August 22nd, 2011
The Huffington Post
By: Linda A. Johnson
The maker of the world’s best-selling diabetes drug is facing hundreds of lawsuits and likely a big sales drop as suspicion grows that taking the pill for more than a year raises the risk of bladder cancer.
In June, Takeda Pharmaceuticals Co. Ltd. halted sales of Actos, its top drug, in Germany and France after pressure from regulators.
Since then, both the U.S. Food and Drug Administration and the European Medicines Agency have issued warnings about the cancer risk based on new research, but they have allowed sales to continue. Doctors are being told not to prescribe Actos for people who have or have had bladder cancer.
The warning will limit patient choices and could spell the end for a once-promising class of Type 2 diabetes drugs that debuted more than a decade ago amid heavy promotion.
The once-a-day pills were appealing. They helped control blood sugar tightly, had few side effects in most patients, boosted the effects of some other diabetes drugs, worked by a new mechanism – improving the body’s sensitivity to insulin – and even allowed patients to reduce or delay use of injected insulin.
Actos, despite links to heart failure risk and other serious side effects, became the No. 1 diabetes pill after Avandia, the only other drug in that class, was found in 2007 to sharply increase risk of heart attacks. Avandia’s use was banned in the EU and sharply restricted here. Actos sales jumped from about $2.9 billion in 2006 to more than $4.3 billion last year.
Now those billions may well shift to Takeda rivals.
In the past week, the first of what lawyers predict will be thousands of lawsuits were filed in courts across the country. They allege Actos triggered bladder cancer, in some cases fatal, in clients who took the pills daily for years.
Nancy Rios, 54, is suing Takeda, blaming her recurrent bladder cancer on Actos, which she took for more than a decade. Rios, a hospital secretary, was diagnosed with bladder cancer in 2009. In June, she had her second surgery to remove tumors. Rios, who lives in Reading, Pa., is worried about missing more work and being able to pay her medical bills. Next month, she will learn whether more treatment is needed.
“I could lose my bladder and possibly need chemo,” she said.
Her attorney, Paul Pennock of Weitz & Luxenberg, said the firm already represents another 104 clients, has about 120 more expected to pursue lawsuits and is getting 30 to 40 possible new cases a week.
“When a manufacturer distributes a drug, they owe it to the public to ensure that their product is safe for use and it appears that Takeda Pharmaceuticals failed to fulfill that fundamental duty,” Pennock said.
Other large law firms are evaluating potential cases by the dozen or more. More than 20 firms, from Florida to Washington state, are advertising for clients on the Internet or in newspapers, a standard practice in personal injury law.
“We don’t think it’s a coincidence that we’ve been contacted by so many people who have been taking Actos and have bladder cancer,” said Marc Jay Bern of Napoli Bern Ripka Shkolnik & Associates. “We have more than 100 (cases) that we’ve confirmed and many more that we’re evaluating.”
Takeda declined to comment on the lawsuits. The company, which is based in Japan, has issued statements that it’s committed to keeping Actos available for patients who need it.
Spokeswoman Elissa Johnsen noted an April study in the journal Diabetes Care found Actos “use for more than two years was weakly associated with increased risk.”
However, the FDA analyzed data from the first five years of a 10-year Actos safety study Takeda begun in 2002 and concluded this June that risk of bladder cancer was 40 percent higher for patients taking Actos for at least a year, although still small: an extra 28 cases a year for every 100,000 people taking it.
Erik Gordon, an analyst and professor at University of Michigan’s Ross School of Business, said Friday that the new safety questions are “a big deal” for Takeda, particularly since the Actos patent expires in August 2012. They mean Actos won’t make as much money as expected in the final months, and they dampen prospects for two experimental drugs Takeda was hoping would succeed Actos.
“One, alogliptin, has been stuck at the FDA over safety concerns, and the other, a combination of alogliptin and Actos, now looks doomed,” Gordon said.
Alogliptin is an experimental drug in the same class as Merck & Co.’s blockbuster Januvia. Those drugs increase production of insulin, which breaks down sugar in the blood, and reduce glucose production in the liver.
Les Funtleyder, an analyst and portfolio manager for the Miller Tabak Health Care Transformation fund, said Januvia is likely to gain sales as patients defect from Actos.
