FDA issues warning letter to researcher about promoting Ipsens Dysport

The U.S. Food and Drug Administration (FDA) has issued a warning to Miami Beach-based researcher Leslie Baumann, M.D., regarding promotional statements she made about Ipsen Biopharm’s (Paris) injectable frown line treatment Dysport (abobotulinumtoxinA), the FDA said in a letter.

Dr. Baumann’s promotional statements about Dysport, which were made to two magazines and NBC’s “Today Show,” were reportedly made in 2006, prior to the drug’s FDA approval. The statements were therefore in violation of the FDA’s regulations on pre-approval promotion, the agency said in its letter.

Dr. Baumann was involved as a researcher in Phase III trials of Dysport, also known as Reloxin, at the time she made the promotional statements, the FDA stated.

Dr. Baumann’s statements about Dysport included claims that its effects “last a month longer than Botox (onabotulinumtoxinA, Allergan, Irvine, Calif.),” the FDA letter cited. The FDA approved Dysport for treating forehead wrinkles and frown lines last spring. Ipsen granted distribution rights for the drug’s cosmetic use to Medicis (Scottsdale, Ariz).

Kaiser questions complexity of drug-safety programs

Kaiser Permanente is concerned that too many diverse drug safety programs will impose a burden on the healthcare system and on patients, and that this will drive up costs and limit access to therapies.

The integrated health plan wants a greater say in how the Food and Drug Administration (FDA) and drug companies design and implement these programs to ensure they don’t discriminate against certain healthcare providers and pharmacies.

In 2007, Congress expanded FDA’s authority to require drug makers to establish Risk Evaluation and Mitigation Strategies (REMS) to enhance the safe and appropriate use of marketed medicines. Most of the 80 or more approved REMS are fairly modest, only providing patients with printed medication guides that describe proper drug use.

But a growing number of these programs also include more extensive Elements to Assure Safe Use (ETASU), which tightly manage prescribing and dispensing of high-risk medicines. ETASU can involve limited distribution of the drug and certification of prescribers and pharmacists to ensure appropriate prescribing and dispensing; in some cases patients have to be tested to ensure they’re not pregnant, for example, or that the drug is not causing harmful reactions.

COST AND ACCESS QUESTIONED

Kaiser is concerned that its physicians and pharmacies will be cut out of such certification and distribution programs, and that its patients will have difficulty gaining access to needed therapies. Such requirements could increase costs for health plans and for consumers, limiting access to needed drugs and the overall benefits of the REMS safety program.

The problem has not been that noticeable so far because most REMS with ETASU have involved drugs for relatively small patient populations. However, FDA is considering a more involved REMS for the broad class of extended-use opioids, and might weigh such an approach for erythropoietin-stimulating agents (for red blood cell production), drugs that are expensive and widely used.

Consequently, Kaiser has formally petitioned FDA to open up its process for designing and approving REMS with ETASU. Kaiser proposes that FDA’s public advisory committees review such processes to make the proposals more transparent and to allow plans and providers to have a say. That would give Kaiser an opportunity to have its own specialty pharmacy operation included in a REMS network.

The health plan also wants to ensure that REMS programs protect the privacy of patient health information.

Fera Pharmaceuticals now shipping erythromycin ophthalmic ointment

Erythromycin ophthalmic ointment is now available after a previous market shortage, manufacturer Fera Pharmaceuticals (New York) said in a press release.

Last summer the company acquired erythromycin and six other ophthalmic ointments; during the transfer period, supplies of both erythromycin and bacitracin became very limited. Erythromycin is currently on a list of drug shortages on the U.S. Food and Drug Administration’s Web site.

Last week, Fera announced the completion of bacitracin’s manufacturing transfer and has begun shipping again to pharmacies and wholesalers.

Fera anticipates the availability of the 3.5-gram tube size of erythromycin in cartons of 24, Hospital-Pak, as well as the single 3.5-gram tube package size over the next few weeks, the company said in the release.

According to the FDA’s Web site, Bausch & Lomb (Rochester, N.Y.), which also manufactures erythromycin, is currently releasing the product in the 50 x 1 gm packaging configuration. Bausch & Lomb is also distributing limited amounts of product in the 3.5-gram tube, the FDA reported.

Steris Responds to FDA’s SS1 Warning

Medical manufacturer Steris says it disagrees with a safety alert the U.S. Food and Drug Administration issued last week, in which the agency urged users of the Steris System 1 to find an alternative method for sterilizing and disinfecting their instruments.

Besides stating that the modified version of the SS1 has not received FDA approval, the safety alert says that the agency has received reports of operational malfunctions in the popular tabletop liquid chemical reprocessor that could cause such “serious injuries” as patient infections. If you have an acceptable alternative to the SS1, the FDA says, you should transition to that alternative.

Steris responded yesterday by saying that the SS1 is safe and effective when used as directed. “We are working to engage in further dialogue with FDA about this matter,” says the company.

Steris notes that there has not been a documented case of infection directly caused by a SS1 when certified health professionals have followed proper guidelines and instructions.

The SS1 was introduced in 1988. More than 23,000 units have been used in more than 5,000 hospitals and clinics in the United States, sterilizing more than 300 million medical devices or about 30,000 per day. Users who have questions or require immediate assistance can contact Steris at (440) 392-7223.

