The saying goes that there’s no such thing as bad publicity. But that is frequently proved untrue in healthcare. The focus on breast cancer, for instance, is often seen as over-emphasized when heart disease for women is a greater cause of mortality. The threat of terror attacks pales against the ongoing mortality produced by chronic diseases.

And few would put chronic obstructive pulomonary disease (COPD) as fourth most deadly.

That was the point being made by presenters at a meeting of the National Press Club in Washington last month. making the case that the general public — and all too few medical professionals — understand the severity of one of the deadliest diseases of modern times.

The press club presentation showcased the roll- out of the “Learn More, Breathe Better” campaign intended to spread awareness of COPD, which is, similar to cancer, a group of related breathing ills: primarily chronic bronchitis, asthma and emphysema. It was described as the fourth leading cause of death in the U.S. and one of the best-kept secrets of modern epidemiologists.

Elizabeth Nabel, MD, director of the National Heart, Lung, and Blood Institute of the National Institutes of Health, told the audience that the “Learn More, Breathe Better” campaign is overdue, given that the disease is probably present in one out of four persons over the age of 45.

“Many people with early signs of COPD simply avoid activities they used to enjoy because they become short of breath more easily,” Nabel said. The NHLBI chief noted that “diagnosis is easy, requiring only a simple breathing test in your doctor’s office.”

NHLBI has struck a partnership with professional societies and health advocates to launch the campaign, geared toward boosting awareness at the demographic groups at greatest risk. According to Nabel, doctors have diagnosed more than 12 million Americans with the condition, and as many as another 12 million may be struggling through long days and sleepless nights with this sometimes crippling state of affairs.

“Through this campaign, we hope to increase recognition of this disease so that those at greatest risk are diagnosed by getting a simple breathing test,” Nabel said

Grace Anne Dorney Koppel, wife of legendary newscaster Ted Koppel, is a patient and advocate, and said that she had the tobacco habit — which is blamed for much of the underlying disease.

“I did smoke for many years, but have not since 1995.” Koppel was diagnosed with COPD after she stopped smoking. She said that those with COPD constitute “a vast legion of people,” and made reference to the insidious nature of the disease, a characteristic of a number of diseases that makes diagnosis difficult.

Koppel remarked that COPD “creeps up on us until we wheeze, cough and gasp for air.” She added that because the condition makes breathing sensitive to posture, “[w]e try to sleep sitting up” in order to maintain respiration. She noted also that COPD patients may not receive the treatment they need because the disease is seen as self-inflicted — the “pariah of diseases because of the stigma of smoking,” she said.

When she was finally diagnosed, Koppel said that she improved rapidly, in part, due to “exercise, exercise, exercise.” She conveyed a very positive message to sufferers, but cautioned, “I don’t want to leave you with the impression that magic was wrought overnight or that my experience” represents the norm for those with the disease. She added though: “I feel better and stronger today than I did 15 years ago.”

Sonja Buist, MD, a professor of medicine at Oregon Health & Sciences University (Portland), said that “as lung specialists, it’s really remarkable that we’ve done such a poor job of informing the public and our colleagues” about COPD. Part of the problem, she said, is that “over the past years . . . we’ve kept on changing the name” and have not pushed spirometry to test for it. Her numbers indicated that if current trends hold, it will become the third leading cause of death worldwide by 2020, which is “remarkable for a disease that nobody has ever heard of.”

Buist made the case that the total of almost 124,000 annual deaths is “a gross under-estimate” because coroners often mistake the cause of death. “What is so striking is the huge increase in the death rate of women” between 1980 and 2000, Buist said. Men were more than twice as likely to die of the disease in 1980, but the death toll in 2000 was essentially the same.

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AHRQ: U.S. health systemmissing ‘important chances’

The Agency for Healthcare Research and Quality (Washington) has issued an overview report saying that “[t]he overall quality of the U.S. healthcare system is improving” — a statement open to debate — but then adding what few would disagree with.

It says that providers “are missing important chances to help Americans avoid disease or serious complications.”

The group’s annual reports, the 2006 “National Healthcare Quality Report” and the “National Healthcare Disparities Report,” say that “the use of proven prevention strategies lags significantly behind other gains in healthcare.” Figures supporting this statement include:

• Only about 52% of adults report receiving recommended colorectal cancer screenings. About 56,000 Americans die from colorectal cancer, and 150,000 new cases are diagnosed each year. In 2002, the AHRQ-supported U.S Preventive Services Task Force urged initial screenings at age 50 and earlier for people at high risk.

• Fewer than half of obese adults report being counseled about diet by a healthcare professional. About one-third of American adults are obese, increasing the risks of high blood pressure, Type 2 diabetes, stroke, heart disease and osteoarthritis. (The Task Force recommends “intensive counseling and behavioral interventions” for obese adults.)

• Only 49% of people with asthma say they were told how to change their environment, and 28% report receiving an asthma management plan. Asthma causes about 500,000 hospitalizations annually.

