05/31/16

To Be or Not to Be Bipolar

53409894_sOn The Oprah Winfrey Show in October 2007, Sinéad O’Connor disclosed that she had been diagnosed with bipolar disorder in 2003. The website, “Famous Bipolar People,” said Sinéad had suffered from depression and had thoughts of suicide since the age of 23. She also experienced voices urging her to harm herself. The voices got so loud, she said, she took herself to hospital. She was put on antidepressants, which helped. “These all confirmed that she had bipolar disorder.” Then a few years ago, she went public with an announcement that she had been misdiagnosed with bipolar disorder for eight years.

During her interview with Oprah, she said she didn’t think she was born with bipolar disorder. She thought her illness was caused by a number of outside pressures. “I believe it was created as a result of the violence I experienced.” She was scared to take the medication at first. But she realized that she had nothing to lose, so she tried them. “It was brilliant because I felt this huge hole. And when I took the meds, within half an hour, it was literally like I felt concrete coming in to fill the hole.” She said she thought she had died and then was ‘born again’ as a result of taking the meds.

But after spending eight years on the medications, she realized her depression was still there. Additionally, “some of the same problems she’d had before being medicated were persisting.” And she received complaints about her weight from people in the music business. By the way, weight gain is one of the side effects from antipsychotic medication. When she mentioned her weight problem to her doctors, they suggested taking her off of the bipolar meds as a remedy.

Writing for About Health, Angel Rouse said O’Connor was alarmed with the casualness of the suggestion and aware that simply stopping meds could be dangerous. So she sought outside opinions, eventually getting three additional ones. Their conclusion was that she was not bipolar. Rather, she actually suffered from PTSD. She revealed that when she cancelled her tour in 2012, she had tried to stop taking her medication cold turkey. Ironically, as a result of that attempt, she struggled with bipolar problems of mania and depression for nearly a year. Interviewed for the Irish Mirror, she said:

The illness was in fact what happens when you don’t go about coming off these meds properly. I’m delighted to be able to say that after ten years of poisoning myself with these drugs and having to live with the extremely difficult side-effects of them I can shortly begin the very, very slow indeed, process of getting them out of my system and my life and getting my life back.

Sinéad O’Connor is not a unique case. The NAMI (National Alliance on Mental Illness) website claims that 2.6% or 6.1 million American adults have a bipolar disorder. NAMI referenced this “mental health fact” on data they took from the National Institute of Mental Health (NIMH), which in turn cited this article by Kessler et al. from JAMA Psychiatry on the prevalence, severity and comorbidity of DSM-IV disorders. See Table 1 in the article for the reported percentage. But if Sinéad O’Connor could be misdiagnosed as having a bipolar disorder and mistakenly placed on potentially harmful medications that are seen as necessary to stabilize and control the bipolar ‘illness,’ how many others are similarly misdiagnosed? Regarding the medications she was on, O’Connor told the Irish Mirror:

They are extremely debilitating drugs. Tiring to the extreme. Ironically, extremely depressing. They can cause suicidal or self-harm type thinking. They can mess up your menstrual cycle very badly and cause you to be incapacitated for a week before. . . . [They] f**k up your liver, your kidneys, your eyes, your appetite, your entire way of thinking and generally your entire life.

Within his seminal book, Anatomy of an Epidemic, Robert Whitaker described “The Bipolar Boom” in chapter nine. He related a talk given by Fredrick Goodwin at the 2008 annual meeting of the American Psychiatric Association (APA). Goodwin said the illness has been altered since 1990. There was more rapid cycling; more mixed states; more lithium treatment failures than when he’d coauthored Manic-Depressive Illness. “The illness is not what Kraepelin described anymore, and the biggest factor, I think, is that most patients who have the illness get an antidepressant before they ever get exposed to a mood stabilizer.” Whitaker said not everyone speaking agreed that antidepressants had been disastrous for bipolar patients, but no one questioned Goodwin’s assessment that bipolar outcomes had noticeably worsened since 1990.

On his website, Whitaker noted that before 1955, bipolar illness had been a rare disorder. Only 12,750 people were hospitalized with the disorder that year. There were only about 2,400 “first admissions” that year in the country’s mental hospitals. Outcomes were fairly optimistic. Seventy-five percent of these first-admissions were projected to recover within 12 months. And only 15% of first-time admissions were expected to become chronically ill. And at least 70% were projected to return to work and have active social lives.

Today, bipolar illness is said to affect one in every 40 adults in the United States. A rare disorder has become a very common diagnosis. There are several reasons for this. First, many drugs–both illicit and legal–can stir manic episodes, and thus usage of those drugs leads many to a bipolar diagnosis. Second, the diagnostic boundaries of bipolar illness have been greatly broadened.

Allen Frances is a psychiatrist and the author of Saving Normal. He was also the chair for the DSM-IV, which expanded the criteria in diagnosing bipolar diagnosis by adding the bipolar II category. In Saving Normal, he described a dilemma when the APA was revising bipolar diagnosis for the fourth edition of the DSM. Patients with “hypomania,” less-than-full-manic episodes, didn’t fit neatly into the unipolar or bipolar depression categories. The bipolar II category was seen as a compromise that would lessen the dangers of classifying them as having unipolar depression and treating them with antidepressant medication that could trigger a manic episode.

We knew that bipolar II would expand the bipolar category somewhat into unipolar territory, but we did not think that it would double. Undoubtedly, our decision resulted in more accurate diagnosis and safer treatment for many previously missed truly bipolar patients. But like all fads, it overshot and had led to unnecessary medication for many unipolar patients who have been misdiagnosed as bipolar on very flimsy grounds and are now receiving unnecessary mood stabilizing drugs.

Whether you agree with Frances’ assessment that adding bipolar II resulted in more accurate diagnosis and safer treatment for many, don’t miss that he also said it led to misdiagnosis and unnecessary medication.  If you follow this link, also given above, to Robert Whitaker’s website, Mad in America, you will find a series of journal articles describing how substance abuse can be related to developing bipolar disorder; the effects of antidepressant use on bipolar disorder and how these drugs can worsen long-term bipolar outcomes; and the deterioration of bipolar outcomes in the modern era.

For a postscript, I want to return to note one last piece of information on Sinéad O’Connor. While she has cast off her diagnosis of bipolar disorder, it isn’t finished with her. Many websites, like that of “Famous Bipolar People” mentioned above, still list her as one of their own. There was a concluding note in the “About Health” article on Sinéad O’Connor that said: “In spite of her having stated clearly on several occasions that she does not have bipolar disorder, O’Connor continues to be included at many sites that compile lists of famous bipolar people.”

Famous Bipolar People, if Sinéad had said it’s over between the two of you, accept it and move on. There are plenty of more fish in the sea. You still have Kay Redfield Jamison. She’s written two books that touch on bipolar disorder, An Unquiet Mind and Touched with Fire. And both have been made into movies. The movie, Touched with Fire, is a fictional love story about two people with bipolar disorder who meet in a psychiatric hospital and fall in love. The trailer has a slight Romeo and Juliet feel to it; two young lovers who family and friends try to keep apart. So there will be plenty of new discussions about who is and who isn’t bipolar related to the movie. Just let go of Sinéad; let her go and move on.

05/27/16

Opium and the Taliban

21028744_sReporting for The New York Times, Azam Ahmed described a successful raid by Afghan special operations forces on July 12, 2014. Two vehicles were intercepted in the desert of southern Nimruz Province in Afghanistan. They were attempting to deliver a cache of weapons and drugs from Helmand Province to Nimruz Province. They seized a metric ton of opium, three AK-47 assault rifles, a PKM machine gun, a rocket-propelled grenade and a man who was the Taliban shadow governor of Nimruz Province, Mullah Abdul Rashid Baluch.

Rashid was said to embody the changing face of the Taliban in Afghanistan. He’s held leadership, logistical and financial support roles for the Taliban since at least 2007. By mid-2013 he was serving as a liaison officer to al-Qa’ida (AQ), arranging planning meetings between Taliban senior leadership and AQ members in Karachi, Pakistan.