HHS sends warning letter on Latisse

After reviewing two sections of a consumer Web site for Latisse (bimatoprost ophthalmic solution 0.03%, Allergan, Irvine, Calif.), the Division of Drug Marketing, Advertising, and Communications, has determined the promotional materials are misleading “because they omit and minimize risks associated with Latisse,” the Food and Drug Administration (FDA) said in its letter to Allergan. According to the FDA, a small display on risk information that is presented is “on a small placard to the lower right of the timeline exhibit. As such, this display fails to present risk information with a prominence and readability reasonably comparable with the presentation of information relating to the effectiveness of the drug.” The FDA also said the risk information presented omits important risks. Noting that the Web site directs consumers to the full prescribing information at the product’s Web site does not “mitigate this misleading omission and minimization of risk information.” Likewise, the FDA said, the “FAQs” and “About Safety” Web pages are misleading because they omit and minimize risks associated with the treatment. Eye itching and redness are not associated with allergic reactions of the eyes related to Latisse treatment, according to the Web sites, and the FDA has determined that is also misleading.

Cardiometabolic Care Links

MANAGED HEALTHCARE EXECUTIVE, its sister publication brands and the Web portal ModernMedicine.com, under parent company Advanstar Communications’ Life Sciences, are collaborating in a coordinated, interdisciplinary initiative to address a major public health concern: cardiometabolic disorders and weight.

This groundbreaking initiative emphasizes core competencies, best practices and shared responsibility among all stakeholders in the member/patient’s healthcare ecosystem. We investigate cardiometabolic disorders and how they interrelate to significantly increase cardiovascular risk. We provide the tools and information that primary care physicians, specialists, midlevels, nurses, pharmacists, managed care professionals and the pharmaceutical industry need to work together to address this growing problem and ultimately improve patient outcomes.

TREATING CARDIOMETABOLIC disorders as a whole is greater than the sum of the parts. However, when defining the disorders and creating clinical diagnostic guidelines, recommendations have been put to the test by a variety of healthcare organizations.

In essence, cardiometabolic disorders manifest through interrelated health issues in an individual—primarily hypertension, elevated fasting glucose, reduced high-density lipoprotein, abdominal obesity and elevated trigylcerides—which promote the development of atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes. Persons with cardiometabolic disorders also have a propensity for inflammation and thrombosis. While guidelines differ in their specificity, they agree that a combination of metabolic and underlying risk factors comprise the disorders.

Managed care’s role includes disease management and integration of programs and data to better assist members in self-care. Working with physicians, managed care’s opportunity is to collaborate in an effort to avoid costly complications.

“Metabolic syndrome is not a disease,” says Gordon Norman, MD, executive vice president of science and innovation for Alere LLC, based in Marietta, Ga., which provides health support solutions. “It is a cluster of factors without one pathophysiological mechanism but linked together and contributing to morbidity.”

The U.S. Department of Health & Human Services (HHS) and the Centers for Disease Control and Prevention (CDC) note the close relationship between glucose, blood pressure and lipid control, which can reduce the risk of cardiovascular disease. For example, blood pressure control reduces the risk of cardiovascular disease among persons with diabetes by 33% to 50%, while increased levels of HDL can reduce complications by 20% to 50%.

Guidelines developed by the World Health Organization (WHO), the International Diabetes Federation (IDF) and the National Cholesterol Education Program’s Adult Treatment Panel III (ATP III), backed by a collaboration between the American Heart Assn. (AHA) and the National Heart, Lung and Blood Institute (NHLBI), vary—which risk factors actually constitute cardiometabolic disorders and what biometrics define risk.

For example, ATP III guidelines say that if a person has three or more of the five primary risk factors, that is sufficient for a diagnosis of “metabolic syndrome,” while the IDF emphasizes central obesity, defining a diagnosis when a person has obesity plus any two other risk factors. WHO focuses on glucose intolerance/resistance plus two other factors.

ATP III also categorizes metabolic syndrome into major risk factors and underlying risk factors, such as obesity, physical activity and poor diet; and emerging factors, including elevated triglycerides, glucose intolerance and insulin resistance.

While many experts warn that diabetes is one of the major results of cardiometabolic disorders, the WHO doesn’t even consider elevated fasting glucose a risk; although, it does factor in the kidney disorder microalbuminuria—an indication of just how variable the guidelines are.

All three sets of guidelines, however, create ranges for blood pressure, triglycerides, HDL cholesterol, fasting glucose and waist circumference that qualify a person as diagnosed with metabolic syndrome. They all provide recommendations for mitigating the risks, including physical activity and changes in diet, followed by appropriate medications, if lifestyle changes are not enough.

The American Diabetes Assn. goes so far as to call the criteria for cardiometabolic disorders “ambiguous or incomplete,” says the medical value of diagnosing the syndrome is “unclear,” considers the treatment of cardiometabolic disorders no different than the treatment for each of the components, and finally, questions the usefulness of including diabetes in the definition of “metabolic syndrome.”

The Endocrine Society created its own workgroup and guidelines that address persons with the various components of cardiometabolic disorders but who have not been diagnosed with cardiovascular disease (CVD) or type 2 diabetes.

“Our objective is to make physicians aware of those with metabolic risk so they can screen for diabetes and CVD, recommend lifestyle changes, measure waist circumference as part of a routine clinical examination and help patients control high blood pressure,” says James Rosenzweig, MD, director of diabetes services, Boston Medical Center, and associate professor, Boston University School of Medicine.

Mary Jane Osmick, MD, vice president and medical director, LifeMasters Supported SelfCare in Irvine, Calif., notes the discrepancies in the three sets of guidelines in a two-part series on metabolic syndrome that she co-authored inCase-in-Point. She notes that none of the definitions is based on prospective clinical trials, but instead on expert consensus panels.

The differences in definitions and guidelines also make it difficult to gauge the prevalence of cardiometabolic disorders. In a study of participants in the National Health and Nutrition Examination Survey (NHANES) 2003–2006, based on ATP III criteria, approximately 34% of adults met the criteria for metabolic syndrome. An estimated 47 million U.S. residents have cardiometabolic disorders. Males and females 40–59 years of age were about three times as likely as those 20–39 years of age to meet the criteria.

