FDA Approves Viekira XR

AbbVie Receives U.S. FDA Approval of Once-Daily Viekira XR (dasabuvir, ombitasvir, paritaprevir and ritonavir) for the Treatment of Genotype 1 Chronic Hepatitis C

NORTH CHICAGO, Ill., July 25, 2016 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has approved a New Drug Application (NDA) for Viekira XR (dasabuvir, ombitasvir, paritaprevir and ritonavir) extended-release tablets. Viekira XR is a once-daily, extended-release co-formulation of the active ingredients in Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) and is for the treatment of patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, including those with compensated cirrhosis (Child-Pugh A). Viekira XR is not for people with decompensated cirrhosis.

Viekira XR is the first co-formulated three direct-acting antiviral (DAA) treatment for adult patients with GT1 HCV. Viekira XR is given once-daily as three oral tablets and must be taken with a meal. It is used without ribavirin (RBV) in GT1b patients and in combination with twice daily RBV in GT1a patients. The approval is supported by Phase 3 clinical trials for Viekira Pak which include data that demonstrated 100 percent sustained virologic response 12 weeks following treatment (SVR12) in GT1b patients with 12 weeks of therapy without ribavirin and 95 percent SVR12 in GT1a patients when used with ribavirin for 12 or 24 weeks of therapy.

"AbbVie's work continues to contribute to the transformation of hepatitis C care through our focus on evolving our current therapies as part of our ongoing commitment to patients," said Rob Scott, M.D., vice president, development and chief medical officer, AbbVie. "The approval of Viekira XR provides a new treatment option for genotype 1 hepatitis C patients in the U.S. with clinical trial data using the components of Viekira XR demonstrating 100 percent cure rates in genotype 1b patients."

There are six major HCV genotypes (GT1-6) and GT1 is the most prevalent form of HCV in the U.S., accounting for approximately 74 percent of all cases.1 Hepatitis C continues to be an important public health issue, with the Centers for Disease Control and Prevention (CDC) estimating that in the U.S. approximately 2.7 million people are chronically infected with HCV.2

The approval of Viekira XR is supported by data from seven Phase 3 clinical trials in more than 2,300 patients who received Viekira Pak with or without RBV for 12 or 24 weeks and two bioavailability studies comparing the formulations.

About Clinical Studies

The components of Viekira XR (administered twice daily with a meal) have been studied in seven Phase 3 clinical trials where 1076 subjects (including 181 with compensated cirrhosis) received the recommended regimen of Viekira +/? RBV for 12 weeks, or for 24 weeks in GT1a patients with compensated cirrhosis. Ninety-five to 100 percent achieved SVR12, which means the hepatitis C virus is not detectable in the blood three months after treatment ends. Cure rates varied by the subtype of hepatitis C and whether or not the person had cirrhosis. Individual results may vary.

USE

Viekira XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets/Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) (Viekira) are prescription medicines used with or without ribavirin to treat adults with genotype 1 chronic (lasting a long time) hepatitis C (hep C) virus infection.

Viekira can be used in people who have compensated cirrhosis.

Viekira is not for people with advanced cirrhosis (decompensated). If people have cirrhosis, they should talk to a doctor before taking Viekira.

About Viekira XR

The components of Viekira XR* have been studied in a broad range of genotype 1 (GT1) patients with chronic hepatitis C virus (HCV) infection, ranging from treatment-naïve to difficult to treat patients, such as those with compensated (mild, Child-Pugh A) cirrhosis of the liver, HCV/HIV-1 co-infection, liver transplant recipients with normal hepatic function and mild fibrosis, and those who have failed previous treatment with pegylated interferon (pegIFN) and ribavirin (RBV).

The extended-release co-formulation of these components, Viekira XR, consists of 200 mg of dasabuvir, 8.33 mg of ombitasvir, 50 mg of paritaprevir, and 33.33 mg of ritonavir per tablet, and is dosed three tablets once daily. Viekira XR must be taken with a meal, and tablets should be swallowed whole. People should not drink alcohol within four hours of taking Viekira XR. Viekira XR is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B and C) due to risk of potential toxicity. Viekira XR is taken for 12 weeks, except in GT1a patients with cirrhosis and all liver transplant recipients with normal hepatic function and mild fibrosis, who should take it for 24 weeks. Ribavirin should be co-administered in GT1a patients and in all patients who have received a liver transplant.

Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. Paritaprevir is used in combination with AbbVie's ombitasvir with or without dasabuvir for the treatment of hepatitis C.

*Given as a fixed-dose combination of ombitasvir 25mg (an NS5A inhibitor), paritaprevir 150mg (an NS3/4A protease inhibitor), and ritonavir 100mg (an HIV-1 protease inhibitor), dosed once daily with a meal, and dasabuvir 250mg (a non-nucleoside NS5B palm polymerase inhibitor), dosed twice daily with a meal.

About AbbVie's Patient Assistance Program

AbbVie supports patient assistance programs to help qualified people access their needed AbbVie medication at no cost. In 2015, more than 81,000 U.S. patients received AbbVie's medicines at no cost3. For those who qualify, AbbVie plans to offer a patient assistance program for people taking Viekira XR. Since Viekira Pak's approval in 2014, AbbVie has supported access to medication for those living with chronic HCV and facing financial difficulties.

About AbbVie's HCV Clinical Development Program

AbbVie's HCV clinical development program is intended to advance scientific knowledge and the clinical care of people with chronic HCV infection. AbbVie is investigating a pan-genotypic (genotypes 1-6) regimen and is in Phase 3 of clinical development. For more information on AbbVie Phase 3 HCV studies, visit www.clinicaltrials.gov (NCT02243293).