He doubts the cost of the bladder cancer litigation will hit the level of Vioxx. That’s the painkiller that Merck pulled off the market in 2004 because it doubled risk of heart attacks and strokes – triggering more than 50,000 lawsuits and, eventually, a $4.85 billion settlement to end most of them.
Whatever the outcome of the Actos litigation, diabetes patients and their doctors will be considering their options now.
Dr. Harlan Krumholz, a Yale School of Medicine professor who directs its Center for Outcomes Research and Evaluation, said more long-term data on the effects of Actos is needed.
“It’s not clear if this (bladder cancer) risk is real,” but Actos and Avandia both are linked to heart risks, weight gain and possibly bone loss and fractures, he said. “The consensus already is that (Actos) should only be considered … after patients have exhausted all other options.”
December 27th, 2010
By: David Gutierrez
The FDA has begun investigations into whether the widely used diabetes drug pioglitazone (marketed as Actos) may increase the risk of bladder cancer.
Actos is already known to carry a risk of “serious side effects on the liver,” writes Phyllis A. Balch in the book Prescription for Nutritional Healing, 4th Edition. Nevertheless, the drug has remained one of the top-prescribed diabetes drugs because although it also increases patients’ risks of heart failure, it is only half as likely to produce heart attacks as its primary competitor Avandia (rosiglitazone).
Following years of controversy, the FDA recently prohibited the prescription of Avandia except as a last resort in cases where all other diabetes drugs and treatments have failed.
According to a five-year study by Actos manufacturer Takeda Pharmaceuticals, patients taking the drug had a non-statistically significant, 20 percent higher risk of bladder cancer diagnosis. The risk was higher among patients who had been taking the drug for more than two years, and was highest among those who had been exposed to the highest levels.
Although the results of this study did not reach statistical significance, they were enough to spur the FDA to investigate further. Two prior clinical trials and a laboratory study in rats have also pointed to a link between the drug and bladder cancer.
Rates of Type 2 diabetes continue to rise worldwide with worsening diet and an ensuing higher prevalence of obesity. Studies have linked higher consumption of red and processed meats, eggs and fruit juice with a higher risk of the disease. Higher intake of coffee, fish, garlic, brown rice, turmeric, omega-3s and certain micronutrients have been linked with a lower risk.
In addition to eating a balanced diet, more exercise and more time in the sun (leading to higher vitamin D levels) are among the most reliable ways to reduce diabetes risk.
October 25th, 2010
By: David Gutierrez
A drug researcher who presided over the trial that first raised concerns over the diabetes blockbuster Avandia has warned that further tests of the drug’s safety would be unethical.
In 2009, David Juurlink of Sunnybrook Health Sciences Center in Toronto was the lead author of a study that compared rates of heart failure and death among older diabetics taking Avandia (known generically as rosiglitazone) and those taking Actos (pioglitazone), another drug in the same family. That study found that patients taking Avandia were 30 percent more likely to suffer heart failure or death.
Now Juurlink has joined with Sidney Wolfe, director of health research for Public Citizen, to call for the cancellation of another planned Avandia-Actos comparison study, known as the Thiazolidinedione Intervention in Vitamin D Evaluation (TIDE) trial.
The TIDE trial is to be performed by Avandia manufacturer GlaxoSmithKline at the behest of the FDA, which in 2007 ordered the company to conduct further safety studies of the drug. The FDA’s order came after it required the company to put a “black box” warning on the drug’s packaging about the risk of heart attack and heart failure.
The strong results of the 2009 study make any further comparison unethical, Juurlink and Wolfe have warned. The TIDE trial would expose “thousands of high-risk patients with diabetes to a drug with an unfavorable safety profile and clinical advantage over its comparator,” they wrote in an open letter to the FDA.
The TIDE study is due to be carried out in 14 different countries, including Third World countries such as Chile, India, Latvia, Mexico and Pakistan.
“[The] price of definitive proof” that Avandia is unsafe, “will almost certainly be measured in the lives of study subjects who have been incompletely informed about the risks and benefits of participation,” Wolfe and Juurlink wrote.
All drugs in the thiazolidinedione class, including Actos and Avandia, have also been linked to increased risk of anemia, edema, macular edema, bony fractures and acute liver injury.
July 23, 2010
More than 90 percent of researchers who have published studies favorable to the controversial diabetes drug Avandia had a financial stake in the issue, according to a study conducted by researchers from the Mayo Clinic.
