The Observatory & Fast Facts

June 21, 2018

FAST FACTS: Opioids in America

What do Americans say about opioid use in America, and their own experience with opioids? These statistics come from a study conducted by Lake Forest, Illinois-based Stericycle.

  • 42 percent of Americans have one to three bottles of unused prescriptions, including opioids, in their medicine cabinet.
  • 9 percent of Americans have four to six bottles.
  • 2 percent of Americans have seven to ten bottles.
  • 15 percent of Americans admit they’ve offered or given unused opioids to a friend or family member.
  • 25 percent of Americans admit they’ve been offered or given unused opioids by a friend or family member.
  • 30 percent of Americans admit they’ve kept leftover prescriptions for future use.
  • 74 percent of Americans believe that sharing and selling of unused prescriptions is contributing to the growth of the opioid epidemic.
  • 25 percent of Americans admit to flushing unused prescriptions.
  • 83 percent of Americans say they have never participated in a “drug takeback program.”
  • 27 percent of Americans say they are concerned about the U.S. government solving the nation’s opioid epidemic.
  • 52 percent of Americans believe that the opioid epidemic can be stopped.

Source: The Opioid Epidemic and Unused Prescriptions Study. 

Infectious Diseases

The immune system does not recover despite cured hepatitis C infection. Changes to the immune system remain many years after a hepatitis C infection is cured, a new study by researchers at Karolinska Institutet and Hannover Medical School shows. The findings, presented in Nature Communications, increase understanding about chronic infection and the way it regulates and impacts composition of the immune system.

Infection with hepatitis C virus (HCV) almost always turns chronic and poses a major health problem around the world. The infection can lead to cirrhosis and cancer of the liver when the immune system fails to fight the virus. Eventually the immune system becomes exhausted. However, most patients with HCV can now be cured in a matter of a few weeks with revolutionary new medications that became available in about 2015.

The current study included 40 patients with chronic HCV infection whom researchers followed before, during, and after treatment with these new medications to investigate impact on the composition and diversity of the immune system. Diversity is vital to the ability of the immune system to fight infections. Of particular importance are natural killer (NK) cells, a type of white blood cells. The researchers used flow cytometry and a new measurement method to derive the composition of the immune system, as well as the appearance of NK cells and their function in the blood.

The results showed that the overall composition of the immune system was affected by the chronic infection, with significantly reduced diversity among the NK cells. Many of the changes remained long after the virus had been eliminated by means of medication. Researchers have not yet determined the long-term implications but are currently exploring whether patients have a harder time fighting future infection.

A number of questions are outstanding. Researchers would like to investigate consequences for a good deal longer than a few years, as well as identify strategies for rejuvenating the immune system and increasing its diversity.

Genomics/Proteomics

Genome-editing tool could increase cancer risk. CRISPR-Cas9 is a molecular machine first discovered in bacteria that can be programmed to go to an exact place in the genome, where it cuts the DNA. These precise ‘molecular scissors’” can be used to correct faulty pieces of DNA and are currently being used in clinical trials for cancer immunotherapy in the United States and China. New trials are expected to be launched soon to treat inherited blood disorders such as sickle cell anemia.

Two independent articles published in the journal Nature Medicine now report that therapeutic application of the genome-editing tool may, in fact, increase the risk of cancer. In one of the studies, scientists from Karolinska Institutet and the University of Helsinki report that use of CRISPR-Cas9 in human cells in a laboratory setting can activate a protein known as p53, which acts as a cell’s “first aid kit” for DNA breaks. Once active, p53 reduces the efficiency of CRISPR-Cas9 gene editing. Thus, cells that do not have p53 or are unable to activate it show better gene editing. Unfortunately, however, lack of p53 is also known to contribute to making cells grow uncontrollably and become cancerous.

“By picking cells that have successfully repaired the damaged gene we intended to fix, we might inadvertently also pick cells without functional p53,” says Dr. Emma Haapaniemi, who was co-first author of one of the studies. “If transplanted into a patient, as in gene therapy for inherited diseases, such cells could give rise to cancer, raising concerns about the safety of CRISPR-based gene therapies.”

“CRISPR-Cas9 is a very powerful tool that has staggering therapeutic potential,” adds Dr. Bernhard Schmierer, who served as co-supervisor of the study. “As is the case with all medical treatments, however, CRISPR-Cas9-based therapies might have side effects, which patients and caregivers need to be aware of. Our study suggests that future work on the mechanisms that trigger p53 in response to CRISPR-Cas9 will be critical in efforts to improve the safety of CRISPR-Cas9-based therapies.”

Diagnostics

Finances are a major factor in patient avoidance of diagnostic testing. Patient preferences for diagnostic testing differ significantly across levels of risk, benefit, and cost of testing, but cost is the strongest and most consistent factor associated with decreased desire for testing. Those are the findings of a study published in the June 2018 issue of Academic Emergency Medicine (AEM), a journal of the Society for Academic Emergency Medicine (SAEM).