About HCV

Hepatitis C is inflammation of the liver caused by an infection with the hepatitis C virus. It is transmitted when an infected person's blood enters the bloodstream of an uninfected person. The Centers for Disease Control (CDC) estimates that approximately 2.7 million people have chronic HCV infection in the U.S. There are six major HCV genotypes (GT1-6), with genotype 1 (GT1) as the most prevalent form in the U.S. It is estimated that of people infected with chronic HCV, about 5 to 20 percent will go on to develop cirrhosis over a period of 20–30 years, and with HCV-related liver transplants on the rise, HCV is a critical public health issue. Presently, there is no vaccine for HCV infection.

About AbbVie

AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

Forward-Looking Statements

Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.

Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2015 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

1 Wedemeyer H. Hepatitis C. Chapter 80: In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. Vol 2. 10th ed. Philadelphia, PA: Saunders Elsevier; 2016.
2 Centers for Disease Control and Prevention (CDC). Hepatitis C FAQs for health professionals. http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm#section1. Accessed June 9, 2016.
3 AbbVie 2016 Impact by the Numbers. http://www.abbvie.com/responsibility/home.html

SOURCE AbbVie

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FDA Approves Adlyxin

Sanofi Receives FDA Approval of Adlyxin (lixisenatide) for Treatment of Adults With Type 2 Diabetes

PARIS, July 27, 2016 /PRNewswire/ -- Sanofi announced today that the U.S. Food and Drug Administration (FDA) approved Adlyxin (lixisenatide), a once-daily mealtime GLP-1 receptor agonist injection indicated as an adjunct to diet and exercise for the treatment of adults with type 2 diabetes.

"The approval of Adlyxin reaffirms our continued commitment to addressing the challenges faced by people living with diabetes when trying to reach and maintain their individual blood glucose (HbA1c) targets," said Peter Guenter, Executive Vice President, Head, Global Diabetes & Cardiovascular Business Unit, Sanofi. "We are pleased with this approval, as it offers us the opportunity to continue helping patients treated with basal insulin who remain uncontrolled."

The approval of Adlyxin was based on FDA review of results from the GetGoal clinical program and findings from the ELIXA trial, which successfully addressed the FDA's request to demonstrate CV safety. The GetGoal clinical program, which included 13 clinical trials involving more than 5,000 adults with type 2 diabetes worldwide, evaluated the safety and efficacy of lixisenatide in adults with type 2 diabetes. All studies of the GetGoal program successfully met the primary efficacy endpoint of HbA1c reduction. The most common adverse events reported for Adlyxin included nausea, hypoglycemia and vomiting.

Adlyxin will be available in a disposable pre-filled pen in a single dose of 20 micrograms. Patients will also receive a disposable pre-filled pen in a single dose of 10 micrograms that they should initiate once daily for 14 days. On Day 15, patients will increase dosage to 20 micrograms once daily.

Adlyxin is approved under the proprietary name, Lyxumia® in more than 60 countries and marketed in over 40. Commercial launches include most EU countries, Japan, Brazil, Mexico and India. Adlyxin was in-licensed from Zealand Pharma A/S (NASDAQ OMX Copenhagen: ZEAL), www.zealandpharma.com.

About Adlyxin

Adlyxin is a once-daily glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of adult patients with type 2 diabetes mellitus as an adjunct to diet and exercise. GLP-1 is a peptide hormone that is released within minutes after eating a meal. It is known to suppress glucagon secretion from pancreatic alpha cells and stimulate glucose-dependent insulin secretion by pancreatic beta cells. Adlyxin increases glucose-dependent insulin release, decreased glucagon secretion, and slows gastric emptying.

About Sanofi Diabetes & Cardiovascular

Diabetes and cardiovascular disease affect millions of people worldwide, with many managing the complex challenges of both. Building on our portfolio evolution, heritage and expertise, Sanofi has a focused business unit dedicated to delivering innovative, value-based medicines and integrated solutions in these therapeutic areas. We are committed to a collaborative approach that involves strategic alliances with professional and patient associations, research institutions and leaders in healthcare and other industries, with the goal of advancing scientific knowledge, driving the convergence of science and technology, helping to improve outcomes and inspiring an evolution in care.

About Sanofi

Sanofi, a global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients' needs. Sanofi is organized into five global business units: Diabetes and Cardiovascular, General Medicines and Emerging Markets, Sanofi Genzyme, Sanofi Pasteur and Merial. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

Sanofi Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words "expects", "anticipates", "believes", "intends", "estimates", "plans" and similar expressions. Although Sanofi's management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the absence of guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives, the Group's ability to benefit from external growth opportunities, trends in exchange rates and prevailing interest rates, the impact of cost containment initiatives and subsequent changes thereto, the average number of shares outstanding as well as those discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in Sanofi's annual report on Form 20-F for the year ended December 31, 2015. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements.

SOURCE: Sanofi

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Novel Therapeutic Advances for Management of Diabetes Mellitus

Diabetes mellitus (DM) has become one of the most challenging health problems in the 21st century. It is a serious public health problem globally, but the good news is that various advances are being made in prevention, detection, and treatment of diabetes. Though prevention is always better than cure, yet sometimes prevention is not possible and the cure seems to take ages. The interest to find a possible cure for diabetes has eventually led to exploration of various new scientific areas of research.

Volanesorsen

Volanesorsen (formerly ISIS-APOCIIIRx)is an antisense drug in development intended to treat patients with severely high triglycerides either as a single agent or in combination with other triglyceride-lowering agents.Elevation in triglycerides has always increased the risk of cardiovascular disorders as well as type 2 diabetes mellitus (T2DM). Researchers from the University of Pennsylvania have found the therapeutic effect of lipid-lowering medication sin improving insulin sensitivity in people with T2DM. Volanesorsen is an oral medication that can help to control the blood sugar levels. Itis believed to improve the insulin sensitivity and significantly decrease the patients’ overall glycated hemoglobin (HbA1c). After taking the medication for 12 weeks, researchers found that adult T2DM patients receiving volanesorsen experienced 69% reduction in triglycerides, and 57% improvement in whole-body insulin sensitivity.Researchers concluded that decrease in triglycerides was strongly related to improved insulin sensitivity and improved HbA1c.

