., professor of neurology and cell and molecular physiology, and director of the UNC Neuroscience Center. "People will have to think carefully about whether giving a drug like lithium to children could have negative effects on the underlying structure of the nervous system."
In a study appearing online October 4th in the journal Nature Neuroscience, Snider and his colleagues created a mouse model in which both forms of the GSK-3 gene - designated alpha and beta - had been deleted. They decided to go after GSK-3 - which stands for glycogen synthase kinase 3 - because it is one of the most studied kinases or signaling molecules in all of biology.
The researchers used a "conditional knock-out" strategy to remove GSK-3 at a specific time in the development of the mouse embryo, when a type of cell called a radial progenitor cell had just been formed.
As the brain develops, neural stem cells evolve through three different stages -- neural epithelial cells, radial progenitor cells and intermediate neural precursors. The radial progenitor cells are especially important because they are thought to provide the majority of the neurons of the developing brain but also differentiate themselves to give rise to all the cellular elements of the brain. The researchers discovered that deleting GSK-3 during this second phase of development caused the radial progenitor cells to be locked in a constant state of proliferation.
"It was really quite striking," said Snider. "Without GSK-3, these neural stem cells just keep dividing and dividing and dividing. The entire developing brain fills up with these neural stem cells that never turn into mature neurons."
GSK-3 is known to coordinate signals for proliferation and differentiation within nerve cells through multiple "signaling pathways." Thus, the researchers looked to see what effect deleting the molecule had on some of these pathways. They found that every one of the pathways that they studied went awry.
Snider and his colleagues now want to see if adding GSK-3 back to their genetically engineered mice can convert the proliferating stem cells into neurons, possibly resulting in three to four times as many neurons in the mutants as normal.
"I find that quite interesting because I can't think of any other manipulation that potentially would enable you to simply dial up and down the number of neurons that are generated in the brain," said Snider.
Funding for the studies led at UNC came from the National Institutes of Health. Study co-authors from Snider's laboratory at UNC include lead author Woo-Yang Kim, Ph.D., postdoctoral research associate; Xinshuo Wang, graduate student and Yaohong Wu, chief technician. Researchers from the laboratory of James R. Woodgett, Ph.D. at the University of Toronto also collaborated on the project.
In populating the growing brain, neural stem cells must strike a delicate balance between two key processes - proliferation, in which the cells multiply to provide plenty of starting materials - and differentiation, in which those materials evolve into functioning neurons.
If the stem cells proliferate too much, they could grow out of control and produce a tumor. If they proliferate too little, there may not be enough cells to become the billions of neurons of the brain. Researchers at the University of North Carolina at Chapel Hill School of Medicine have now found that this critical balance rests in large part on a single gene, called GSK-3.
The finding suggests that GSK-3 controls the signals that determine how many neurons actually end up composing the brain. It also has important implications for patients with neuropsychiatric illness, as links have recently been drawn between GSK-3 and schizophrenia, depression and bipolar disorder.
One of the genes associated with schizophrenia appears to use GSK-3 as an intermediary to exert its effects on nerve cells. In addition, lithium, a popular treatment for bipolar disorder, acts, in part, by shutting down GSK-3. "I don't believe anyone would have imagined that deleting GSK-3 would have such dramatic effects on neural stem cells," said senior study author William D. Snider, M.D., professor of neurology and cell and molecular physiology, and director of the UNC Neuroscience Center. "People will have to think carefully about whether giving a drug like lithium to children could have negative effects on the underlying structure of the nervous system."
In a study appearing online October 4th in the journal Nature Neuroscience, Snider and his colleagues created a mouse model in which both forms of the GSK-3 gene - designated alpha and beta - had been deleted. They decided to go after GSK-3 - which stands for glycogen synthase kinase 3 - because it is one of the most studied kinases or signaling molecules in all of biology.
The researchers used a "conditional knock-out" strategy to remove GSK-3 at a specific time in the development of the mouse embryo, when a type of cell called a radial progenitor cell had just been formed.
As the brain develops, neural stem cells evolve through three different stages -- neural epithelial cells, radial progenitor cells and intermediate neural precursors. The radial progenitor cells are especially important because they are thought to provide the majority of the neurons of the developing brain but also differentiate themselves to give rise to all the cellular elements of the brain. The researchers discovered that deleting GSK-3 during this second phase of development caused the radial progenitor cells to be locked in a constant state of proliferation.
