March 2013

Cover story by Francis James B. Gatdula

Cover illustration by Arjane Encarnacion

CME Digest – February 2013

Is JNC 8, ATP 4 guidelines ever coming out?

JNC 8, ATP 4 will be mainly evidence-based, not eminence-based

Many practicing clinicians are eagerly awaiting the 8th report of the Joint National Committee on the Detection, Evaluation, and Treatment of Hypertension (JNC 8), as well as the other guidelines including the 4th report of the Adult Treatment Panel Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP 4).

Browsing on the National Heart, Lung, and Blood Institute (NHLBI) website, one reads a table that tracks the progress of three “expert panels” and two “working groups” charged with devising an overarching, interdependent set of guidelines for reducing cardiovascular risk in clinical practice.

According to the table, the expert-panel recommendations on blood pressure, cholesterol management, and obesity, are at different stages of review and are nearing completion. But many would say that this advisory that the guidelines are nearing completion have been issued since several years ago, and many have expressed their impatience about the seeming lack of transparency of the process.

The ATP 3 document came out in 2001 yet, with an update in 2004. JNC 7 was released in 2003 with no updates. The first Managing Overweight and Obesity in Adults: Report from the Obesity Expert Panel (Obesity 1) was published way much longer – in 1998.

“When no new guidelines come out on blood pressure and cholesterol risk assessment for so many years, people start to wonder whether there are controversies or anything new and that maybe we shouldn’t bother as much with risk-factor management. Nothing could be further from the truth,” Prof. Roger S. Blumenthal, MD, of the Johns Hopkins University, in Baltimore, Maryland, was quoted in a Heartwire publication report. “It’s time to move forward. It’s not fair to all the people on the committees who did the hard work to have it drag on.”

The NHLBI website advises that drafts of JNC 8 and Obesity 2 have yet to be reviewed by at least three separate bodies before they’re ready for public comment.

According to Dr Suzanne Oparil, internationally renowned book author on hypertension from the University of Alabama at Birmingham, and co-chair of the JNC 8 expert panel, the hypertension report has had so many “false starts” by various societies announcing its release, and these raised but subsequently dashed expectations have likely added to the frustration of many.

Dr. Oparil said that the delays are partly due to a new set of procedures followed in developing the guidelines. It was also decided that the guideline statements are going to be almost entirely evidence-based, not “eminence-based,” as some would describe opinions or recommendations of experts.

“We’re trying to use strictly what’s in the literature based on randomized controlled trials of blood-pressure treatment and not rely too heavily on the opinions of the panel members,” said Dr. Oparil. She added that meta-analyses and observational studies have not been as strongly considered as in previous guidelines. In fact, they have been “mostly left out.”

Furthermore, limitations in budget has also hounded the expert panel. “This is a government document,” she said. “We didn’t have resources for a lot of face-to-face meetings, so everything was done by teleconference and sometimes videoconferencing. That’s somewhat more cumbersome—if you spend a couple days together you sometimes get more done than if you spend, say, 90 minutes every week,” added Dr. Oparil.

She assured that the delays occurred “not because there’s a lot of conflict,” and in general, there is agreement in most of the recommendations which were supported by evidence.

The good news though is that JNC 8 “is in the home stretch,” assured Dr. Oparil, and its release is hopefully this spring. The draft just needs to be “integrated, to some extent, with the work of the other panels” and then reviewed by other government-sponsored panels before the public’s comments are asked.

For ATP 4, insiders say that an LDL goal of <70 mg/dL has been recommended, but whether or not it is adopted as the official primary target in ATP 4 remains to be seen.

There have been several updates from 2004 to 2011 in lipid guidelines wherein an LDL goal of <70 mg/dL—based on randomized trials—has evolved as an optional target in patients with coronary heart disease and other high-risk patients. With Heartwire & NHLBI reports

Last Call – February 2013

Time to Reward Thy Self, Santa

By Saturnino P. Javier, MD, FPCP, FPCC, FAC

Just a few days after New Year’s Day, my eldest son, Luigi asked me to accompany him to get some casual walking shoes in some shops in Makati. By then, many shops were offering huge discounts on their rack merchandise – by as much as 70 percent off the actual retail price. My 12-year-old daughter Sofia joined us later in the day and she exclaimed, “How could anyone let that opportunity pass?” Never mind that there was really very little need for the merchandise – whether it was a shirt, a pair of shoes or toiletries.

I guess many of us sometimes find it hard to resist the marketing wizardry and sales pitch of most department stores and malls, especially after the holidays.