PEGylated Lispro

PEGylated lispro (LY2605541) has been developed by the addition of polyethylene glycol (PEG) to insulin lispro, leading to its extended half-life. Early phase evaluations of PEGyalted lispro confirm its non-inferiority to glargine with a potential weight advantage when used in T2DM. Since insulin therapy is anabolic and its initiation is commonly associated with weight gain, an insulin preparation associated with a beneficial weight profile would represent a particularly valuable therapeutic entity.

Pre-clinical studies indicate that LY2605541 has low mitogenic potency, exerting a preferential hepatic effect on glucose homeostasis. However, LY2605541 appears to cause elevated transaminases and derangement of lipid profiles. On the basis of these initial observations, LY2605541 requires further extensive clinical evaluation to fully assess its risk/benefit profile in the management ofdiabetes.

Islet Transplantation

A novel technology has been developed to help treat type 1 diabetes mellitus (T1DM) and potentially negate the need for insulin injections. Islets are organoids that produce multiple hormones, including insulin, and donated islets are already treating severe cases of T1DMeffectively. Islet transplantation can transform the lives of T1DM patients, and may result in long-term freedom from insulin injections with excellent glucose control.

Natural Products

Plants possessing antidiabetic properties may be suitable as an adjunct to the existing therapies or as a prospective source of new hypoglycemic compounds. Many new bioactive drugs isolated from plants demonstrate antidiabetic activity equal to known oral hypoglycemic agents such as tolbutamide and chlorpropamide. Several plant species with terpenoids, flavonoids, phenols, coumarins, and other bioactive constituents have shown their potency in reducing blood glucose levels. Plants likeAllium sativum(Liliaceae),Gymnema sylvestre(Asclepiadaceae),Murraya koenigii(Rutaceae),Allium cepa(Liliaceae),Withania somnifera (Solanaceae), andFerula foetida (Umbelliferae) have exhibited antidiabetic properties when assessed in experimental models of diabetes. These traditional approaches might prove to bebeneficial in treatment of diabetic complications.

Great strides have been made clinically in the management of diabetes. Extensive research may lead to discovery of newer and better options for diabetes. With new technologies revolutionizing the treatment possibilities, the search for an effective medication is not far ahead.

Turacoz Healthcare Solutions aims to create awareness for such healthcare issues like diabetes mellitus which pose a serious threat to people, irrespective of race, gender, or age. We consider it our corporate responsibility to share the knowledge related to therapeutic research and development, and keep you updated with the recent medical advancements in the healthcare industry.“Being aware of a disease and its deleterious consequences”is the first-step towards its prevention. So stay healthy and stay long.

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Fascinating Facts About Your Body

Even though you’re around human bodies all day (after all, you have one of your very own), you probably don’t know everything there is to know about them. Each of our bodies are a miracle; it’s amazing they work the way they do, day in and day out. If you thought what our bodies could do before, once you read this list of insane facts about the human body, you’ll be in awe. Never take your own body for granted, because some of the things it can do are mind-blowing.

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Does This Cause Cancer?

Cancer is a class of diseases characterized by out-of-control cell growth. There are over 100 different types of cancer, and each is classified by the type of cell that is initially affected. Cancer harms the body when damaged cells divide uncontrollably to form lumps or masses of tissue called tumors (except in the case of leukemia where cancer prohibits normal blood function by abnormal cell division in the blood stream). Tumors can grow and interfere with the digestive, nervous, and circulatory systems, and they can release hormones that alter body function. Tumors that stay in one spot and demonstrate limited growth are generally considered to be benign.

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How to Have a Healthy Day From Morning to Night

We work, we plan, we organize, we go, fueling ourselves on coffee and pure determination. Until, that is, we fall onto the sofa in a stupor. More of us are struggling with energy issues, experts say; they point to the weak economy, which has us working harder and plugging in longer, and the belief that we can have it all (so what if we’re up till midnight making it happen).
“Just like houseplants need water, our energy reserves need regular replenishing,”

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Protect Yourself From Medical Costs and Disability

An estimated 22.4% of women 18 years of age or older and 29.3% of women 40 years of age or older had a self-reported disability.Women 40 years of age or older with a disability were less likely to have had a mammogram (72.2%) than were women without a disability (77.8%)

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Foods to Avoid If You Have High Triglycerides

When you have high triglyceride levels, there's a good chance you also have abnormal cholesterol numbers: specifically, low levels of HDL "good" cholesterol and high levels of LDL "bad" cholesterol. This combination increases the likelihood that you’ll have a heart attack orstroke.

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Tips to Stay Smart, Sharp, and Focused

We all want to keep our minds sharp and fresh. By working to keep your mind sharp, you can improve your attitude. Nothing angers a person more than not being able to remember mportant things or events. By having a sharp mind you can figure situations out more effectively and make wiser decisions. There are numerous ways to keep your mind sharp while keeping a good, well-rounded attitude. Reading this article will tell you those ways.

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Interactive DRI for Health Care Professional

Use this tool to calculate daily nutrient recommendations for dietary planning based on the Dietary Reference Intakes (DRIs). These represent the most current scientific knowledge on nutrient needs, developed by the National Academy of Science’s Institute of Medicine. Individual requirements may be higher or lower than the DRIs.

Mobile app now available: download from the Apple Store or Google Play.

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What is a case-control study in medical research?

