Orencia(R) (Abatacept) Demonstrates Consistent Safety And Effectiveness Over 7 Years

Bristol-Myers Squibb Company (NYSE: BMY) announced results of two ORENCIA® (abatacept) studies at the 2009 Annual European Congress of Rheumatology (EULAR) currently being held in Copenhagen, Denmark.

I. Phase IIb 100 trial (7 years)[1]

The first, a long-term extension (LTE) study, analysed ORENCIA’s safety and efficacy profile over 7 years of treatment in rheumatoid arthritis (RA) patients who have had an inadequate response to methotrexate (MTX).

Study design

During the 1 year randomised, double-blind (DB) placebo controlled period of this Phase IIb study, 339 patients with active RA and an inadequate response to MTX were randomised to receive either ORENCIA plus MTX or placebo plus MTX. On completion of the DB period, 219 patients entered the open-label LTE, receiving a fixed dose of ORENCIA 10 mg/kg (according to weight range) plus MTX every 4 weeks. During the LTE, safety assessments were performed once a month, and efficacy assessments quarterly.

Outcomes

During the LTE, treatment with ORENCIA and MTX in combination was generally well tolerated, with no increase in the frequency of safety events over time. The cumulative incidence of adverse events (AEs) was 366.1 per 100 patient years, serious AEs was 17.4 per 100 patient years and serious infections was 3.18 per 100 patient years. These data are consistent with previous data on ORENCIA in combination with MTX.

After 7 years, over half (52.1%) of ORENCIA patients (n=85) entering the LTE period remained on treatment. Over this 7 year period, discontinuations due to lack of efficacy and AEs were 11.0% and 19.2%, respectively.

While the LTE was principally designed to examine the long-term safety of ORENCIA, efficacy data were also collected (as observed) in those patients who remained in the LTE. At 7 years, of those patients still on ORENCIA (n=85):

- 69.7% achieved a low disease activity score (LDAS)
- 51.5% achieved remission (DAS28-CRP defined)
- 51.4% achieved an ACR 70 score

“The relevance of these long-term data should not be underestimated for a chronic and progressive disease such as rheumatoid arthritis,” commented Professor Ren?© Westhovens, University Hospital Leuven, Belgium. “These patients have to live with the disease, and in many cases, undergo treatment, for the rest of their lives. For both patients and clinicians therefore, it is important that a treatment has a proven long-term safety and efficacy profile.

As part of a comprehensive clinical trial programme, ORENCIA’s safety profile has already been studied through more than 10,000 patient years of exposure. These new data further reinforce ORENCIA, in combination with MTX, as a proven treatment option for moderate to severe active RA in adult patients who have had an insufficient response or intolerance to other disease-modifying anti-rheumatic drugs, including at least one tumour necrosis factor (TNF) inhibitor.[2]

II. AIM trial (5 years)[3]

The second study, also presented in Copenhagen this week is the AIM (Abatacept in Inadequate responders to Methotrexate) study LTE, which reinforces the long-term safety and efficacy profile of ORENCIA.

Study design

Of the 433 ORENCIA and 219 placebo treated patients who completed the 1 year, randomised DB, placebo controlled AIM trial, 378 ORENCIA and 161 placebo treated patients entered the open-label LTE period, receiving ORENCIA [~10 mg/kg] plus MTX.

Outcomes: efficacy & safety

ORENCIA patient retention rates remained high in the AIM LTE, with 70.4% of patients (n=266/378) remaining on treatment with ORENCIA plus MTX at year 5. Of these, 33.7% achieved clinical remission (DAS28 defined), and ACR 20, 50 and 70 response rates were 83.6%, 61.1% and 39.6%, respectively, at 5 years.

The types and incidence of AEs and serious AEs were similar between the DB and cumulative (combined DB + LTE) phases. During the DB phase, incidence rates of AEs were 303.4 per 100 patient years and serious AEs, 17.7 per 100 patient years. During the cumulative phase, incidence rates of AEs were 242.3 per 100 patient years and serious AEs, 13.9 per 100 patient years. Incidence rates of serious infections were 4.2 per 100 patient years in the DB period and 2.8 per 100 patient years in the cumulative phase.

Outcomes: inhibition of structural damage progression[4]

X-ray data from the AIM LTE, also presented at EULAR this week, demonstrated that over 5 years, ORENCIA inhibited structural damage progression in the majority of patients on treatment. 45.1% of patients (n=120) assessed at year 5 continued to show no progression in structural damage. 98% of patients who were non-progressors during years 1-4 remained non-progressors at year 5.