It is a shrewd marketing strategy when stores would slash the price of an item by half the price to entice the customer to purchase it. The unsuspecting and initially unwilling customer who bites the bait of a markedly reduced item now feels empowered financially since he has been able to save from this purchase and, thus, ready to procure another discounted item (even if frivolously at all). In the end, the same customer will probably end up spending more than what he originally intended.

For many of us, the whole holiday season must have been spent looking for presents for everyone we remember and care for, think about, and thank for the year that was – the family, the house help, drivers, secretaries, mentors, colleagues, friends, co-workers, and subordinates among others. The many days before the Yuletide season must have been devoted getting something for everyone and anyone – except thy self.

In the holiday frenzy that sent traffic to a standstill, the malls to a sea of humanity and the parking areas to chaos, the race to the cash register to obtain presents for those we care about was a tedious challenge. How much of that purchase was driven by fatigue and time constraints (“I just want to get this over and done with.”), sincerity (“She will truly appreciate this.”) and financial constraints (“I better get this for him because it is on sale.”) is subject to lengthy dissertation, which the recipient will probably never ever know.

Come Christmas time, many of us watched at the sides as others excitedly opened the presents we had painstakingly obtained for them. We smiled at the thought that someone liked our gifts, we were elated at the sight of the driver eagerly trying on his new shirt, and we gloated at the compliments thrown our way for the best paella we sent (ordered for) them.

In the gift-giving melee of the season, many of us appropriately took the back seat. The syndrome of “I, me and myself” was relegated to the background. As the cliché goes, it is infinitely better to give than to receive. Playing Santa Claus to others surely brought out the true Christian in some of us.

But pray tell! Who does not want to be at the receiving end, too? Who does not want to open a handsomely wrapped package adorned with multi-hued glittering ribbons, bearing a personalized gift card embodying the heartfelt greetings of the Christmas season?

I always get ribbed no end by the children when my concept of wrapping gifts is requesting the secretary or the house help to buy those ubiquitous ready-to-use Christmas bags – or the “instant” package – that just requires a little tape to fasten and seal the contents from immediate scrutiny. Someone once expressed disdain for such Christmas bags saying it is the laziest and most impersonal way to gift someone you care about. I apologize that I have yet to abandon this practice totally.

When the Christmas dust has settled (or the drizzle has stopped), the holiday frenzy has ebbed, the alcohol has waned off and the lechon stains on the shirt have been washed off, what now, Santa Claus? Should this now be a time for Santa to reward thy self? A time for self-gifting – since after all, he has been good during the season?

Alas! Self-gifting is now an increasing trend in the world. As some consumer studies have documented, there has been an increase in the incidence of people who feel they ought to reward themselves by self-gifting. Retail experts and economists have reasoned out that tougher economic times have somehow driven consumers to justify buying presents for themselves by availing of the generally steeper discounts during the holidays.

(To be concluded in the next issue)

A Dose of Faith – February 2013

Healing Wonders of Love
By Richard G. Mendoza, MPH, PhD

In May 1996, Reader’s Digest featured the story of newborn twin girls who were in separate incubators of a hospital. One was not expected to survive. Going against hospital policy, an insightful nurse placed the ill baby with her sister in one incubator. Very soon, the healthier twin placed her little arm over her sick sister, tenderly embracing her. Not only did the smaller twin’s heart rate stabilized, but her temperature normalized as well! Both babies survived and thrived! As a result, this hospital changed its policy and now puts twins together in the same incubator – warmer, as they were in the womb.

Whoever said, “A hug a day keeps the doctor away” must have understood the power of a hug and a loving touch. They help to take away pain, promote sleep, relieve stress, strengthen family relations, boost the body’s immune system, fight against disease, take away depression and more. Hug as an expression of love, heals.

Many researches have already been done about the healing wonders of love. One study seems to indicate that a lack of love is an almost certain recipe for health problems and early death. A Swedish study followed seventeen thousand men and women aged twenty-nine to seventy-four for six years. Those most lonely and isolated had almost four times the risk of dying prematurely during this period.

A Duke University research led by Dr. Redford Williams, which studied almost fourteen hundred men and women who underwent coronary angiography with severely blocked coronary arteries, found that five years later, 50 percent of those who were unmarried or had no confidant were dead. They were more than three times as likely to have died as those who were married or had a confidant. Other studies indicate that people who are shown affection are less likely to see a doctor or feel sick. They also report a zest for life, love for work, and a sense that their existence is meaningful.

