BioMed Israel 2012

 

Target Health is pleased to announce that Dr. Jules T. Mitchel will again be attending BioMed Israel which this year is taking place on 21-23 May 2012, at the David Intercontinental Hotel, Tel Aviv. BioMed is a leading international conference covering the fast-growing field of innovation in the biomedical, health care and life sciences industries where industry and academia meet to learn about the latest developments and explore opportunities for new business ventures.

 

Target Health is currently working with 18 Israeli biotech and service companies in the areas of Regulatory Affairs, Clinical Trials, Biostatistics, Data Management and Medical Writing. Please let us know if you will be attending so we can plan to meet.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com

Too Many Pills for Aging Patients

 

 

Overmedication of the elderly is an all too common problem, a public health crisis that compromises the well-being of growing numbers of older 1) ___. Many take fistfuls of prescription and over-the-counter medications on a regular basis, risking serious and sometimes fatal side effects and drug interactions.A series of research-based guidelines, recently updated and published in The Journal of the American Geriatrics Society, calls attention to specific medications most likely to have calamitous effects in the 2) ___. If adopted by practicing physicians and their patients, the guidelines should help to avert the kind of costly, debilitating disaster that befall many of the elderly.

 

In early March, a 93 year old female patient was hospitalized for an episode of extreme weakness, sleepiness and confusion. She was found to be taking a number of medications and supplements: Synthroid, for low thyroid hormone; Tenormin and Benicar, for high 3) ___ pressure; Lexapro, for depression; Namenda, for symptoms of Alzheimer’s disease; Xanax, for nighttime anxiety attacks; Travatan eye drops, for glaucoma; a multivitamin; vitamin C; calcium with vitamin D; low-dose aspirin; a lutein supplement; and Colace, a stool softener.

 

Diagnosis at the hospital: low sodium, prompting a stoppage of Lexapro, known to cause such a side effect, and substitution of the antidepressant Viibryd. Noting her confusion, the hospital neurologist also added Aricept, another treatment for 4) ___ disease, although she is only suspected of having this condition. Her cardiologist doubled the dose of Tenormin, stopped the Benicar and added another blood 5) ___ medication, Apresoline. This caused a precipitous drop in blood pressure to 70/40 (120/80 is normal), leaving her completely disoriented and unable to stand or sit up. After 10 days in the hospital, as she was being discharged, the patient collapsed and started turning blue. CPR was administered (which fractured three ribs), followed by resuscitation in the emergency room and then transfer to intensive care, where she suffered three seizures. She was put on Dilantin to control them. She developed double 6) ___, and the end seemed near. A do-not-resuscitate order was issued. One night, when she was too agitated to fall sleep, she was given a dose of Ativan, a sedative, that left her unable to wake up for 30 hours.

 

Miraculously, she responded to antibiotics and administration of oxygen, and she has since been discharged to a rehabilitation facility where she is steadily getting stronger, less confused and refreshingly feisty. Older adults are the largest consumers of medications. More than 40% of people over age 65 take five or more 7) ___, and each year about one-third of them experience a serious adverse effect, like a bone-breaking fall, disorientation, inability to urinate, even heart failure. With the support of the geriatrics society, an interdisciplinary panel of 11 experts in geriatric care and pharmacology has updated the so-called Beers Criteria, guidelines long used to minimize such drug-related disasters in the elderly. After reviewing more than 2,000 high-quality research studies of drugs prescribed for older adults, the team highlighted 53 potentially inappropriate medications or classes of medication and placed them in one of three categories: 8) ___ to avoid in general in the elderly; drugs to avoid in older people with certain diseases and syndromes; and drugs to use with caution in the elderly if there are no acceptable alternatives.