"It was really quite striking," said Snider. "Without GSK-3, these neural stem cells just keep dividing and dividing and dividing. The entire developing brain fills up with these neural stem cells that never turn into mature neurons."
GSK-3 is known to coordinate signals for proliferation and differentiation within nerve cells through multiple "signaling pathways." Thus, the researchers looked to see what effect deleting the molecule had on some of these pathways. They found that every one of the pathways that they studied went awry.
Snider and his colleagues now want to see if adding GSK-3 back to their genetically engineered mice can convert the proliferating stem cells into neurons, possibly resulting in three to four times as many neurons in the mutants as normal.
"I find that quite interesting because I can't think of any other manipulation that potentially would enable you to simply dial up and down the number of neurons that are generated in the brain," said Snider.
Funding for the studies led at UNC came from the National Institutes of Health. Study co-authors from Snider's laboratory at UNC include lead author Woo-Yang Kim, Ph.D., postdoctoral research associate; Xinshuo Wang, graduate student and Yaohong Wu, chief technician. Researchers from the laboratory of James R. Woodgett, Ph.D. at the University of Toronto also collaborated on the project.
четверг, 15 сентября 2011 г.
Doctors Must Look After Their Health Too - British Medical Journal
Short term counselling followed by a modest cut in work hours may help reduce emotional exhaustion (burnout) and sick leave in doctors, according to a study published on bmj today.
It is well known that doctors have higher rates of depression and suicide than the general population and are less likely to seek help. There have been calls for early intervention programmes to help doctors with mental distress and burnout before their problems interfere with the welfare of patients.
Although such programmes have been shown to reduce stress and exhaustion, it is not clear what type of intervention is best suited to which individual or personal characteristics, or which factors contribute to positive changes.
Dr Karin R?? and colleagues from Norway examined levels of burnout and predictors of reduction in emotional exhaustion after one year, in 227 stressed doctors who participated in voluntary counselling.
Initially, 187 doctors attended a one day individual session, and 40 a one week group based course. Of the 185 doctors who completed follow-up assessments, 70 returned for an additional intervention during the follow-up year, 51 to a one week course and 19 to an individual session.
They completed self report assessments in the four weeks before and the three weeks after the counselling, and a follow-up questionnaire after one year. The data was compared with data obtained from a representative sample of Norwegian doctors in 2003.
One year after a counselling intervention stressed doctors reported a reduction in emotional exhaustion and job stress similar to the level found in a representative sample of Norwegian doctors.
The researchers also found that the number of doctors on full time sick leave had reduced substantially in the year after counselling (35% to 6%), and that the use of psychotherapy also substantially increased from 20% to 53% in the follow-up year.
Interestingly, they found that reduction in work hours after the intervention was also associated with a reduction in emotional exhaustion.
"Our findings indicate that seeking a counselling intervention could be conducive to reduction of burnout among doctors. Considering doctors' reluctance to seek help??¦it is important to offer interventions that facilitate access", conclude the authors.
"Research paper: Counselling for burnout in Norwegian doctors: one year cohort study."
Karin E Isaksson R??, Tore Gude, Reidar Tyssen, Olaf G Aasland
BMJ 2008;337:a2004
Click here to view abstract online
British Medical Journal
It is well known that doctors have higher rates of depression and suicide than the general population and are less likely to seek help. There have been calls for early intervention programmes to help doctors with mental distress and burnout before their problems interfere with the welfare of patients.
Although such programmes have been shown to reduce stress and exhaustion, it is not clear what type of intervention is best suited to which individual or personal characteristics, or which factors contribute to positive changes.
Dr Karin R?? and colleagues from Norway examined levels of burnout and predictors of reduction in emotional exhaustion after one year, in 227 stressed doctors who participated in voluntary counselling.
Initially, 187 doctors attended a one day individual session, and 40 a one week group based course. Of the 185 doctors who completed follow-up assessments, 70 returned for an additional intervention during the follow-up year, 51 to a one week course and 19 to an individual session.
They completed self report assessments in the four weeks before and the three weeks after the counselling, and a follow-up questionnaire after one year. The data was compared with data obtained from a representative sample of Norwegian doctors in 2003.
One year after a counselling intervention stressed doctors reported a reduction in emotional exhaustion and job stress similar to the level found in a representative sample of Norwegian doctors.