In his book, Love and Survival, Dr. Dean Ornish states, “Our survival depends on the healing power of love, intimacy, and relationships… I have found that perhaps the powerful intervention is the healing power of love and intimacy, and the emotional and spiritual transformation that often result from these. Love and intimacy are at the root of what makes us well, what causes sadness and what brings happiness, what makes us suffer and what leads us to healing.”

It has been said that, “the greatest human need is to be loved”. Once a person feels loved, this produces not only the physical healing but also the emotional healing as well. No one can claim that nobody loves him for there is Someone who loves everyone. He even gave the life of His son to express His love (John 3:16).

I wish I can cite more studies to prove the healing wonders of love, but my column space won’t permit this. So, I will just share with you what I got from the Internet site, Tommy’s Windows. May you experience healing from this message
of God’s love:

CME Nuggets – February 2013

CHOP Therapy for Indolent Lymphoma Eclipsed by Bendamustine

By Ed Susman

Atlanta, Georgia–Researchers suggest that the combination treatment for indolent non-Hodgkin’s Lymphoma, known as CHOP, is rapidly being replaced by the drug bendamustine.

CHOP – cyclophosphamide, doxorubicin, vincristine and prednisone – accounted for just 16 percent of treatment for patients with indolent lymphoma while bendamustine is part of the first-line therapy in 71 percent of patients, said Wolfgang Knauf, MD, professor of hematology at Onkologische Gemeinschaftspraxix, Frankfurt/Main, Germany.

Most often, CHOP and bendamustine are combined with rituximab, resulting in the R-CHOP or R-bendamustine acronyms. But soon, doctors may only be talking about the latter.

“R-CHOP is dead,” Dr. Knauf said at his poster presentation during the 54th annual meeting of the American Society of Hematology. “The registry data we are showing is a description of what is going on in Germany.”

The registry is recruiting 1000 patients with indolent lymphomas; 1000 with chronic myelogenous leukemia; 500 with myeloma and 1000 patients with aggressive lymphomas. He said that the researchers in Germany expected to (be able to) present the outcome of the data next year, but he cited recent clinical trials that showed an advantage for patients treated with bendamustine-based regimens when compared with CHOP-based treatment schedules.

Knauf said that rituximab is used in 94 percent of treatment of the 645 patients in the registry who are diagnosed. It is combined with bendamustine in 66 percent of the cases. Bendamustine-rituximab was employed 428 times. Another two percent of doctors used bendamustine as a monotherapy.

As a second-line therapy, bendamustine again is used more often than CHOP, Knauf illustrated. Of those 121 cases, rituximab was administered to 102 patients; bendamustine was used in 82 patients – in combination with rituximab in 72 patients. Rituximab-CHOP was used as a second line treatment in nine patients.

“Our message, as of now, is that rituximab-CHOP can no longer be considered as a standard-of-care,” Knauf said.

While the role of CHOP therapy is diminished, its obituary might be premature, said Andre Goy, MD, chief of the lymphoma division at Hackensack University Medical Center in New Jersey.

“There is no question that the progression free survival is dramatically different with bendamustine,” Dr. Goy said. “We have to be careful the way we look at these data. There was no difference in complete response rate and in overall survival. Progression free survival in follicular lymphoma does not necessarily translate into overall survival. And there are some hints that bendamustine may be a bit more toxic than its perception.”

The real world of Gleevec

In the real world, treatment of patients on imatinib (Gleevec) works as well in patients with chronic myelogenous leukemia (CML) as in clinical trials – but doctors at the community hospital level may not be testing their patients enough, researchers reported.

In one study, about 75 percent of patients (who were treated in clinical trials) and about 75 percent of patients (who declined to be in a trial) – but were both on imatinib – achieved event-free survival at 10 years (P=0.860), said Musa Yilmaz, MD, clinical fellow in leukemia at the University of Texas MD Anderson Cancer Center, Houston.

“These results suggest that patients with CML treated outside a clinical trial may have the same excellent outcome as those treated on a clinical trial – provided they are managed and followed with the same rigor,” Dr. Yilmaz said.

However, in a second study, researchers found that after six months, 37 patients on imatinib at community hospitals had achieved either a major molecular response or a complete molecular response – yet just 21 of these patients (57 percent) had undergone testing within six months from achieving those responses, said James Gilmore, PharmD, vice president of Georgia Cancer Specialists, Atlanta, a group of 40 practitioners. That is despite guideline recommendations of such a monitoring test every six months.