What is a case-control study in medical research?

Markus MacGill

A case-control study is a type of medical research investigation often used to help determine the cause of a disease, particularly when investigating a disease outbreak or a rare condition.

If public health scientists want a relatively quick and easy way to find clues about the cause of, for example, a new disease outbreak, they can compare two groups of people:

• Those who already have the disease – ‘cases’
• Similar people who have not been affected – ‘controls.’

A case-control study is retrospective – the researchers look back at data collected in the past, enabling them to test whether a particular outcome can be linked back to a suspected risk factor. To test for specific causes, the scientists need to formulate a hypothesis about what they think could be behind the outbreak or disease. They then compare how often the group of cases had been exposed to the suspected cause (risk factor), versus how often the controls had been exposed. If the risk factor has a greater prevalence among the cases, then this is some evidence to suggest that it is a cause of the disease.Risk factors could be uncovered by researchers studying the medical and lifestyle histories of the people in each group. A pattern may emerge that links the condition under investigation to certain factors.Case-control research is a central tool used by epidemiologists, who look into the factors that affect the health and illness of populations.Just one risk factor could be investigated for a particular disease outcome. A good example of this is to analyze how many people with lung cancer, versus how many without, have a history of smoking.

A case control study .pdf

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The Truth About Probiotics and Your Gut

Probiotics are live bacteria and yeasts that are good for your health, especially your digestive system. We usually think of bacteria as something that causes diseases. But your body is full of bacteria, both good and bad. Probiotics are often called “good” or “helpful” bacteria because they help keep your gut healthy.Probiotics are naturally found in your body. You can also find them in some foods and supplements.It’s only been since about the mid-1990s that people have wanted to know more about probiotics and their health benefits. Doctors often suggest them to help with digestive problems. And because of their new found fame, you can find them in everything from yogurt to chocolate.

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Healthy Living Can Prevent Cancer From Developing, Progressing, or Recurring

Many of the greatest reductions in cancer morbidity and mortality are a result of advances in cancer prevention and early detection. These advances were enabled by translating the discoveries of the causes and progressive nature of cancer into effective new clinical practices and public education and policy initiatives.Central to preventing cancer is the identification of factors that increase a person’s risk of developing cancer and eliminating or reducing these factors where possible (see Figure 4). As research has enhanced our knowledge of cancer risk factors, we have learned that more than 50 percent of the 585,720 cancer deaths expected to occur in the United States in 2014 will be related to preventable causes (16).Many factors that increase the risk of developing cancer are related to lifestyle; thus, adopting a healthy approach to living, where possible, can eliminate or reduce the risk of some cancers (seeFigure 5). Moreover, many healthy approaches to living can also reduce cancer recurrence and improve outcomes following a cancer diagnosis. However, a great deal more research and many more resources are needed to understand how best to help individuals change their lifestyle.

Adopting Healthy Approaches to Living

Tobacco use is responsible for almost 30 percent of cancer deaths each year in the United States (1) (see Figure 6). As a result, one of the most effective ways a person can lower the risk of developing cancer is to eliminate tobacco use (see sidebar on Reasons to Eliminate Tobacco Use). This relationship between tobacco use and cancer was first brought to the public’s attention 50 years ago, when the U.S. Surgeon General’s report on “Smoking and Health” was published (17). Since then, smoking rates among U.S. adults have more than halved, and as a result, an estimated 800,000 deaths from lung cancer were avoided between 1975 and 2000 (18).Unfortunately, the rate of decline in smoking prevalence in the United States has slowed in recent years (18). In fact, almost 70 million individuals age 12 or older are regular users of tobacco products (20).If we are to eradicate one of the biggest threats to public health, researchers, clinicians, advocates, and policymakers must continue to work together. Several steps that could be taken to achieve this goal are outlined in this year’s Surgeon General’s report, “The Health Consequences of Smoking—50 Years of Progress,” (see sidebar on Eliminating Tobacco Use Faster) (18). Of particular importance is the regulation of additional tobacco products by the FDA.Other healthy approaches to living that can significantly reduce cancer risk are maintaining a healthy weight, which is defined as a body mass index (BMI) between 18.5 and 24.9 kg/m2 for adults over 20 years of age; keeping active; and eating a balanced diet (see sidebar on Reasons to Maintain a Healthy Weight and Keep Active). The impact of adopting these aspects of a healthy lifestyle could be enormous because it is estimated that one-third of all new cancer diagnoses in the United States are related to being overweight or obese, not getting enough physical activity, and/or having poor dietary habits (10, 16). Moreover, more than one-third of adults, or more than 72 million individuals, and 17 percent of youth in the United States are obese (21, 22).Fortunately, regular physical activity, independent of body fatness, can decrease the risk of developing certain cancers (23). However, nearly half of adults in the United States do not meet the recommended guidelines for aerobic physical activity (25) (see sidebar on Physical Activity Guidelines). Moreover, sedentary behavior, independent of body mass and periodic physical activity, can increase the risk of developing certain types of cancer (24).

Beyond preventing the development of some cancers, following these recommendations may also improve outcomes for individuals diagnosed with certain types of cancer, in particular breast, colorectal, and prostate cancers, reducing risk of disease recurrence and metastasis and increasing chance of long-term survival (27-29).

Although small improvements in maintaining a healthy weight and increasing physical activity have been made, more action is urgently needed. Concerted efforts by individuals, families, communities, schools, workplaces and institutions, health care professionals, media, industry, government, and multinational bodies are required to develop effective and comprehensive strategies to promote the maintenance of a healthy weight and the participation in regular physical exercise. One new strategy, Park Rx, an initiative of the National Park Service seeks to encourage health care providers to help patients establish an exercise routine by effectively using their neighborhood parks.