The Mayo Clinic is one of the few research organizations in the United States that does not accept corporate funding.
Sales of GlaxoSmithKline’s bestselling drug Avandia plunged in 2007, after evidence emerged linking the drug to an increased risk of heart attack and death. These reports sparked a debate over the drug’s safety that continues to this day.
In an analysis of more than 200 studies, articles, editorials and letters published in scientific journals since 2007, Mayo Clinic researchers have concluded that financial conflict of interest continues to play a major role in that debate. Fully 87 percent of all authors who expressed positive views about Avandia had financial ties to GlaxoSmithKline, while another 7 percent had ties to other pharmaceutical companies involved with diabetes. Among authors with financial conflicts of interest, only 30 percent “expressed unfavorable views” of the drug.
In contrast, authors who were critical of Avandia were “largely free of identifiable conflicts of interest,” the researchers said.
The conflicts of interest cut both ways. Of 29 authors who recommended the drug Actos as a safer alternative to Avandia, 25 had ties to that drug’s maker, Eli Lilly.
In order to identify conflicts of interest, the Mayo Clinic researchers searched through multiple published works by each given author, as well as conducting investigations on the Internet. This research uncovered that while 47 percent of all authors surveyed had a financial stake in the diabetes drug debate, 23 percent failed to disclose these links. Most of these authors merely remained silent about their conflicts of interest, while three actually lied and said they had none.
“The implication is that there should be better disclosure,” lead researcher Mohammad Murad said. “People [with financial links to companies] should realize they are probably biased, and as readers we should be aware of probable bias.”
July 14, 2010
by Rita Rubin
A large clinical trial of Avandia, sponsored by its maker, “was inadequately designed and conducted to provide any reassurance” that the controversial diabetes drug does not increase cardiovascular risk, a Food and Drug Administration scientist wrote in a memo released Friday.
The lengthy memo by Thomas Marciniak, a medical team leader in the Division of Cardiovascular and Renal Products, is part of a 765-page briefing document prepared by FDA scientists in advance of next week’s advisory committee meeting on Avandia’s fate.
The RECORD trial, a study ordered by the European Medications Agency, enrolled 4,447 patients. It compares Avandia, the trade name for rosiglitazone, combined with metformin or a sulfonylurea, which are two other diabetes drugs, to metformin combined with sulfonylurea.
It is an “open label” trial, which means that the patients and researchers are aware of who’s getting which drugs, knowledge that could bias the findings, Marciniak wrote.
He cited a number of other problems with the study, including a lack of complete information about which study participants had died, information that could have made Avandia look riskier.
Next Tuesday and Wednesday’s advisory committee meeting will be the second in three years to review Avandia’s risk/benefit profile.
At a July 2007 meeting, the panelists voted 20-3 that Avandia did raise heart attack risk. Yet, the panel voted 22-1 to recommend keeping the drug on the market. The FDA usually, but not always, follows its advisory committee recommendations.
Although their terms have expired, the FDA has taken the unusual step of inviting the 2007 advisory committee members to vote alongside their successors at next week’s meeting.
Concerns surfaced in ’07
Concerns about Avandia’s safety were raised in May 2007, when Steven Nissen, chair of cardiovascular medicine at the Cleveland Clinic, and coauthor Kathy Wolski published a report in The New England Journal of Medicine suggesting Avandia increased users’ risk of heart attacks. That term refers to problems related to an inadequate blood supply to the heart, including angina and heart attacks.
In February of this year, an investigation by the Senate Finance Committee concluded that maker GlaxoSmithKline, or GSK, knew of possible Avandia heart risks for several years before publication of Nissen’s study.
In a statement Friday, Murray Stewart, vice president for clinical development at GSK, said the company stands by its conviction that Avandia does not have unique cardiovascular risks.
“Since 2007 we have seen results from six controlled clinical trials looking at the cardiovascular safety of Avandia,” Stewart said, “and together they show that this medicine does not increase the overall risk of heart attack, stroke or death.”
The FDA has compiled a list of eight questions for the advisory panel members to consider. The next-to-last question asks them to recommend a specific regulatory action, ranging from keeping Avandia on the market and removing all warnings on its label about heart attack risk to pulling the drug off the market.
A split decision?