“Our retrospective review of patients with Philadelphia chromosome-positive chronic phase CML receiving imatinib in a community outpatient setting found there is under-monitoring of treatment response,” said co-author Mansoor Saleh, MD, director of clinical research at Georgia Cancer Specialists. “This may result in under-detection of patients with treatment resistance or suboptimal response which limits the ability to modify or switch tyrosine kinase inhibitor treatment accordingly and ultimately compromises patient outcomes.”

The researchers noted that among 36 patients in their study, who were compliant with monitoring guidelines, there was no indication of disease progression or death. Among the 98 patients who were not in monitoring compliance, 10 had progression of the disease. Three had progressive disease and seven died.

In the MD Anderson study, Dr. Yilmaz and colleagues identified 71 patients who were treated with imatinib as per clinical trial protocol and 65 patients who were treated off protocol. “I compared patients who were treated with 100 mg of imatinib in a clinical trial versus that out of a clinical trial,” he told MedPage Today at his poster presentation. “We thought that the treatment of people treated on protocol and off protocol should be the same, right? That’s what we wanted to determine.

“There is controversy over whether patients off protocol who are not followed as strictly as those in a clinical trial would have the same results. We are reporting that we observe no differences in outcomes.”

In commenting on the studies, Stuart Goldberg, MD, chief of the leukemia division at John Theurer Cancer Center at Hackensack University Medical Center, New Jersey, said, “Imatinib, dasatinib (SpryCel), nilotinib (Tasigna) – all these medicines work well in chronic myelogenous leukemia. “The key to success in treating CML is not the drugs,” he said. “They work. The key to success is the skill of the doctor to perform the necessary tests.”

He suggested that in community hospitals, CML is uncommon and doctors may not be familiar with the critical value of testing. “When the patient is not properly monitored, the first time you realize something is wrong is when he or she loses their hematologic response and move into blast crisis and the patient may die. If you monitor the patient properly, you can spot signs of changes in response and you can intervene. By monitoring, you can catch problems before they become clinically significant. If it becomes clinically significant, it’s too late.”

New drug shows promise

An all-oral regimen for treatment of patients newly diagnosed with multiple myeloma appears active and tolerable. Weekly oral doses of MLN9708 resulted in 58 percent of 64 evaluable patients in the Phase 1/2 trial achieving either a complete response in eliminating detectable M-protein (23 percent) or a very good partial response (35 percent), said Shaji Kumar, MD, associate professor of hematology and medicine at the Mayo School of Medicine, Rochester, Minn.

“The all-oral combination of weekly MLN9708 (ixazomib citrate), lenalidomide, and dexamethasone appears to be generally well tolerated,” Dr. Kumar said in his oral presentation at the meeting that has drawn more than 20,000 blood disorder specialists and allied healthcare professionals.

He said the study was the first attempt to initially treat multiple myeloma with a front-line oral therapy. The researchers enrolled adults with performance status of 0-2 and adequate liver, kidney and hematologic function. They also had to have measurable M-protein in their blood and urine. Patients were not eligible if they had Grade 2 or greater peripheral neuropathy, prior or current deep vein thrombosis or pulmonary emboli or prior systemic multiple myeloma therapy.

Median age was 50 years and about 55 percent of the patients were men. The dose limiting toxicity was established at 2.97 mg/m2 noted as an urticarial rash. The researchers went forward with a recommended Phase 2 dose of 2.23 mg/m2. One person died on the study drug of underlying pneumonia caused by respiratory syncytial virus after cycle 4. It’s considered possibly related to treatment; alternatively related to underlying disease state. Peripheral neuropathy was reported in 21 patients. Grade 3 peripheral neuropathy was reported by two patients.

The median time to response was about one cycle,” Dr. Kumar said. “The duration of response has not yet been reached.” The median time on the regimen was about six months. He suggested that more patients would move into the complete response of very good partial response with time. He said similar responses were seen in patients with favorable and unfavorable cytogenetics.

“At data cut-off, with a median drug exposure of six months, 92 percent of patients overall had achieved partial response or better,” Dr. Kumar said.

For comments, write me at edwardsusman@cs.com

February 2013

Cover stories by Dr. Reuben Ricallo, Emil Karlo A. dela Cruz, Michaela Sarah de Leon,Francis James B. Gatdula, Mylene C. Orillo

Cover illustration by Carla Gamalinda

Addressing Obesity Among Filipino Children

By Sen. Edgardo J. Angara

Over the years, the prevalence of obesity and obesity-related diseases among children in the country has risen sharply. The numbers have doubled over the past couple of decades and tripled over the last 30 years. A report by the World Health Organization (WHO) shockingly reveals that over 3 million children in the Philippines are overweight or obese.