Another way that individuals can reduce their risk of developing cancer, specifically the three main types of skin cancer—basal cell carcinoma, squamous cell carcinoma, and melanoma—is by limiting their exposure to ultraviolet (UV) radiation (see sidebar on Reasons to Protect Your Skin). In fact, the International Agency for Research on Cancer (IARC), an affiliate of the World Health Organization, considers exposure to UV radiation from any source as “carcinogenic to humans” (30), alongside agents such as plutonium and cigarettes.

Despite this, half of all adults in the United States report at least one sunburn in the past 12 months and 5 percent report using a UV indoor tanning device at least once, with many using these devices 10 or more times a year (37, 38). Moreover, 13 percent of all high school students and 21 percent of high school girls report using an indoor UV tanning device in the past year (39).Given that many cases of skin cancer are preventable, it is important that everyone work together to develop and implement more effective policy changes and public education campaigns to help reduce the health and economic burdens of the disease. For example, initiatives aimed at increasing the number of individuals who adopt sun-safe habits and tighter regulation of indoor tanning would dramatically reduce the incidence of skin cancer (see sidebar on Sun-safe Habits).

Persistent infection with a number of pathogens—bacteria, viruses, or parasites that cause disease—can result in certain types of cancer (40, 41) (see Table 4). In fact, pathogens are estimated to cause about 2 million cancer cases each year, with more than 90 percent of these cases attributable to just four pathogens—Helicobacter pylori, hepatitis B virus (HBV), hepatitis C virus (HCV), and human papilloma virus (HPV) (42) (see Figure 7).This knowledge has enabled the development of strategies to eliminate or prevent infection with these cancer-associated pathogens (see sidebar on Cancer-causing Pathogens: Prevention and Elimination). Consulting with a physician and following his or her advice regarding the use of these strategies can reduce an individual’s risk of certain cancers and is part of a healthy approach to living.

Despite the availability of strategies to eliminate or prevent infection with some cancer-associated pathogens, researchers estimate that pathogen-related cancers account for about 20 percent of cancer diagnoses worldwide (40) (see Figure 7). Thus, it is clear that these strategies are not being used optimally and that a dramatic reduction in the global cancer incidence could be achieved by more effective implementation. In fact, the CDC estimates that in 2012, only 33 percent of girls ages 13–17 in the United States had received the recommended three doses of HPV vaccine (60). Moreover, this percentage varies widely among states, with fewer than 26 percent of girls completing the vaccine course in six states, and the lowest rate being just 12.1 percent (44). Further, the “President’s Cancer Panel 2012–2013 Report” stated that in the United States alone, more than 50,000 cases of cervical cancer and thousands of cases of other types of cancer could be prevented if 80 percent of those for whom the HPV vaccine is recommended—girls and boys ages 11 and 12, respectively—were to be vaccinated (44) (see sidebar on The “President’s Cancer Panel Report”).

Research has provided and continues to increase our knowledge of the causes of cancer and the timing, sequence, and frequency of the genetic, molecular, and cellular changes that drive cancer initiation and development. This knowledge provides us with unique opportunities for developing ways to prevent cancer onset or to detect a cancer and intervene earlier in its progression. Finding a cancer early, asCongressman Ron Barber did in 2012, before it has spread to other parts of the body, makes it more likely that a patient can be treated successfully. Cancer screening is therefore an important part of a healthy lifestyle.

Screening to detect cancer in individuals showing no signs or symptoms of the disease they are being screened for can have tremendous benefits (see sidebar on Cancer Screening). However, it can also cause unintended harm, and this has made it difficult to develop strategies for screening for the majority of cancer types. For a screening program to be successful, it must meet two important criteria: It must decrease deaths from the screened cancer, and the benefits it provides must outweigh any harms. Determining whether a screening program meets these criteria requires an enormous amount of research and careful analysis of the data generated.

In the United States, an independent group of experts convened by the Public Health Service rigorously evaluates clinical research to make evidence-based recommendations about clinical preventive services, including cancer-screening tests. These experts form the U.S. Preventive Services Task Force (USPSTF). As of Aug. 1, 2014, the USPSTF recommended that certain segments of the general population be screened for just four types of cancer (see sidebar onUSPSTF Cancer-screening Recommendations). In addition to considering evidence regarding potential new screening programs, the USPSTF routinely evaluates new research regarding established screening programs, and can revise recommendations if deemed necessary.

Although cancer screening is part of a healthy approach to living, it can be difficult for individuals to ascertain which cancers to be screened for and when. The USPSTF and other relevant professional societies’ recommendations are evidence-based guidelines that can help, but they are only one factor to consider when making decisions about cancer screening.

People have their own unique risks for developing each type of cancer. These risks are determined by genetic, molecular, cellular, and tissue makeup, as well as by lifetime exposures to the large number of factors that can increase the risk of developing cancer (see Figure 4). As a result, each individual should consult with his or her physicians to develop a personalized cancer-screening plan that takes into account evidence-based recommendations; the individual’s own cancer risks, including family history; and the individual’s tolerance to specific benefits and harms of screening (see sidebar on Cancer Screening). Importantly, the risk for different types of cancer can vary over time—for example, risk for most cancers increases with age—so it is important that individuals continually evaluate, and update if necessary, their personalized cancer-screening plans.

Some generally healthy individuals are at increased risk of certain cancers because they inherited a cancer-predisposing genetic mutation (see sidebar on How Do I Know If I Am at High Risk for Developing an Inherited Cancer?). However, inheriting a cancer-predisposing genetic mutation is a relatively rare occurrence. In fact, only about 5 percent of all new cases of cancer diagnosed in the United States each year are caused by such mutations (63). To date, not all potentially inheritable causes of cancer have been identified, but if an individual suspects that a relative has a cancer caused by one of the 17 known cancer-predisposing genetic mutations (see Table 5), he or she should consult a physician and consider genetic testing for verification.