In mid-2013, Rashid ordered the emplacement of an improvised explosive device (IED) in Nimruz Province which resulted in an explosion that killed one U.S. soldier.  Additionally, Rashid transported IEDs to Afghanistan that were used by the Taliban to target Coalition Forces.  As of early 2008, Rashid and a Taliban associate facilitated the movement of three suicide bombers for attacks in Nimruz Province.  He has also played a role in the deployment of suicide bombers to conduct vehicle-borne IED attacks on senior Afghan government officials and non-governmental organization workers.

Rashid was also involved in multiple narcotics-related financial activities, including delivering funds collected from narcotics traffickers to Taliban commanders. He collected payments for the coordination of Taliban protective services for narcotics shipments and disbursed payments to Taliban subordinates. Azam Ahmed commented that picking him up during a drug raid, and not a counterterrorism operation, was a fitting end. “He was, in the eyes of many, more of a criminal than an insurgent ideologue.” Rashid is now serving an 18-year prison sentence.

Mullah Rashid is just one of dozens of senior Taliban leaders who are so enmeshed in the drug trade that it has become difficult to distinguish the group from a dedicated drug cartel. While the Taliban have long profited from the taxation and protection of the drug trade in Afghanistan, insurgents are taking more direct roles and claiming spots higher up in the opium chain, according to interviews with dozens of Afghan and Western officials, as well as smugglers and members of the communities where they reside.

According to UN monitors, the new Taliban leader, Mullah Akhtar Muhammad Mansour, has amassed a huge personal fortune from sitting at the top of a hierarchy of tribal drug traffickers. Reportedly, he used some of his drug money to buy off rivals when he claimed the supreme leadership of the Taliban in the summer of 2015. “This trend has real consequences for peace and security in Afghanistan, as it encourages those within the Taliban movement who have the greatest economic incentives to oppose any meaningful process of reconciliation with the new government.”

In “How Opium Profits the Taliban,” a report for the United States Institute for Peace, Gretchen Peters described how the poppy trade has played a critical role in bankrolling the Taliban and corrupting and destabilizing the Afghan government. When the U.S. invaded Afghanistan in October of 2001, a Taliban ban on poppy cultivation had been in place for fifteen months. Throughout the southern part of Afghanistan, there were essentially no poppy fields under cultivation. Most of the 185 metric tons of opium produced in Afghanistan that year came from northern provinces outside of Taliban control. However, by 2008, nearly 98 percent of the Afghan poppy crop was grown in six southern and southwestern provinces, Farah, Helmand, Kandahar, Nimroz, Uruzgan, and Zabu.

The 2015 World Drug Report said that in 2014 opium cultivation for Afghanistan was at its highest level since estimated first became available. Global opium production was at the second highest level since the late 1930s. The following graphic, taken from 2015 World Drug Report, puts the significance of Afghan poppy cultivation in context. Except for the one-year anomaly due to the Taliban’s temporary ban on poppy cultivation, Afghanistan has been the largest worldwide producer of opium by a large margin since at least 1998.

opiumThe 2015 Afghanistan Opium Survey, from the same UN Office on Drugs and Crime, reported that in 2015 there was a 19% decrease in the total area under opium poppy cultivation. But it was still the fourth highest level since the estimations began in 1994. The Fix reported Afghanistan produces 85% of the world’s supply of heroin and morphine, an estimated 380 tons annually. It’s worth an estimated $4 billion.

In “How Opium Profits the Taliban,” Gretchen Peters described how the drug trade became a central part of the Taliban’s Afghan activities. She said many people who encountered the Taliban at their beginnings said they were well intentioned, “even if their methods were medieval.” Their initial commitment to stamp out the opium trade was dropped as the need for funds overcame their original objectives. She said the Taliban’s rise to power had more to do with their reliance “on the financial backing of an unholy alliance of drug smugglers, traders, and trucking groups” than the grace of Allah, as they claimed.

She concluded that while opium has played a long-standing supportive role in the Afghan conflict, “today the drug trade has moved to center stage.” Not only have narcotics corrupted the Afghan government, they have begun to transform the nature of the insurgency “from one based on ideology to one increasingly driven by profit.”

 It is crucial that the international community stop thinking of Afghanistan’s drug problem as Afghanistan’s drug problem. The poppy may be grown there and processed into morphine base or heroin along the border, but to a significant degree, the southern Afghan poppy trade is managed from Pakistan. Drug profits get laundered between Karachi and the United Arab Emirates, and U.S. financial crime experts who have studied the trade believe some funds end up in Western banking institutions. A successful strategy to combat the issue must take into account both the multinational nature of the opium trade and work to dismantle financial flows keeping insurgent fighters funded and armed.

Peters argued that the best strategy against the Taliban is not to try and wipe them out militarily, but to make them irrelevant, by offering Afghans and Pakistanis a better alternative. “The ultimate goal should not be the end of the Taliban and al-Qaeda, but the creation of a prosperous and stable Afghanistan and greater region.” And this will mean helping the locals grow a better cash crop then opium poppies.

05/24/16

Why is the Sky Blue?

© Pakhnyuschchyy | stockfresh.com

© Pakhnyuschchyy | stockfresh.com

Some biblical scholars hold that Genesis 1 either used the Babylonian creation myth, the Enuma elish, or was generally dependent upon it and other Mesopotamian traditions. Drawing on the work of Alexander Heidel in Babylonian Genesis, we find both parallels and differences between the Enuma elish and Genesis 1. Ultimately Heidel felt that the differences were far too great and the similarities far too insignificant. “In my estimation, no incontrovertible evidence can for the present be produced for either side.” Poetically, he said: “the resemblances fade away almost like the stars before the sun.” However, some of the similarities are striking.

In the Enuma elish, we find a story of how the earth came to be. In the beginning there was only the divine parents—Apsu and Tiamat—and their son, Mummu (Remember, this was ancient Babylon. Maybe Mummu was a popular name back then). Apsu was the primeval sweet-water ocean and Tiamat was the primeval salt-water ocean. Mummu was the mist rising from the two bodies of water and hovering over them. When Apsu and Tiamat comingled their waters, they gave birth to Lahmu and Lahamu, two silt deposits who eventually formed land. The three types of water were mingled together, forming an undefined mass in which were all the elements from which the universe was later made. But as yet, there was no heaven or earth.

In time, Apsu and Tiamat had more children, Anshar and Kishar. Together they had a son named Anu, who was the sky-god. Anu’s son was Ea, who became the god of the subterranean sweet-waters, the god of magic and eventually the mastermind of all the divinities. “He had no rival among his fellow-gods.” The younger gods were noisy and loud, disturbing the older gods, Apsu and Tiamat. When peaceful attempts to quiet them failed, Apsu determined to destroy them. But Ea through the power of the spoken word of a magic spell put Apsu to sleep. He then took Apsu’s royal tiara and supernatural radiance for himself and killed Apsu, the father of all the gods. Ea then established a spacious place for himself and all the remaining gods to live, calling that place “Apsu.”

So far, there is no real parallel between the two accounts, but we now come to the time of Marduk the son of Ea and “the wisest of the gods.” Tiamat resented the death of her consort, and sought revenge against the other gods for killing Apsu. So she decided to revolt against the other gods, but was defeated in battle by Marduk. He divided her body in two forming the universe, “with one half he formed the sky, with the other he fashioned the earth.”

 Next, he created stations in the sky for the great gods; he organized the calendar, by setting up stellar constellations to determine by their rising and setting the year, the months, and the days; he built gates in the east and in the west for the sun to enter and depart; in the very center of the sky he fixed the zenith; he caused the moon to shine and entrusted the night to her.

The story continues with a discussion of the further creation acts of Marduk. They have some similarity to the biblical account in Genesis as seen in this chart reproduced from the Babylonian Genesis. Note that in both accounts, light is created before the luminaries. But even in what follows, there is not complete correspondence. In fact, “the differences far outweigh the similarities.”

Enuma elish

Genesis

Divine spirit and cosmic matter are coexistent and coeternal

The divine spirit creates cosmic matter and exists independently of it

There is primeval chaos; Tiamat is enveloped in darkness

The earth is a desolate waste, with darkness covering the deep.