The idea that big kids are healthy kids no longer holds true. A big child used to be a sign of wealth and prosperity and was never seen as a bad thing.
Today, childhood obesity is being regarded as the newest form of malnutrition, which has affected not only the affluent Western countries, but also the Asian countries like the Philippines, as it poses numerous health risks.

A considerable number of our school-aged children are overweight. According to studies, children who are fat between the ages of four to 11 tend to carry the problem into adulthood. If left unchecked, the current generation of children will have a shorter life span than their parents because they are at greater risk of contracting a myriad of diseases such as type II diabetes, hypertension, stroke, cancer, metabolic disease, respiratory diseases, liver disease, and coronary heart disease.

Inadequate physical activity, hormonal conditions and poor nutrition are often cited as the culprits for the rapid increase in obesity among children. For me, the lack of concerted action to address the disturbing levels of obesity in the country should also be blamed. We have to develop various strategies to lessen this condition along with the health hazards associated with it.

Last year, I launched what I believe is one of the most meaningful and viable health advocacies in the country: the “Oh My Gulay! (OMG!)” campaign, which pushes for ensuring the proper nourishment of children, especially those in elementary school.

This project aims to impart the importance and advantage of eating vegetables as a solution to malnutrition. Through planting squash, string beans, eggplant, tomato, bitter gourd, and other crops, children have access to nutritious food.

According to the World Hunger Education Service, there are two types of malnutrition. The first is the protein-energy malnutrition or the lack of protein and food that provides energy which is referred to when world hunger is discussed. The other type is the micronutrient (vitamin and mineral) deficiency, which may cause obesity.

Obesity, therefore, is not a result of lack of calories but excessive calories and poor nutrition. Hence, we need to encourage our schoolchildren to consume vitamin- and mineral- enriched food like fruits and vegetables to prevent obesity and other related diseases. Aside from this, the government should also adopt an international manual for the monitoring of the marketing and selling of food to schools.

More importantly, we should teach our kids the importance of proper nutrition as well as the diseases that they may acquire as a result of poor diet and sedentary lifestyle. This may be done by incorporating health and nutrition modules into our basic educational curriculum as I believe that proper information and education are the most important steps in preventing obesity in children.

Email: angara.ed@gmail.com Web site: http://www.edangara.com

Last Call – January 2013

How the Holidays Can Be Bad for the Heart

By Saturnino P. Javier, MD, FPCP, FPCC, FAC

The Philippines has the distinction of having the longest Christmas season (and, thus, the longest holiday) in the world. It is customary to see malls and shops putting up Christmas decorations and hear Christmas carols being played as early as September. Morning programs immediately start a countdown to Christmas day as early as October.

Holidays are expectedly associated with conditions and situations that pose threats to wellness and health. They are synonymous with partying, excessive drinking and overeating. Ironically, the supposedly ‘holy’ days bring about an abundance of health ‘sins’ – alcohol, salt, sweets, smoking, stress, sleeplessness, even ‘shabu’ and other drugs.

In another column, I wrote about the benefits one may get from wine and alcohol when taken in moderation. The American Heart Association (AHA) maintains that moderate alcohol consumption, which is one to two drinks per day, is associated with a reduction in the risk of death from cardiovascular disease.

Drinking excessive alcohol can raise the level of some fat molecules in the blood, particularly the triglycerides. Alcohol products also have calories which can lead to obesity and thus a greater predisposition to diabetes. Furthermore, some binges of excessive drinking can lead to undue increase in blood pressure and stroke.

In fact, there are conditions that are specifically related to holidays. Holiday heart syndrome is the occurrence of irregular heartbeats brought about by a binge of alcohol consumption during a holiday drinking spree. It can occur in individuals with or without known heart disease. Stress, dehydration and undue excitement can all contribute to a heightened predisposition to having an episode of this holiday phenomenon.

While generally not serious, the palpitations that an individual experiences can lead to an emergency room visit. The most common irregularity is called atrial fibrillation where the heart rate can go up to as high as 600 beats/min (the normal is 60-100).

The irregular rhythm or “arrhythmias” usually resolves in less than 24 hours, especially in those whose hearts basically have no structural abnormalities. It generally does not require maintenance therapy, but one must keep in mind that a similar alcohol exposure can trigger the same bout.