As part of a healthy approach to living, persons who are at risk for developing an inherited cancer—both those who learn they carry a known cancer-predisposing genetic mutation and those who fulfill criteria for being at risk—should consult with their doctors to determine how this influences their personalized cancer prevention and screening plans. Some patients may be able to reduce their risk of developing cancer by modifying their behaviors. Others might need to increase their participation in screening or early detection programs or even consider taking a preventive medicine or having risk-reducing surgery (see Tables 6 and 7).

Beyond inherited cancers, a number of medical conditions place an individual at higher risk for certain types of cancer. For example, ulcerative colitis and Crohn disease increase an individual’s risk for colorectal cancer sixfold, but they are relatively rare conditions (64). A far more prevalent medical condition that increases an individual’s risk for developing cancer is type 2 diabetes, which raises the risk of developing liver, pancreatic, and endometrial cancers (65, 66). These factors are important considerations when developing a personalized cancer prevention and screening plan.

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A Simple Method for Evaluating the Clinical Literature

The “PP-ICONS” approach will help you separate the clinical wheat from the chaff in mere minutes.

Robert J. Flaherty, MD

Keeping up with the latest advances in diagnosis and treatment is a challenge we all face as phycians. We need information that is both valid (that is, accurate and correct) and relevant to our patients and practices. While we have many sources of clinical information, such as CME lectures, textbooks, pharmaceutical advertising, pharmaceutical representatives and colleagues, we often turn to journal articles for the most current clinical information.

Unfortunately, a great deal of research reported in journal articles is poorly done, poorly analyzed or both, and thus is not valid. A great deal of research is also irrelevant to our patients and practices. Separating the clinical wheat from the chaff can take skills that many of us never were taught.

KEY POINTS

• Reading the abstract is often sufficient when evaluating an article using the PP-ICONS approach.
• The most relevant studies will involve outcomes that matter to patients (e.g., morbidity, mortality and cost) versus outcomes that matter to physiologists (e.g., blood pressure, blood sugar or cholesterol levels).
• Ignore the relative risk reduction, as it overstates research findings and will mislead you.

The article “Making Evidence-Based Medicine Doable in Everyday Practice” in the February 2004 issue of FPM describes several organizations that can help us. These organizations, such as the Cochrane Library, Bandolier and Clinical Evidence, develop clinical questions and then review one or more journal articles to identify the best available evidence that answers the question, with a focus on the quality of the study, the validity of the results and the relevance of the findings to everyday practice. These organizations provide a very valuable service, and the number of important clinical questions that they have studied has grown steadily over the past five years. (See “Four steps to an evidence-based answer.”)

FOUR STEPS TO AN EVIDENCE-BASED ANSWER

When faced with a clinical question, follow these steps to find an evidence-based answer:

1. Search the Web site of one of the evidence review organizations, such as Cochrane (http://www.cochrane.org/cochrane/revabstr/mainindex.htm), Bandolier (http://www.jr2.ox.ac.uk/bandolier) or Clinical Evidence (http://www.clinicalevidence.com), described in “Making Evidence-Based Medicine Doable in Everyday Practice,” FPM, February 2004, page 51. You can also search the TRIP+ Web site (http://www.tripdatabase.com), which simultaneously searches the databases of many of the review organizations. If you find a systematic review or meta-analysis by one of these organizations, you can be confident that you’ve found the best evidence available.
2. If you don’t find the information you need through step 1, search for meta-analyses and systematic reviews using the PubMed Web site (see the tutorial athttp://www.nlm.nih.gov/bsd/pubmed_tutorial/m1001.html). Most of the recent abstracts found on PubMed provide enough information for you to determine the validity and relevance of the findings. If needed, you can get a copy of the full article through your hospital library or the journal’s Web site.
3. If you cannot find a systematic review or meta-analysis on PubMed, look for a randomized controlled trial (RCT). The RCT is the “gold standard” in medical research. Case reports, cohort studies and other research methods simply are not good enough to use for making patient care decisions.
4. Once you find the article you need, use the PP-ICONS approach to evaluate its usefulness to your patient.

If you find a systematic review or meta-analysis done by one of these organizations, you can feel confident that you have found the current best evidence. However, these organizations have not asked all of the common clinical questions yet, and you will frequently be faced with finding the pertinent articles and determining for yourself whether they are valuable. This is where the PP-ICONS approach can help.

What is PP-ICONS?

When you find a systematic review, meta-analysis or randomized controlled trial while reading your clinical journals or searching PubMed (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi), you need to determine whether it is valid and relevant. There are many different ways to analyze an abstract or journal article, some more rigorous than others.1,2 I have found a simple but effective way to identify a valid or relevant article within a couple of minutes, ensuring that I can use or discard the conclusions with confidence. This approach works well on articles regarding treatment and prevention, and can also be used with articles on diagnosis and screening.

The most important information to look for when reviewing an article can be summarized by the acronym “PP-ICONS,” which stands for the following:

• Problem,
• Patient or population,
• Intervention,
• Comparison,
• Outcome,
• Number of subjects,
• Statistics.

For example, imagine that you just saw a nine-year-old patient in the office with common warts on her hands, an ideal candidate for your usual cryotherapy. Her mother had heard about treating warts with duct tape and wondered if you would recommend this treatment. You promised to call Mom back after you had a chance to investigate this rather odd treatment.

When you get a free moment, you write down your clinical question: “Is duct tape an effective treatment for warts in children?” Writing down your clinical question is useful, as it can help you clarify exactly what you are looking for. Use the PPICO parts of the acronym to help you write your clinical question; this is actually how many researchers develop their research questions.