Light emanated from the gods

 

Light is created

The creation of the firmament

The firmament is created

The creation of dry land

 

Dry land is created

The creation of the luminaries

The luminaries are created

The creation of humanity

Humanity is created

The gods rest and celebrate

God rests and sanctifies the seventh day

If Genesis 1:1-2:3 really was influenced by Enuma elish, then it is reasonably certain that at least the following elements go back to the Babylonian epic: (1) part of the outline; (2) the conceptions of an immense primeval body of water containing the component parts of the earth; (3) the idea of the primeval waters; and (4) the existence of light before the luminaries.

There were also parallels with other Near Eastern cultures and their own creation stories as well. The Egyptians and the Phoenicians referred to a watery chaos in their cosmologies. There was primeval darkness within the cosmologies of the Greeks and the Phoenicians. However, in his commentary on Genesis 1-15, Gordon Wenham seems to capture the right view. He said the known links of the Hebrew patriarchs with Mesopotamia and the other areas of the Near East make it improbable that the writers of Genesis were completely ignorant of Babylonian and other similar creation stories.

Most likely they were conscious of a number of accounts of creation current in the Near East of their day, and Gen 1 is a deliberate statement of the Hebrew view of creation over against rival views. It is not merely a demythologization of oriental creation myths, whether Babylonian or Egyptian; rather it is a polemical repudiation of such myths.

Drawing on Scripture and Cosmology by Kyle Greenwood, Brad Kramer elaborated on the similarities between Hebrew and other Near Eastern cosmologies. The people of the biblical world assumed that rather than what we think of as “outer space”, there was a universally-wide cosmic ocean. For them this was an entirely rational belief based upon everyday observation and intuition. Why was the sky blue? Where did rain come from? “Ancient people figured that the sky was blue because there was a giant cosmic ocean high above the earth.” And rain came in through the windows and doors of a heavenly dome.

It was a nearly universal belief in biblical times that the sky was a solid structure, serving as a barrier for the upper waters. Aligned with the common experience of finding water deep in the ground, “The ancients conceived of the earth arising out of primordial waters, called the cosmic ocean…the earth was thought to be surrounded by these cosmic waters.” So the ancient Hebrew understanding of the universe looked something like the following:

Hebrew conception of the universe

Biblical evidence for this ancient cosmology exists within Genesis 1 itself. Genesis 1:6 through 9, covering the second day and part of the third day of creation, described how God created an expanse or firmament (rāqîaʿ) in the midst of the waters. This firmament separated the waters above and below. This firmament was thought to be a beaten metal plate or bow; a gigantic heavenly dome. Kramer concluded:

These verses only make sense if the whole universe is filled with water. The picture here is God blowing a bubble of habitable space in the middle of the cosmic sea and placing a barrier to keep the waters from crashing down onto earth. Interestingly, the heavenly bodies (sun, moon, and stars) are “set…in the dome” (1:17), under the “waters above”, rather than above them. So again, the picture is of cosmic waters encircling the entire universe, including stars and planets (which ancients assumed were attached to the solid dome). Greenwood concludes: “As was the case with ancient Israel’s neighbors, the land mass they called earth was thought to be surrounded by water—east and west, above and below.”

Further Biblical evidence that the Hebrews seemed to have a three-tiered cosmology of the universe, with the earth situated in the middle between the heaven above and the deep beneath can be found in passages such as: Genesis 49:25, Deuteronomy 33:13, and Psalm 135:6. This three-tiered cosmology continued even into the early days of the church. To give but one example, in The Literal Meaning of Genesis, which Augustine wrote in 416 AD, he discussed why he thought the “star” Saturn was actually cold and not hot, as others speculated.

Indubitably, therefore, what makes it cold is the nearness of those waters set in places above the heavens, which these people refuse to believe who argue in the way I have summarized about the movement of the sky and the constellations. It is by drawing such inferences that some of our people meet those who refuse to believe there are any waters above the heavens and still insist on the coldness of that star whose circuit is nearest to the highest heaven.

For Christians with a modern scientific worldview such a cosmology is nonsensical. So they tend to import (sometimes unconsciously) the criteria of modern scientific accuracy into their reading of Genesis 1. This adds an “artificial middleman” to its interpretation. Attempting to combine an ancient cosmology with a modern scientific one will ultimately render both incoherent or out of focus at some point. And if we are attempting to convince a modern, science-minded person of the truth and authority of the Bible, “Do we really want an apologetic in which the truth of the Bible depends on the accuracy of scientific beliefs of ancient cultures?”

For more articles on creation in the Bible, see the link “Genesis & Creation.”

05/20/16

Riding the Hep C Gravy Train

12992431_sGilead Science launched its revolutionary drug, Solvadi to treat hepatitis C in December of 2013. At $1,000 per pill, a twelve-week course of treatment costs $84,000. Combined with some other necessary medications, the cure rate was projected to be over 90%. Then on October 10, 2014 Gilead launched Harvoni, a combination of Solvadi and ledipasir, which meant that only one pill taken daily for twelve weeks was needed. Gilead priced Harvoni at $95,000 per 12-week treatment.  Patient cure rates for Harvoni were in the mid-to high 90% range. Gilead justified its price for Harvoni and Solvadi by pointing to longer-term savings on costly complications from hepatitis C, such as liver transplants, liver cancer and repeated hospitalizations for advanced cases of Hep C. Then the company booked a ride on the gravy train.

Drawing on the annual financial reports noted in the company’s press releases, Gilead Sciences grossed $10.3 billion in sales for Solvadi in 2014; $8.5 billion of which was in the U.S. Harvoni sales in 2014 grossed $2.1 billion; $2 billion of which was in the U.S. Solvadi sales for 2015 dropped to $5.3 billion; $2.4 billion of which was in the U.S. This was likely because of the huge sales for Harvoni in 2015, $13.9 billion; $10.1 billion of which was in the U.S. Full year product sales for Gilead Sciences for 2013 was a respectable $11.2 billion, an increase of 15% over 2012 product sales. In 2014, full product sales were $24.5 billion, an increase of 137 percent. And in 2015, full product sales were $32.2 billion, an increase of 31 percent.

This was enough of a sales boost for Gilead Sciences to jump from the 21st ranked pharmaceutical company by global sales in 2013 to the 9th ranked company by global sales in 2014. This means that Gilead Sciences had an estimated 95% share of the U.S. market for hepatitis C treatment, where 3.2 million people are infected. AbbVie, the 11th ranked pharmaceutical company in 2014, launched its own hep C drug treatment, Viekira Pak, in December of 2014. There wasn’t much of a discount, as it was priced at $83, 320 for a 12-week treatment, according to Hanna Ishmael for Bidness ETC.

Express Scripts, the U.S.’s largest pharmacy benefits manager, secured a discount from AbbVie for Viekira Pak and announced it was dropping coverage for Gilead’s treatments, except under certain medical conditions. The Chief Medical Officer for Express Scripts said the discount put it in the range of Western European levels for Gilead’s hepatitis C treatment, between $51,000 and $66,000. That is correct. Gilead negotiated a better deal for its treatments with countries outside the U.S. “The dynamic will save Express Scripts customers $1 billion in 2015, with a total of $4 billion in savings across the United States when all payers and employers are included.”

In response to the deal between Express Scripts and AbbVie, Gilead began offering discounts that averaged 46% off its listed price for Solvadi and Harvoni, meaning they cost would $45,360 and $51,300 respectively. However, some payers continued to restrict access to Gilead’s drugs, so in return, Gilead began to limit enrollment in its patient assistance program for hepatitis C drugs. These programs help patients obtain Solvadi and Harvoni treatments when they don’t have the finances or sufficient insurance coverage to get the medicines. Beginning on July 1, 2015, Gilead announced that patients who were insured, but did not meet their payers coverage criteria would no longer be eligible for Gileads Patient Assistance Program. Ed Silverman said: “The drug maker is taking this step after finding that some payers, despite receiving discounts in recent months, have continued to restrict patient access to its hepatitis C medicines.”