There are some studies which indicate that these “ber” months of the Christmas season are, in fact, associated with deadlier heart attacks compared to other months of the year. In other countries, where the cold winters take its toll on the people during the holidays, the cold season is another factor thought to contribute to the increased incidence of heart attacks and strokes aside from fatty foods, alcohol, depression and emotional stress. Additionally, reduced hospital staffing and absence of medical professionals could be considered as aggravating factors.

A study by Kroner, published in Circulation 2008, indicated that deaths from heart attacks increased by 33 percent during the months of November to January – with its peak on Christmas and New Year’s eve. The authors explained that the increased incidence of heart attacks was brought about by the well known effect of stress on the release of chemicals (catecholamines) in the body. These can increase the blood pressure and heart rate which have deleterious effects on the heart and blood vessels.

A related 2004 study in the Tufts University School of Medicine that examined 53 million death certificates from 1973 to 2001 at the University of California in San Diego indicated a five percent increase in deaths involving heart conditions during the holiday season. Christmas alone was associated with a 12 percent increase in deaths and illness, with heart disease as the main cause.

This is further validated by a 2004 Harris Interactive survey, which established that about 80 percent of adults suffering from high blood pressure in the United States engaged in unhealthy behavior during the holiday season, which expectedly placed them at risk of a heart attack. The survey showed that these people ate about 60 percent more than usual while their levels of stress mounted by about 50 percent.

This should not really come as a surprise, given how holidays and celebrations have a way of making everyone, with or without a heart condition, throw caution to the wind. When complacency and stubbornness set in, many things are bound to happen. Physicians’ visits are cancelled or postponed for later dates. Prescription refills are missed. Regularity of drug intake goes haywire.

In congested cities like Metro Manila, the situation is worsened by the perennial holiday rush that creates the deadly mix of overcrowding, heavy traffic, frayed nerves and temper outbursts.

Furthermore, the extremely clannish Filipino culture brings about depression and added stress for those whose relatives and loved ones are gone, or are working and living in another country. All these are key elements for developing acute heart conditions.

For comments, spjavier2958@yahoo.com

A Dose of Faith – January 2013

What Lies Ahead?

By Richard G. Mendoza, MPH, PhD

The year 2012 is a mixture of good and bad events for our country. Better economic growth, fight against corruption, better awareness on health issues, and the passage of beneficial laws are just some of the blessings we’ve received. Pacquiao’s knock-out, the death and destructions brought by typhoon Pablo, unresolved crimes, the high price of goods, and unemployment are a few of the misfortunes. But it’s a good year for us Filipinos in general. Let’s hope and pray that the momentum could be sustained until 2013. May the “daang matuwid” (righteous path) continue to thrive under a lively and vibrant democracy.

But who knows what lies ahead? Definitely not the psychics, whose predictions are based on statistical probability. Nor the card-readers or the self-proclaimed prophets, who make guesses than prophecies and sound more cultic. Only an omniscient being knows the future. The term “omniscient” refers to the all-knowing nature of God. Webster defines it as “the quality of knowing all things at once; universal knowledge; knowledge unbounded or infinite.” Omniscience is the attribute of God by which He perfectly and eternally knows all things which can be known – past, present, and future. He knows our very thoughts, our feelings, our desires and our needs. He knows our words before we say them and he knows our thoughts before we think them. He knows all of our ways. In fact, God even knew us before we were born.

The Bible says: 1.) O Lord, you have searched me and you know me; 2.) You know when I sit and when I rise; you perceive my thoughts from afar; 3.) You discern my going out and my lying down; you are familiar with all my ways; 4.) Before a word is on my tongue you know it completely, O Lord; 5.) You hem me in – behind and before; you have laid your hand upon me; 6.) Such knowledge is too wonderful for me, too lofty for me to attain; 13.) For you created my inmost being; you knit me together in my mother’s womb; 14.) I praise you because I am fearfully and wonderfully made; your works are wonderful, I know that full well; 15.) My frame was not hidden from you when I was made in the secret place, when I was woven together in the depths of the Earth; 16.) Your eyes saw my unformed body. All the days ordained for me were written in your book before one of them came to be.” Psalms 139:1-6, 13-16 (NIV)

