Pew finds serious gaps in oversight of US drug safety

Americans' medicines are increasingly manufactured in developing countries, where oversight is lower than in the U.S., according to a new white paper by the Pew Health Group. The U.S. Food and Drug Administration (FDA) estimates 40 percent of finished drugs and 80 percent of active ingredients and bulk chemicals used in U.S. drugs come from overseas.

The white paper, After Heparin: Protecting Consumers from the Risks of Substandard and Counterfeit Drugs, finds that increased outsourcing of manufacturing, a complex and globalized supply chain and criminal actors create the potential for counterfeit or substandard medicines to enter the supply chain and reach patients. For economic reasons, the migration of manufacturing abroad is likely to continue. At the same time, industry and government agencies have failed to adapt to the changing environment.

"Today's prescriptions are being produced under last century's oversight," said Allan Coukell, director of medical programs at the Pew Health Group. "Compared with a decade ago, pharmaceutical supply lines stretch around the world and out to a complex web of suppliers. Regulators and industry must modernize supervision of the manufacturing process to ensure the drugs we consume are safe. The After Heparin white paper indentifies links in the supply chain that government and business should strengthen," Coukell added.

Substandard or adulterated pharmaceutical materials from abroad have entered the U.S. on multiple occasions. In addition, the risks of domestic counterfeiting and diversion of stolen drugs are well documented. The white paper presents several case studies, including incidents involving heparin, a blood thinner adulterated during its manufacture in China, counterfeit vials of the anemia drugEpogen and stolen vials of insulin to illustrate the threats and suggest solutions.

After Heparin is based on public information, including FDA documents, U.S.Government Accountability Office (GAO) reports, congressional testimony, peer-reviewed journals and interviews with more than 50 supply chain experts and stakeholders. The findings and recommendations were discussed during a recent two-day convening on the white paper that included a diverse group of industry representatives, ranging from ingredient manufacturers to community pharmacists. 

No difference in brand name and generic drugs regarding thyroid dysfunction

There is no difference between brand-name and generic drug formulations of amiodarone -- taken to control arrhythmia – in the incidence of thyroid dysfunction, according to a study in CMAJ (Canadian Medical Association Journal).

Amiodarone, prescribed to control irregular heartbeats, is known for causing hypo- and hyper-thyroidism. Amiodarone is available in Canada in brand-nameformulations as well as less costly generic versions. Generic formulations may be substituted if considered bioequivalent to the brand name drug. However, in some drugs there are concerns that generic formulas may be less effective or increase the number of adverse events.

Thyroid dysfunction occurs in one in five patients on amiodarone.

There is no information on the effects of brand-name versus generic versions of amiodarone on the incidence of thyroid dysfunction. Researchers from McGill University Health Centre and Jewish General Hospital, Montreal, Quebec; Western University of Health Sciences, Pomona, California; University of British Columbia, Vancouver, BC and the Institute for Clinical Evaluative Sciences in Toronto, Ontario sought to examine the incidence of thyroid dysfunction in patients taking brand name formulations of amiodarone compared with generic versions.

They looked at data on 60 220 patients aged 66 and older with atrial fibrillation taking amiodarone. Of these, 2804 (4.7%) used the brand-name formulation and 6278 (10.4%) took the generic formulation. There was no significant difference in rates of thyroid dysfunction between the two groups, measured in hospital admissions, visits to physicians for the condition or taking drugs for thyroid dysfunction.

"The incidence rate for thyroid dysfunction was estimated at 14.1 per 100 person-years, similar for both formulations," writes Dr. Louise Pilote, physician and researcher at the McGill University Health Center, with coauthors. "The incidence rates for hypothyroidism and hyperthyroidism per 100 person-years were comparable between brand-name and generic formulations, with hypothyroidism occurring more commonly than hyperthyroidism."

They caution that patients should be warned of the risks of amidarone when they begin the drug so they can recognize and report symptoms.

"We found no difference in the incidence of thyroid dysfunction between generic and brand-name formulations," conclude the authors. "The results from this study provide valuable information for both clinicians and policy makers concerning the prescription of brand name versus generic drugs."

In a related commentary, Dr. Aaron Kesselheim of Brigham and Women's Hospital in Boston states, "Decades of experience and numerous clinical studies suggest that patients and physicians can be confident in the bioequivalence of brand-name and generic drugs approved by Health Canada, the FDA or other similar regulatory authorities. In the rare circumstances where there is concern over interchangeability, such as for high-risk patients, it may be reasonable for physicians to take extra precautions, such as additional monitoring, when substitution occurs."

Provided by Canadian Medical Association Journal (news : web)

Parkinson's disease patients may benefit from virtual-reality-based therapies

In people with Parkinson's Disease (PD), the inability to make quick movements limits basic functioning in daily life. Movement can be improved by various cueing techniques, such as providing visual or auditory stimuli when movements are started. In a study scheduled for publication in the August issue of the Archives of Physical Medicine and Rehabilitation, researchers report that virtual reality (VR) and physical reality exercises can be used to provide effective stimuli to increase movement speeds in PD patients.