Committee members have their choice of five answers to that question, reducing the odds “of an overwhelming/unanimous vote for any one option,” according to a report released Friday by Concept Capital’s Washington Research Group, which advises institutional investors.
The Concept Capital report speculated that the FDA advisory panel might end up evenly split between allowing Avandia to stay on the market, with additional label revisions and restrictions on prescribing, or taking it off the market.
However, the Concept Capital report said, the most important question might be the one before that: “Based on the available data, please discuss the benefit-to-risk profile of rosiglitazone in the context of other available anti-diabetic therapies.”
As Concept Capital’s Cole Werble, Michael McCaughan and Ramsey Baghdadi write, “this is the critical question FDA decision-makers ask of a therapy that might have serious safety risks when other therapies exist on the market.” The agency did not ask that question of advisory committee members in 2007.
David Graham, the FDA scientist who made headlines in 2004 when he testified before a Senate committee that the agency was not equipped to prevent another Vioxx — the pain-reliever pulled from the market after a study found it increased heart attack risk — said in an interview Thursday that studies consistently have shown that Actos, the only other drug in the same class as Avandia, protects against heart attacks.
On the other hand, Graham says, Avandia, which has never been shown to be more effective than Actos in controlling blood sugar in diabetes, consistently appears to be riskier to the heart in comparisons with other drugs. Graham will be presenting an overview of the research at the advisory committee meeting.
“Really, what is most clinically relevant is the comparison of Avandia vs. Actos in the same study,” Graham said.
In a paper published online June 28 by The Journal of the American Medical Association, Graham and his coauthors analyzed data from 227,571 Medicare beneficiaries who’d been prescribed Avandia or Actos. They concluded that Avandia was associated with a higher risk of stroke, heart failure and death from any cause than Actos.
At the advisory meeting, Graham will report on eight other studies comparing patients prescribed Avandia to those prescribed Actos. All eight, he says, suggest Actos is safer.
To definitively answer whether Avandia increases cardiovascular risk, the FDA asked GSK to conduct the TIDE trial. The trial, which aims to study 16,000 patients in countries around the world, began enrolling participants in May. It is designed to compare the risk of heart attacks, stroke and cardiovascular death in diabetes patients randomly assigned to take either Avandia or Actos. It is also designed to test the impact of vitamin D supplement use on risk of death and cancer.
He called the TIDE trial unethical because “it’s treating humans as if they are laboratory rats. Why on Earth would anyone want to be randomized to Avandia in a clinical trial the purpose of which is to prove with absolute certainty that Avandia increases risk?”
In April 2010, the FDA asked the Institute of Medicine, or IOM, to answer five questions about ethical and scientific issues in studying the safety of approved drugs. The IOM is part of the National Academies, created to advise the government and the public. In light of the Avandia advisory committee meeting, the FDA asked the IOM to answer one question first: “What are the ethical and informed consent issues that must be considered when designing randomized clinical trials to evaluate potential safety risks?”
In a letter released today, the IOM said, “It is appropriate for FDA to require that a properly designed trial be conducted to provide additional evidence about an approved drug’s efficacy and safey” when there is too much uncertainty about risks vs. benefits to make “a responsible policy decision.”
In addition, the IOM said, the FDA should ensure that the trial includes an ongoing, “comprehensive and meaningful” informed consent process. But Graham says the TIDE informed consent process is more like “misinformation.” For example, he says, it does not mention the 2007 advisory committee’s overwhelming vote that Avandia raises heart attack risk or that the American Diabetes Association says Avandia shouldn?t be prescribed.
Graham and colleague Kate Gelperin?s critique of both the TIDE and RECORD trials is among the briefing documents for the advisory committee.
At a news conference Thursday, Deputy FDA Commissioner Joshua Sharfstein said he couldn’t predict when the agency would make a decision based on the advisory committee’s recommendations.
“Obviously, we’re going to have to look at a lot of information,” Sharfstein said. “We’re going to try to make a decision as quickly as we can under the circumstances.”
April 29, 2010
by Alicia Chang
People with a common, obesity-related liver disease that has no known treatment got a surprising benefit from vitamin E pills, researchers reported Wednesday.
It appears to be the first time that a vitamin supplement has been shown to help treat a major ailment not caused by a nutrient deficiency. However, doctors warned that this does not mean people should automatically take vitamin E since some research suggests it might raise the risk of other problems.
