Over the Counter Pain Medication as Effective as Opioids in ER Patients-Study

Emergency rooms are where many patients are first introduced to powerful opioid painkillers, but what if doctors offered over-the-counter pills instead? A new study tested that approach on patients with broken bones and sprains and found pain relievers sold as Tylenol and Motrin worked as well as opioids at reducing severe pain.

The results challenge common ER practice for treating short-term, severe pain and could prompt changes that would help prevent new patients from becoming addicted.

The study has limitations: It only looked at short-term pain relief in the emergency room and researchers didn’t evaluate how patients managed their pain after leaving the hospital.

But given the scope of the U.S. opioid epidemic — more than 2 million Americans are addicted to opioid painkillers or heroin — experts say any dent in the problem could be meaningful.

Results were published Tuesday in the Journal of the American Medical Association.

Long-term opioid use often begins with a prescription painkiller for short-term pain, and use of these drugs in the ER has risen in recent years. Previous studies have shown opioids were prescribed in nearly one-third of ER visits and about 1 out of 5 ER patients are sent home with opioid prescriptions.

“Preventing new patients from becoming addicted to opioids may have a greater effect on the opioid epidemic than providing sustained treatment to patients already addicted,” Dr. Demetrios Kyriacou, an emergency medicine specialist at Northwestern University, wrote in an accompanying editorial.

The study involved 411 adults treated in two emergency rooms at Montefiore Medical Center in New York City. Their injuries included leg and arm fractures or sprains. All were given acetaminophen, the main ingredient in Tylenol, plus either ibuprofen, the main ingredient in Motrin, or one of three opioids: oxycodone, hydrocodone or codeine. They were given standard doses and were not told which drug combo they received.

Patients rated their pain levels before taking the medicine and two hours later. On average, pain scores dropped from almost 9 on a 10-point scale to about 5, with negligible differences between the groups.

Ibuprofen and acetaminophen affect different pain receptors in the body so using the two drugs together may be especially potent, said Dr. Andrew Chang, an emergency medicine professor at Albany Medical College in upstate New York, who led the study.

He noted that a pill combining ibuprofen and acetaminophen is available in other countries; his findings echo research from Canada and Australia testing that pill against opioids for pain relief.

Personal neoantigen vaccine prompts strong anti-tumor response in patients, study shows

A personal cancer treatment vaccine that targets distinctive “neoantigens” on tumor cells has been shown to stimulate a potent, safe, and highly specific immune anti-tumor response in melanoma patients, report scientists from Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard.

The study, published online by Nature “provides proof-of-principle that a personal vaccine tailored to a patient’s tumor can be produced and generates highly specific responses to that patient’s tumor after vaccination,” said the researchers, led by Catherine J. Wu, MD, senior author of the report. She is a researcher at Dana-Farber, the Broad Institute, and Harvard Medical School.

The scientists said that while most therapies are based on the on-size-fits-all model of medicine, “we’ve long recognized in cancer that every patient’s tumor is different. With recent advances in technology, it’s now becoming possible to create a therapy that’s suited to target an individual’s tumor.”

The researchers say the results warrant further development of neoantigen vaccines, both alone and in combination with other immunotherapy weapons such as checkpoint inhibitors. The vaccine, known as NeoVax, prompted strong activity by the patients’ immune systems while causing negligible side effects.

First authors of the report are Patrick A. Ott, MD, PhD, and Zhuting Hu, PhD, of Dana-Farber. Other senior authors include Nir Hacohen, PhD, of the Broad Institute and Massachusetts General Hospital, Edward Fritsch, PhD, formerly of Dana-Farber and now at Neon Therapeutics in Cambridge, Mass, and Eric Lander, PhD, of the Broad Institute.

Antigens are molecules that are displayed on the surface of cells and stimulate the immune system. Neoantigens are molecules on cell’s surfaces that are produced by DNA mutations that are present in cancer cells but not in normal cells, making neoantigens ideal targets for immune therapy against cancer, say the scientists. The vaccines used in the phase I trial contained up to 20 neoantigens, derived from an individual patient’s tumor. The vaccines were administered to patients to train their immune system to recognize these neoantigens, with the goal of stimulating the immune system to destroy the cancer cells that display them.

While other immunotherapies, such as checkpoint inhibitor drugs, also trigger immune responses against cancer neoantigens, they are not designed to be specific. They can also induce responses against normal tissue antigens, leading the immune system to attack normal tissues and cause toxicity in a subset of patients. The researchers found that the personal vaccine induced a focused T cell response against several tumor neoantigens, beyond what is normally seen in response to existing immunotherapies.

The vaccine was administered to six patients with melanoma whose tumors had been removed by surgery and who were considered at high risk for recurrence. The vaccinations were started at a median of 18 weeks after surgery. At a median of 25 months after vaccination, four of the six patients showed no evidence of cancer recurrence. In the other two patients, whose cancer had spread to their lungs, the disease recurred after vaccination. At that point, they began treatment with the drug pembrolizumab, which inhibits the PD-1 immune checkpoint. Both patients had complete resolution of their tumors and remain free of disease according to imaging scans.

The study results suggest, that a personalized neoantigen vaccine can potentially overcome two major hurdles in cancer therapy.

One is the heterogeneity of tumors – the fact that they are made up of cells with a variety of different traits, which often allows cancers to evade drugs targeted to malignant cells having a single genetic abnormality. The vaccine, because it contains many different neoantigens from the tumor, targets multiple genetic types of tumor cells. Wu added that in this respect, the response generated by a neoantigen vaccine is similar to the new wave of combination therapies, which are showing more promise in treating cancers that typically develop resistance to single drugs. “We are leveraging the immune system’s natural ability to detect and attack many target antigens, as it does every time we get an infection,” she said.