The researchers also found that the number of doctors on full time sick leave had reduced substantially in the year after counselling (35% to 6%), and that the use of psychotherapy also substantially increased from 20% to 53% in the follow-up year.
Interestingly, they found that reduction in work hours after the intervention was also associated with a reduction in emotional exhaustion.
"Our findings indicate that seeking a counselling intervention could be conducive to reduction of burnout among doctors. Considering doctors' reluctance to seek help??¦it is important to offer interventions that facilitate access", conclude the authors.
"Research paper: Counselling for burnout in Norwegian doctors: one year cohort study."
Karin E Isaksson R??, Tore Gude, Reidar Tyssen, Olaf G Aasland
BMJ 2008;337:a2004
Click here to view abstract online
British Medical Journal
понедельник, 12 сентября 2011 г.
The International Neuromodulation Society Reports Record Growth In Professional Membership And Attendance At World Congress
The International Neuromodulation Society (INS) announced that it now represents a professional association of more than 1200 members worldwide, approximately twice as many members as recorded at the close of 2006. With a presence in 33 countries internationally, the INS also welcomed five new national chapters last year: Brazil, Canada, China, France and Korea. The Society's burgeoning growth mirrors the expected growth of the neurotechnology market, which is projected to reach $8.8 billion by 2012.*
Neuromodulation is the alteration -- or modulation -- of nerve activity through the delivery of electrical stimulation or chemical agents to targeted sites of the body.
"Our surge in membership reflects not only the tremendous progress that is taking place in the neuromodulation industry, but also an increased appreciation for the International Neuromodulation Society's dedication to its members and representation of the industry worldwide," said Elliot S. Krames, MD, President of the INS and Editor-in-Chief of the journal "Neuromodulation." "The role of the INS is three-fold: to increase awareness and understanding of neuromodulation, to accelerate physician and patient access to therapies and to provide a forum for researchers, physicians, engineers and other key contributors to foster education for this fastest growing segment in medicine today."
Analysts predict a 27 percent annual growth rate in the neuromodulation industry between 2008 and 2012. As regulators approve new treatments for such ailments as psychiatric disorders, epilepsy and traumatic brain injury using deep brain stimulation, the market for this branch of neuromodulation is projected to reach $461 million in 2008 and $1.36 billion by 2012. It is also projected that sales of neuromodulation devices for treatment of obesity-related disorders will reach $479 million by 2012.* Neuromodulation treatments also address conditions such as chronic pain, incontinence, overactive bladder, hearing disorders, Parkinson disease, essential tremor and dystonia. Treatments for blindness, tinnitus and gastrointestinal disorders are currently in development.
"Neuromodulation has now reached a level of commercial and scientific maturity that is producing enormous benefits to patients and profits to investors," said James Cavuoto, Editor and Publisher of Neurotech Reports. "As the epicenter for neuromodulation, the INS is positioned to have a unique and profound role in the continued growth of this industry."
In addition to reporting its highest achievement in membership, the biennial INS World Congress in Acapulco, Mexico last December marked the Society's largest conference to date. Nearly 700 individuals representing 30 countries attended the five-day conference, and more than 260 poster and oral presentations covered the latest developments in neuromodulation. The 2009 World Congress is scheduled to take place in South Korea.
Also in 2007, the INS was named the Most Valuable Nonprofit Society by Neurotech Reports and was awarded the Golden Electrode Award at the 2007 Neurotech Leaders Forum. Additionally, the INS was a recipient of a grant from the National Institute of Neurological Disorders and Stroke (NINDS), a branch of the National Institute of Health (NIH), in support of its scientific meetings.
About The International Neuromodulation Society
The International Neuromodulation Society (INS) is a non-profit group of clinicians, scientists and engineers dedicated to the scientific development and awareness of neuromodulation -- the alteration of nerve activity through the delivery of electrical stimulation or chemical agents to targeted sites of the body. Founded in 1989 and based in San Francisco, CA, the INS educates and promotes the field through meetings, its journal Neuromodulation and chapter websites. For more information, please visit neuromodulation.
* Neurotech Reports. "Neurotech Reports Releases Market Projections through 2012."December 2007.
The International Neuromodulation Society
Neuromodulation is the alteration -- or modulation -- of nerve activity through the delivery of electrical stimulation or chemical agents to targeted sites of the body.