 

For example, instead of a sedative hypnotic – like the Ativan which can cause extreme sedation, serious confusion and mental decline in older adults, the panel notes that an alternative sleep remedy, perhaps an herbal or nondrug option, is safer. Many sedating antihistamines, in a class of drugs called anticholinergics, should be avoided in older adults because they can cause such side effects as confusion, drowsiness, blurred vision, difficulty urinating, dry mouth and constipation, the panel concluded. Mineral oil taken by mouth can, if accidentally inhaled, cause 9) ___ pneumonia, and many commonly used anti-inflammatory medications, including over-the-counter drugs like ibuprofen and naproxen, increase the risk of gastrointestinal bleeding in adults age 75 and older, as well as in those age 65 and older who also take medications like prednisone and warfarin. In adults over age 80, the team warned, aspirin taken to prevent heart attacks “may do more harm than good,” and any antidepressant may lower sodium in the blood to dangerous levels The team said its criteria should be used by physicians and patients within and outside of institutional settings. But the experts also emphasized that the guidelines should not override a doctor’s clinical judgment or a patient’s needs and values, nor be used as grounds for malpractice disputes.

 

The geriatric society’s Foundation for Health in Aging has produced a one-page “drug and supplement diary” that can help patients keep track of the drugs and 10) ___ they take. They should show the list to every health care provider they see. The form can be found at www.americangeriatrics.org/files/documents/beers/MyDrugDiary.pdf. Too often, people with multiple health problems have one doctor who does not know what another has prescribed. A new prescription can lead to a 11) ___ drug interaction, or simply be ineffective, because it is counteracted by something else being taken.

 

There is nothing to be gained, and potentially much to lose, by failing to disclose to health care professionals the use of prescribed, over-the-counter or recreational drugs, including alcohol. Nor should any chronic medical condition or prior adverse drug 12) ___ be kept from one’s doctor. Whenever a medication is prescribed, patients should ask about side 13) ___ to watch for. If a bad or unexpected reaction occurs or the drug does not seem to be working, the prescribing doctor should be told without delay. But patients should never stop taking a prescribed medication without first consulting a health care professional. Nor should they add any drug or supplement to a prescribed regimen without first consulting a doctor. Even something as seemingly innocent as ibuprofen, acetaminophen, St. John’s wort or an antihistamine purchased over the counter can sometimes lead to dangerous adverse reactions when combined with certain prescribed medications or pre-existing health problems.  But just because a drug is on one of the lists in the Beers Criteria does not mean every older person would be adversely affected by it. The drug may be essential for some patients, and there may be no safer alternative. When all is said and done, a doctor must weigh the benefits and 14) ___.     Source: The New York Times, April 2012, by Jane E. Brody

 

ANSWERS: 1) adults; 2) elderly; 3) blood; 4) Alzheimer’s; 5) pressure; 6) pneumonia; 7) medications; 8) drugs; 9) aspiration; 10) dosages; 11) toxic; 12) reaction; 13) effects; 14) risks

Geriatric Medicine

 

Ignatz Leo Nascher MD, 1863-1944, Chief of Clinic at the Mount Sinai Hospital, New York City. Considered “Father” of geriatrics in the United States.

 

 

The Canon of Medicine, written by Avicenna in 1025, was the first book to offer instruction in the care of the aged, foreshadowing modern gerontology and geriatrics. In a chapter entitled “Regimen of Old Age,” Avicenna was concerned with how “old folk need plenty of sleep” and how their bodies should be anointed with oil, and recommended exercises such as walking or horse-riding. Thesis III of the Canon discussed the diet suitable for old people, and dedicated several sections to elderly patients who become constipated.

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The famous Arabic physician, Ibn Al-Jazzar Al-Qayrawani (Algizar, circa 898-980), also wrote a special book on the medicine and health of the elderly, entitled Kitab Tibb al-Machayikh.He also wrote a book on sleep disorders and another one on forgetfulness and how to strengthen memory and a treatise on causes of mortality. Another Arabic physician in the 9th century, Ishaq ibn Hunayn (died 910), the son of Hunayn Ibn Ishaq, wrote a Treatise on Drugs for Forgetfulness.