Unfortunately, reporting for FiercePharma, Emily Wasserman said there have been reports of serious liver injuries tied to Viekira Pak, which led to changes in the meds’ labels warning doctors against using them for the sickest patients. AbbVie countered by saying that its drugs are safe for the vast majority of patients. The risk of serious injury is only for 3% to 5% of patients with the most serious stage of the disease.

The FDA and Gilead announced in March of 2015 that a serious slowing of the heart rate (symptomatic bradycardia) can occur when Harvoni or Solvadi is used in conjunction with the antiarrhythmic drug amiodarone. Nine patients had had serious reactions and one of the nine died. Three others had to receive pacemakers. Gilead said the mechanism of the potential interaction is unknown. “Gilead said that 6 cases of symptomatic bradycardia happened within 24 hours of starting one of the drugs and the other three in two to 12 days.”

Now their the competition is expanding. Johnson & Johnson has its own next-generation hep C treatments in the pipeline and Merck just had its hep C drug, Zepatier, approved by the FDA in January of 2016. Like Harvoni, Zepatier is a once-daily single-tablet of two drugs. The new drug is priced at $54,600 for a 12-week regimen, which Merck said puts it in the range of discounts for other competing hep C treatments like Harvoni and Viekira Pak.

Reportedly, Zepatier also has a better safety profile than Solvadi. Advera Health Analytics looked at the clinical trials data for all three drugs and concluded it was less risky than Solvadi. “The general conclusion is that Zepatier looks safer than Sovaldi, just based on clinical trial information.” Gilead, of course, disagrees. They said the analysis was “deeply flawed.” It wasn’t based on a head-to-head comparison of the three drugs. There wasn’t consideration given for the underlying condition for which patients were taking Harvoni or Solvadi. Nor was there adjustment made for the drugs given along with Solvadi, which have their own serious side effects.

The first-generation hepatitis C treatments take longer, have more known adverse side effects and don’t have as high of a patient cure rate. The second-generation treatments, like Solvadi and Harvoni will save lives. But patients in the U.S. are at a financial disadvantage as they are forced to pay a much higher cost for their treatment. See “Hepatitis Hostages” and “Is There No Balm in Gilead?” for more on this topic. It is getting better, but the initial gravy boat of profits launched Gilead into the top ten of pharmaceutical companies in global sales for 2014. When the dust settles from all the above noted concerns, the bottom line is that the pharmaceutical companies, especially Gilead Sciences, will make a huge profit off their hepatitis C treatments. There is a balm in Gilead, but it’s going to cost you.

05/17/16

Overdosing

© banerwega | stockfresh.com

© banerwega | stockfresh.com

Melanie (not her real name) was one of the first persons I counseled at White Deer Run in the late 1980s. She was 18 at the time, and a heroin addict before it was being called a national epidemic. She completed treatment; relapsed and returned about a year later as an adult patient. I think she even completed treatment that time as well. I can’t tell you much more about her, except that she was from Philly; and she is the first person I worked with who became an overdose statistic. There have been many more since then.

Most of the places I’ve worked as a drug and alcohol counselor have been within Pennsylvania. So when I heard of the study done by Balmert et al. on the accidental poisoning deaths in Pennsylvania from 1979 to 2014, I was interested in reading it. There aren’t too many ways that statistics, especially death statistics, can be interesting reading. But buried within those tables and figures are people I knew.

Within a data set attached to the study, I found the reported deaths by accidental drug poisoning for the years 1987 through 1989.  In 1987, there were 41 individuals between the ages of 15 and 24 who died from accidental poisoning, 6 of whom were female; in 1988 there were 39, 12 of whom were female; in 1989 there were 54, 9 of whom were female. Somewhere in those statistics is Melanie’s overdose.

When I compared those deaths with the last three in the data set, 2012, 2013 and 2014, the stats grew exponentially. In 2012, there were 224 individuals between the ages of 15 and 24 who died from accidental poisoning, 63 of whom were female; in 2013 there were 203, 47 of whom were female; in 2014 there were 277; 70 of whom were female.  That’s a lot of Melanie’s.

The CDC published a data brief indicating drug poisoning became the leading cause of injury-related death in 2008, surpassing deaths from motor vehicle accidents. 90% of those deaths were from drug poisoning. From 1999 to 2008 the number of drug poisoning deaths from opioid analgesics more than tripled. “Of the 36,500 drug poisoning deaths in 2008, more than 40% (14,800) involved opioid analgesics.”

Most of those 14,800 deaths involved natural and semi-synthetic opioid analgesics such as morphine, hydrocodone and oxycodone. The number of drug poisoning deaths from methadone, a synthetic opioid, increased sevenfold from 1999 to 2007. Then it decreased between 2007 and 2008. The age group with the highest death rate from opioid poisonings was between 45 and 54 years of age.

In 2007-2008 48% of Americans reported the use of at least one prescription drug in the past month. Not surprisingly, this was related to increases in drug use, misuse and nonfatal health outcomes. Over 5 million reported using prescription pain relievers nonmedically in the previous month.

In 2012 the CDC looked specifically at drug-poisoning deaths from opioid analgesics and heroin. Their report in Health E-Stats noted that from 1999 to 2012 the drug poisoning deaths from opioid analgesics increased from 1.4 per 100,000 in 1999 to 5.1 in 2012. The death rates from heroin overdoses nearly tripled from .7 per 100,000 in 1999 to 1.9 in 2012. The states with death rates significantly higher than the overall U.S. rate of 13.1 per 100,000 included Pennsylvania, Ohio and West Virginia, which had the highest overall rate at 32.0 per 100,000. See the linked CDC reports for more detailed information.

Returning to the Balmert et al. study on accidental poisoning deaths in Pennsylvania, we can see how the Pennsylvania rates compare to those just reviewed. Table 1 in Balmert et al. indicated the overall death rate for Pennsylvania in 2014 was 29.16 per 100,000. The death rate was highest for the 25-34 age group (39.87), and lowest among the 15-24 age group (16.25). See  Table 1 in the Balmert et al. article.

Examining the mortality patterns by county showed that the highest rates for males from 2010 to 2014 were in the counties of southwestern PA (the Pittsburgh metro area), the counties surrounding Philadelphia and those near Scranton in the Northeast part of the state. The highest rates for females were in the same areas.

The county level findings provide possible avenues for targeting interventions to areas with the highest mortality from accidental poisoning. Counties with the highest 2010–2014 rates in females are primarily in suburban southwest PA. In males, the highest prevalence rates are more widespread and include both southwest and southeast PA, plus the northeast area including Carbon and Susquehanna. These patterns emphasize that, currently, accidental poisoning deaths especially among white females are occurring in suburban and rural areas. Other area-specific analyses should focus on non-urban mortality patterns.

In September of 2014 legislation went into effect allowing first responders to carry naloxone for reversing the effects of an overdose. As of September 1, 2015, 302 overdoses had been reversed with naloxone. The following graphic represents the drug-related overdose deaths by county in Pennsylvania for 2014. See the original here.

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In September of 2015, Tom Wolf, the governor of Pennsylvania, announced that the CDC had granted the Pennsylvania Department of Health $900,000 to prevent overdose deaths related to prescription opioids. Governor Wolf said: “Too many citizens of our commonwealth are dying from drug overdose, and Pennsylvania families in hardworking communities are impacted by prescription drug addiction every day.” The “Prevention for States” grant will support 16 states with annual awards between $750,000 and $1 million over the next four years. The goal is to hopefully turn the tide on the prescription drug overdose epidemic by implementing prevention strategies and improving safe prescribing practices.

On March 18, 2016, the CDC published revised guidelines for primary care physicians when prescribing pain medication. Nearly half of all opioid prescriptions are dispensed by primary care clinicians. An estimated 20% of patients with noncancer pain symptoms or pain-related diagnoses receive an opioid prescription. While evidence supports the short-term efficacy of opioids for reducing pain, few studies have assessed the long-term benefits of opioids for chronic pain. An estimated 9.6 to 11.5 million adults (3% to 4% of the adult U.S. population) were prescribed long-term opioid therapy in 2005.