You search Cochrane and Bandolier without success, so now you search PubMed, which returns an abstract for the following article: “Focht DR 3rd, Spicer C, Fairchok MP. The efficacy of duct tape vs cryotherapy in the treatment of verruca vulgaris (the common wart). Arch Pediatr Adolesc Med. 2002 Oct;156(10):971-974.”

You decide to apply PP-ICONS to this abstract (see “Abstract from PubMed”) to determine if the information is both valid and relevant.

ABSTRACT FROM PUBMED

Using the PP-ICONS approach, physicians can evaluate the validity and relevance of clinical articles in minutes using only the abstract, such as this one, obtained free online from PubMed,http://www.ncbi. nlm.nih.gov/entrez/query.fcgi. The author uses this abstract to evaluate the use of duct tape to treat common warts.

Problem. The first P in PP-ICONS is for “problem,” which refers to the clinical condition that was studied. From the abstract, it is clear that the researchers studied the same problem you are interested in, which is important since flat warts or genital warts may have responded differently. Obviously, if the problem studied were not sufficiently similar to your clinical problem, the results would not be relevant.

Patient or population. Next, consider the patient or population. Is the study group similar to your patient or practice? Are they primary care patients, for example, or are they patients who have been referred to a tertiary care center? Are they of a similar age and gender? In this case, the researchers studied children and young adults in outpatient clinics, which is similar to your patient population. If the patients in the study are not similar to your patient, for example if they are sicker, older, a different gender or more clinically complicated, the results might not be relevant.

Intervention. The intervention could be a diagnostic test or a treatment. Make sure the intervention is the same as what you are looking for. The patient’s mother was asking about duct tape for warts, so this is a relevant study.

Comparison. The comparison is what the intervention is tested against. It could be a different diagnostic test or another therapy, such as cryotherapy in this wart study. It could even be placebo or no treatment. Make sure the comparison fits your question. You usually use cryotherapy for common warts, so this is a relevant comparison.

Outcome. The outcome is particularly important. Many outcomes are “disease-oriented outcomes,” which are based on “disease-oriented evidence” (DOEs). DOEs usually reflect changes in physiologic parameters, such as blood pressure, blood sugar, cholesterol, etc. We have long assumed that improving the physiologic parameters of a disease will result in a better disease outcome, but that is not necessarily true. For instance, finasteride can improve urinary flow rate in prostatic hypertrophy, but it does not significantly change symptom scores.3

DOEs look at the kinds of outcomes that physiologists care about. More relevant are outcomes that patients care about, often called “patient-oriented outcomes.” These are based on “patient-oriented evidence that matters” (POEMs) and look at outcomes such as morbidity, mortality and cost. Thus, when looking at a journal article, DOEs are interesting but of questionable relevance, whereas POEMs are very interesting and very relevant. In the study on the previous page, the outcome is complete resolution of the wart, which is something your patient is interested in.

Number. The number of subjects is crucial to whether accurate statistics can be generated from the data. Too few patients in a research study may not be enough to show that a difference actually exists between the intervention and comparison groups (known as the “power” of a study). Many studies are published with less than 100 subjects, which is usually inadequate to provide reliable statistics. A good rule of thumb is 400 subjects.4 Fifty-one patients completed the wart study, which is a pretty small number to generate good statistics.

Statistics. The statistics you are interested in are few in number and easy to understand. Since statistics are frequently misused in journal articles, it is worth a few minutes to learn which to believe and which to ignore.

Relative risk reduction. It is not unusual to find a summary statement in a journal article similar to this one from an article titled “Long-Term Effects of Mammography Screening: Updated Overview of the Swedish Randomised Trials”

“There were 511 breast cancer deaths in 1,864,770 women-years in the invited groups and 584 breast cancer deaths in 1,688,440 women-years in the control groups, a significant 21 percent reduction in breast cancer mortality.”

This 21-percent statistic is the relative risk reduction (RRR), which is the percent reduction in the measured outcome between the experimental and control groups. (See “Some important statistics” for more information on calculating the RRR and other statistics.) The RRR is not a good way to compare outcomes. It amplifies small differences and makes insignificant findings appear significant, and it doesn’t reflect the baseline risk of the outcome event. Nevertheless, the RRR is very popular and will be reported in nearly every journal article, perhaps because it makes weak results look good. Think of the RRR as the “reputation reviving ratio” or the “reporter’s reason for ‘riting.” Ignore the RRR. It will mislead you. In our wart treatment example, the RRR would be (85 percent – 60 percent)/60 percent x 100 = 42 percent. The RRR could thus be interpreted as showing that duct tape is 42 percent more effective than cryotherapy in treating warts.

SOME IMPORTANT STATISTICS

Absolute risk reduction (ARR): The difference between the control group’s event rate (CER) and the experimental group’s event rate (EER).

Control event rate (CER): The proportion of patients responding to placebo or other control treatment. For example, if 25 patients are in a control group and the event being studied is observed in 15 of those patients, the control event rate would be 15/25 = 0.60.

Experimental event rate (EER): The proportion of patients responding to the experimental treatment or intervention. For example, if 26 patients are in an experimental group and the event being studied is observed in 22 of those patients, the experimental event rate would be 22/26 = 0.85.

Number needed to treat (NNT): The number of patients that must be treated to prevent one adverse outcome or for one patient to benefit. The NNT is the inverse of the ARR; NNT = 1/ARR.

Relative risk reduction (RRR): The percent reduction in events in the treated group compared to the control group event rate.