• Only 48% of adults with diabetes received all three recommended screenings — blood sugar tests, foot exams and eye exams — to prevent complications. AHRQ estimates about $2.5 billion could be saved each year by eliminating hospitalizations related to diabetes complications.

While the “National Healthcare Quality Report” tracks the healthcare system through quality measures — such as what proportion of heart attack patients received recommended care when they reached the hospital — the “National Healthcare Disparities Report” summarizes which racial, ethnic or income groups are most likely to benefit from healthcare improvements. And, as in previous years, the disparities report found access to care varied widely between racial, ethnic and economic groups.

• Blacks received poorer quality care than whites for 73% of the core measures included in the disparities report.
• Hispanics received poorer quality of care than non-Hispanic whites for 77% of the measures.
• Poor people received lower quality of care than high-income people for 71% of the measures.

The variations were particularly apparent in the area of prevention.

Obese blacks were less likely to be told they were overweight by their doctor or other healthcare provider. Colorectal cancer screening rates were significantly lower for blacks and Asians when compared with whites. Among people 65 and older, blacks, Hispanics and those in lower income groups were less likely to have ever received a vaccine to prevent pneumonia.

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FDA to bar BSE-linkedmaterials from devices, drugs, biologics

The FDA is proposing to limit the materials used in some medical products in order to keep them free of the agent thought to cause mad cow disease, also known as bovine spongiform encephalopathy (BSE).

The agency said that this is the latest in a series of BSE safeguards that would bar material that has been found to harbor the highest concentrations of this fatal agent in infected cattle. These materials would be prohibited from use as ingredients in medical products or elements of product manufacturing.

The proposed rule would cover medical devices, drugs (prescription, over-the-counter, and homeopathic) and biologics (such as vaccines) intended for use in humans, as well as drugs intended for use in ruminant animals such as cattle and sheep. Cattle can get mad cow disease, while sheep can get a similar disease known as scrapie.

“These measures build on a series of barriers FDA and the U.S. Department of Agriculture have erected to further protect humans from exposure to the fatal agent linked to BSE,” said Andrew von Eschenbach, MD, commissioner of the FDA.

The cattle materials prohibited in the proposed rule are those that pose the highest risk of containing infectious material and include: the brain, skull, eyes and spinal cords from cattle 30 months and older; the tonsils and a portion of the small intestines from all cattle regardless of their age or health; any material from “downer” cattle — those that cannot walk; any material from cattle not inspected and passed for human consumption; fetal calf serum if appropriate procedures have not been followed to prevent its contamination with materials prohibited by this proposed rule; tallow that contains more than 0.15% insoluble impurities if the tallow is derived from materials prohibited by this proposed rule and; mechanically separated beef.

FDA proposes to require that records be kept to demonstrate that any cattle material used as an ingredient in these medical products or as part of their manufacturing process meet the rule’s requirements.

Transmission of the BSE agent to humans, leading to vCJD, is believed to occur via ingestion of cattle products contaminated with the BSE agent; however the specific products associated with this transmission are unknown.

About 200 cases of vCJD have been identified worldwide, including three cases in the U.S. However, there is no evidence that those three patients contracted the BSE agent in the U.S.

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FDA issues new draft guidance forcord blood

The FDA has issued a draft guidance recommending a streamlined path to licensure for establishments that manufacture cord blood for certain medical conditions.

Placental/umbilical cord blood is a rich source of precursor cells capable of differentiating into mature blood cells. These precursor cells are known as hematopoietic stem/progenitor cells and can be used to replenish the bone marrow in patients with blood-based malignancies such as leukemia.

The draft guidance describes FDA’s regulatory approach to the regulation of cord blood hematopoietic stem/progenitor cells that are: minimally manipulated (processing does not alter the original characteristics of the cells); used to replenish the bone marrow in patients with blood-related malignancies; and used in recipients unrelated to the donor of the stem cells.

Jesse Goodman, MD, MPH, director of FDA’s Center for Biologics Evaluation and Research (CBER), said that the draft guidance “provides recommendations on a streamlined path to licensure for these promising products that also ensures their safety and effectiveness.”

FDA first proposed a new regulatory framework for human cells, tissues and cellular and tissue-based products (HCT/P), including cord blood, in 1997. This tiered approach, implemented in May of 2005, requires that establishments register with FDA and list their products, ensure quality control by adhering to the agency’s current good tissue practices and follow the agency’s rules on donor eligibility. Under this framework, cord blood hematopoietic stem/progenitor cells from unrelated donors are regulated as both HCT/P and as biologic drugs subject to licensure.

FDA said it has determined that cord blood hematopoietic stem/progenitor cells are safe and effective for certain indications, based on the data submitted to the public docket and the large body of published literature. Therefore, the new draft guidance offers cord blood banks a less burdensome path to licensure. Rather than having to submit their own clinical data, they may cite existing data in the docket.

The draft guidance also provides manufacturers with recommendations on the content and format of information to be submitted with an application, discusses the manufacture of cord blood hematopoietic stem/progenitor cells and elaborates on how to comply with applicable regulatory requirements.