 

The first modern geriatric hospital was founded in Belgrade, Serbia in 1881 by doctor Laza Lazarevic. In 1909, the term geriatrics was proposed by Dr. Ignatz Leo Nascher, former Chief of Clinic in the Mount Sinai Hospital Outpatient Department (New York City) and a “Father” of geriatrics in the United States.

 

Modern geriatrics in the United Kingdom really began with the “Mother” of Geriatrics, Dr. Marjorie Warren. Warren emphasized that rehabilitation was essential to the care of older people. Using her experiences as a physician in a London Workhouse infirmary, she believed that merely keeping older people fed until they died was not enough; they needed diagnosis, treatment, care, and support. She found that patients, some of whom had previously been bedridden, were able to gain some degree of independence with the correct assessment and treatment. The practice of geriatrics in the UK is also one with a rich multi-disciplinary history. It values all the professions, not just medicine, for their contributions in optimizing the well-being and independence of older people.

 

Another “hero” of British Geriatrics is Bernard Isaacs, who described the “giants” of geriatrics mentioned above: immobility and instability, incontinence, and impaired intellect.Isaacs asserted that, if examined closely enough, all common problems with older people relate back to one or more of these giants. The care of older people in the UK has been advanced by the implementation of the National Service Frameworks for Older People, which outlines key areas for attention.

 

In the United States, geriatricians are primary-care physicians who are board-certified in either family medicine or internal medicine and who have also acquired the additional training necessary to obtain the Certificate of Added Qualifications (CAQ) in geriatric medicine. Geriatricians have developed an expanded expertise in the aging process, the impact of aging on illness patterns, drug therapy in seniors, health maintenance, and rehabilitation. They serve in a variety of roles including hospital care, long-term care, home care, and terminal care. They are frequently involved in ethics consultations to represent the unique health and diseases patterns seen in seniors. The model of care practiced by geriatricians is heavily focused on working closely with other disciplines such as nurses, therapists, social workers, and pharmacists.

 

In the United Kingdom, most geriatricians are hospital physicians, whereas some focus on community geriatrics. While originally a distinct clinical specialty, it has been integrated as a specialization of general medicine since the late 1970s.Most geriatricians are, therefore, accredited for both. In contrast to the United States, geriatric medicine is a major specialty in the United Kingdom; geriatricians are the single most numerous internal medicine specialists.

 

Few psychiatrists know the name I.L. Nascher, M.D. Wrote Ewald Busse, M.D., and Dan Blazer, M.D., Ph.D., in their Textbook of Geriatric Psychiatry, published by American Psychiatric Publishing Inc., that Nascher is frequently considered the father of geriatrics and has been credited with coining the word“ geriatrics.”

Ignatz Leo Nascher, M.D., coined the term“ geriatrics.”

Credit: Courtesy of the NYU School of Medicine, Ehrman Medical Library Archives

In an article headlined “Geriatrics” in the New York Medical Journal in 1909, Nascher wrote that the word geriatrics is from the Greek word “geras, meaning old man, and iatrikos, relating to the [word] physician….” In Greek mythology, Geras is an old, shriveled man who represents the spirit of old age; his mother was Nyx, the so-called goddess of the night.

So the term geriatrics means a physician who specializes in the medical care of individuals in old age—the opposite of the term“ pediatrics,” relating to the medical care of children.

Senility “is a distinct period of life,” Nascher wrote,“ a physiological entity … a period of life where degeneration and decay are natural and physiological…. [S]enility and its diseases should be considered apart from maturity and assigned to a separate place in medicine.”

Ignatz Leo Nascher was born in Vienna, Austria, and was brought to the United States as an infant. His formal schooling in New York City led to a degree in pharmacy in 1882 and his M.D. in 1885 from the Department of Medicine of New York University.