About ORENCIA

ORENCIA is a selective co-stimulation modulator of T-cell activation. ORENCIA is designed to prevent full T-cell activation and inhibit the release of chemicals leading to joint inflammation and destruction as observed in RA.[5]

ORENCIA is the first biologic discovered and developed in Bristol-Myers Squibb research centres and was approved in May 2007 by the European Commission.

ORENCIA in combination with methotrexate is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have had an insufficient response or intolerance to other disease-modifying anti-rheumatic drugs including at least one tumour necrosis factor (TNF) inhibitor.

A reduction in the progression of joint damage and improvement of physical function have been demonstrated during combination treatment with ORENCIA and methotrexate.

The safety profile of ORENCIA has been studied through more than 10,000 patient-years of exposure and has demonstrated a consistent safety profile to 7 years.[2]

Medicinal products, including ORENCIA, which affect the immune system, may affect host defences against infections and malignancies. Serious infections, at least possibly related to treatment, were reported in 1.8% of patients with ORENCIA and in 1.0% of patients not treated by ORENCIA (receiving placebo). There is a need to evaluate and monitor patients regarding the risk of infection prior to and during treatment. In the placebo-controlled clinical trials, the frequency of malignancies with ORENCIA was 1.4% and with placebo 1.1%. These rates are similar to that observed in the general RA population.[6]

ORENCIA, like other biologics, is contraindicated in patients with severe and uncontrolled infections such as sepsis and opportunistic infections and in patients with hypersensitivity to the active substance or to any of the excipients. Allergic reactions have been reported uncommonly with ORENCIA in clinical trials, where patients were not required to be pretreated to prevent allergic reactions. In the case of any serious allergic/anaphylactic reaction, ORENCIA should be discontinued.

About Rheumatoid Arthritis

RA is a systemic, chronic, autoimmune disease characterised by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness and swelling. RA causes limited range of motion and decreased function as a result of affected joints losing their shape and alignment. RA may affect up to 7 million people in Europe.[7],[8]

References:

[1] Westhovens, R et al. Consistent Safety and Sustained Improvement in Disease Activity and Treatment Response Over 7 Years of Abatacept Treatment in Biologic-Na??ve Patients with RA. EULAR 2009, abstract no. FRI0108.

[2] Smitten, A et al. Descriptive Analysis of Serious Infections, Hospitalized Infections and Malignancies Over Time in the Abatacept Clinical Development Program: A Safety Update with >10,000 Person-Years of Exposure. EULAR 2008, abstract no. 1065.

[3] Kremer JM et al. Abatacept Demonstrates Consistent Safety and Sustained Improvements in Efficacy Through 5 Years of Treatment in Biologic-Na??ve Patients with RA. EULAR 2009, abstract no. FRI0263.

[4] Genant, HK el al. Abatacept Increases the Proportion of Patients who Remain Free From Structural Damage Progression Through 5 Years in Methotrexate Inadequate Responders with RA.EULAR 2009, abstract no. FRI0253.

[5] Kremer, JM et al. Treatment of Rheumatoid Arthritis by Selective Inhibition of T-Cell Activation with Fusion Protein CTLA4Ig. N. Engl. J. Med. 2003;349:1907-1915.

[6] Simon, T et al. Ann Rheum Dis 2006;65(Suppl II):489.

[7] United Nations. 2008 Revision Population Database. esa.un/unpp/ Accessed 14-05-09.

[8] Symons, D et al. The Global Burden of Rheumatoid Arthritis in the Year 2000. See here. Accessed 14-05-09.

Source
Bristol-Myers Squibb

View drug information on Orencia.

Cortex’s AMPAKINE CX1739 Improves Respiratory Parameters In Obstructive Sleep Apnea Patients

Cortex Pharmaceuticals, Inc. (OTCBB (CORX)) announced top-line results from an exploratory clinical study with its AMPAKINE® compound, CX1739 in subjects with sleep apnea. The study enrolled 20 relatively healthy adults with moderate-to-severe obstructive sleep apnea, 16 of which were administered a single oral dose of CX1739 and 4 of which received matching placebo for one night. The objective of the study was to further explore safety and tolerability in the sleep apnea population, as well as to assess putative efficacy of CX1739 on a range of sleep apnea parameters assessed by overnight polysomnography.

The study demonstrated that selected oxygen saturation parameters were statistically improved by one dose of CX1739, but the interpretation of these results was complicated by a reduced sleep time during the night following drug treatment. CX1739 did not reduce the mean apnea/hypopnea index (AHI; frequency of apnea or hypopnea events per hour of sleep). However, in the AHI responder analysis, defined as a greater than 40% reduction in the AHI, three subjects (20%) in the CX1739 treatment group were responders, and there were no responders in the placebo group. Furthermore, CX1739 significantly (p
The single center study was a double-blind, placebo-controlled design. Subjects who met inclusion/exclusion and other eligibility criteria were screened for sleep apnea severity by polysomnography during an overnight stay in the clinic sleep laboratory. Acceptable subjects returned for a second overnight polysomnography session and those subjects who met certain consistency criteria on key sleep apnea parameters between screening and baseline polysomnogram nights were enrolled and returned to the sleep clinic for a third overnight polysomnography session when they randomly received a single dose of either CX1739 (900mg) or matching placebo capsules in a four to one ratio just prior to the beginning of the sleep session.