This guideline is intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death.

The guidelines are not mandatory, but if they are followed, maybe the opioid-related overdose deaths will start to decrease and people like Melanie will live instead of die.

05/13/16

Inspite of Delusions

© Bruce Rolff | 123rf.com

© Bruce Rolff | 123rf.com

At the height of his popularity, Edward Irving decided to complete a preaching tour of Scotland in May of 1828. He timed his visit to occur during the gathering of the ministers of the Church of Scotland for their annual General Assembly in Edinburgh. He decided to give a series of twelve lectures on the Apocalypse. So that his lectures would not conflict with the sessions of the Assembly, he held them at six o’clock in the morning. Although he had engaged one of the largest churches in the city, it was immediately overcrowded. He moved to the largest church in Edinburgh, with the same difficulty. Two ministers almost came to blows when one accused the other of bribing an usher to let him in through a back door.

Less than ten years before, he had been the assistant to Thomas Chalmers, the most celebrated minister of Scotland at the time.  Even Chalmers failed to gain entrance the first time he went to hear Irving. He was eventually able to hear Irving and said: “I have no hesitation in saying it is quite woeful.” Nevertheless, Irving continued to speak to packed audiences throughout his twelve lectures. Everywhere he went in Scotland, he drew large, excited crowds.

About thirty-five miles northwest of Glasgow, in the Gare Loch district, Irving met a ministerial probationer named A.J. Scott. Like Irving, he believed that the charismata (the miraculous spiritual gifts of the Apostles) had been withdrawn from the Church because of a lack of faith and coldness of heart. Where Irving believed these gifts would be restored in the soon-coming Millennium, Scott held that they were still available. Irving was so impressed with Scott, that he asked him to be his assistant in London. Irving would later write:

 … as we went out and in together, he used often to signify to me his conviction that the spiritual gifts ought still to be exercised in the Church; that we are at liberty, and indeed are bound to pray for them.

Scott would later return to the Gare Loch area and preach to some of the Godly people there. Among them was a woman named Mary Campbell. Scott was not able to convince her of his belief that there was a distinction between regeneration and the baptism of the Holy Ghost. So as he left, he charged her to read through the Acts of the Apostles with that distinction in mind, “to beware of how she rashly rejected what he believed to be the truth of God.”  In a letter to her minister a few weeks later, Mary Campbell described her new relationship with the Holy Spirit.

She expected to receive two of the Apostolic gifts—tongues and prophecy. In her thinking, these gifts were tied to the calling of foreign missionary work. She believed the educational system  for ministers was of the Devil. “If God has promised to furnish His servants with every necessary qualification for their great work, what have they to do but step into the field, depending upon Him for all?” She believed “no language study was necessary” for her to be a missionary, because all the requirements would be met supernaturally. A group of individuals had gathered around her who began to pray for her healing from “consumption” and to receive the gift of tongues. Arnold Dallimore, in his biography on Edward Irving, quoted her minister as saying:

On a Sunday evening in the month of March [1830], Mary, in the presence of a few friends, began to utter sounds to them incomprehensible, and believed by her to be a tongue such a of old might have been spoken on the day of Pentecost, or among the Christians of Corinth.

Mary was certain she was speaking the language of a people group she had been reading about, the Pelew Islanders of the South Pacific. Mary also began to exhibit another “gift,” that of automatic handwriting. Dallimore said she would pass into a trance-like state and fill pages of paper with script. “The characters she used were not those of the English nor any other known language.” So they were believed to be miraculous; the writings were attributed to a foreign language.

News of her ‘gift of tongues’ spread rapidly and others in the Gare Loch area began to report receiving gifts of tongues, prophecy and even healing. After receiving a letter from one James McDonald, commanding her to arise from her sickbed, Mary Campbell herself was ‘healed.’ Unfortunately, Mary’s brother Samuel, wasn’t so fortunate. Rising from his sickbed below the room where Mary and her friends met to sing and pray, he entered their room and asked them to be quiet. But the dying man was told by some of Mary’s companions, “Get behind me, Satan!” He returned to his sickbed and died a few days later.

The news of Gare Loch events led to a party of Londoners traveling to visit the area and see for themselves what was happening. This was about five months after Mary Campbell’s initial experience. The group visited the Campbells and the McDonalds, where they heard people speaking in tongues. After three weeks, they returned to London to report their findings. J.B. Cardale, a lawyer who was part of the group said: “The persons, while uttering the unknown sounds, as also while speaking in the Spirit in their own language, have every appearance of being under supernatural direction.”

Several people in London opened their homes to prayer meetings that earnestly sought for the outpouring of the Spirit. These meetings continued throughout the autumn and winter of 1830-1831. Then in April, Mrs. Cardale ‘spoke in tongues.’ A few days later, a young woman who attended Irving’s church, both spoke and sang in tongues. The work continued through the summer, and by the beginning of September, a number of people in Irving’s church were claiming to be able to ‘speak in tongues’.

Mary Campbell had also moved to London and began attending Irving’s church. Along with five others, including Mrs. Cardale and her husband’s sister, an inner circle of ‘the gifted ones’ formed abound Irving. But Irving himself never claimed or received a charismatic gift of any kind. It was suggested by Dallimore that he sought an experience that was so clearly miraculous “that it would constantly affirm his faith and strengthen his conviction that the whole activity was of God.”

By September of 1831, division over speaking in tongues had occurred in Irving’s church. The traditional, more Presbyterian members denounced the exercise of tongues during Sunday worship as a disgrace to the House of God. The supporters of tongues said that criticism was blasphemy against the Holy Spirit. The dispute continued for several months. Finally the Trustees demanded that Irving forbid the use of tongues in the church services. Certain that forbidding tongues at any time would be silencing the Holy Spirit, Irving refused. As a consequence, many of the traditional members left the Church.

This led to the Trustees bringing charges against Irving before the London Presbytery to the effect that “he had allowed the services of the Church to be disturbed.” He was ordered to stand trial before them on April 26th of 1832. On the morning of his trial one of his inner circle of gifted ones, Robert Baxter, came to see Irving.  Baxter proceeded to tell Irving he had come to the conviction that the manifestations were merely a grand illusion. Baxter had been the strongest advocate of the manifestations. The decision of the Presbytery was that Irving was unfit to remain a minister of the National Church of Scotland and he was removed from his position as a minister in the denomination.

Several other core members experienced a loss of faith in the manifestations of the gifts. Miss Hall, one of the six original ‘gifted ones’, said she had given up all belief in the manifestations. She even admitted that she sometimes rehearsed the utterances she intended to speak at the church. A.J. Scott could see nothing supernatural in the tongues and healing practices of Irving’s church. So he withdrew himself from fellowship with Irving.

Mary Campbell and her husband traveled to Europe with her husband, intending to become missionaries. “But they were immediately forced to recognize her gift of tongues did not enable her to speak any of the languages they came upon.” They returned to England and Mary gave up the missionary idea completely. Within a few years, she has also largely dropped her belief in the charismatic gifts.

Irving and those members of his church who supported him organized an independent church. In their new church, all authority lay in the hands of gifted ones called Apostles and Prophets. Irving was subject to them and their leadership. He functioned as little more than a servant to them. Lacking any of the gifts, he was subject to their declarations and commands. “He preached only when the Prophets wished him to do so and they exerted their control over what he said.” He gave up writing. He became a recluse and seldom ventured from home.

In September of 1834 a church Prophet declared it was the command of God for Irving to leave London and travel to Glasgow, for “God had a great work for him to do there.” By now Irving’s health was seriously failing, but he went anyway, believing the Prophet spoke for God. He hoped that God would not only heal his consumption, but also grant him the whole array of charismatic gifts, resulting in a powerful and lasting ministry. Irving believed that prayer and faith alone should be employed to deliver him from sickness.

He once said, “No Christian ought ever to be overcome by sickness.” The Lord would either maintain believers in perfect health, or grant them healing in case of sickness. All you needed was sufficient faith. If a healing didn’t take place, it was because your faith was lacking. When there was a cholera epidemic in Britain, Irving called for nation-wide prayer and fasting as the only means of deliverance. He believed the cholera epidemic was sent by God as a judgment for sin.