There are no secrets before the Almighty God. He knows what lies ahead for the world, for our country, for you and me. Through the Bible, in the form of prophecy, God accurately foretells the future. “… I am God and there is none like Me …declaring the end from the beginning, and from ancient times things that are not yet done …” Isaiah 46:9, 10. Yes, as God pulls back the curtain of time, He is giving us a glimpse of the future. Before Babylon reached the height of its power and glory, God in His Book foretold its fall: “And Babylon, the glory of kingdoms, the beauty of the Chaldeans’ pride, will be as when God overthrew Sodom and Gomorrah.” Isaiah 13:19. The Bible even foretold the power that would overthrow this mighty kingdom. “…The Lord has raised up the spirit of the kings of the Medes. For His plan is against Babylon to destroy it…” Jeremiah 51:11

The name of the man who would lead the armies against Babylon was prophesied 150 years before his birth, as was the very way he would do it. “Thus says the Lord to His anointed, to Cyrus … I will … open before him the two leaved gates…” Isaiah 45:1. Were these prophecies fulfilled? To the very letter! In the Persian Hall of the British Museum stands the Cyrus cylinder—discovered in the ruins of Babylon. On this clay cylinder, Cyrus tells of his conquest! The details are accurate! The Bible not only foretold Babylon’s destruction, it further stated: “Babylon shall become heaps …” Jeremiah 51:37

Isaiah wrote: “It shall never be inhabited…but wild beasts of the desert shall lie there … and owls shall dwell there …” Isaiah 13:20, 21

What lies ahead before the second coming of Christ is foretold in the 24th chapter of Matthew. War, famine, pestilence, and natural disasters are some of the signs.

But the Bible does not foretell what will happen specifically to our country this year 2013. But God knows what lies ahead and we don’t. Thus, we can face the future unafraid, if we believe that our life is in His hands.

In the coming year of uncertainty we can only cling to God by faith. This prayer-poem by Martha Snell Nicholson could be our supplication too.

The New Year
Dear Lord, as this new year is born
I give it to thy hand.
Content to walk by faith what paths
I cannot understand.

Whatever coming days may bring
of bitter, or gain.
Or every crown of happiness:
Should sorrow come, or pain.

Or, Lord, if all unknown to me
Thy angel hovers near
To bear me to that farther shore
Before another year.

It matters not,- my hand in Thine,
Thy light upon my face.
Thy boundless strength when I am weak,
Thy love and saving grace!

only ask, loose not my hand,
Grip fast my soul, and be
My guiding light upon the path
Till, blind no more, I see!

CME Nuggets – January 2013

Long-term Benefits with Tamoxifen in Breast Cancer

By Ed Susman

San Antonio, Texas–Tamoxifen adjuvant therapy for women diagnosed with breast cancer appears to be a treatment that gets better with age, researchers said here at the 35th annual San Antonio Breast Cancer Symposium.

Fifteen years after initial therapy with tamoxifen, women who had received the endocrine therapy for 10 years had significantly better survival than women treated with tamoxifen for five years, said Richard Gray, MSc, professor of medical statistics at Oxford University in the United Kingdom.

In presenting the results of the ATLAS (Adjuvant Tamoxifen: Longer Against Shorter), Gray demonstrated that treatment with tamoxifen benefitted patients over no treatment, but there was no apparent addition advantag of treatment in patients over five-nine years, who discontinued tamoxifen after five years. But when the researchers reviewed the outcomes after 15 years, there was a significant difference.

Gray explained that in comparing women on five years of tamoxifen versus those not on tamoxifen at all, there was a 29 percent reduction in the risk of breast cancer death (P=0.00001) after years 0-4.. After five-nine years, the risk of breast cancer death was reduced by 34 percent (P=0.00001). And after 10-plus years, the women on tamoxifen had a 27 percent reduced risk of breast cancer death (P=0.0001) compared to women who were not on tamoxifen to start.

When comparing women who took 10 years of tamoxifen to those who took five years of therapy, there was no difference
after five years; and a three percent non-significant difference after 10 years, but a 29 percent difference after 10 years in favor of longer use of tamoxifen (P=0.0016).

When comparing a 10-year usage of tamoxifen to women who did not have tamoxifen at all, the risk of breast cancer death was reduced to 29 percent in years 0-4; reduced 36 percent in years five-nine, and reduced 48 percent in years 10-14.

The absolute reduction in mortality by 10 year use of tamoxifen was 12 percent, Gray said, which was a far greater benefit than a loss of 0.4 percent due to endometrial cancer – a 30-fold difference. “The risks of taking long term tamoxifen are far less than not taking tamoxifen,” he said.