Compare the guidelines by visiting www.managedhealthcareexecutive.com/chart.

MORE CONFUSION

Not only is there no consensus on the definition of cardiometabolic disorders and the guidelines for diagnosing them, but the cluster of risk factors poses another issue: whether it should be treated as a single condition/syndrome or each underlying factor should be treated independently. Unfortunately, while many primary care physicians understand the relationship between the components of cardiometabolic disorders, they don’t have the time or the appropriate reimbursement to manage all of the factors simultaneously.

Persons with cardiometabolic disorders are estimated to have twice the risk of developing CVD and a five-fold greater risk of developing type 2 diabetes, according to information from the National Heart, Lung, and Blood Institute. Experts disagree on how effectively the disorder predicts cardiovascular risk and whether the disorder has a single underlying cause. Because of that, physicians might not identify patients requiring preventive treatment.

Dr. Osmick outlines two primary treatment goals: addressing the underlying causes of cardiovascular risk, namely obesity and lack of physical exercise; and supporting the treatment of all other identified risk factors. The primary focus should be lifestyle changes, and she is a strong advocate of care managers to coach patients.

To meet that objective, LifeMasters uses the Patient Activation Measure, developed by Judith Hibbard of the University of Oregon. Based on the individual score, coaches customize education and support for the individual patient’s level of engagement, Dr. Osmick says.

TREATING COMORBIDITIES

Prevention and treatment of cardiometabolic disorders reads like a child’s primer. Reduce the major risk factors, stop smoking, maintain physical activity, a healthy diet and weight control. The goal is to decrease the risk of heart disease and prevent the onset of type 2 diabetes.

Boston Medical Center’s Dr. Rosenzweig believes that most primary care physicians continue to treat individual factors even though the components are interrelated. He says that proper weight, diet and exercise can reduce the risk of diabetes by 60% to 70%.

“There is not enough prevention in primary care,” he says. “Metabolic syndrome is not seen as a public health issue. It needs to be addressed earlier in a systematic way.”

Dexter Shurney, MD, chair, DMAA’s Obesity with Associated Comorbidities Workgroup, focuses on obesity as the culprit for cardiometabolic disorders, driving elevated lipids and glucose intolerance.

“Most primary care physicians are not trained to deal with obesity, exercise and behavioral lifestyle changes for their patients,” he says. “There has to be emphasis on root causes, not on the byproduct.”

Dr. Shurney points out several studies that indicate a “reversal” in high A1c, levels allowing patients to stop taking medications, due to intense lifestyle changes. Moderate physical activity is of key importance, followed by smoking cessation and weight loss and control.

“It’s remarkable how little we know about the approach to this disease using principles of population-based care management,” says Jaan Sidorov, a consultant in Harrisburg, Penn. “Rather, the approach seems to be one of identifying folks by the risk factor—high blood pressure, abnormal labs or a big belly—and then using that as a hinge to subsequently diagnose and treat metabolic syndrome. The disease management folks would argue that they have programs in place and ready to go for high blood pressure, cholesterol, high sugar or for obesity, and that the elements of those programs include the type of interventions necessary to also treat the concurrent syndrome.”

He recommends identifying patients through claims data with more specificity and through health risk assessments, then marshaling resources to provide dietary and exercise advice. He agrees with the need for physician incentives and a greater role for the primary care physician.

Care is physician-dominated and with short 15-minute office encounters, doctors should look to other providers, such as nurses and dieticians, who can emphasize lifestyle changes, he says.

A study conducted by Hart Research Associates addresses both diet and reimbursement. It shows that an overwhelming majority of primary care physicians believe that nutrition plays a major role in the prevention, treatment and management of chronic disease. A large majority admits that if costs were reimbursed, they would spend more time counseling their patients on nutrition. A lack of time is second on the list of reasons why nutrition may be overlooked.

Paul Handel, MD, chief medical officer of Health Care Services Corp. (HCSC), a Blue Cross and Blue Shield health insurer, says that cardiometabolic disorders are the most prevalent and preventable causes of chronic disease today.

“It could ultimately break Medicare’s bank or for that matter, the nation’s bank,” he says.

In February, HCSC initiated a 10-week cardiometabolic disorders program for its own employees using face-to-face meetings and Web-based education. The program focused on eating habits, hydration, exercise and fitness, stress management and managing emotional and psychological needs. Each of the 200 participating employees was assigned a health coach who monitored progress, weekly dietary intake and exercise as well as improvements in weight, body mass index (BMI), waist circumference, triglycerides, cholesterol, blood glucose and blood pressure. Although the program did not prescribe a diet, it emphasized reduced sugar intake and portion control.

“It is an educational, behavioral change program,” says Dr. Handel, “not a specific diet or exercise regimen. The program’s classroom experience and Web-based program offer continual support to help foster changes.”

If employees attended fewer than eight of the 10 sessions, they reimbursed the company $75; otherwise, the company paid for the program. Dr. Handle says the biometrics are measured after three months and one year. He hopes to follow participants for three to five years.

Kevin Casey, 42, a manager for HCSC in its Chicago headquarters, qualified for the program because he had three of the five components the company had designated as “metabolic syndrome”—being overweight, having diabetes, and as he says, having “large amounts of belly fat.” His blood pressure and cholesterol, however, were within the normal range.

In the 10-week program, he lost 58 pounds.

“I eat only when my body tells me it’s hungry,” Casey says. “I found that I was really only hungry once a day.”