The latest study tested it for nonalcoholic fatty liver disease. Fat buildup can cause the liver to become inflamed and scarred over time and in severe cases, to fail.
The disease usually develops in people who are middle-aged and overweight or obese. Up to 5 percent of Americans have the most serious form of it, and as many as 20 percent have fat in their livers but no organ damage.
In the study published online in the New England Journal of Medicine, 247 adults with advanced fatty liver disease were randomly assigned to take a high dose of vitamin E (800 international units), the diabetes drug Actos or dummy pills for nearly two years.
The vitamin and drug were tested because earlier research suggested liver cell deterioration and insulin resistance might be involved in the development of the disease.
Biopsies before and after treatment showed that liver function improved in 43 percent of those in the vitamin E group compared with 19 percent in the placebo group.
“In all honesty, I was surprised,” said the lead researcher, Dr. Arun Sanyal of Virginia Commonwealth University. “A vitamin has not been previously used to cure a serious disease” that is not caused by a deficiency.
Vitamin deficiency has been blamed for a range of health problems from rickets and osteoporosis from a lack of vitamin D to scurvy from not enough vitamin C.
Study participants on the diabetes drug Actos also improved, but to a lesser degree and with a drawback: gaining 10 pounds on average, which remained even after they stopped taking the drug. Four people who took vitamin E developed diabetes, but the study was too small to determine if the vitamin played any role.
The National Institutes of Health was the study’s main sponsor. A U.S. subsidiary of Japan-based Takeda Pharmaceutical provided the drug and California-based supplement maker Pharmavite supplied the vitamin E capsules. Sanyal, the lead researcher, has received consulting fees from Takeda and other drug companies.
Liver expert Dr. Sammy Saab at the University of California, Los Angeles, believes vitamin E could potentially become the initial treatment for advanced cases of the liver problem.
“For patients who are really at risk of progressive liver disease, I think it’s worthwhile. For the vast majority who just have fatty liver, I’m not sure it will help them at all,” said Saab, who had no role in the study.
Dr. Zobair Younossi, executive director of research at the nonprofit Inova Health System in Virginia, said people with nonalcoholic fatty liver disease at the very least should make lifestyle changes such as eating a healthy diet and exercising to shed the pounds.
While vitamin E may help certain people with obesity-related liver disease, “I wouldn’t get started on high-dose vitamin E without discussing it first with a doctor,” said Younossi, who has no connection to the research.
In recent years, hype over vitamin supplements in treating major diseases has not panned out. A 2008 study found that vitamins C and E pills do not ward off heart disease in men and vitamin E even appeared to raise the risk of bleeding strokes. Another study found the same supplements do not help prevent cancer in men.
April 19, 2010
Wall Street Journal
By Alicia Mundy and Jennifer Corbett Dooren
The Food and Drug Administration is weighing whether to halt a safety study involving thousands of patients taking GlaxoSmithKline PLC’s Avandia diabetes drug, a decision that could also determine whether the drug stays on the U.S. market.
Studies during the past three years have tied the medicine to an increased risk of heart attacks. In 2007, the FDA approved a trial comparing Avandia with a rival drug called Actos made by Takeda Pharmaceutical Co. that hasn’t raised as many safety flags.
Some scientists inside and outside the FDA have said it is unethical to compare a drug with known cardiac …
October 26, 2009
By Marni Jameson
By harnessing the power of lifestyle, the following people are managing their Type 2 diabetes without insulin, and in some cases without any medication at all. Some made the commitment when they were first diagnosed, but others reversed a condition that had been spiraling downward for years. Here’s how they did it:
“I’m controlled, not cured, but I’m not going back.”
Aaron Snyder, San Diego
Occupation: Commodities analyst for Shell Oil
Diagnosed: 10 years ago. (Diabetes is diagnosed by a fasting blood sugar of higher than 126 and an A1C of 6.5 or higher.)
Weight then: 220 pounds
Height: 5 feet 6
Background: “I was a math major at UC Berkeley and the pressure was enormous. I solved a lot of problems with food.” One evening, after he went out to dinner with a diabetic friend, she tested his blood sugar out of curiosity. It was 215. His A1C was in the 7s. “I had a long family history of diabetes; I just never thought I’d be part of it.”
Lifestyle changes: Over the next year he lost 50 pounds on a low-carb diet, and 10 more pounds the year after that. His doctor put him on insulin and metformin, a non-insulin medication that decreases the liver’s output of sugar and boosts cells’ ability to metabolize insulin. He began exercising daily.