Risk for death from breast cancer five to 14 years after diagnosis was 12.2 percent among those who continued use versus 15 percent among those who stopped — an absolute gain of 2.8 percent. “The greatest benefit during 10 to 14 years after diagnosis,” Gray said.

The trial accrued 12,894 women, but he reported only on those with estrogen- receptor positive disease, a total of 6846 women.

Something new for breast cancer

In another exciting presentation, researchers demonstrated that the investigational cyclin-dependent kinase 4/6 inhibitor (with the catchy name of PD 0332991) when combined with letrozole in first-line treatment appears to dramatically increase time to progression among estrogen-positive, HER2-negative advanced breast cancer patients.

When PD 0332991 was added to letrozole, median time to disease progression was 26.1 months among the 84 women treated with that combination compared to 7.5 months’ time to progression among 81 women treated with letrozole alone (P<0.001), said Richard S. Finn, M.D., associate professor of medicine at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. “These results are significantly and clinically meaningful,” Dr. Finn said. The Phase II trial is sponsored by Pfizer, the developer of PD 0332991. Dr. Finn said a Phase III trial with the combination is to begin in 2013.

The combination is generally well-tolerated with uncomplicated neutropeniaas the most frequent adverse event, he said.

He explained that PD 0332991 is an oral, highly selective inhibitor of the cyclin-dependent 4/6 kinase activity that prevents cellular DNA synthesis by prohibiting progression of the cell cycle from G1 to S phase

The median age of the women was about 63 years and all were in 0-1 performance status. About 30 percent of the women had experienced recurrence following adjuvant therapy within a year.

About 34 percent of those on the combination achieved an objective response compared with 26 percent of letrozole alone. The only complete response was observed with a woman on letrozole monotherapy. Seventy percent of the patients taking PD 0332991 achieved clinical benefit from treatment compared with 36 percent of those just on letrozole.

High dose works better

In another study, treatment with a higher dose of fulvestrant – 500 mg in two infusions verse 250 mg in one infusion on days 0, 14, 28 and every 28 days thereafter – appears to be a more successful option in treating post-menopausal women with advanced breast cancer.

In looking at the mature results of the so-called CONFIRM trial – after 75 percent of the original population had died – the median time to death was 26.4 months compared to 22.3 months with fulvestrant 250 mg. However, Angelo DiLeo, MD, PhD, head of the department of medical oncology at the Hospital of Prato, Istituto Toscano Tumori in Italy, explained that the p=0.016 does not’ necessarily indicate significance due to the non-prespecified nature of the analysis.

The pre-specified analysis was performed after 50 percent of the patients in the studied had died, and in that analysis there was no difference in treatment arms (P=0.091). Originally 362 patients were assigned to 500 mg fulvestrant and 374 women received 250 mg fulvestrant.

Dr. Di Leo noted that because the tolerability of the two doses was similar, he would recommend using the higher dose of fulvestrant in women who were candidates for the treatment.

Sentinel node biopsies

In two other trials at the meeting which drew more than 7,500 clinicians, specialists and other allied health care professionals, researchers discussed treatment with sentinel node biopsy.

In one trial, researchers determined that performing sentinel node biopsy on women post-chemotherapy was associated with a false negative rate of more than 12 percent — a greater percentage than most clinicians would be comfortable with — when considering when a full axillary lymph node dissection was necessary.

Judy C. Boughey, MD, associate professor of surgery at the Mayo Clinic in Rochester, Minn., suggested that the improvement in diagnosis using the sentinel lymph node could be accomplished by using dual tracers or resecting a minimum of two sentinel lymph nodes. That would have brought the false negative rate down to around 10 percent, she said.

In the second study, researcher said that black women appear to undergo sentinel lymph node biopsy procedures at a rate that occurs less often than Caucasian women, said Dalliah Black, MD, assistant professor of surgery at the University of Texas MD Anderson Cancer Center, Houston.

Reviewing database information on breast cancer surgery, Dr. Black found that from 2002 to 2007, black women were consistently about 12 percent less likely to undergo the treatment, and were also more likely to develop lymphedema than white women.

Dr. Black said the reasons for those differences are unclear, but might have to do with lack of access to sentinel node therapy at individual hospitals, patient preference of physicians preference – considerations beyond the scope of the database.

She said that researchers are scrutinizing data to see if obesity and body mass index – generally higher in black women than in whites – may account for the discrepancy in lymphedema. Obesity is a risk factor for that complication from axillary dissection.

For comments, write me at edwardsusman@cs.com