When he arrived in Scotland, a minister’s wife said Irving bore all the marks of age and weakness from consumption. He was only able to preach on two Sundays, sitting in a chair, “with little strength and very feeble voice.” After being in Glasgow only three weeks, he was so weak he had to remain in bed.

Ultimately realizing he would not be healed, his last spoken words were: “if I die, I die unto the Lord, Amen.” Fittingly, Irving died on a Sunday. His life-long friend, the Scottish philosopher and writer Thomas Carlyle, said Irving was the sun in his firmament.

But for Irving I had never known what the communion of man with man means. He was the freest, brotherliest, bravest human soul mine ever came in contact with: I call him, on the whole, the best man I have ever . . . found in this world, or hope to find.

Tragically, Irving stubbornly clung to his mistaken understanding of Scripture with regard to the second coming of Christ (see “No One Knows”) and the charismata. His enthusiastic endorsement of these wrong interpretations seems to have contributed to both his meteoric rise to popularity and his rapid fall from favor. They also seemed to play a part in his early death, as he felt compelled to obey the spoken word of the “Prophet” to travel to Scotland despite being so ill with tuberculosis (consumption).

Irving’s mistaken belief with regard to spiritual gifts was that those who had received the baptism of the Holy Spirit, confirmed by their speaking in tongues, were of a higher spiritual level. His biographer Arnold Dallimore noted where this brought him into subjection to the Prophets. Since they spoke in tongues, they were in a superior spiritual position to him. So he submitted to their control. “The Irving we have seen in the last two years of his life, a recluse, robbed of his liberty and with little ambition to write or be active, was the results of his acceptance of the Prophets and their gifts.”

Carlyle wasn’t alone in his assessment of Irving as a person. Robert Murray M’Cheyne wrote the following of Irving when he heard of his death: “I look back on him with awe, as on the saints and martyrs of old. A holy man, in spite of all his delusions and errors. He is now with his God and Saviour, whom he wronged so much, yet, I am persuaded, loved so sincerely.”

The above discussion was largely taken from: The Life of Edward Irving: The Forerunner of the Charismatic Movement, by Arnold Dallimore.

05/10/16

Opening the Off-Label Floodgates

© Christa Eder | 123rf.con

© Christa Eder | 123rf.con

On March 8, 2016 the FDA made a settlement agreement with the pharmaceutical company Amarin that allows Amarin to promote its drug Vascepa for off-label use to treat patients with hypertriglycerdemia, persistently high triglycerides. That is, as long as its promotion is truthful and not misleading. Amarin wanted to widen the population for whom they could recommend Vascepa to include other patients with different cardiovascular diseases, but the FDA initially ruled against this. Amarin’s stock price took a nosedive. Concerned with how their investors were reacting, the company fought back by suing the FDA. So what was this breakthrough medication worth taking on the FDA? Fish oil; Vascepa is prescription strength fish oil.

Amarin argued that it had a First Amendment right to market its drug for a broader patient group, “despite the lack of regulatory approval and the lack of evidence of an outcomes benefit for patients.” Justin Karter of Mad in America noted how the FDA settlement strikes at the heart of the drug regulatory system in the U.S. Amarin argued that companies should have the right to market their products consistent with what “a judge would consider to be neither false or misleading.” Be clear on what Amarin was saying. A judge, not the FDA, should rule on whether or not the marketing claims for their product were truthful and not misleading.

Where does a judge get the expertise to discern whether or not a company has made misleading, untruthful medical claims about their product? Pharmaceutical companies have paid millions of dollars for violating off-label promotion of their medications. One example is the blockbuster drug Neurontin, which has cost its parent drug companies millions of dollars in fines for “illegal and fraudulent promotion of unapproved uses.” An internal company email referred to Neurontin as “the ‘snake oil’ of the twentieth century.” This is but one example of the violations from multiple drug companies under the more restrictive FDA guidelines forbidding all off-label marketing.

In August of 2015, a judge in the district court of Manhattan ruled that Amarin could market its drug to the desired broader population. He also ruled the company could claim that Vascepa “may reduce the risk of coronary heart disease.” This was despite the fact that the FDA had called the claim misleading, as there was “supportive but not conclusive research” to that effect. The Amarin ruling, according to attorney Amy Kapczynski, “has the potential to unleash a flood of misleading marketing to physcians.” She believes that at some point, the FDA will have to take the issue to the Supreme Court.

Writing for FDA Law Blog, David Gibbons gave a detailed description of the legal aspects of the case. While Amarin was attempting to gain FDA approval for its off-label promotion of Vespacia, data from several high-profile cardiovascular outcomes trials cast doubt on the clinical benefit of triglyceride lowering. After reviewing the data, the FDA then asked an Advisory Committee to express its opinion on whether or not “Vascepa’s triglyceride lowering effect was sufficient to approve the drug for use in patients with persistently high triglycerides. The Advisory Committee voted 9 to 2 against approval for that indication.” So Amarin sued the FDA.

In a bold move, Amarin filed a civil complaint against FDA claiming that FDA’s threat of prosecution for misbranding Vascepa had a chilling effect on Amarin’s commercial speech that was otherwise protected by the First Amendment.  For that reason, Amarin sought declaratory and injunctive relief that would prevent FDA from prosecuting the Company for truthful, non-misleading speech concerning Vascepa, going so far as to detail, in its complaint, certain off-label promotional content regarding Vascepa that the Company proposed to disseminate.  Early in the litigation proceedings, Amarin filed a motion for preliminary injunction and the court heard oral arguments on the motion on July 7, 2015, and, on August 7, the court handed down a 71-page opinion in which it granted Amarin’s requests.

Commenting on the FDA settlement agreement in Amrain Pharma v. U.S. Food & Drug Administration for Mad in America, lawyer and mental health advocate Jim Gottstein said he thought that for all practical purposes, the FDA ban against off-label promotion of drug companies was dead. He noted that the ruling in the Amarin case was based upon a 2012 decision in Unites States v. Caronia that reversed a criminal conviction for off-label promotion.

In light of the settlement I think it is fair to ask where things stand with the FDA’s enforcement of its ban against off-label promotion and Department of Justice prosecutions of drug companies for off-label promotion leading to false claims.  I think the ban against off-label promotion is dead for all practical purposes.  The FDA could try and get a different ruling in another circuit and, if successful, ask the Supreme Court to rule, but since it didn’t ask the Supreme Court to take the case in Caronia, it doesn’t seem likely that it has any intention of trying to overturn Caronia.  This will give the drug companies free rein for off-label promotion.  Of course, anything that is false or misleading is still grounds for charges, but that is a far harder case to make.

Eric Palmer, writing for FiercePharma, noted that the free speech argument has been closely monitored by the pharmaceutical industry to see just how much leeway they might expect from the FDA in their ability to market for off-label use of their products. Another pharmaceutical company, Pacira, filed suit against the FDA after the August 2015 ruling in favor of Amarin.

Tracy Staton noted on FiercePharma that the FDA agreed to remove its limits on Pacira’s marketing of Exparel, which is now approved for pain treatment at any surgical site. She said that by making a deal with Pacira, the FDA avoided another court ruling on the free-speech issue, as it seeks to adjust its marketing rules. In an attempt to limit any broader application of the Amarin ruling, the FDA has said its Vascepa promotions would not have broken FDA rules in any case. As it did with Amarin, the FDA said regarding its agreement with Pacira: “It’s important to note that this resolution is specific to the parties involved in this matter.”

Parallel to these attempts to weaken the FDA regulations against off-label marketing, there was a January 2016 article published in JAMA Internal Medicine by Eguale et al. that looked at the association between off-label drug use and the risk of adverse drug events (ADEs).  Commenting on Medscape, Eguale said to his knowledge, theirs was the first systematic evaluation of the association between off-label use of drugs and the risk for ADEs. They concluded that off-label use of prescription drugs was associated with ADEs. “Caution should be exercised in prescribing drugs for off-label uses that lack strong scientific evidence.”