He entered medical practice in New York and served in the outpatient clinics of Mt. Sinai Hospital. Years later, in 1916, he took a position at the Department of Public Welfare, then at the Department of Hospitals. In 1931, at his request, he was put in charge of the 1,200-bed City Farm Colony on Roosevelt Island in Manhattan. That facility later became Goldwater Hospital and today is named Coler-Goldwater Memorial Hospital.

He lectured on geriatrics at several medical schools in New York, Boston, and Chicago. He organized the New York Geriatric Society, though its existence was short-lived.

In 1914 Nascher published a 500-page textbook, Geriatrics: The Diseases of Old Age and Their Treatment, which included physiological home and institutional care and medical-legal relations. A second edition was published in 1916. The book is said to be the first publication on geriatrics since the 1881 book by J.M. Charcot, M.D., and Alfred L. Loomis, M.D. titled Clinical Lectures on the Diseases of Old Age. An introduction to Nascher’s book was written by Abraham Jacobi, M.D., president of the New York Academy of Medicine. Jacobi is credited with coining the word“ pediatrics” and establishing pediatrics as a separate medical discipline.

Nascher’s bibliography includes more than 70 titles (among them “The Senile State,” “Senile Debility,” and “The Senile Mentality”) published in various medical journals.

In 1944 he read a paper on chronic brain syndrome at the annual meeting of the recently organized American Geriatric Society, which dedicated the meeting to Nascher and made him an honorary president.

Nascher divided the span of life into three distinct periods: development, maturity, and senescence. His writings constantly emphasized that maturity and senility are different entities and that diseases of each phase require different treatment. Drugs reactions in maturity are different from those in old age, he said. He viewed old age as a period of degenerating and decaying cells and tissues, where the goal is not to cure disease as in maturity, but to return the old person to the previous physiological degenerating phase and retard death.

“Senile degeneration is not a pathology and cannot be halted, though it may be retarded,” he wrote.

He was aware of the social implications of aging and urged that old individuals be encouraged to feel young, maintain a good appearance and positive attitude, and keep occupied. “Courtship and marriage between an old person and one much younger … will produce marked mental rejuvenation.”

In the 1995 book Profiles in Gerontology: A Biographical Dictionary by W. Andrew Achenbaum, Ph.D., and D.M. Albert, the authors wrote that Nascher “was a prophet in every sense of the word.”▪

Brain-Activated Muscle Stimulation Restores Monkeys’ Hand Movement After Paralysis

 

Functional electrical stimulation (FES) devices are currently used for foot drop, a clinical condition seen in patients with stroke or partial spinal cord injury where weak or paralyzed muscles cause the toes to catch on the ground while walking, leading to trips and falls. FES can be activated with shoe sensors, or coordinated with walking movements, to stimulate muscles and lift the toes at the appropriate time during a step. Other FES devices in current clinical use take advantage of the patient’s residual muscle activity. For example, a prosthetic arm can use sensors built into the shoulder, sensing a shrugging motion that is used to stimulate muscles to open or close the hand. However, this is a less precise and less natural method of control, and it is not an option for patients with higher level spinal cord injuries and little or no shoulder and arm movement. For these patients, the creation of a brain-controlled FES device that connects brain activity directly to muscle stimulation would provide an opportunity to restore hand function.

 

According to an article published online in the journal Nature (18 April 18, 2012), an artificial connection between the brain and muscles was able to restore complex hand movements in monkeys following paralysis. The study combined two pieces of technology to create a neuroprosthesis – a device that replaces lost or impaired nervous system function. One piece was a multi-electrode array implanted directly into the brain which served as a brain-computer interface (BCI). The array allowed the study team to detect the activity of about 100 brain cells and decipher the signals that generate arm and hand movements. The second piece was a FES device that delivered electrical current to the paralyzed muscles, causing them to contract. The brain array activated the FES device directly, bypassing the spinal cord to allow intentional, brain-controlled muscle contractions and restore movement. Prior to testing the neuroprosthesis, the authors recorded the brain and muscle activity of two healthy monkeys as the animals performed a task requiring them to reach out, grasp a ball, and release it. The authors then used the data from the brain-controlled FES device to determine the patterns of muscle activity predicted by the brain activity.