"Our surge in membership reflects not only the tremendous progress that is taking place in the neuromodulation industry, but also an increased appreciation for the International Neuromodulation Society's dedication to its members and representation of the industry worldwide," said Elliot S. Krames, MD, President of the INS and Editor-in-Chief of the journal "Neuromodulation." "The role of the INS is three-fold: to increase awareness and understanding of neuromodulation, to accelerate physician and patient access to therapies and to provide a forum for researchers, physicians, engineers and other key contributors to foster education for this fastest growing segment in medicine today."
Analysts predict a 27 percent annual growth rate in the neuromodulation industry between 2008 and 2012. As regulators approve new treatments for such ailments as psychiatric disorders, epilepsy and traumatic brain injury using deep brain stimulation, the market for this branch of neuromodulation is projected to reach $461 million in 2008 and $1.36 billion by 2012. It is also projected that sales of neuromodulation devices for treatment of obesity-related disorders will reach $479 million by 2012.* Neuromodulation treatments also address conditions such as chronic pain, incontinence, overactive bladder, hearing disorders, Parkinson disease, essential tremor and dystonia. Treatments for blindness, tinnitus and gastrointestinal disorders are currently in development.
"Neuromodulation has now reached a level of commercial and scientific maturity that is producing enormous benefits to patients and profits to investors," said James Cavuoto, Editor and Publisher of Neurotech Reports. "As the epicenter for neuromodulation, the INS is positioned to have a unique and profound role in the continued growth of this industry."
In addition to reporting its highest achievement in membership, the biennial INS World Congress in Acapulco, Mexico last December marked the Society's largest conference to date. Nearly 700 individuals representing 30 countries attended the five-day conference, and more than 260 poster and oral presentations covered the latest developments in neuromodulation. The 2009 World Congress is scheduled to take place in South Korea.
Also in 2007, the INS was named the Most Valuable Nonprofit Society by Neurotech Reports and was awarded the Golden Electrode Award at the 2007 Neurotech Leaders Forum. Additionally, the INS was a recipient of a grant from the National Institute of Neurological Disorders and Stroke (NINDS), a branch of the National Institute of Health (NIH), in support of its scientific meetings.
About The International Neuromodulation Society
The International Neuromodulation Society (INS) is a non-profit group of clinicians, scientists and engineers dedicated to the scientific development and awareness of neuromodulation -- the alteration of nerve activity through the delivery of electrical stimulation or chemical agents to targeted sites of the body. Founded in 1989 and based in San Francisco, CA, the INS educates and promotes the field through meetings, its journal Neuromodulation and chapter websites. For more information, please visit neuromodulation.
* Neurotech Reports. "Neurotech Reports Releases Market Projections through 2012."December 2007.
The International Neuromodulation Society
пятница, 9 сентября 2011 г.
New Data Suggests Doctors Might Not Be Considering Depression Symptoms That Are Important To Patients, Such As Pain And Anxiety
Doctors and depressed patients judge symptom severity and improvement following pharmacotherapy differently, according to data presented at the 20th Annual Meeting of the European College of Neuropsychopharmacology (ECNP) in Vienna, Austria. The data suggest physicians might not be considering symptoms that are important in the eyes of patients, such as pain and anxiety.1
The results are based on a post-hoc analysis of a double-blind, placebo-controlled, multi-center European study in adults with major depressive disorder (MDD) and non-specific pain (n=327). This analysis aimed to compare how patients and physicians estimate overall disease severity at baseline and symptom improvement during short-term treatment of major depression, regardless of treatment group.1 Results showed that physicians treating these patients consider only physician-rated depressive symptoms (as assessed by the Montgomery-Asperg-Depressions Scale or MADRS) when assessing how sick the patient is and whether the patient is getting better. Patients, on the other hand also consider pain and anxiety when judging their own improvement.1
"Previous evidence has suggested that treating both the emotional and the physical symptoms of depression provides patients with the best chance of reaching remission," said Professor Koen Demyttenaere, Department of Psychiatry, University Hospital Gasthuisberg, Leuven, Belgium and lead author of this study. "These qualitative results highlight the need for physicians to also consider a broad spectrum of symptoms including pain and anxiety when treating patients with Major Depressive Disorder and associated pain."