The Principal Investigator of the study, Adrian J. Williams, FRCP, Dip AASM, Professor of Sleep Medicine at King’s College, London commented, “The results from this pilot study are encouraging, and warrant undertaking a larger clinical study to better understand the sleep apnea patient population most responsive to the treatment of CX1739.”

Mark Varney, Ph.D., President and Chief Executive Officer of Cortex stated, “A single dose of CX1739 improved a number of sleep apnea parameters across most of the 16 subjects who were given the drug, and there were some CX1739-treated subjects who demonstrated a robust reduction in sleep apnea symptoms. We may find that repeated daily treatment with CX1739 for several weeks may provide additional benefit over a single dose and improve sleep apnea symptoms in those subjects who did not respond after a single dose. Additionally, testing this drug in a population which suffers from predominantly central apneas also appears to hold some potential for Cortex.”

About Sleep Apnea

Sleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur many times per hour. Sleep apnea is typically diagnosed with an overnight sleep test called a polysomnogram. There are three forms of sleep apnea: central (CSA), obstructive (OSA), and complex or mixed sleep apnea. Sleep apnea is associated with increased risk of cardiovascular disease including hypertension, heart failure and stroke, and with increased risk of daytime sleepiness and auto vehicle fatalities. The current standard of care for sleep apnea patients is treatment of the disease using a variation of a continuous positive airway pressure device (CPAP), which has been shown to be effective in reducing the apnea-hypopnea index in sleep apnea patients. However, the overall clinical benefit of CPAP is limited by relatively poor patient compliance rates reported for OSA patients. Despite low rates of patient compliance, the global CPAP device market exceeded one billion dollars in 2007. Other less frequently prescribed treatment options for OSA patients include surgery, dental appliances and sleep position training. Currently there are no FDA-approved drugs for the safe and effective treatment of sleep apnea.

Source:

Cortex Pharmaceuticals, Inc.

UNICEF Identifies Clean Water As The Number One Challenge Facing Relief Efforts In South Lebanon

Preliminary assessments have revealed major destruction done to water and sanitation systems by the month-long conflict in south Lebanon.

In 10 out of 12 war-affected communities visited by UNICEF in recent days, underground pipes and other water-related infrastructure had been seriously damaged or destroyed.

“I have never seen destruction like this,” said UNICEF water and sanitation specialist Branislav Jekic. “Wherever we go, we ask people what they need most and the answer is always the same: water.”

Jekic added that the acute shortage of clean water risked hindering the process of reconstruction.

“People want to move back to their communities. But whether they stay or not will depend on the availability of water.”

Similar conclusions have emerged from other assessments. In the district of Tyre, for example, water and sanitation systems in 42 out of 70 villages are reported to have been damaged.

UNICEF’s response to the situation is gathering pace. In the immediate term, distribution of bottled water is being stepped up. Since the beginning of the crisis on 12 July, more than quarter of a million litres of bottled water has been sent to some of the worst-hit communities including Bint Jubail, Ait el Shaab and Tibnin.

Currently, around 50,000 litres a week are being sent south by truck, but this quantity will more than double by the weekend.

Increasingly, bottled water provision is being complemented by the installation of large water tanks that better serve community needs. This week, forty rubber water bladders – each with a capacity of 5,000 litres – are being delivered to Nabatiyah and villages along the Israeli border. Partner NGOs Islamic Relief and Mercy Corps will deliver and install the tanks, and will also be responsible for ensuring the bladders are kept replenished.

Two 45,000 litre pre-fabricated metal tanks, provided by Oxfam, are being sent to the district of Al Khiam.

UNICEF Lebanon Representative, Roberto Laurenti, says collaboration with Lebanon’s four water authorities will be a crucial aspect of the agency’s longer-term response.

“The new agreement we have with the Beirut and Mount Lebanon water authority means we can give support in whatever form it’s needed,” said Laurenti. He said that with UNICEF’s support – including the provision of generators for water pumps, the supply of diesel fuel, and repairs to damaged equipment – 30,000 cubic metres of water would be provided to affected areas daily.