 

To test the device, the researchers gave monkeys an anesthetic to locally block nerve activity at the elbow, causing temporary paralysis of the hand. With the aid of the neuroprosthesis, both monkeys regained movement in the paralyzed hand, could pick up and move the ball in a nearly routine manner and complete the task as before. The study also performed grip strength tests, and found that their system restored precision grasping ability. The device allowed voluntary and intentional adjustments in force and grip strength, which are keys to performing everyday tasks naturally and successfully.

 

This new research moves beyond earlier work showing that a similar neuroprosthesis restores monkeys’ ability to flex or extend the wrist despite paralysis. In 2008, a team led by Eberhard Fetz, Ph.D. at the University of Washington in Seattle coupled the activity of single neurons to an FES device similar to the one used for the present study. Monkeys learned to activate individual neurons to control the FES device and move a joystick, and could adapt neurons previously unassociated with wrist movement to complete the task. The authors suggested that this process of learning and adaption plays an important role in how the BCI translates the brain’s activity patterns into adaptive control of the FES device.

ONCOLOGY

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Radiotherapy with or without Chemotherapy in Muscle-Invasive Bladder Cancer

 

Radiotherapy is an alternative to cystectomy in patients with muscle-invasive bladder cancer. In other disease sites, synchronous chemotherapy and radiotherapy has been associated with increased local control and improved survival, as compared with radiotherapy alone. As a result, a study published in the New England Journal of Medicine (2012; 366:1477-1488), was performed to evaluate clinical outcomes when radiotherapy is combined with chemotherapy in muscle-invasive bladder cancer.

 

The multicenter clinical trial randomly assigned 360 patients with muscle-invasive bladder cancer to undergo radiotherapy with or without synchronous chemotherapy. The regimen consisted of fluorouracil (500 mg per square meter of body-surface area per day) during fractions 1 to 5 and 16 to 20 of radiotherapy and mitomycin C (12 mg per square meter) on day 1. Patients were also randomly assigned to undergo either whole-bladder radiotherapy or modified-volume radiotherapy (in which the volume of bladder receiving full-dose radiotherapy was reduced) in a partial 2-by-2 factorial design. The primary end point was survival free of loco-regional disease. Secondary end points included overall survival and toxic effects.

 

Results showed that at 2 years, rates of loco-regional disease-free survival were 67% in the chemo-radiotherapy group and 54% in the radiotherapy group. With a median follow-up of 69.9 months, the hazard ratio in the chemo-radiotherapy group was 0.68; P=0.03). Five-year rates of overall survival were 48% in the chemo-radiotherapy group and 35% in the radiotherapy group (hazard ratio, 0.82; P=0.16). Grade 3 or 4 adverse events were slightly more common in the chemo-radiotherapy group than in the radiotherapy group during treatment (36% vs. 28%, P=0.07) but not during follow-up (8% vs. 16%; P=0.07).

 

According to the authors, synchronous chemotherapy with fluorouracil and mitomycin C combined with radiotherapy significantly improved loco-regional control of bladder cancer, as compared with radiotherapy alone, with no significant increase in adverse events.

ONCOLOGY

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Carboplatin and Paclitaxel with vs. without Bevacizumab in Older Patients with Advanced Non-Small Cell Lung Cancer

 

An earlier randomized clinical trial demonstrated that adding bevacizumab (Avastin) to carboplatin and paclitaxel improved survival in advanced non-small cell lung cancer (NSCLC). However, longer survival was not observed in the subgroup of patients aged 65 years or older.

 

As a result, a study published in the Journal of the American Medical Association (2012;307:1593-1601) was performed to examine whether adding bevacizumab to carboplatin and paclitaxel chemotherapy is associated with improved survival in older patients with NSCLC.