A second hurdle in cancer is to generate an immune response sharply focused on cancer cells while avoiding normal cells and tissues. This aim was achieved by the vaccine, which appeared to have few “off-target” effects, causing only flu-like symptoms, fatigue, rashes, and irritation at the site of the vaccine injection, according to the report.

Despite decades of attempts to develop effective cancer treatment vaccines, they have mostly failed at producing potent antitumor immune responses. The study authors say that is because these vaccines have generally been made with tumor antigens that are too similar to antigens on normal cells: as a result, the body generates a weaker immune response to avoid harming normal cells, a process called immune tolerance. By contrast, the neoantigen vaccine is custom-made for each patient using antigens produced by mutations unique to the patient’s cancer and only present on cancer cells, thus bypassing the nature immune tolerance process.

To create the vaccine, samples of a patient’s tumor and normal DNA from the patient’s blood underwent whole-exome sequencing to reveal mutations present only in the tumor’s genetic program. Because some mutations are present in the DNA but the gene is not made into RNA and protein, the researchers used RNA sequencing to identify mutations that caused the production of a mutated RNA, which is then normally translated into a protein.

Since T cells can only recognize neoantigens that are “presented” to them by HLA molecules of the immune system, a key step in making the vaccine is using computer algorithms to predict which neoantigen peptides will bind strongly to the HLA molecules for recognition by T cells. Algorithms, such as NetMHC, have been developed in recent years, making it feasible to select HLA-binding neoantigen peptides for the vaccine. Applying this tool to the six patients’ tumor samples yielded dozens of unique neoantigens for each patient’s personal vaccine.

Finally, the selected neoantigen peptides were synthesized and mixed with an adjuvant – a biochemical substance that helps to jump-start the immune response. The vaccine was then injected under the skin of the patient, with five priming doses followed by two booster doses of the vaccine.

The vaccine was aimed at generating responses to the neoantigens from T cells of two kinds – CD8+ killer cells and CD4+ helper cells. When the team monitored the vaccine’s effects on the immune system in each patient, they found that both T cell types had indeed been activated by the vaccine and could recognize the neoantigens bound to HLA molecules. Most importantly, many of the T cells were able to recognize the tumor cells directly, demonstrating that the vaccine had triggered a tumor-specific immune response that could target the patient’s tumor.

“Future neoantigen vaccine trials will recruit more patients with advanced disease to test the efficacy of the vaccine, take advantage of improved methods for predicting antigen presentation to boost the number of effective neoantigens and test for synergy with checkpoint blockade and other immunotherapeutics,” the scientists said. “If successful in subsequent trials, a personal vaccine has the potential to be applied to any cancer that harbors a sufficient numbers of neoantigens for vaccination.”

Study: Breastfeeding Moms May Be at Lower Risk of Heart Attack and Stroke

We have known for a long time that breastfeeding is healthy for babies; however studies have shown that it can provide long term health benefits for the moms too. This new information comes from recent research published in the Journal of the American Heart Association. The comprehensive study followed 300,000 adult women in China.

Previous studies showed different health benefits from breastfeeding were short term including lower cholesterol, blood pressure, glucose levels, and weight loss after pregnancy. However, this study explored long term results for the 300,000 subjects who had breastfed their babies. The research was performed by researchers from the University of Oxford, Peking University, and the Chinese Academy of Medical Sciences. The 300,000 women that took part in the study were between 30 and 79 years old and from 10 urban and rural areas across China, they tracked their health through hospital records and death registries and were part of the prospective China Kadoorie Biobank of half a million adults. The observations were as follows:

  • Nearly all gave birth and 97 percent of the women breastfed each of their babies for an average of 12 months.
  • Compared to women who had never breastfed, mothers who ever breastfed their babies had a 9 percent lower risk of heart disease and an 8 percent lower risk of stroke.
  • Among mothers who breastfed each of their babies for two years or more, heart disease risk was 18 percent lower and stroke risk was 17 percent lower than among mothers who had never breastfed.
  • Each additional 6 months of breastfeeding per baby was associated with a 4 percent lower risk of heart disease and a 3 percent lower risk of stroke.

More research is needed to determine a better correlation between breastfeeding and the health results since it is possible that women who breastfed might also engage in other healthy behaviors that might also lower their risk for cardiovascular diseases. However, the researchers did take into consideration other lifestyle choices and a range of risk factors so the observed benefits from breastfeeding were calculated independently of the other lifestyle factors.

A research fellow from The George Institute for Global Health at the University of Oxford, Dr. Sanne Peters was the study author. He explains, “Although we cannot establish the causal effects, the health benefits to the mother from breastfeeding may be explained by a faster “reset” of the mother’s metabolism after pregnancy.” It is believed that breastfeeding might eliminate the stored fat accrued during pregnancy faster and more completely and that is what leads to reduced risk of cardiovascular diseases later in life. The study co-author is Liming Li from the Peking University explains, “Nearly all women in the study were born before 1970s and the rate of breastfeeding was much higher than that in the Western populations and younger generations in China.”

The American Heart Association suggests trying to maintain breastfeeding for 12 months if possible. According to WHO’s data, about 30 percent of women in the US managed to breastfeed their baby for 12 months in 2016. In China, only 30 percent of rural women and 16 percent of urban women now managed to breastfeed their baby for 6 months or more.

This is just one of many important and informative medical research studies from The George Institute for Global Health, a health and medical research institute. Their mission is to improve the health of millions of people worldwide. One of the ways The George Institute for Global Health achieves their mission is through George Clinical, a leading contract research organization (CRO) headquartered in Sydney, Australia but with operational hubs in ten countries throughout Asia.