The lead author of the study is Jonathan D. Porath, University of Michigan Medical School. The emergency department-based study by Porath and colleagues utilized a copay to “penalize” for the test. The results suggest that a credit for foregoing the test (comparable to a safe driver discount) might be an interesting direction for future research. With patients having a growing personal contribution to healthcare, the findings support the need for further study to determine how best to implement financial considerations to alter testing behavior.

Erik P. Hess, MD MSc, professor and vice chair for research at the University of Alabama at Birmingham Department of Emergency Medicine, comments: “This study highlights the importance patients may place on the cost of low-value diagnostic testing. Implementing these findings requires careful consideration, as discussing cost in this context may have unintended effects on physician trust and runs the risk of disproportionately influencing decision-making in uninsured patients. Nonetheless, it is important for physicians to recognize the importance of cost as a driver of patient decision-making in low-value diagnostic testing.”

Vitamin D

High vitamin D levels linked to lower cholesterol levels in children. There is a link between higher serum vitamin D levels and lower plasma cholesterol levels in primary school children, University of Eastern Finland research shows. Children whose serum 25-hydroxyvitamin D levels exceeded 80 nmol/l had lower plasma total and low-density lipoprotein (LDL) cholesterol levels than children whose serum 25-hydroxyvitamin D levels were below 50 nmol/l, which is often regarded as a threshold value for vitamin D sufficiency. 25-hydroxyvitamin D is the major circulating form of vitamin D. The findings were reported in the Journal of Clinical Endocrinology and Metabolism.

Vitamin D is known to be essential for bone metabolism, and low serum 25(OH)D levels increase the risk of rickets, osteomalacia, and osteopenia. Vitamin D may also improve plasma lipid levels and have beneficial impact on other risk factors of cardiovascular diseases.

Lifestyle factors, such as healthy diet, physical activity, and spending time outdoors leading to the production of vitamin D in the skin, may be linked to both higher serum vitamin D levels and lower plasma lipid levels. The researchers found that the link between higher serum vitamin D levels and lower plasma cholesterol levels was independent of body adiposity, dietary factors, physical activity, parental education, and day length prior to blood sampling. Moreover, hereditary factors that have been linked to serum vitamin D levels did not modify the observed association. More research is needed to uncover the reasons behind the inverse association of serum vitamin D with plasma lipid levels.

The new findings provide support for the importance of following recommendations for vitamin D intake, which vary from country to country. The most important dietary sources of vitamin D are vitamin D fortified products such as dairy products and spreads, and fish.

In addition to the dietary intake, vitamin D supplement use is also recommended for the general population in several countries. The recommended use of vitamin D supplements varies considerably among these countries (mostly 5-50 μg/d, corresponding to 200-2000 IU/d), depending on age group and other factors.

Vitamin D is synthetized endogenously in the skin in the presence of UV-radiation from the sun. However, in northern latitudes, exposure to sunlight alone is inadequate to maintain sufficient serum 25(OH)D levels, especially during winter.

Molecular Diagnostics

Mayo Clinic researchers take a step closer to developing a DNA test for liver cancer. A group of researchers from Mayo Clinic and Exact Sciences Corporation have completed a phase II study comparing a set of DNA markers to alpha fetoprotein as a method to test for liver cancer. The researchers presented their findings last month at the 2018 Digestive Disease Week conference in Washington, D.C.

“We currently test for liver cancer using ultrasound and a blood protein marker called alpha fetoprotein,” says John Kisiel, MD, a gastroenterologist at Mayo Clinic. “Unfortunately, these tests are not very sensitive for curable stage liver cancers, and most patients who need this testing do not have it easily available or [are] not able to receive it often enough to be effective.”

Dr. Kisiel and his colleagues developed a simple blood test using abnormal DNA markers that are known to exist in liver cancer tissues. They were able to confirm that the abnormal DNA markers were present in the overwhelming majority of blood samples that came from people with primary liver cancers. Simultaneously, these markers were absent in healthy individuals and individuals with cirrhosis of the liver, but no evidence of tumors on their clinical follow-up.

“We were most excited that our DNA markers were able to detect more than 90 percent of patients with curable stage tumors,” says Dr. Kisiel. “This is the main reason why we think a DNA test will make a difference, compared to currently available tests.” Dr. Kisiel says the next step will be to validate these markers in blood testing on much larger patient cohorts.

According to the National Cancer Institute, the number of new cases of liver and bile duct cancer in the U.S. was 8.8 per 100,000 men and women per year. Dr. Kisiel says primary liver cancer is a major cause of suffering and death for patients who have cirrhosis of the liver or patients with hepatitis B infections. Worldwide, liver cancer is the second most common cause of cancer death.