Study results
The two main findings of this new analysis are:
- Disease Severity: At the beginning of the study, physician assessment of the overall disease severity was significantly predicted by depression severity (using the MADRS evaluation tool) and paranoid ideation (as measured by the Symptom Checklist, or SCL-90-R); pain was not a consideration.1 After eight weeks of treatment, physicians' assessment of overall disease severity was significantly predicted by decrease in depression severity (MADRS), being female and of younger age. Among physicians, pain again was not predictive of disease severity.1
- Disease Improvement: Among physicians, overall disease improvement at study end, measured by the Clinical Global Impression of Improvement scale (CGI-I), was significantly positively predicted by decrease in MADRS-rated severity; by decrease in distress in interpersonal sensitivity (measured by the SCL-90-R); and negatively predicted by an older age.1 In contrast, patient rated improvement included improvement in pain. Significant predictors of patient-assessed improvement (as measured by the Patient Global Impression of Improvement scale) were a decrease in pain severity (based on average pain, as measured by the Brief Pain Inventory scale or BPI) depression and anxiety according to SCL-90-R subdomains.1
Furthermore, in this study, the similarity of patient rated disease improvement (PGI-I) and physician rated disease improvement (CGI-I) was investigated by descriptive statistics and a prediction model. In 44.7 percent of cases there was a discrepancy in improvement assessments. In cases of discrepancy, the mean improvement was usually judged higher by physicians than patients (36.3 percent versus 8.4 percent) irrespective of treatment. A lower decrease in MADRS assessed depression severity, pain interference in relation with other people and in interpersonal sensitivity significantly predicted a lower discrepancy between patient and physician improvement. A lower decrease in patient rated pain severity (BPI) and depression (SCL-90-R) significantly predicted a higher discrepancy between physician and patient rated improvement, with the physician rating improvement being higher.
These results provide evidence on the relative importance of different symptoms in depression from a patient perspective and the need to focus beyond core depressive symptoms, when treating depressed patients.
About the Study1
Methodology
Data were derived from a double-blind, placebo-controlled, multi-center study conducted in Belgium, Finland, France, Germany and Slovakia in outpatients ?‰?18 years of age who presented with major depressive disorder (baseline disease severity defined as a Montgomery-Asberg Depression Rating Scale [MADRS] ?‰?20 and Clinical Global Impression-Severity [CGI-S] scale ?‰?4) and moderate pain not attributable to a diagnosed organic pain syndrome (Brief Pain Inventory-Short Form [BPI-SF] average pain score ?‰?3). Physicians were asked to rate severity of depression by using the MADRS, CGI-Severity and Improvement scales. Patients were asked to assess pain using the BPI-SF, psychological symptomatology (including depression) with the symptom checklist 90 items revised (SCL-90-R), and overall improvement after pharmacotherapy with the Patient Global Impression of Improvement (PGI-I). Using a five percent threshold, multivariate regressions were performed as post-hoc analyses to identify predictors of disease assessment at baseline and at the end of the study (LOCF). The study was sponsored by Eli Lilly and Company and Boehringer Ingelheim GmbH.
About Depression
Major Depressive Disorder (MDD) affects approximately 121 million people worldwide.2 The World Health Organization estimates depression will be among the highest-ranking causes of disability in developed countries by 2020, second only to ischemic heart disease worldwide.3 It can happen to anyone of any age, race or ethnicity; however, women are nearly twice as likely to experience depression as men.4 Although it is one of the most frequently seen psychiatric disorders in the primary care setting,5,6 it often goes undiagnosed or is under-treated.2,7 This might be because depressed people often present with physical symptoms rather than emotional complaints; in one large study, 69 percent of patients with MDD reported only physical symptoms as the reason for visiting their physician.8
Complete elimination of symptoms, or remission, is the primary goal of depression treatment. Treating the full spectrum of emotional and physical symptoms to remission significantly decreases a patient's risk of relapse.9
Eli Lilly and Company and Boehringer Ingelheim
In November 2002, Eli Lilly and Company and Boehringer Ingelheim signed a long-term agreement to jointly develop and commercialize duloxetine hydrochloride. This partnership covers neuroscience indications in most countries outside of the United States and Japan, with few exceptions.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world`s most urgent medical needs.
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 137 affiliates in 47 countries and
38,400 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2006, Boehringer Ingelheim posted net sales of 10.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.
References:
1 Demyttenaere KD, et al. Patient-versus Physician-assessed Disease Severity and Outcomes in Patients with Non- specific Pain Associated with Depression
2 World Health Organization. Factsheet - Depression, 2005. Available here. Last visited 26 April 2007
3 Murray CJL, Lopez AD, eds. The Global Burden of Disease; 1996.
4 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision. Washington DC: American Psychiatric Association; 2000:345-428.