The study found that the majority of prescriptions (88.2%) were for approved uses. Another 9.5% involved off-label use without strong supportive evidence; and 2.3% were off-label, but had strong evidence supporting its use off-label. The ADE rate was higher for off-label use than for on-label use, “at 19.7 per 10,000 person-months vs 12.5 per 10,000 person-months.” When analysis was done according to the strength of supporting evidence for off-label use, there was an even higher rate (at 21.7 per 10,000 person-months) for use unsupported by strong scientific evidence. “Off-label use indicated by solid scientific evidence had a rate of 13.2 per 10,000 person-months, which was virtually the same as its on-label counterpart.”

The risk for adverse events also rose with the number of prescription drugs used by individual patients. Individuals taking eight or more medications had “a more than fivefold increased risk for ADEs compared to patients who used one or two drugs.”

[P]hysicians and physician organizations should recognize the enormity of the problem and be active participants in the promotion of cautious prescribing of drugs for off-label uses lacking strong scientific evidence.

Within an invited commentary of the study, “Off-Label Drug Use and Adverse Events,” Chester Good and Walid Gellad warned that the FDA and the courts needed to carefully consider the study’s findings as they contemplate any further relaxation of regulations to permit the promotion of drugs beyond their labeled indications. “In light of these concerns, the study of off-label drug use and adverse drug events by Eguale and colleagues … is particularly timely.”

Too bad the Eguale et al. study wasn’t published earlier. Maybe it would have had some influence on the FDA settlement with Amarin. The response of pharmaceutical companies with psychiatric medications to the Amarin settlement is a serious concern. They have already demonstrated a history of flaunting the more restrictive FDA regulations to the tune of billions of dollars in fines.

On March 31, 2016, the nonprofit organization Public Citizen published an updated analysis of all major financial settlements and court judgments between pharmaceutical companies and the federal and state governments. The time period covered by their analysis ran from 1991 through 2015 and included 373 settlements for a total of $35.7 BILLION. Financial penalties have declined sharply since 2013. The most striking decrease occurred with criminal penalties. “For 2012 and 2013 combined, criminal penalties totaled $2.7 billion, but by 2014-2015, the total had fallen to $44 million, a decrease of more than 98%.”

From 1991 through 2015, GlaxoSmithKline and Pfizer reached the most settlements—with 31 each— and paid the most in penalties, $7.9 billion and $3.9 billion respectively. Six additional companies, Johnson & Johnson, Merck, Abbott, Eli Lilly, Teva, Schering-Plough, Novartis, and AstraZeneca paid more than $1 billion in financial penalties. Six of the above eight were listed in the top 14 pharmaceutical companies by global sales in 2014. Thirty-one companies entered repeat settlements. Pfizer (11), Merck (9), GlaxoSmithKline, Novartis, and Bristol-Myers Squibb (8 each) finalized the most federal settlements.

Financial penalties continued to pale in comparison to company profits, with the $35.7 billion in penalties from 1991 through 2015 amounting to only 5% of the $711 billion in net profits made by the 11 largest global drug companies during just 10 of those 25 years (2003-2012). To our knowledge, a parent company has never been excluded from participation in Medicare and Medicaid for illegal activities, which endanger the public health and deplete taxpayer-funded programs. Nor has almost any senior executive been given a jail sentence for leading companies engaged in these illegal activities. Much larger penalties and successful prosecutions of company executives that oversee systemic fraud, including jail sentences if appropriate, are necessary to deter future unlawful behavior. Otherwise, these illegal but profitable activities will continue to be part of companies’ business model.

It seems to this point, risking the fines has just been a potential cost of doing business with medications. With the FDA failing to challenge the decision in Caronia and its recent settlement with Amarin, the floodgates for off-label marketing of medications may have been opened. I hope that Jim Gottstein’s prediction that FDA opposition to off-label marketing is “dead” turns out to be wrong. If he is correct, and the FDA does not actively oppose future off-label marketing of psychiatric medications, we will be flooded with adverse events from their off-label use.

05/6/16

Fading Flakka Fad

© ARTHIT BUARAPA | 123rf.com

© ARTHIT BUARAPA | 123rf.com

In the summer of 2015 when flakka was at its zenith in Broward County Florida, police needed four or five officers to subdue one agitated person high on flakka. In The Washington Post, Todd Frankel said people high on flakka were everywhere. “Running into traffic. Zoned-out on curbs. Sometimes naked. Sometimes in the grips of a drug-fueled psychosis.” Emergency departments were overwhelmed. A drug treatment counselor in Florida said: “At the height of the flakka craze, you were almost praying for crack cocaine to come back.”

In the summer of 2015, 12 new cases of flakka-related delirium were admitted daily to South Florida hospitals. Flakka users are resistant to pain and sometimes have superman strength. Tasers were sometimes ineffective. Deputies sometimes had to wrestle users to the ground and punch them to gain control. Talking didn’t work. Reporting for The Fix, Valerie Tejeda said CNN reported there were 63 deaths attributed to using flakka in South Florida between September 2014 and December 2015. Also for The Fix, McCarton Ackerman said some Florida EMS departments were training to use ketamine to sedate flakka users who showed signs of aggression.

Then almost as quickly as flakka came onto the scene, it went away. Returning with Todd Frankel to a gas station that had been a local gathering place to buy and sell flakka, a police lieutenant in Pompano Beach Florida couldn’t find even one person. In a short period of time flakka has disappeared from South Florida. “Experts say drug epidemics almost never burn out like this.”

In March of 2015, the United Way of Broward County organized the Flakka Action Team. The task force consisted of substance abuse counselors, local police officers and others. They developed a plan “to educate the community, to teach the police how to respond and figure out how to stop flakka production.” Anti-flakka posters were put up around the county. Community forums were held. Education presentations were done at schools, jails and homeless shelters.

Traditional drug treatment didn’t work with flakka users. One of the post acute withdrawal effects with chronic users was concentration. “Even filling out paperwork was a challenge.” Some people were light sensitive, so sessions occurred in darkened rooms. Some others struggled with paranoia and insomnia.

Jim Hall, an epidemiologist at Nova Southeastern University in Fort Lauderdale, publicized the Chinese connection with flakka. You could place an online order for flakka from a Chinese manufacturer and have it delivered to your door. A kilo of flakka cost $1,500 and had a street value of $50,000. In mid–October of 2015, the U.S. Treasury imposed sanctions on one alleged synthetic drug producer in China. In November, Florida law enforcement officials and local DEA agents went to China to plead their case directly with the Chinese government.

Afterwards, China announced they had banned 116 different synthetic drugs, including flakka and fentanyl. Confusingly, the announcement said this action had been taken on October 1st. Reported hospital cases of flakka in Broward County went from 306 in October of 2015 to 54 in December. There have been no reported deaths from flakka in 2016 as of the beginning of April 2016. There were only six flakka users admitted to Florida treatment centers in January. In February the Flakka Action Team dropped “flakka” from its name.

Michael Bauman of the National Institute on Drug Abuse (NIDA) said: “History has shown that one of the unintended consequences to banning certain drugs is that it typically leads to an explosion of new replacement drugs.” Whether or not that will occur in response to the 116-drug ban remains to be seen. But there is a next step to be taken, if the recommendations of a Broward County grand jury are activated. They recommended that entire classes of drugs, such as synthetic cathinones or bath salts, which includes flakka, should be banned.

Florida Attorney General Pamela Bondi has proposed the “2016 Florida Designer Drugs Enforcement Act.” The legislation would ban synthetic cathinones, synthetic opioids and synthetic cannabinoids. It could potentially outlaw as many as 1,000 different chemical compounds, according to Jim Hall.

But what’s next? The next “designer-drug battlefield” would seem to be variations of the synthetic opioid fentanyl. Craig Mallak, the Chief Medical examiner for Broward County said: “Flakka is gone … fentanyl is the next big thing.” His office is in the process of developing a database to track the trend of fatalities with fentanyl.

For more information on flakka, read “Flack from Flakka,” “High on Flakka” and “Emerging Public Health Threat.”