View/Print Table

	When the experimental treatment reduces the risk of a bad event:	Example: Beta-blockers to prevent deaths in high-risk patients with recent myocardial infarction:	When the experimental treatment increases the probability of a good event:	Example: Duct tape to eliminate common warts.
Relative risk reduction (RRR)	CER-EER/CER	(.66 -. 50)/.66 = .24 or 24 percent	EER-CER/CER	(.85-.60)/.60 = .42 or 42 percent
Absolute risk reduction (ARR):	CER-EER	(.66 – .50) = .16 or 16 percent	EER-CER	.85-.60 = .25 or 25 percent
Number needed to treat (NNT)	1/ARR	1/.16 = 6	1/ARR	1/.25 = 4

Absolute risk reduction. A better statistic is the absolute risk reduction (ARR), which is the difference in the outcome event rate between the control group and the experimental treated group. Thus, in our wart treatment example, the ARR is the outcome event rate (complete resolution of warts) for duct tape (85 percent) minus the outcome event rate for cryotherapy (60 percent) = 25 percent. Unlike the RRR, the ARR does not amplify small differences but shows the true difference between the experimental and control interventions. Using the ARR, it would be accurate to say that duct tape is 25-percent more effective than cryotherapy in treating warts.

Number needed to treat. The single most clinically useful statistic is the number needed to treat (NNT). The NNT is the number of patients who must be treated to prevent one adverse outcome. To think about it another way, the NNT is the number of patients who must be treated for one patient to benefit. (The rest who were treated obtained no benefit, although they still suffered the risks and costs of treatment.) In our wart therapy article, the NNT would tell us how many patients must be treated with the experimental treatment for one to benefit more than if he or she had been treated with the standard treatment.

Now this is a statistic that physicians and their patients can really appreciate! Furthermore, the NNT is easy to calculate, as it is simply the inverse of the ARR. For our wart treatment study, the NNT is 1/25 percent =1/0.25 = 4, meaning that 4 patients need to be treated with duct tape for one to benefit more than if treated by cryotherapy.

Wrapped up in this simple little statistic are some very important concepts. The NNT provides you with the likelihood that the test or treatment will benefit any individual patient, an impression of the baseline risk of the adverse event, and a sense of the cost to society. Thus, it gives perspective and hints at the “reasonableness” of a treatment. The value of this statistic has become appreciated in the last five years, and more journal articles are reporting it.

What is a reasonable NNT? In a perfect world, a treatment would have an NNT of 1, meaning that every patient would benefit from the treatment. Real life is not so kind (see “Examples of NNTs”). Clearly, an NNT of 1 is great and an NNT of 1,000 is terrible. Although it is hard to come up with firm guidelines, for primary therapies I am satisfied with an NNT of 10 or less and very pleased with an NNT less than 5. Our duct tape NNT of 4 is good, particularly since the treatment is cheap, easy and painless.

EXAMPLES OF NNTS

The number needed to treat (NNT) is one of the most useful statistics for physicians and patients. It calculates the number of patients that must be treated to prevent one adverse event or for one patient to benefit. Note that NNTs for preventive interventions will usually be higher than NNTs for treatment interventions. The lower the NNT, the better.

The following examples of NNTs are borrowed from an excellent list available through the Bandolier Web site at http://www.jr2.ox.ac.uk/bandolier/band50/b50-8.html.

View/Print Table

Therapy	NNT
Triple antibiotic therapy to eradicate H. pylori	1.1
Isosorbide dinitrate for prevention of exercise-induced angina	5
Short course of antibiotics for otitis media in children	7
Statins for secondary prevention of adverse cardiovascular outcomes	11
Statins for primary prevention of adverse cardiovascular outcomes	35
Finasteride to prevent one operation for benign prostatic hyperplasia	39
Misoprostol to prevent any gastrointestinal complication in nonsteroidal anti-inflammatory drug users	166

Note that NNTs for preventive interventions (e.g., the use of aspirin to prevent cardiac problems) will usually be higher than NNTs for treatment interventions (e.g., the use of duct tape to cure warts). Prevention groups contain both higher-risk and lower-risk individuals, so they produce bigger denominators, whereas treatment groups only contain diseased patients. Thus, an NNT for prevention of less than 20 might be particularly good.

When discussing a particular therapy, I explain the NNT to my patient. Since this statistical concept is easy to understand, it can help the patient be a more informed partner in therapeutic decisions.

You will soon start to see a similar statistic, the number needed to screen (NNS), which is the number of patients needed to screen for a particular disease for a given duration for one patient to benefit.6Although few NNSs have been calculated, they are likely to involve higher numbers, since the screening population consists of patients with and without the disease. For example, in the article on mammography screening mentioned above, the NNS was 961 for 16 years. In other words, you would need to screen 961 women for 16 years to prevent one breast cancer death.

The good news and the bad

Using PP-ICONS to assess the wart study, the problem, the patient/population, the intervention, the comparison and the outcome are all relevant to your patient. The number of subjects is on the small side, making you a little wary, but the intervention is cheap and low-risk. The statistics, particularly the NNT, are reasonable. On balance, this looks like a fair approach, so you call the patient’s mother and discuss it with her.

The PP-ICONS approach is an easy way to screen an article for validity and relevance, and the abstract often contains all of the information you need. Even the statistics can be done quickly in your head. You can apply PP-ICONS when searching for a particular article, when you come across an article in your reading, when data are presented at lectures, when a pharmaceutical representative hands you an article to support his or her pitch, and even when reading news stories describing medical breakthroughs.

Don’t be discouraged if you find that high-quality articles are rare, even in the most prestigious journals. This seems to be changing for the better, although many careers are still being built on questionable research. Nevertheless, screening articles will help you find the truth that is out there and will help you practice the best medicine. And as we become more discerning end-users of research, we might just stimulate improvements in clinical research in the process.

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Dr. Flaherty is a family physician with the Student Health Service and WWAMI Medical Program, Montana State University-Bozeman, and a clinical professor in the Department of Family Medicine, University of Washington.

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