 

The investigation was a retrospective cohort study of 4,168 Medicare beneficiaries aged 65 years or older with stage IIIB or stage IV non-squamous cell NSCLC diagnosed in 2002-2007 in a Surveillance, Epidemiology, and End Results (SEER) region. Patients were categorized into 3 cohorts based on diagnosis year and type of initial chemotherapy administered within 4 months of diagnosis: (1) diagnosis in 2006-2007 and bevacizumab-carboplatin-paclitaxel therapy; (2) diagnosis in 2006-2007 and carboplatin-paclitaxel therapy; or (3) diagnosis in 2002-2005 and carboplatin-paclitaxel therapy. The main outcome measure was overall survival measured from the first date of chemotherapy treatment until death or the censoring date of December 31, 2009.

 

Results showed that the median survival estimates were 9.7 months for bevacizumab-carboplatin-paclitaxel, 8.9 months for carboplatin-paclitaxel in 2006-2007, and 8.0 months for carboplatin-paclitaxel in 2002-2005. One-year survival probabilities were 39.6% for bevacizumab-carboplatin-paclitaxel vs. 40.1% for carboplatin-paclitaxel in 2006-2007 and 35.6% for carboplatin-paclitaxel in 2002-2005. The statistical analysis did not demonstrate a survival advantage for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel cohorts alone.

 

According to the authors, adding bevacizumab to carboplatin and paclitaxel chemotherapy was not associated with better survival among Medicare patients with advanced NSCLC.

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.

 

Draft Guidance Issued on Nanotechnology

 

Nanotechnology is an evolving technology that allows scientists to create, explore, and manipulate materials on a scale measured in nanometers – particles so small that they cannot be seen with a regular microscope. The technology has a broad range of potential applications, such as  sophisticated delivery systems targeting specific diseased organs of the body,  packaging of food or altering the look and feel of cosmetics.

 

FDA has issued 2 draft guidance documents that address the use of nanotechnology by the food and cosmetics industries. The two draft guidance documents are: “Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact Substances, Including Food Ingredients that are Color Additives“ and “Safety of Nanomaterials in Cosmetic Products.”

 

The food draft guidance describes the factors manufacturers should consider when determining whether changes in manufacturing processes, including those involving nanotechnology, create a significant change that may:

 

  • affect the identity of the food substance;
  • affect the safety of the use of the food substance;
  • affect the regulatory status of the use of the food substance; or
  • warrant a regulatory submission to FDA.

 

The cosmetic product draft guidance discusses the FDA’s current thinking on the safety assessment of nanomaterials when used in cosmetic products. Key points include:

 

  • The legal requirements for cosmetics manufactured using nanomaterials are the same as those for any other cosmetics. While cosmetics are not subject to premarket approval, companies and individuals who market cosmetics are legally responsible for the safety of their products and they must be properly labeled.
  • To conduct safety assessments for cosmetic products containing nanomaterials, standard safety tests may need to be modified or new methods developed.

 

Both guidances encourage manufacturers to consult with the agency before taking their products to market. Such consultation can help FDA experts address questions related to the safety or other attributes of nanotechnology products, or answer questions about their regulatory status. Strong science is critical to FDA’s ongoing review of the products it regulates. FDA is investing in an FDA-wide nanotechnology regulatory science program to further enhance FDA’s scientific capabilities, including developing necessary data and tools to identify properties of nanomaterials and assess the impact they may have on products.

 

The FDA’s current thinking concerning nanomaterials for food and cosmetics uses, explained in the two guidance documents, is not intended to provide guidance to manufacturers about the use of nanomaterials in other products, such as drugs or medical devices, regulated by the FDA. In order to ensure that FDA considers comments on these draft guidances in developing the final guidances, electronic or written comments should be submitted within 90 days of the publication of the notices of availability in the Federal Register. The FDA will carefully consider all relevant, substantive comments during the development of the final guidance documents. Electronic comments can be submitted. Written comments should be submitted to the Division of Dockets Management, (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852.