5 Ormel J, et al. Common mental disorders and disability across cultures: results from the WHO Collaborative Study on Psychological Problems in General Health Care. JAMA. 1994;272:1741-1748.
6 Spitzer RL, et al. Utility of a new procedure for diagnosing mental disorders in primary care: the PRIME-MD 1000 study. JAMA. 1994;272:1749-1756.
7 Ormel J, Koeter MWJ, van den Brink W, van de Willige G. Recognition, management, and course of anxiety and depression in general practice. Arch Gen Psychiatry. 1991;48:700-706.
8 Simon GE et al. An International Study of the Relation Between Somatic Symptoms and Depression. New Engl J Med. 1999;341(18):1329-35.
9 Paykel ES, et al. Psychol Med. 1995;25(6):1171-1180.
boehringer-ingelheim
The results are based on a post-hoc analysis of a double-blind, placebo-controlled, multi-center European study in adults with major depressive disorder (MDD) and non-specific pain (n=327). This analysis aimed to compare how patients and physicians estimate overall disease severity at baseline and symptom improvement during short-term treatment of major depression, regardless of treatment group.1 Results showed that physicians treating these patients consider only physician-rated depressive symptoms (as assessed by the Montgomery-Asperg-Depressions Scale or MADRS) when assessing how sick the patient is and whether the patient is getting better. Patients, on the other hand also consider pain and anxiety when judging their own improvement.1
"Previous evidence has suggested that treating both the emotional and the physical symptoms of depression provides patients with the best chance of reaching remission," said Professor Koen Demyttenaere, Department of Psychiatry, University Hospital Gasthuisberg, Leuven, Belgium and lead author of this study. "These qualitative results highlight the need for physicians to also consider a broad spectrum of symptoms including pain and anxiety when treating patients with Major Depressive Disorder and associated pain."
Study results
The two main findings of this new analysis are:
- Disease Severity: At the beginning of the study, physician assessment of the overall disease severity was significantly predicted by depression severity (using the MADRS evaluation tool) and paranoid ideation (as measured by the Symptom Checklist, or SCL-90-R); pain was not a consideration.1 After eight weeks of treatment, physicians' assessment of overall disease severity was significantly predicted by decrease in depression severity (MADRS), being female and of younger age. Among physicians, pain again was not predictive of disease severity.1
- Disease Improvement: Among physicians, overall disease improvement at study end, measured by the Clinical Global Impression of Improvement scale (CGI-I), was significantly positively predicted by decrease in MADRS-rated severity; by decrease in distress in interpersonal sensitivity (measured by the SCL-90-R); and negatively predicted by an older age.1 In contrast, patient rated improvement included improvement in pain. Significant predictors of patient-assessed improvement (as measured by the Patient Global Impression of Improvement scale) were a decrease in pain severity (based on average pain, as measured by the Brief Pain Inventory scale or BPI) depression and anxiety according to SCL-90-R subdomains.1
Furthermore, in this study, the similarity of patient rated disease improvement (PGI-I) and physician rated disease improvement (CGI-I) was investigated by descriptive statistics and a prediction model. In 44.7 percent of cases there was a discrepancy in improvement assessments. In cases of discrepancy, the mean improvement was usually judged higher by physicians than patients (36.3 percent versus 8.4 percent) irrespective of treatment. A lower decrease in MADRS assessed depression severity, pain interference in relation with other people and in interpersonal sensitivity significantly predicted a lower discrepancy between patient and physician improvement. A lower decrease in patient rated pain severity (BPI) and depression (SCL-90-R) significantly predicted a higher discrepancy between physician and patient rated improvement, with the physician rating improvement being higher.
These results provide evidence on the relative importance of different symptoms in depression from a patient perspective and the need to focus beyond core depressive symptoms, when treating depressed patients.