Investigators from the Departments of Occupational Therapy, Neurology, andMechanical Engineering, the Institute of Education, and Allied Health Sciences, the National Cheng Kung University, Tainan, Taiwan, studied a group of 13 women and 16 men with PD who were age-matched against 14 women and 11 men without PD. Each participant was asked to reach for and grasp a stationary ball as quickly as possible. Then, moving balls were rolled down a ramp and the participants were asked to catch them when they reached a particular point on the ramp. When trying to catch the moving balls, the targets were visible for periods from 1.1 to 0.5 seconds. These trials were done in both normal physical reality and in a virtual reality environment.

"This study contributes to the field of rehabilitation by providing evidence about how to manipulate task and environmental constraints to improve movement in persons with PD," commented lead investigator Hui-Ing Ma. "Specifically, this study shows how to manipulate VR scenarios to improve movement speed in persons with PD, while at the same time depicting their movement characteristics in VR. Our study extends the previous findings of the moving target effect in physical reality to VR. Our findings suggest that with an appropriate choice of cueing speed, VR is a promising tool for offering visual motion stimuli to increase movement speed in persons with PD."

The authors highlight three main findings. First, in both VR and physical reality, the PD group had longer movement time and lower peak velocity than the control group when reaching for a stationary ball at a self-determined maximum speed. Second, for both VR and physical reality, movement time was significantly shorter and peak velocity was higher in the faster cueing conditions. Third, when moving targets were provided, the PD group showed more improvement than the control group in movement time and peak velocity, thus reaching a performance level similar to that of the control group.

More information: The article is "Comparison of Virtual Reality Versus Physical Reality on Movement Characteristics of Persons With Parkinson's Disease: Effects of Moving Targets" by Ching-Yi Wang, MS, OT, Wen-Juh Hwang, MD, Jing-Jing Fang, PhD, Ching-Fan Sheu, PhD, Iat-Fai Leong, PhD, and Hui-Ing Ma, ScD, OT. It will appear in Archives of Physical Medicine and Rehabilitation, Volume 92, Issue 8 (August 2011). doi:10.1016/j.apmr.2011.03.014

State should take obese kids from parents: US doctors July 13, 2011

"State intervention may serve the best interests of many children with life-threatening obesity, comprising the only realistic way to control harmful behaviors," wrote Lindsey Murtagh of the Harvard School of Public Health and David Ludwig of Children's Hospital in Boston.

"In severe instances of childhood obesity, removal from the home may be justifiable from a legal standpoint because of imminent health risks and the parents' chronic failure to address medical problems."

Some two million children in the United States are considered severely obese with a body mass index at or above the 99th percentile, the doctors wrote.

"Obesity of this magnitude can cause immediate and potentially irreversible consequences, most notably type 2 diabetes," they said.

Child abuse laws have long addressed situations in which children are starved or neglected, but "only a handful of states, including California, Indiana, Iowa, New Mexico, New York, Pennsylvania, and Texas, have legal precedent for applying this framework to overnourishment and severe obesity."

Murtagh, who is also a lawyer by training, and Ludwig said that while it may be an undesirable option, placing a child in temporary foster care could allow better habits to take root and avoid the risks of weight loss surgery.

"Although removal of the child from the home can cause families great emotional pain, this option lacks the physical risks of bariatric surgery."

The opinion piece in the Journal of the American Medical Association made waves in the medical community and US media, and JAMA issued a statement pointing out that the piece did not reflect the institution's view.

"This commentary does not reflect policy or opinion of the American Medical Association (AMA) or JAMA. The content of this commentary is solely the responsibility of the authors," it said.

Research provides insight into new drug resistance in hospital microbes

Research provides insight into new drug resistance in hospital microbes


Hospitals struggle to prevent the infections that complicate treatment for cancer, joint replacement, heart surgery and other conditions. Hospital-acquired infections are often resistant to multiple antibiotics, leading to approximately 100,000 deaths and more than $30 billion in additional health care costs yearly. New drugs are being developed to combat these infections, but resistance invariably emerges to these last-line drugs.

Daptomycin, a new antibiotic approved by the FDA in 2003, is used to treat infections caused by multi-drug resistant bacteria, including staph and microbes known as enterococci. Scientists in the Department of Ophthalmology at Mass. Eye and Ear and Harvard Medical School, and the pharmaceutical company Cubist, which produces daptomycin under the trade name Cubicin, teamed up to discover the basis for resistance that has now begun to emerge to daptomycin in the enterococci. Their discovery of a new mechanism of resistance is described in an article in the current (July) issue of Antimicrobial Agents and Chemotherapy.

In a two-week experiment, investigators were able recreate the development of resistance in the laboratory in a manner similar to that which occurred in the hospital. Using new genome sequencing technology, they resequenced the entire genome of the resistant enterococcus strain to identify all of the genetic changes. The researchers found changes in genes that they were also able to identify in hospital daptomycin resistant strains. Mutations in a gene encoding an enzyme called cardiolipin synthase were able by itself to confer daptomycin resistance to a laboratory strain of enterococcus.

"Knowing the changes that correspond with resistance not only tells us what happens in resistant strains, it tells us much about how exactly how the antibiotic works, providing new ideas for better treatment and next generation drugs," observed Dr. Michael S. Gilmore, a scientist at Harvard Medical School and the Mass. Eye and Ear, and the corresponding author.

Provided by Massachusetts Eye and Ear Infirmary