Since the start of the crisis in Lebanon, UNICEF has provided:

– 51 water tanks with a 5,000 litres capacity, to centres for internally displaced people (IDPs) in Beirut, Aley, Metn and Chouf areas; Beneficiaries reached: 25,300 persons. 1 x 5,000 litre tank and 2 x 1,500 litre tanks supplied to Marjayoun;

– Over 1 million litres of drinking water has been provided weekly to IDP centres in Beirut and Metn areas (300,000 litres weekly);

– 284,800 litres of bottled water to communities in south Lebanon;

– 385 water kits (containing collapsible containers, purification tablets and other items) throughout Beirut, Mount Lebanon, the South, North, and Bekaa; IDPs reached: 78,000;

– 3,150 boxes of water purification tablets to Beirut and the South; IDPs reached: 63,000;

– Essential drugs (including ORS & lice treatment) reaching 70,000;

– Vaccination against measles to 16,500 children: vaccination against polio to more than 9,000 ; Vitamin A capsules for more than 9,000;

– Implementation of public awareness campaign on the threat posed by unexploded ordnance. TV and radio spots have been produced and aired; 100,000 leaflets are being distributed at army checkpoints in south Lebanon;

– 27,840 bags/bars of soap to Beirut, Mount Lebanon, the South, North, Bekaa; IDPs reached: 101,000;

– 279,000 diapers to Beirut, Mount Lebanon, the South, North, and Bekaa; Children reached: 91,000;

– 370 recreation kits containing footballs and other games equipment. Children reached: 21,000.

About UNICEF

For 60 years UNICEF has been the world’s leader for children, working on the ground in 156 countries and territories to help children survive and thrive, from early childhood through adolescence. The world’s largest provider of vaccines for developing countries, UNICEF supports child health and nutrition, good water and sanitation, quality basic education for all boys and girls, and the protection of children from violence, exploitation, and AIDS. UNICEF is funded entirely by the voluntary contributions of individuals, businesses, foundations and governments.

unicef

$11 Million NIH Grant For Stem Cell Research Awarded To Rhode Island Hospital

Rhode Island Hospital has received an $11 million grant to fund research that will lead to a general understanding of stem cell biology and identify unique approaches to tissue regeneration in lung and marrow diseases. The 5-year grant, awarded to Peter Quesenberry, MD, director of hematology/oncology at Rhode Island Hospital, also provides funding for the development of a major stem cell research center at Rhode Island Hospital. It is a Center of Biomedical Research Excellence (COBRE) grant from the National Center for Research Resources (NCRR) of the National Institutes of Health (NIH).

The grant will allow Quesenberry and investigators at Rhode Island Hospital to focus their research efforts on determining the true phenotype (what the cells actually looks like as a result of their interaction with their environment) of marrow stem cells and their fate as tissue. The researchers’ goal is to translate basic stem cell studies into clinical trials on tissue restoration or correction in patients with chronic obstructive lung disease and malignant blood diseases. Through the grant they will study how the phenotype information is transferred via microvesicles from injured tissue. They will then define the mechanisms by which the cells are differentiated.

Quesenberry, who is also a physician with the University Medicine Foundation, says, “The beauty of the COBRE grant is not only will it allow us to develop a stem cell research center at Rhode Island Hospital, but it will also help us to assemble a group of outstanding, talented investigators who excel in these areas.” He adds, “Those investigators can then serve as mentors to young, up-and-coming researchers, who we can recruit and then retain right here at this research center.” Their research will be conducted in a new 10,000 square foot lab in the Coro building, where Rhode Island Hospital has established other major research labs.

Senator Jack Reed commented on the hospital’s grant. “Rhode Island Hospital is nationally renowned for pioneering efforts in stem cell research. This federal award will allow the hospital to expand and enhance existing research initiatives and help attract more talented researchers and promising young scientists to the state,” said Reed, a member of the Appropriations subcommittee, which oversees federal funding for NIH programs. Reed wrote a letter in support of Rhode Island Hospital’s application earlier this spring.

Congressman Jim Langevin also said, “I have long believed that stem cell research will help change the direction of medicine for the better,” said Langevin. “I congratulate Dr. Quesenberry and the entire Rhode Island Hospital research community for securing this prestigious award. Grants such as this will drive both scientific innovation and economic development in our state. I look forward to following this study and learning about its outcomes.”

The work in the stem cell research center will also include general stem cell biology. An experienced group of scientists will be mentoring three promising young investigators, and potentially more in three specific studies. Quesenberry, who also holds the Paul Calabresi, MD, professorship in oncology and is director of the division of Hematology/Oncology at The Warren Alpert Medical School of Brown University, comments further, “This grant holds real promise for expanding our understanding of stem cell biology. We appreciate the support of the National Center for Research Resources.”