05/3/16

“The Deep” in Scripture

© aliencat | stockfresh.com

© aliencat | stockfresh.com

In the Mach 2014 issue of the science journal Nature Pearson et al. presented evidence from which they concluded that the origin of the Earth’s water was deep in the mantle of the Earth. The excitement was over the accidental discovery by Pearson and his co-authors of the presence of a mineral called ringwoodite within a diamond that been expelled from deep within the Earth’s mantle by a violent volcanic eruption. The researchers were looking for a way to date the diamond when they discovered a small piece of ringwoodite enclosed in the diamond. In a Live Science article, Pearson said: “It’s actually the confirmation that there is a very, very large amount of water that’s trapped in a really distinct layer in the deep Earth.” He indicated the volume of water deep within the Earth’s mantle approaches that of the mass of water currently present in all the oceans on the surface of the Earth.

Read the Live Science article if you are interested in more information on how the researchers got from the presence of ringwoodite in a diamond to the conclusion of all that water deep beneath the Earth’s surface. It was the first time that the mineral has been discovered on the Earth’s surface in “anything other than meteorites,” because it only forms under extreme pressure, like what exists at about 320 miles deep below the Earth’s surface. Then Christian media outlets like Christianity Today reported that the discovery confirmed the Bible’s explanation of where water on the Earth came from. “The Holy Bible is clear about water on Earth coming from below the ground.” But where did the waters below the ground come from?

The answer offered by Andre Mitchell for Christianity Today went on the say the book of Genesis tells us how God created the earth as a water-covered sphere and then separated the waters to create the Sky. He then gathered together the waters under the Sky to let dry land appear, which he called Earth (Genesis 1:2, 6-11). Further biblical support for this was noted by Mitchell to be found in the Flood account, where “the fountains of the great deep” broke open and covered the entire Earth with water (Genesis 7:11).

Writing for BioLogos, Brad Kramer commented that explanations like that given in Mitchell’s Christianity Today article stem from well-meaning but misguided efforts to show that the Bible is divine revelation, since it contains scientific information that the authors could not possibly have known without divine revelation—such as the presence of water with the equivalent mass of all the oceans 320 miles below the surface of the Earth. The issue Kramer points to is one where Christians, raised within a culture rich in the knowledge and evidence of modern science, will sometimes unconsciously impose their scientific worldview onto the Bible and its interpretation.

For Christians, the purpose of the entire Bible is first and foremost to reveal Christ. Therefore, it ultimately draws its authority from the fact that it truly speaks of God and his Son. Suggesting that the Bible’s authority rests on its scientific accuracy adds an artificial middleman to this chain of authority, wherein the Bible first speaks truly of science, and therefore is trusted to speak truly of Christ.

We can wander far into the weeds of disagreement over how to interpret Genesis one, but here I want to limit our discussion to idea of the deep. Kramer observed that young earth creationists and old earth creationists seem to share a similar approach to biblical authority and interpretation. While they disagree on exactly what the Bible reveals scientifically, “they agree that the Bible is full of science prophecies that can be used to convince skeptics of the Bible’s authority.” So by this interpretive and apologetic method, a person with a modern scientific worldview can be shown where the Bible contains references to scientific knowledge that could only be from a divine source.

Referencing a quote by Richard Bube, a theistic evolutionist, Kramer referred to the idea of “arbitrary inerrancy,” within this shared method of interpretation. In his essay, “A Perspective on Scriptural Inerrancy,” Bube said the term “arbitrary” meant that inerrancy had to be maintained and defended against arbitrary criteria. In other words, biblical inerrancy itself had an all-or-nothing sense:

Oftentimes conservative theologians have spoken out in defense of Scriptural inerrancy as if there were only one kind of inerrancy imaginable-a kind of all or nothing inerrancy. They argue that the Scriptures are either completely inerrant in every way and with respect to every criterion for inerrancy which may be applied, or they are not inerrant at all.

This then leads to the Christianity Today discussion that Pearson et al. confirmed the Biblical explanation of where water on the Earth came from—the Deep. But a truly modern individual with a scientific worldview would ask, “So then were did the waters below the ground come from?” And he or she would likely dismiss the answer of Genesis one described above by Andre Mitchell, that God created the earth as a water-covered sphere. This would be an example of what Bube meant by arbitrary inerrancy. Pearson et al. confirms the Biblical declaration that surface water on the earth came from beneath the earth. But the answer to the next logical question, where did that water come from, switches to the unscientifically unsatisfactory response that “God did it.”

The Dictionary of Biblical Imagery indicated that the imagery surrounding the word deep in the Bible had five distinct categories, one of which meant “the literal, physical quality of being far below the surface of the ground.” So this sense would fit within the understanding of Genesis 1:2 given by Andre Mitchell. Scriptures where the Hebrew word for deep, tĕhôm, has that meaning are: Psalm 69:2 or Proverbs 20:5. But that is not how the word is used in Genesis 1:2.  Here is the ESV translation of Genesis 1:2: “The earth was without form and void, and darkness was over the face of the deep. And the Spirit of God was hovering over the face of the waters.”

The more common sense for tĕhôm (around 30 or 40 references) is how it is used in Genesis 1:2, indicating the ocean or the sea. For the Hebrew people, the sea was a fearsome and alien place of monsters and storms. See Isaiah 51:10 and Psalm 104, especially verses 5-6, and 25-26. Some references to the sea as “the deep” appear to imply an ancient cosmology or ancient explanation for the origin and development of the universe. Some notable examples of where this ancient cosmology seems to be the subtext of a Biblical passage are Genesis 1:2 and Genesis 7:11 and 8:2, in the Genesis account of Noah and the Flood.

The authors of the Dictionary of Biblical Imagery acknowledge the difficulty in untangling the cosmological from the merely metaphoric statements on Scripture. Nevertheless, it does seem that ancient Hebrews saw the ocean as being fed by fountains or springs (Genesis 7:11, 8:2; Job 38:16; Proverbs 8:28). They also seemed to accept a three-tiered cosmology of the universe, with the earth situated in the middle between the heaven above and the deep beneath (Genesis 49:25; Deuteronomy 33:13; Psalm 135:6). And the “deeps” were believed to be the abode of sea monsters and forces of chaos (Psalm 74:13-14).

These and other oblique references suggest that there was one or more ancient worldviews or cosmologies behind these and other Biblical passages. This would reject a hermeneutical assumption that when discussing creation and the cosmology of the “heavens and earth,” the biblical writers were alluding to scientific information that the authors could not possibly have known without divine revelation. If you read Genesis 1 through an “ancient scientific mindset” for “an ancient audience” you avoid what Brad Kramer referred to as a false dichotomy between Biblical truth and its humanity. “If God chose to communicate through and to ordinary people in real human cultures, then we should expect the Bible be written in such a way that reflects the cultural mindset of its original context.”

So a Christian who is trying to be faithful to the authority of Scripture is not required to celebrate the news from Pearson et al.’s research as a confirmation that in the Bible, water on the surface of the Earth came from below ground. Brad Kramer said that biblical references to an underground ocean reflect “an ancient cosmology that is completely, categorically, and irreconcilably different than our own.”

Equating the “great deep” in Scripture with any scientifically detectable underground body of water is to fundamentally misunderstand the ancient world in which it was written.

There is a sense in Scripture when “the deep” references a literal, physical presence of water or some other quality existing far below the surface of the ground. But there is so much more to be found in its Biblical use. It can represent chaos, danger, and evil. Within apocalyptic visions, we see the deep as a combination of sea and earth. The beasts and the antichrist emerge from the deep in the end time (Daniel 7:3; Revelation 11:7).  After the ultimate defeat of Satan and the beast, there is no longer any sea (Revelation 21:1).

From the beginning of Scripture to the end, references to “the deep” and “the depths” are images of terror with associations of danger, chaos, malevolent evil and death. “The deep” is a major negative archetype in the biblical imagination-a place or state of mind or soul that one would wish to avoid but that no one can completely avoid.

For more articles on creation in the Bible, see the link “Genesis & Creation.”