His exercise regimen consisted of walking or riding a stationery bike, and now includes running four miles a day. When Casey started the program, he was taking 5 mg of glipizide and 1,000 mg of metformin twice a day for his diabetes. During the study, he monitored his blood sugar daily, reduced the metformin to 250 mg twice per day and stopped taking glipizide.

Although he admits to sneaking a snack now and then since the program ended, he still lost an additional 40 pounds in the 12 weeks following the program.

In another pilot of the program with an HCSC employer group, 53% of the participants showed a significant reversal for risk and lost an average of 15 pounds each during a 10-week period.

DIABETES

Diabetes is a chronic condition in which the body does not produce or properly use insulin to transport sugar from the blood into the cells. As many as 23.6 million people in the United States have diabetes, 90% to 95% with type 2. About 80% of people with type 2 diabetes are overweight, according to HHS. Unfortunately, about 5.7 million have not yet been diagnosed. Insulin resistance and elevated fasting glucose can lead to type 2 diabetes over time, which in conjunction with high blood pressure, low HDL, elevated triglycerides and obesity, increase the chance of cardiovascular disease.

“Many persons with [cardiometabolic disorders] are unaware that they have diabetes because there are no symptoms,” Alere’s Dr. Norman says. “And then it can evolve into a stroke. To stay ahead of that kind of morbid event, you have to attack early on before the syndrome escalates.”

In order to determine whether or not a patient has prediabetes or diabetes, healthcare providers conduct a Fasting Plasma Glucose Test (FPG) or an Oral Glucose Tolerance Test (OGTT). The American Diabetes Assn. recommends the FPG because it is easier, faster, and less expensive to perform.

Diabetes is the fifth most deadly disease in the United States, increasing by 45% since 1987. Based on death certificate data, diabetes contributed to 233,619 deaths in 2005. If trends continue, one-third of Americans born in 2000 will develop diabetes, according to the American Diabetes Assn.

Type 2 diabetes is associated with older age, obesity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity and race/ethnicity.

The association estimates the total annual economic burden of diabetes in 2007 was $174 billion. Medical expenditures consumed $116 billion of that total, and accounted for 15 million work days absent and 120 million work days with reduced performance. One in 10 healthcare dollars is attributed to the disease.

The main prescription for diabetes, as well as prediabetes, is a healthy diet, regular exercise and proper weight maintenance. Since most people with type 2 diabetes still produce some insulin, these three suggestions may suffice, but in some cases, oral medications may be needed. The American Diabetes Assn. reports that among adults with diagnosed diabetes (type 1 or type 2), 14% take insulin only, 13% take both insulin and oral medication, 57% take oral medication only and 16% do not take either insulin or oral medication.

Prescription insulin is characterized by three features: onset, the time it takes for the insulin to reach the bloodstream and begin lowering blood glucose; peak time, the time during which insulin is at its maximum strength; and duration, how long the insulin continues to lower blood glucose. Adding to the complexity of finding the right insulin for each patient, there are different types of insulin, ranging from rapid-acting to long-acting.

In addition, insulin may be of a human form; an analogue, which is an altered from of insulin not available in nature but capable of glycemic control; and insulin recombinant, which is made through recombinant DNA technology.

“The main goal of insulin therapy is to mimic the body’s natural response to glucose. The trick is to calculate the patient’s food intake and time of meals and use the various products to control the glucose level,” says Ron Alexander, vice president, clinical services for Diplomat Pharmacy in Flint, Mich. “Too much insulin may drop the patient’s blood level too low, and the patient could have serious reactions. The other side of the coin is too little insulin, and other serious reactions can occur. Thus, there is the need to monitor the blood glucose levels and administer insulin or create a need to increase the patient’s glucose level.”

With the spark in the numbers with diabetes, pharmaceutical research and biotechnology companies have risen to the occasion with 133 drugs for type 2 diabetes under development—either in clinical trials or awaiting approval by the U.S. Food and Drug Administration. The rate of new cases has increased by more than 90% among adults, according to a 2008 study by the CDC.

Late last year, the FDA recommended that all new drugs developed to treat type 2 diabetes show that they do not increase the risk of cardiovascular events. The agency is requesting more stringent trials that collect data on cardiovascular end points and studies that include real-world patients likely to be seen in clinical practice. Bristol-Myers Squibb analyzed data for evidence of cardiovascular harm in pooled data from phase II and III studies of its drug, saxagliptin, which was approved by FDA on July 31, 2009. The drug produced lower major adverse cardiovascular events in nearly all high-risk groups compared with controls.

HYPERTENSION

Hypertension is another primary component of cardiometabolic disorders and occurs when the blood moves through the arteries at a higher pressure than normal (120/80 mmHg). ATP III and IDF guidelines consider any reading equal or greater than 130/85 to qualify for “metabolic syndrome,” while the WHO considers equal or greater than 140/90 as a cardiometabolic risk.

Although hypertension usually has no symptoms, it damages blood vessels, which in turn can raise the risk of stroke, kidney failure, heart disease and heart attacks. It is important for members to have their blood pressure checked regularly to identify risk early. Like the other cardiometabolic disorder components, hypertension can be addressed through healthy lifestyle choices and medications.

Hypertension occurs in about one in every three adults in the United States, according to NHLBI, with an estimated price tag in 2006 of $63.5 billion.

Antihypertensives lower blood pressure by opening and widening the blood vessels, which prevents them from tightening and reduces the load on the heart. These drugs, however, do not cure hypertension and may lose their effectiveness over time, making it necessary to change medications or add another drug to leverage both drugs’ actions. Most physicians start patients with high blood pressure at a relatively low dose and assess the effectiveness over the course of several weeks. If the blood pressure remains elevated, the dose of the medication is gradually increased.