Peter Snyder, PhD, Lifespan’s vice president of research, says, “A grant of this magnitude is especially welcome during these difficult economic times and is a definite boon for the research sector of our state. Dr. Quesenberry is already a renowned scientist, and this grant will undoubtedly result in breakthroughs that will have a direct impact on the care of patients who will benefit from advances in tissue restoration. I know we all look forward to that day.”

The project described was supported by Award Number P20RR025179 from the National Center for Research Resources (NCRR). The content6 is solely the responsibility of the authors and does not necessarily reflect the view of the NCRR or the National Institutes of Health.

Source: Nancy Cawley Jean

Lifespan

Susan G. Komen For The Cure(R) Calls On Global Cancer Leaders To Help Avert Japanese Cancer Crisis

Susan G. Komen for the Cure®, the world’s leading breast cancer organization, announced a call to global cancer leaders to help avert a cancer crisis in the wake of the nuclear disaster in Japan. Humanitarian assistance can take many forms, and the global cancer community has a vital role to play. Susan G. Komen for the Cure is urging that global cancer leaders start working together now to develop a cancer action plan for Japan. The plan would draw on lessons learned from past nuclear catastrophes at Chernobyl, Kyshtym and Three Mile Island.

Radiation exposure from these nuclear incidents has caused thousands of deaths by cancer. Health issues such as cataract development, cancer and birth defects are all related to the amount of exposure. In the five-year period immediately following the meltdown at Three Mile Island, the number of persons living within 10 miles of the nuclear site who were diagnosed with cancer rose 64 percent. Although it has been 25 years since Chernobyl, exposure to fallout may be responsible for thyroid cancers that are still occurring among people who lived in the region.

The global cancer community must act now to help Japan contend with a looming cancer crisis. Chernobyl produced the biggest group of cancers ever from a single incident, and the world may be facing a disaster of similar magnitude in Japan. Susan G. Komen for the Cure will therefore convene a panel of global experts to immediately begin addressing the future cancer risks generated from this accident and draft a plan of action.

Susan G. Komen for the Cure will also be asking their vast network of global friends and supporters to sign a petition here calling for the release of all information regarding the incident and the potential effects of migrating radiation. As Japan works to contain the impact of the current crisis and provide for the immediate needs of its citizens, the organization urges the government to partner with the global cancer community to help protect the long term public health of people in Japan and around the world.

“It is imperative for the global cancer community to draft a plan of action for Japan to help plant workers, decontamination workers, and the residents of contaminated areas in every way possible,” said Ambassador Nancy G. Brinker, founder and chief executive officer for Susan G. Komen for the Cure. “As someone who served on the National Cancer Advisory Board at the time of the Chernobyl disaster, I know the long-term implications of this type of nuclear tragedy. I encourage people to sign the petition and join in our efforts to help the people of Japan and those affected by radiation exposure.”

Source:

Susan G. Komen for the Cure®

Association Between Delusions And Consistent Pattern Of Brain Injury

A new study provides a novel theory for how delusions arise and why they persist. NYU Langone Medical Center researcher Orrin Devinsky, MD, performed an in-depth analysis of patients with certain delusions and brain disorders revealing a consistent pattern of injury to the frontal lobe and right hemisphere of the human brain. The cognitive deficits caused by these injuries to the right hemisphere, leads to the over compensation by the left hemisphere of the brain for the injury, resulting in delusions. The article entitled “Delusional misidentifications and duplications: Right brain lesions, left brain delusions” appears in the latest issue of the journal of Neurology.

“Problems caused by these brain injuries include impairment in monitoring of self, awareness of errors, and incorrectly identifying what is familiar and what is a work of fiction,” said Dr. Devinsky, professor of Neurology, Psychiatry and Neurosurgery and Director of the NYU Epilepsy Center at NYU Langone Medical Center. “However, delusions result from the loss of these functions as well as the over activation of the left hemisphere and its language structures, that ‘create a story’, a story which cannot be edited and modified to account for reality. Delusions result from right hemisphere lesions, but it is the left hemisphere that is deluded.”

Often bizarre in content and held with absolute certainty, delusions are pathologic beliefs that remain fixed despite clear evidence that they are incorrect. “Delusions are common problems in a variety of psychiatric and neurological disorders,” said Dr. Devinsky. “Psychiatric disorders with delusions, for example- schizophrenia, have been proven to have functional and structural brain pathology. But now improved diagnostic techniques are allowing us to have increased identification of neurologic disorders among other patient populations with delusions.”

In the study, the author finds that most neurologic patients with delusions usually have lesions in the right hemisphere and/or bifrontal areas. For example, the neurological disorders of Confabulation (incorrect or distorted statements made without conscious effort to deceive), Capgras (the ability to consciously recognize familiar faces but not emotionally connect with them) and Prosopagnosia (patients who may fail to recognize spouses or their own face but generate an unconscious response to familiar faces) result from right sided lesions.