Today: He still weighs 160 pounds, and sticks to his low-carb diet. Two years ago, he stopped taking all his diabetes medications, and his blood pressure and cholesterol are normal. He works out every day, lifting weights four days a week, and riding a stationary bike 30 minutes three days a week.
Advice: “I wish people understood that what you eat now influences what you want to eat next. A low-carb diet is the best way to curb your appetite and maintain your weight.”
What keeps him on track: His great grandmother had a stroke and lost a leg to diabetes, and his grandfather went blind and died of kidney disease, also due to diabetes. Besides, he adds, “I like how I look now, and more important, how I feel.”
“I went from eating frequently from the vending machine to knowing where all the yoga classes and running trails are around town and shopping at the farmers market.”
Occupation: Cable consultant for Time Warner Cable
Diagnosed: Six years ago
Weight then: 240 pounds
Height: 5 feet 8
Background: While working at a communications call center, Yosha developed gout in his legs and feet, which triggered a toe infection that wouldn’t heal. His doctor suspected diabetes. Tests revealed his blood sugar was 415 and his A1C was approaching 13. His doctor started him on Actos, a drug that helps reverse early diabetes and increase the body’s sensitivity to insulin. He put Yosha on a 1,400-calorie diet and sent him to a hospital-sponsored class.
Lifestyle changes: He took the six-week class “very seriously,” he said. He made losing weight a priority, joined e-diets and downloaded hundreds of healthy recipes. “I learned to cook and shop at the local farmers market.” He got on a strict schedule, and programmed his Palm Pilot to sound every time he was supposed to sleep, eat, check his blood or take his meds. He started walking 2 miles at lunch and after work. He eventually lost 65 pounds and started taking yoga.
Today: He’s medication-free and weighs 175; his A1C is 5.2 and his blood sugar stays around 98. He eats and sleeps at the same time every day. He takes two to four yoga classes a week and walks or jogs 2 to 8 miles a day. Last December, his employer sponsored him to run the O.C. half-marathon. He ran the 13-mile race again in May.
Advice: “Make moving more [of] a habit. I park on the top floor of my office’s parking structure . . . and I pick the farthest parking space at the shopping center.”
What keeps him on the program: “I will do anything to avoid that terrible foot pain I had. I had uncles lose limbs to diabetes. I never want that to happen to me.”
“Don’t underestimate the body’s potential to heal on its own.”
John Burgess, Irvine
Diagnosed: 18 years ago
Weight then: 220 pounds
Height: 5 feet 11
Background: For a long time Burgess controlled his disease with diet and exercise, but eventually he needed medication. He started taking metformin and Actos, and ultimately, in July 2007, insulin, which caused weight gain. By December 2008, he weighed 250, had become more insulin resistant and needed medications to manage blood pressure and cholesterol. His sedentary job didn’t help. He ultimately needed the strongest insulin available, five injections a day of U-500. In six months he gained 50 more pounds, peaking at 305. In July 2009, he saw Dr. Wei-An Lee.
Lifestyle changes: Lee put Burgess on a strict, 700-calorie-a-day diet. One week later he was off all insulin. After two weeks, he graduated to a 1,000-calorie diet, and added some exercise. He got a pedometer and aimed for 5,000 steps a day. He lost 84 pounds in 85 days. All his numbers, which he charts meticulously, have improved.
Today: He weighs 211 pounds, has dropped eight prescription meds in three months, including all his diabetes medications, two blood pressure medications, and medicine for his triglycerides. He’s halved his cholesterol medication. He does 5 1/2 miles a day on the elliptical and sometimes runs an additional half a mile on the treadmill, for a total of 6 miles. He focuses on carb control and relies on Lean Cuisine. “Last summer I couldn’t walk 100 steps; now I’m jogging.”
Advice: Because taking clients to lunch is part of his job, he looks at the restaurant’s menu online and when possible, the nutritional content of certain dishes, so he can decide in advance what to order. If he can’t get the nutritional information, he orders meat and vegetables.
What keeps him on track: Results. “The program sounds drastic, but sticking with it is easy when you understand the payoffs.”
“I’ve had plenty of Ben & Jerry’s Ice Cream, plenty of cocktails; now I just want to live.”