About the Study1
Methodology
Data were derived from a double-blind, placebo-controlled, multi-center study conducted in Belgium, Finland, France, Germany and Slovakia in outpatients ?‰?18 years of age who presented with major depressive disorder (baseline disease severity defined as a Montgomery-Asberg Depression Rating Scale [MADRS] ?‰?20 and Clinical Global Impression-Severity [CGI-S] scale ?‰?4) and moderate pain not attributable to a diagnosed organic pain syndrome (Brief Pain Inventory-Short Form [BPI-SF] average pain score ?‰?3). Physicians were asked to rate severity of depression by using the MADRS, CGI-Severity and Improvement scales. Patients were asked to assess pain using the BPI-SF, psychological symptomatology (including depression) with the symptom checklist 90 items revised (SCL-90-R), and overall improvement after pharmacotherapy with the Patient Global Impression of Improvement (PGI-I). Using a five percent threshold, multivariate regressions were performed as post-hoc analyses to identify predictors of disease assessment at baseline and at the end of the study (LOCF). The study was sponsored by Eli Lilly and Company and Boehringer Ingelheim GmbH.
About Depression
Major Depressive Disorder (MDD) affects approximately 121 million people worldwide.2 The World Health Organization estimates depression will be among the highest-ranking causes of disability in developed countries by 2020, second only to ischemic heart disease worldwide.3 It can happen to anyone of any age, race or ethnicity; however, women are nearly twice as likely to experience depression as men.4 Although it is one of the most frequently seen psychiatric disorders in the primary care setting,5,6 it often goes undiagnosed or is under-treated.2,7 This might be because depressed people often present with physical symptoms rather than emotional complaints; in one large study, 69 percent of patients with MDD reported only physical symptoms as the reason for visiting their physician.8
Complete elimination of symptoms, or remission, is the primary goal of depression treatment. Treating the full spectrum of emotional and physical symptoms to remission significantly decreases a patient's risk of relapse.9
Eli Lilly and Company and Boehringer Ingelheim
In November 2002, Eli Lilly and Company and Boehringer Ingelheim signed a long-term agreement to jointly develop and commercialize duloxetine hydrochloride. This partnership covers neuroscience indications in most countries outside of the United States and Japan, with few exceptions.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world`s most urgent medical needs.
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 137 affiliates in 47 countries and
38,400 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2006, Boehringer Ingelheim posted net sales of 10.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.
References:
1 Demyttenaere KD, et al. Patient-versus Physician-assessed Disease Severity and Outcomes in Patients with Non- specific Pain Associated with Depression
2 World Health Organization. Factsheet - Depression, 2005. Available here. Last visited 26 April 2007
3 Murray CJL, Lopez AD, eds. The Global Burden of Disease; 1996.
4 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision. Washington DC: American Psychiatric Association; 2000:345-428.
5 Ormel J, et al. Common mental disorders and disability across cultures: results from the WHO Collaborative Study on Psychological Problems in General Health Care. JAMA. 1994;272:1741-1748.
6 Spitzer RL, et al. Utility of a new procedure for diagnosing mental disorders in primary care: the PRIME-MD 1000 study. JAMA. 1994;272:1749-1756.
7 Ormel J, Koeter MWJ, van den Brink W, van de Willige G. Recognition, management, and course of anxiety and depression in general practice. Arch Gen Psychiatry. 1991;48:700-706.
8 Simon GE et al. An International Study of the Relation Between Somatic Symptoms and Depression. New Engl J Med. 1999;341(18):1329-35.
9 Paykel ES, et al. Psychol Med. 1995;25(6):1171-1180.
boehringer-ingelheim
вторник, 6 сентября 2011 г.
Total Antidepressant Prescriptions Rise By 16 Million, USA
Prescriptions filled for antidepressant drugs increased from 154 million in 2002 to 170 million in 2005, according to the latest News and Numbers from the Agency for Healthcare Research and Quality.
Among the prescriptions (not including refills) which were written after patients talked with doctors in-person or over the phone. AHRQ data found that in 2005:
-- Psychiatrists - medical doctors who specialize in the treatment of mental disorders - prescribed 29 percent.
-- General practitioners - physicians who provide primary care but are specialty-trained - prescribed 23 percent.
-- Family practitioners - primary care physicians who complete a residency in family medicine -- prescribed 21 percent.
-- Internal medicine specialists - physicians who complete a residency in internal medicine and who focus on the diagnosis and non-surgical treatment of illnesses in adults that are often difficult to diagnose or manage - prescribed 10 percent.