There are many classes of drugs that treat high blood pressure, and finding the one that works best with limited side effects may be an exercise of trial and error. Since most people with hypertension do not feel any symptoms, it also may be difficult to determine how well a drug is working.

Diuretics—Often taken in conjunction with other antihypertensives, these “water pills” promote the development of urine in the kidneys, causing the body to flush out fluid and minerals, such as sodium. The result is a reduction in fluid volume and sodium level, which opens bloods vessels wider. Side effects include frequency of urination and increased urinary excretion of potassium.

Beta Blockers—These medications reduce nerve impulses to the heart and blood vessels, making the heart beat more slowly and with less force. They may slow heart rate excessively.

Vasodilators—They directly open blood vessels by relaxing the muscle in the vessel walls, allowing the blood to flow more freely and the heart pump more efficiently. Vasodilators include angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and calcium channel blockers.

ACE inhibitors block the formation of the hormone angiotensin II, which tightens blood vessels. About 10% of patients develop a chronic cough.

Producing the same effects as ACE inhibitors, ARBs inhibit the action of angiotensin II by blocking it from entering angiotensin receptors in the body. Angiotensin receptor blockers (also known as angiotensin II receptor antagonists) are generally well tolerated by most people, and serious side effects are rare. Some reported side effects include dizziness, headaches, runny nose and muscle cramps.

Calcium channel blockers prevent calcium from entering the muscle cells of the heart and blood vessels, thus, causing the vessels to relax. These medications may exacerbate pulmonary arterial hypertension as well as headaches, swelling of the ankles and feet and congestive heart failure symptoms.

HYPERLIPIDEMIA

Hyperlipidemia—increased fats in the blood including cholesterol and triglycerides—is easily diagnosed through standard lipid blood tests, which include a measurement of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides. Like hypertension, hyperlipidemia has no recognizable symptoms.

Although a total cholesterol level of 200 mg/dl is considered desirable and a value of more than 240 is high, most readings are recorded by looking at both LDL and HDL, the former a more important indicator of risk for heart disease. None of the three organizations producing guidelines even include a measurement of LDL cholesterol in their identification of metabolic disorders; however, both the APT III and the IDF agree that an HDL (“good” cholesterol) reading of less than 40 mg/dl for men and 50 mg/dl for women is a risk factor, while the WHO is stricter—less than 35 mg/dl for men and less than 39 mg/dl for women. All three organizations identify those with triglycerides equal to or greater than 150 mg/dl as at high risk for heart disease and type 2 diabetes.

According to the AHA, approximately 102.3 million American adults have total blood cholesterol values of 200 mg/dl and higher, and of these, about 41.3 million American adults have levels of 240 or above.

The cost of a first time heart attack or stroke occurring in people who failed to reduce their cholesterol was more than $13 billion in terms of both lost wages and hospitalization. For recurring heart attacks or fatal strokes the cost continues at $13 billion per year. Other indirect costs bring that total up to $53.6 billion per year according to theJournal of the American Heart Association.

HMG-CoA reductase inhibitors—statins—are a class of drugs that lower the level of cholesterol in the blood by reducing the production of cholesterol by the liver. Statins block the enzyme in the liver that is responsible for making cholesterol.

Although cholesterol is critical to the normal function of every cell in the body, it also contributes to the development of atherosclerosis, in which cholesterol-containing plaques form within arteries, block them and reduce the flow of blood to the tissues that the arteries supply. In addition to lowering cholesterol levels, statins also reduce inflammation, which often affects those at high risk for cardiometabolic disorders.

In general, for every doubling of the dose of a statin, LDL levels fall by approximately 6%, according to the Third Report of the National Cholesterol Expert Panel on ATP III.

While statins have amassed a worthy track record, they are not without side effects, primarily affecting liver function and damage to muscle tissues, which can be exacerbated by combining statins with other cholesterol-lowering drugs.

The most serious side effect of statins, though rare, is rhabdomyolysis, which begins with muscle pain and may progress to loss of muscle cells and kidney failure.

In addition to stains, there are other cholesterol-lowering drugs: selective cholesterol absorption inhibitors; resins; fibrates; and Niacin.

OBESITY

Obesity is a medical condition in which excess body fat is enough to cause an adverse effect on health. It is the leading preventable cause of death worldwide. The majority of obesity is most commonly caused by a combination of excessive dietary calories, lack of physical activity and genetic susceptibility. Like the other factors associated with cardiometabolic disorders, obesity can be treated through diet modification and regular physical activity. However, in some instances, medications to reduce appetite or inhibit fat absorption or surgery may be needed.

The risk criteria for qualifying for surgery is one of the biggest issues associated with obesity, Sidorov notes.

“Surgery is a very high price tag for insurers and self-insured employers, who therefore, have a substantial economic incentive to do everything to keep the overweight from getting obese, and to keep the obese from having to go through surgery,” he says.

About 97 million adults in the United States are overweight or obese, according to the NHLBI. A study from the Centers for Disease Control and Prevention estimates 34% of adults over age 20 are obese; however, the obesity prevalence has not measurably increased in the past several years. From 1960 to 2004, the prevalence of overweight increased from 44.8% to 66% in U.S. adults age 20 to 74, according to the National Center for Health Statistics.

In 2008, only one state (Colorado) had a prevalence of obesity less than 20%. Thirty-two states had a prevalence equal to or greater than 25%; six of those states (Alabama, Mississippi, Oklahoma, South Carolina, Tennessee and West Virginia) had a prevalence of obesity equal to or greater than 30%. In 2000, obesity-related healthcare costs totaled an estimated $117 billion, according to the CDC.