The right hemisphere of the brain dominates self recognition, emotional familiarity and ego boundaries. After injury, the left hemisphere tends to have a creative narrator leading to excessive, false explanations. The resistance of delusions to change despite clear evidence that they are wrong likely reflects frontal dysfunction of the brain, which impairs the ability to monitor self and to recognize and correct inaccurate memories and familiarity assessments. Thus, right hemisphere lesions may cause delusions by disrupting the relation between and the monitoring of psychic, emotional and physical self to people, places, and even body parts. This explains why content specific delusions involve people places or things of personal significance and distort ones relation to oneself, the author explains.

“Our knowledge of delusions is limited by our ability to comprehend the patients irrational thought process,” said Dr. Devinsky. “The pathogenesis of delusions likely includes many mechanisms that span overlapping psychological, cognitive and neurological disorders. Future research should explore the psychological, cognitive, and pyschologic-anatomic systems that change during the emergence and resolution of delusions as well as strategies to treat delusions.”

Examples of Various Research Reviewed

In one study, nine patients with right hemisphere infarctions at a stroke rehabilitation unit had frequent delusion. While size of the stroke did not correlate when compared to the control group, the presence of brain atrophy was a significant predictor of delusions. When delusions occurred, it was usually caused by a right hemisphere lesion. Also, one study pointed out that delusional patients with Alzheimer’s disease usually have significantly more right frontal lobe damage.

Other research showed that Reduplicative Paramnesia and Capgras syndrome cases with unilateral brain lesions strongly implicate the right hemisphere, usually the frontal lobe of the brain. Among 69 patients with Reduplicative Paramnesia, lesions were primarily in the right hemisphere in 36 cases (52%), bilateral in 28 (41%) and left hemisphere in 5 (7%) — a sevenfold increase of right over left-sided lesions. Similarly in 26 Capras patients, lesions were primarily in the right hemisphere in 8 (32 %), bilateral in 16 (62 %) and left sided in 2 (7%)- a four-fold increase of right – over left-sided lesions. For both delusional syndromes, many bilaterial cases had maximal damage in the right hemisphere.

Among another study of 29 cases of delusional misidentification syndromes, all patients had right hemisphere pathology, while 15 (52 %) had left hemisphere damage. Fourteen had exclusively right hemisphere damage but none had isolated left hemisphere damage. When lateralized lesions are found, right hemisphere lesions are more common in other delusional misidentification and content specific delusions. Frontal lesions are strongly implicated in misidentification syndromes. Exclusively frontal lesions were associated with delusions in 10 of 29 (34.5) cases- four with right frontal and six with bifrontal lesions. None had lesions sparing the frontal lobes.

About NYU Langone Medical Center

Located in the heart of New York City, NYU Langone Medical Center is a premier center for health care, biomedical research, and medical education. For over 167 years, NYU physicians and researchers have contributed to the practice and science of medicine. Today the Medical Center consists of NYU School of Medicine; Rusk Institute of Rehabilitation Medicine, the first and largest facility of its kind; NYU Hospital for Joint Diseases, a leader in musculoskeletal care; and such nationally recognized programs as the NYU Cancer Institute, the NYU Child Study Center, and the NYU Cardiac and Vascular Institute.

Source: Lauren Woods

NYU Langone Medical Center / New York University School of Medicine

Osteoarthritis: Which Treatments Work And Which Don’t?

A newly released set of
treatment recommendations for knee and hip osteoarthritis may help millions
of people worldwide who live in pain due to inconsistent treatment
approaches and confusion about what therapies are most effective.

The 25 evidence-based, expert-consensus recommendations appear in the
February issue of Osteoarthritis and Cartilage and can be found at
oarsi.

These are the first evidence-based recommendations developed by a
committee that was brought together two years ago by the Osteoarthritis
Research Society International (OARSI). The goals were (1) to review all of
the published national and regional treatment guidelines together with the
more recent evidence from clinical trials and (2) to produce a single set
of up-to-date, evidence-based recommendations for the worldwide treatment
of knee and hip osteoarthritis.

“What the committee did was take the scientifically proven
commonalities it found in the international literature, evaluate the level
of scientific evidence, propose a strength of recommendation for each
modality, and condense them into one comprehensive ‘playbook’ of what
works,” says OARSI President Dr. Steve Abramson, director of Rheumatology
and professor of Medicine at New York University School of Medicine.

The first of OARSI’s 25 evidence-based recommendations is that optimal
treatment requires both nonpharmacologic and pharmacologic modalities. The
remaining 24 recommendations fall into three categories —
nonpharmacologic, pharmacologic and surgical.