AHRQ, which is part of the U.S. Department of Health and Human Services, works to enhance the quality, safety, efficiency, and effectiveness of health care in the United States. The data in this AHRQ News and Numbers summary are taken from the Medical Expenditure Panel Survey, a detailed source of information on the health services used by Americans, the frequency with which they are used, the cost of those services, and how they are paid. For more information, go to Antidepressants Prescribed by Medical Doctors in Office-Based and Outpatient Settings for the U.S. Civilian Noninstitutionalized Population, 2002 and 2005.
ahrq
Among the prescriptions (not including refills) which were written after patients talked with doctors in-person or over the phone. AHRQ data found that in 2005:
-- Psychiatrists - medical doctors who specialize in the treatment of mental disorders - prescribed 29 percent.
-- General practitioners - physicians who provide primary care but are specialty-trained - prescribed 23 percent.
-- Family practitioners - primary care physicians who complete a residency in family medicine -- prescribed 21 percent.
-- Internal medicine specialists - physicians who complete a residency in internal medicine and who focus on the diagnosis and non-surgical treatment of illnesses in adults that are often difficult to diagnose or manage - prescribed 10 percent.
AHRQ, which is part of the U.S. Department of Health and Human Services, works to enhance the quality, safety, efficiency, and effectiveness of health care in the United States. The data in this AHRQ News and Numbers summary are taken from the Medical Expenditure Panel Survey, a detailed source of information on the health services used by Americans, the frequency with which they are used, the cost of those services, and how they are paid. For more information, go to Antidepressants Prescribed by Medical Doctors in Office-Based and Outpatient Settings for the U.S. Civilian Noninstitutionalized Population, 2002 and 2005.
ahrq
суббота, 3 сентября 2011 г.
Royal College Of Nursing Welcomes New Guidance For Providing Acute Mental Health Care For Women, UK
Commenting on today's publication of 'Informed Gender Practice, Mental health Acute Care That Works for Women', by the Care Services Improvement Partnership, Dr. Peter Carter, Chief Executive & General Secretary, of the Royal College of Nursing (RCN), said:
"The RCN welcomes this guidance as it highlights the importance of equality practices in mental health care and should enable women to receive support tailored specifically to their needs.
"We are particularly keen to support this initiative as it is compatible with RCN values and our 8 Principles for Practice which promote effective and meaningful mental healthcare services for women.
"Nurses also acknowledge the vital role they have to play in ensuring that women are able to access services which are safe, provide choice, address experiences of violence and abuse, and promote well-being and recovery approaches.
"This guidance is an effective resource which will be of great use to busy mental health professionals trying to deliver high quality, gender specific care."
The RCN's 8 Principles for Practices was launched in 2005 aiming to promote anti- oppressive practice for all women in any health care setting, thereby promoting good mental health. Copies are available to downloaded at: rcn.uk/__data/assets/word_doc/0005/8843/8_principles_short.doc
Copies of the Informed Gender Practice- Mental Health Acute for Women are available to download at: nimhe.csip.uk/our-work/gender-and-womens-mental-health.html
Royal College of Nursing (RCN) is the voice of nursing across the UK and is the largest professional union of nursing staff in the world. The RCN promotes the interest of nurses and patients on a wide range of issues and helps shape healthcare policy by working closely with the UK Government and other national and international institutions, trade unions, professional bodies and voluntary organisations.
rcn.uk
"The RCN welcomes this guidance as it highlights the importance of equality practices in mental health care and should enable women to receive support tailored specifically to their needs.
"We are particularly keen to support this initiative as it is compatible with RCN values and our 8 Principles for Practice which promote effective and meaningful mental healthcare services for women.
"Nurses also acknowledge the vital role they have to play in ensuring that women are able to access services which are safe, provide choice, address experiences of violence and abuse, and promote well-being and recovery approaches.
"This guidance is an effective resource which will be of great use to busy mental health professionals trying to deliver high quality, gender specific care."
The RCN's 8 Principles for Practices was launched in 2005 aiming to promote anti- oppressive practice for all women in any health care setting, thereby promoting good mental health. Copies are available to downloaded at: rcn.uk/__data/assets/word_doc/0005/8843/8_principles_short.doc
Copies of the Informed Gender Practice- Mental Health Acute for Women are available to download at: nimhe.csip.uk/our-work/gender-and-womens-mental-health.html
Royal College of Nursing (RCN) is the voice of nursing across the UK and is the largest professional union of nursing staff in the world. The RCN promotes the interest of nurses and patients on a wide range of issues and helps shape healthcare policy by working closely with the UK Government and other national and international institutions, trade unions, professional bodies and voluntary organisations.
rcn.uk
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