While being overweight is closely related to heart disease, diagnosis of metabolic disorders places more emphasis on waist circumference as a predictor of cardiovascular disease. Body fat that accumulates around the stomach area poses a greater health risk than fat stored in the lower half of the body.

The ATP III guidelines for waist circumference are more lenient than those established by the IDF: 102 centimeters for men and 88 centimeters for women, versus 94 and 80 centimeters, respectively, for IDF. Physicians measure waist circumference an inch above the belly button.

In conjunction with waist circumference is body mass index (BMI), which assesses body weight relative to height. Normal values range from 18.5 to 24.9. Those with a BMI of 25.0 to 29.9 are overweight and those with a BMI of 30 or higher are classified as obese.

The WHO outlines guidelines for a waist-to-hip ratio—the circumference of the waist divided by that of the hips—as more than 0.9 for men and more than 0.85 for women. The AHA says that this measurement is less accurate than BMI.

The National Institute of Diabetes and Digestive and Kidney Diseases recommends that prescription weight-loss medications should be used only by patients who are at increased medical risk and not be used for “cosmetic” weight loss. Some of the more common medications to treat obesity—most of which are recommended for short-term use—include sibutramine and phentermine, both appetite suppressants; orlistat, a lipase inhibitor; and bupropion for depression.

Alere’s Dr. Norman says that obesity is a common feature of metabolic syndrome but not necessarily the cause. Nonetheless, he believes there is not enough attention being paid to the epidemic and that few physicians make an attempt to correct the problem.

“There is definitely a moral hazard when patients can take Lipitor and then eat a Big Mac,” he says. “We credit medicine to offset our egregious behavior.”

Alere’s Personal Health Coaching program provides communication tools—e-mail, phone, instant messaging—and access to a health coach for one year. The program is designed to address willingness to change rather than just the specific condition. Coaches, who are registered dieticians, fitness instructors, nurses and others, reach out to members according to results of their health risk assessments and develop behavior change plans.

Besides managing diet, exercise and weight, those with cardiometabolic risks can monitor their own progress to ensure treatment plans are appropriate. Stepping on a scale and self-administered, daily blood sugar tests for those with type 2 diabetes can provide trend data for the patient and the clinician. High blood pressure also can be tracked by the patient with the use of a simple manual or digital monitor.

In addition, patients should visit their providers quarterly for an A1c test. It is recommended that patients with type 2 diabetes who don’t use insulin and maintain blood sugar levels consistently within range have A1c tests twice a year. An A1c level of 6.5% or higher on two separate tests indicates the presence of diabetes. A person who has poor control of blood sugar will typically have an A1c over 7%.

The AHA recommends that everyone over age 20 get a cholesterol test to check total cholesterol, LDL, HDL and triglycerides. Tests are taken after nine to 12 hours of fasting. Normal readings are 200 mg/dl or less for total cholesterol, more than 60 mg/dl for HDL, less than 100 mg/dl for LDL and less than 150 mg/dl for triglycerides.

Considering the recent attention drawn to prevention efforts, cardiometabolic disorders and weight issues deserve further exploration.

Implantable Miniature Telescope (IMT)

The IMT is a micro-sized precision telescope, about the size of a pea, that is implanted in one eye in an outpatient surgical procedure conducted under local anesthesia. The IMT provides magnification of 3.0X or 2.2X, depending on the IMT model used. A magnified image is projected over a wide field of the retina to improve the ability to recognize images that were previously either difficult or impossible to see. The IMT is implanted in one eye of patients who present with untreatable late-stage AMD (end-stage AMD). The telescope provides central vision, while the non-implanted eye provides peripheral vision.

Stephen Lane, M.D., principal investigator at Associated Eye Care, Stillwater, MN who implanted six IMTs in VisionCare’s Phase I trial, commented, “We are excited about the potential the IMT provides for improving visual acuity and the quality of life for individuals with severe AMD. We are encouraged with the results produced in the Phase I trial and look forward to studying the IMT in a larger patient population in this Phase II/III evaluation.”

“We see many patients in the clinic with advanced AMD for whom we have no real viable treatment options. The IMT technology may give ophthalmologists a method of improving vision and function in the more than 500,000 U.S. patients who have bilateral permanent vision loss due to macular degeneration,” said vitreo-retina disease specialist and Phase I investigator, Baruch D. Kuppermann, M.D., Ph.D., University of California, Irvine.

Fourteen patients were implanted with the IMT in the Phase I trial. Patients were monitored for safety and efficacy. One year after implantation, the majority of patients gained three or more lines (a doubling) of distance or near visual acuity and improvement in their activities of daily living. The most common complication was transient inflammation.

Patients at over 25 leading medical universities and ophthalmic centers into its US Phase II/III pivotal trial for untreatable end-stage AMD and Stargardt’s macular dystrophy.

In a presentation to the joint meeting of the American Academy of Ophthalmology (AAO) and the European Society of Ophthalmology (SOE) in New Orleans, LA, on October 23-26, 2004, VisionCare reported that the ongoing Phase II/III trial was assessing the safety and efficacy of the IMT. Phase I trial results demonstrated that one year after implantation, 77% (10/13) of patients gained two or more lines of distance or near visual acuity and 62% (8/13) of patients gained three or more lines (a doubling) of visual acuity as measured on a standard (ETDRS) eye chart. The most common complication was transient inflammation.

On October 19, 2005, Paul Sternberg, M.D. and Henry Hudson, M.D., announced positive results from VisionCare’s Phase I/III clinical trials of the IMT. After one year, subjects showed a mean improvement of over 3 lines in both distance and near visual acuity. 90% exceeded the primary endpoint of the trial with a 2-line improvement. Significant improvement in quality of life and daily living activities was also measured. A 2-year follow-up has revealed no serious safety issues. In July 2006, however, the company suffered a setback when the IMT was voted down for approval by an FDA advisory panel.