The effectiveness of each recommendation is associated with a level of
scientific evidence available to support it. The higher the level of
support (expressed as a percentage out of 100), the more evidence in the
scientific literature that the treatment is effective. The following are
the recommendations:

— Nonpharmacologic — These 11 recommendations include education and
self-management (97%); regular telephone contact (66%); referral to a
physical therapist (89%); aerobic, muscle strengthening and water-based
exercises (96%); weight reduction (96%); walking aids (90%); knee
braces (76%); footware and insoles (77%); thermal modalities (64%);
transcutaneous electrical stimulation (58%); and acupuncture (59%).

— Pharmacologic — These eight recommendations include acetaminophen
(92%); non-selective and selective oral nonsteroidal anti-inflammatory
drugs (NSAIDs) (93%); topical NSAIDs and capsaicin (85%);
intraarticular injections of corticosteroids (78%); intraarticular
injections of hyaluronans (64%); glucosamine and/or chondroitin
sulphate for symptom relief (63%); glucosamine sulphate, chondroitin
sulphate and/or diacerein for possible structure-modifying effects
(41%); and the use of weak opioids and narcotic analgesics for the
treatment of refractory pain (82%).

— Surgical — These five recommendations include total joint replacement
(96%); unicompartmental knee replacement (76%); osteotomy and joint
preserving surgical procedures (75%); joint lavage and arthroscopic
debridement in knee OA (60%); and joint fusion as a salvage procedure
when joint replacement had failed (69%).

“Our goal was to make these guidelines as simple as possible so that
healthcare providers could determine which therapies would be most useful
for an individual patient,” says Dr. Francis Berenbaum, president elect of
OARSI and a faculty member in the Department of Rheumatology at Pierre &
Marie Curie University, APHP Saint-Antoine Hospital in Paris.

Nearly all of the previous guidelines were created before the recent
discussion about the potential cardiovascular risks of nonsteroidal
anti-inflammatory drugs (NSAIDs) took place. In recent years, there has
been a decline in the use of NSAIDs to reduce pain and inflammation caused
by osteoarthritis, primarily due to their potential for causing
gastrointestinal side effects and the perceived cardiovascular risks
associated with these drugs.

However, members of the OARSI committee found that NSAIDs are often
effective pain relievers and their short-term use should be considered on a
case-by-case basis and not as a long-term option.

“As a consequence of the confusion over NSAIDs, some people may not be
getting the care they need for pain,” says Abramson.

The OARSI recommendations make up the first truly international
guidelines for the treatment of knee and hip osteoarthritis. The guideline
committee was made up of experts from six countries, including 11
rheumatologists, two primary care physicians, one orthopedic surgeon, and
two experts on evidence-based medicine.

Osteoarthritis is the most common type of arthritis and the major cause
of chronic musculoskeletal pain and mobility limitation in elderly
populations worldwide.

The Osteoarthritis Research Society International (OARSI) is a
non-profit organization dedicated to promoting and encouraging fundamental
and applied research, and to disseminate the results of that research in
order to permit better knowledge of osteoarthritis and its treatment. For
more information about OARSI visit oarsi.

Osteoarthritis Research Society International
oarsi

Use Of High Humidity Does Not Improve Symptoms For Children With Croup

For children with moderate to severe croup treated in the emergency department, use of high humidity did not improve symptoms more than low humidity or mist therapy, according to an article in the March 15 issue of JAMA.

Viral croup is the most common cause of acute upper airway obstruction in children and is diagnosed in up to five percent of children younger than six years old; approximately one percent of these children are hospitalized, according to background information in the article. Symptoms of croup include a “seal-like” barking cough and difficulty breathing. Steam or humidity, thought to soothe the inflamed larynx and decrease the thickness of secretions, has long been used to treat croup. Despite the lack of scientific evidence for its efficacy, blow-by humidity (e.g., humidifiers), croup tents and face masks are still used.

Dennis Scolnik, M.B., Ch.B., and colleagues from the Hospital for Sick Children and University of Toronto, conducted a randomized, single-blind, controlled trial to determine whether humidity improved symptoms of moderate to severe croup in children. One hundred-forty children, aged three months to ten years, who were admitted to the emergency department were randomly treated with either 100 percent humidity (high humidity), 40 percent humidity (low humidity) via a nebulizer or blow-by humidity for 30 minutes.

“Our trial shows that, in children with moderate to severe croup, 100 percent humidity, even when delivered in water-particle size designed to deposit in the larynx, does not result in greater clinical improvement than either controlled delivery of 40 percent humidity (optimally delivered placebo) or humidity delivered using the blow-by method (commonly used placebo),” the researchers write. They also found no significant difference in changes in respiratory rate, heart rate or oxygen saturation at 30 or 60 minutes among the three groups.