FDA is accepting public comment for 90 days from the date of guidance publication in the Federal Register.

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Obesity surgeries on the rise,says AHRQ

Obesity surgeries for patients between the ages of 55 and 64 in the U.S. soared from 772 procedures in 1998 to 15,086 surgeries in 2004 — a nearly 2,000% increase, according to a new report by the Agency for Healthcare Research and Quality (Rockville, Maryland). The report also found a 726% increase in surgeries among patients age 18 to 54. A total of 121,055 surgeries were performed on patients of all ages in 2004.

AHRQ said that among the reasons for the dramatic increase is that mortality outcomes from obesity surgery have sharply declined. It said that the national death rate for patients hospitalized for bariatric surgery declined 78%, from 0.9% in 1998 to 0.2% in 2004. Collectively known as bariatric surgery, these procedures include gastric bypass operations, vertical-banded gastroplasty, and gastric banding or “lapband.” Doctors may recommend bariatric surgery for patients who have a Body Mass Index of 40 or greater — a person who is 5 feet 2 inches tall and weighs 276 pounds, for example — or a BMI of 35 or more for patients who have serious, obesity-related medical conditions such as Type 2 diabetes or severe sleep apnea.

The report also found that:

• Patients ages 18 to 54 still account for the highest number of surgeries: 103,097 bariatric surgeries, 85% of the total.
• Adolescents ages 12 to 17 accounted for 349 bariatric procedures in 2004.
• Women have bariatric surgery more often than men. They accounted for more than 99,000 operations, 82% of the total.
• The in-hospital death rate for men in 2004 was only 0.4%, but it was 2.8 times higher than that of women. In 1998, the in-hospital death rate for men was six times higher than that of women.
• Gastric bypass surgery — which reduces the size of the stomach and bypasses a section of the intestines to decrease food absorption — accounted for 94% of bariatric procedures.
• The average hospital cost for a bariatric surgery patient stay, excluding physician fees, was $10,395 in 2004 as compared with $10,970 in 1998, adjusted for inflation.
• The vast majority (78%) of bariatric surgery patients were privately insured. Only 5% of patients were uninsured, but their numbers increased by 810% over the period.
• The overall hospital costs for bariatric surgery patients increased more than eightfold — from $147 million in 1998 to $1.3 billion in 2004. However, the average cost per patient decreased by 5%.

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Gene therapy/nanoparticle comboenlisted in fight vs.lung tumors

Combination gene therapy delivered in lipid-based nanoparticles drastically reduces the number and size of human non-small cell lung cancer tumors in mice, researchers at The University of Texas M. D. Anderson Cancer Center (Houston) and the University of Texas Southwestern Medical Center (Dallas) reported in the Jan. 15 edition of Cancer Research.

Two tumor-suppressing genes given intravenously reduced cancer separately but had their most powerful effect when administered together, cutting the number of tumors per mouse by 75% and the weight of tumors by 80%.

“In cancer treatment we have combination chemotherapy, and we also combine different modes of therapy — surgery, radiation and chemotherapy. Now you’ve got the possibility of combined targeted gene therapy,” said Jack Roth, MD, chair of the M. D. Anderson Department of Thoracic and Cardiovascular Surgery and a senior researcher on the project.

The genes wrapped in the nanoparticles were p53, a tumor suppressor that causes defective cells to commit suicide and is often shut down or defective in cancer cells, and FUS1, a tumor-suppressor deficient in most human lung cancers. Each nanoparticle carried one of the two genes.

The Cancer Research paper reports that FUS1 works with p53 to force the lung cancer cells to kill themselves — a process known as apoptosis. Further analysis showed that the combination achieved greater cell suicide because FUS1 suppresses a gene that expresses a protein known to rapidly degrade p53, says senior author Lin Ji, Ph.D., M.D. Anderson associate professor of thoracic and cardiovascular surgery. The FUS1/p53 combination also activates a cell suicide pathway based in the cells’ mitochondria, their energy powerhouse.

Lab experiments first showed that the gene combination cut the number of viable cells in four lines of human non-small cell lung cancer by 70% to 80% 48 hours after treatment while leaving a control group of normal cells unaffected. The cancer cell lines treated with the gene combination had two-to- three times more cells killed by apoptosis than either gene nanoparticle had individually. The research team then confirmed these findings in the mouse studies.

The nanoparticle delivery system consists of a plasmid gene expression cassette loaded with DNA that encodes either the p53 or the FUS1 protein. This is wrapped tightly in a form of cholesterol to protect it from the body’s defense mechanisms. “You can’t deliver naked DNA for cancer therapy,” Ji says.

The nanoparticles accumulate mainly in the lungs, particularly in the tumors, Ji said. The positively charged nanoparticles are delivered to the negatively charged cancer cell membrane and taken into the cell, where the genes repeatedly express either p53 or FUS1 tumor-suppressing proteins.

Roth expects the research team to advance combination therapies to clinical trials in the coming years, either of genes or of genes with other biologic or chemotherapy agents.