The November 2006 issue of Ophthalmology (Volume 113, Issue 11, Pages 1895-2134) published an article titled “Implantable Miniature Telescope for the Treatment of Visual Acuity Loss Resulting from End-Stage Age-Related Macular Degeneration” (Hudson HL, Lane SS, Heier JS, Stulting RD, Singerman L, Lichter PR, Sternberg P, Chang DF, IMT-002 Study Group) which detailed the results from the IMT002 trial. 217 patients at 28 U.S. investigational sites had severe vision loss due to the characteristic central blind spot caused by end-stage macular degeneration. The publication reports 90% of patients met or exceeded the protocol-specified primary efficacy endpoint of visual improvement, defined as a 2-line gain in either distance or near vision on the study eye chart. The protocol stated the endpoint would be achieved if at least 50% of patients met this target.

At 1 year after the telescope implantation procedure, 67% of patients achieved a 3-line (doubling of vision) or greater improvement in their study eye distance visual acuity, compared with 13% of unimplanted fellow eye controls. Approximately 25% of telescope-implanted eyes achieved a 5-line or greater improvement in visual acuity, compared with 2% of fellow eyes. Loss of 3 lines or more was encountered in 1.6% of implanted eyes, compared with 3.1% of fellow eyes. Secondary efficacy outcome measures suggest improvement in patients’ vision-related quality of life and activities of daily living. On the National Eye Institute 25-item Visual Function Questionnaire, patients improved significantly from baseline (range 7 to 14 points) in 7 of 8 relevant vision-specific and psychosocial subscales, including General Vision, Social Functioning, and Dependency. Corneal endothelial cell density, a safety endpoint, was reduced 20% from preoperative at 3 months and 25% at one year (compared with the 17% protocol-specified target).

Patients enrolled in the study were at least 55 years of age and had central vision loss caused by disciform scars (end-stage wet AMD) or geographic atrophy (advanced dry AMD). Exclusion criteria included active choroidal neovascularization (wet AMD) or treatment of wet AMD in the preceding six months. Patients with early-stage AMD, mildly visually impairing AMD, or unilateral affection were not eligible.

The IMT002 trial was a prospective, open-label, multicenter clinical trial conducted under an investigational device exemption from the U.S. Food and Drug Administration (FDA). Patients averaged 76 years of age. The telescope prosthesis was generally well tolerated in the eye. 206 of the 217 enrolled patients had the device successfully implanted in their study eye, while 11 patients received a standard intraocular lens due to an aborted procedure. The most common complications or adverse events included transient intraocular pressure, transient corneal edema, iris prolapse, and inflammatory deposits on the device. There were 2 cases of corneal decompensation. The published results were published online at www.ophsource.org/periodicals/ophtha/article/PIIS016164200600933X/abstract.

On December 28, 2007, Optolight Vision Technology (now called VisionCare Ophthalmic Technologies, Inc.) announced success from implantation of a second generation of the IMT, called the Lipshitz macular implant (LMI). The LMI is named for its inventor, Dr. Isaac Lipshitz, who also developed the IMT.

Researchers at Dr. Agarwal’s Eye Hospital and Eye Research Centre, Chennai, India, investigated visual and surgical outcomes of the intraocular mirror telescopic intraocular lens implanted in patients with bilateral macular pathology and visual acuity worse than 20/200 in whom vision improved with a ×2.5 external telescope preoperatively. They reported that the LMI may be an effective solution for optical rehabilitation of patients with ARMD or other macular pathology by increasing the central image on the retina while preserving peripheral vision. The abstract of this research was published online at www.sciencedirect.com.

In November 2008, the American Journal of Ophthalmology* published two-year results from the Phase II/III IMT002 trial showing substantial visual acuity improvement in end-stage AMD patients. The study device has received CE Mark approval in Europe and is currently investigational and under regulatory review by the U.S. Food and Drug Administration.

The publication details the two-year safety profile of the device and found rates of cornea endothelial cell loss, while higher than conventional small-incision anterior segment eye surgery, were consistent with anterior segment procedures employing more similar incision sizes required for telescope implantation. According to one co-author of the study, the risks of surgery are outweighed by the benefits.

“The published data show improved visual acuity in end-stage AMD patients that was maintained over two years — a three-line improvement that we have previously shown makes a real impact on our patients’ independence and quality of life,” said Henry L. Hudson, M.D., lead author for the IMT002 study and retina specialist at Retina Centers, P.C. in Tucson, AZ.

For more information on the research, see www.visioncareinc.net or call (408) 872-0526.

*Hudson HL, Stulting RD, Heier JS, Lane SS, Chang DF, Singerman LJ, Bradford CA, Leonard RE; IMT002 Study Group. Implantable Telescope for End-Stage Age-related Macular Degeneration: Long-term Visual Acuity and Safety Outcomes. Am J Ophthalmol. 2008: 146; 664-673.

Weight-Loss Drug Shows Promise and Other Health News

Experimental Weight-Loss Drug Successful in Clinical Trials

Contrave, an experimental weight-loss drug developed by Orexigen Therapeutics Inc., has been shown to significantly aid weight loss in three late-stage clinical trials, the Associated Press reports. Findings from two trials showed that patients lost on average 17.6 pounds and 17.5 pounds, respectively. A third trial involved people with type 2 diabetes and showed that patients lost on average 13.5 pounds, according to the AP. The three trials each lasted 56 weeks and about 3,800 patients in total participated. Orexigen announced that it plans to seek approval from the Food and Drug Administration for Contrave in 2010. Common side effects of the drug included nausea and constipation. A few patients experienced more serious complications, including gallbladder infection and seizure.