“Our results suggest that the use of humidity in children with croup admitted to emergency departments is not warranted,” the researchers write. “Humidity may actually have been found useful because of other factors associated with its use such as the comfort of being close to parents or the low temperature used for delivery in certain humidification devices.”

(JAMA. 2006; 295: 1274 ??” 1280. Available pre-embargo to the media at jamamedia/)

Editor’s Note: This study was funded as a peer-reviewed grant by the Physicians’ Services Incorporated Foundation of Ontario.

Contact: Chelsea Gay
JAMA and Archives Journals

FDA Clears Silver-Coated Breathing Tube For Marketing – Reduces Risk Of Pneumonia For Patients Using Ventilators

The U.S. Food and Drug Administration announced that it has cleared for marketing a breathing tube coated with a thin layer of silver. The coating, a material known to have antimicrobial properties, reduces the risk that patients on ventilators will acquire pneumonia while in the hospital.

The Agento endotracheal tube, manufactured by C.R. Bard Inc., is intended for patients who must rely on a ventilator to breathe for 24 hours or more.

Patients requiring such a breathing support system are at risk of exposure to hospital-acquired bacteria that can build up on the breathing tube or pass through the tube to their lungs, eventually causing a lung infection known as ventilator-associated pneumonia (VAP).

Fifteen percent of the patients on ventilators develop VAP every year and 26,000 die from the infection, according to the Centers for Disease Control and Prevention.

“Patients who require ventilator support are at increased risk for pneumonia, which poses a significant public health issue. This product can help to lower this risk,” said Daniel Schultz, M.D., director of FDA’s Center for Devices and Radiological Health.

Silver has been known for its antimicrobial properties for decades and has been used for this purpose on several types of devices. This is the first endotracheal tube coated with silver.

In a multicenter clinical trial comparing the Agento breathing tube to an uncoated tube, the percentage of patients who developed pneumonia was reduced from 7.5 percent to 4.8 percent. The Agento also delayed the onset of pneumonia.

The FDA in July issued a proposed guidance document on antimicrobial device submissions stating that when companies claim their product reduces or prevents device-related infections, the claim should be supported by such clinical data.

C.R. Bard is located in Murray Hill, N.J.

fda

British Researchers Identify Link Between Childhood IQ And Vascular Dementia

Scottish researchers funded by the UK’s leading dementia research charity, the Alzheimer’s Research Trust, have found a link between childhood IQ and vascular dementia later in life.

Their research, published in the journal Neurology, found that lower childhood intelligence increases the risk of vascular dementia, a disease which currently affects 112,000 people in the UK. The results suggest that interventions to lower blood pressure and smoking targeted from early in life to those with a lower IQ could reduce the numbers of people developing dementia in old age. They also help scientists to understand what is happening in the brains of people with dementia and the best way to tackle different dementias.

Researchers based at the University of Edinburgh compared the records of 173 people who participated in the Scottish Mental Survey of 1932, when almost every child aged 11 years in Scotland took a mental ability test. They showed that lower childhood IQ increased the risk of vascular dementia, but not Alzheimer’s disease. Because the difference was not seen in Alzheimer’s, this suggests that increased risk of ‘dementia’ may be due to vascular causes.

Lead researcher, Dr Brian McGurn, formerly from the University of Edinburgh now based at Hairmyres hospital, East Kilbride said, “Our work suggests a possible link between mental ability in early life and risk of developing vascular dementia. The unique data available from the Scottish Mental Survey means the link can be demonstrated independent of factors like socio-economic status and education.”

Rebecca Wood, Chief Executive of the Alzheimer’s Research Trust said, “This research confirms that vascular risk factors are very important in tackling dementia. If we live a healthier lifestyle and reduce our risk of high blood pressure, cholesterol and don’t smoke, then this gives us a much better chance of avoiding dementia later in life.

With 700,000 people in the UK with dementia today, we urgently need to fund more research to find ways to prevent, treat or cure dementia, but research is seriously under-funded”.

Notes

- The Alzheimer’s Research Trust is the UK’s leading research charity for dementia. For free information on dementia and the treatments available, visit alzheimers-research or phone 01223 843899.

- Vascular dementia is the second most common form of dementia after Alzheimer’s disease and is linked to high blood pressure, high cholesterol or smoking. There are 112,000 people with vascular dementia and 417,000 with Alzheimer’s disease, and a total of 700,000 people with all types of dementia in the UK.

- The research ‘Childhood cognitive ability and risk of late-onset Alzheimer and vascular dementia’ by Dr Brian McGurn, Prof Ian Deary and Prof John Starr at the University of Edinburgh and is published in Neurology on 25th June 2008.

Alzheimer’s Research Trust