Read about weight-loss ingredients the FDA says may endanger your health, along with 28 weight-loss products that contain them.

10 Salt Shockers That Could Make Hypertension Worse

Does too much salt cause high blood pressure, or doesn’t it? Two new studies out yesterday in the journal Hypertension tip the scales in favor of reducing sodium, particularly for those Americans—1 in 4—who have high blood pressure, U.S. News’s Deborah Kotz reports. One study found that reducing salt intake from 9,700 milligrams a day to 6,500 milligrams decreased blood pressure significantly in blacks, Asians, and whites who had untreated mild hypertension. Another study found that switching to a reduced-salt diet helped lower blood pressure in folks with treatment-resistant hypertension. Cutting sodium intake, though, involves a lot more than setting aside the salt shaker. Kotz lists 10 foods high in sodium that could make hypertension worse. The culprits include cottage cheese, which may pack more than 900 mg of sodium into a 1-cup serving, and dill pickles—one of which typically contains 830 mg of sodium, Kotz writes.

Find out whether drinking alcoholic beverages can spoil your plan to lose weight. In June, U.S. News dished about the high-calorie offerings of popular restaurant chains. And consider why you should avoid dining out: Researchers have found that restaurants are full of environmental cues—from plate size to bread condiments—that encourage us to eat more.

Is a Cash-Only or Direct-Pay Medical Practice Right for You?

With the unemployment rate above 9 percent and some 46 million Americans lacking insurance, the market for affordable healthcare is ripe. There’s a growing movement toward cash-only medical practices, which do away with third-party billing and waiting for reimbursement and put responsibility for payment squarely on the patient. Cash-only, or direct-pay, medical practices cater to the uninsured or those with high-deductible health plans that kick in only for major expenditures. Across the country, there are now 500 to 1,000 family medicine practices operating on a cash-only model, according to one experts estimate. The cash-only model is based on the idea that rather than charging higher, so-called retail rates for uninsured patients while negotiating discounted rates with insurance companies for covered patients, it’s fairer—and possible—to offer flat and reasonable rates to all, U.S. News’s January Payne reports.

Here are some tips on getting affordable health insurance for young adults, along with a quick guide to health insurance lingo. Consider 7 ways laid-off baby boomers can find health insurance.

Kidney Transplant Drug Warnings and Other Health News

FDA Requires Transplant Drug Labels to Indicate Infection Risk

The Food and Drug Administration will require a new warning on the labels of drugs used by kidney transplant patients, Reuter’s reports. The immunosuppressant medications Rapamune, Sandimmune, Neoral, Cellcept, and Myfortic increase patients’ risk of opportunistic infections, the FDA said in a statement on its website. For example, the BK virus can cause the kidney to be damaged or rejected. BK viral infections have also been linked to Prograf, another drug used by transplant patients. Its prescribing information, however, already indicates such risks, according to the FDA.

Consider 4 ways to avoid dangerous drug errors and 5 hazardous drug combinations you need to avoid.

Cancer and Supplements: What Vitamins, Herbs, and Botanicals Can (and Can’t) Do

Recent clinical trials suggest that supplements of single nutrients like vitamins B, C, and E and the mineral selenium do not, as once thought, prevent chronic or age-related diseases including prostate and other kinds of cancer. Some substances, like green tea and ginger, seem to have potential in preventing or helping to treat cancer, but they may also actually interfere with treatment or have other serious side effects, U.S. News’s Katherine Hobson reports. Hobson uncovers 5 reasons why researchers haven’t determined which vitamins, herbs, or botanicals help prevent or relieve symptoms of cancer—and offers guidance on what to do in the face of incomplete information.

One reason their effects are difficult to study is that the pills and capsules on health-food store shelves vary enormously in quality and dose. Moreover, the botanical—and then how it acts in the body—can vary depending on where it’s grown, how much sunlight it receives, the soil, and other factors, says one expert. That can make botanicals tough to standardize, which is essential in order to study and take advantage of their effects, Hobson reports. So what’s a person concerned about cancer prevention—or who is fighting the disease—to do? Two good databases of information on specific supplements are produced by the American Cancer Society and Memorial Sloan-Kettering Cancer Center. Both outline the evidence for the role of herbals, botanicals, and vitamin or mineral supplements in preventing and treating cancer, plus any possible risks and drug interactions. Continue reading.

Learn what experts say on whether you can get vitamins and minerals through diet alone. Here’s the latest evidence for the use of vitamins and supplements.

Hormones Linked to Ovarian Cancer: What to Do

A new study published in the Journal of the American Medical Association shows a link between hormone use and ovarian cancer. In the study, which culled the health records of nearly 1 million Danish women, researchers found a 38 percent greater risk of ovarian cancer among women who were currently taking hormone therapy. The risks didn’t appear to be affected by the types of hormones women were taking, the dose, the duration, or whether they were taking estrogen alone or a combination of estrogen and progesterone. The actual increased risk of ovarian cancer was very low, however, U.S. News’s Deborah Kotz reports. Previous research has also found a link between hormones and ovarian cancer. How much should this latest news factor into a woman’s decision about taking hormones? The risk should inform decisions about hormone therapy, writes one expert. Another says that the heightened caution may be unnecessary. Read more.

Consider 3 reasons not to panic if you’re taking hormone replacement therapy. And read how three women are dealing with their hormone therapy dilemmas.

FDA accepts Isolagens BLA

The Food and Drug Administration (FDA) has accepted a Biologics License Application (BLA) on a nasolabial fold/wrinkles product candidate from Isolagen (Exton, Pa.), the company said in a press release.

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