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Sunday, September 30, 2018

270 Painkillers Per Person: DEA Probes Pill Mills in Small Tenn. Town


DEA agents discover another small town in America’s Rust Belt with an overabundance of opioids
The Drug Enforcement Administration (DEA) last week conducted inspections at several pharmacy locations in the Clay County, Tennessee town of Celina, following a massive spike of painkiller purchases from drug distribution companies.
According to the sales data, obtained by the DEA, several pharmacies purchased nearly 1.5 million pills in 2017, a number that is considered an anomaly of a rural area in America’s Rust Belt region.
Home to just 7,800 people, the pharmacies last year purchased enough opioids to provide 270 pain pills for every man, woman, and child living in the small Tennessee town.
In response to the opioid crisis, the DEA is now aggressively monitoring supply chains of pill distributors that primarily feed into hard-hit states.
“DEA’s action today is one of many proactive measures we are taking to help prevent drug diversion, abuse, and trafficking that end lives and destroy families and communities,” said Louisville Division Special Agent in Charge Chris Evans, who runs DEA operations in Tennessee, West Virginia, and Kentucky.
“When DEA sees abnormal patterns such as this one, we must act. Too many rural communities like Clay County are often targets for both addicts and drug traffickers who exploit the most vulnerable and who profit from addiction. We’ve lost too many Americans to opioid abuse,” Evans said.
Notice of inspection was issued to Anderson Hometown Pharmacy, LLC at 151 MacArthur Avenue, and Walgreens at 1000 Gainesville Highway. The DEA said an administrative inspection warrant was also issued to another pharmacy, Clay County Express Pharmacy, LLC at 651 Brown Street. Some of these inspections included a complete review of receipts and distributions, employee interviews, and all other pharmacy activities.
Last week, the Centers for Disease Control reported that drug overdose deaths in 2017 were up 7% from 2016 and that more than 72,000 American died the previous year — that is more than American soldier deaths in the Vietnam War (58,220 US military fatal casualties). This is a more than 200% increase over a decade. Of those overdose deaths, just over 49,000 were from synthetic opioids, which include prescription painkillers, heroin, fentanyl, and fentanyl analogs. Pain management, then pill abuse, is often the starting point for heroin and fentanyl addicts.
Days ago, we reported a similar incident in Williamson, West Virginia, where two pharmacies just four blocks apart pumped 20.8 million prescription painkillers in a town of only 3,191 residents.
It was reported that in December 2002 to January 2010, more than 335,000 prescriptions for painkillers were issued by Dr. Katherine Hoover at a small clinic in the struggling West Virginia town, a rate of about 130 per day.
Williamson is a small blue-collar city of some 3,000 residents just across the Tug Fork River from Kentucky. When the coal industry collapsed, it left behind many miners – many of whom were already reliant on painkillers.
However, like Williamson, Clay County is similar, both areas are located in America’s Rust Belt, where de-industrialization and high unemployment fuels the deadly cycle of addiction.
Now, these lost and forgotten towns in the Rust Belt are being pumped with record amounts of opioids by large pharmaceutical firms, who then in return, have local doctors and pharmacies dish out painkillers to residents.
Yet while the DEA is finally cracking down on opioid abuse, the one question left is: why did the government allow pharmaceutical companies and pill mills to pump millions of highly addictive opioids into the Rust Belt in the first place?

Tymlos Benefits Bone in Older Women


The benefits seen on bone mineral density (BMD) and fracture incidence reduction with abaloparatide (Tymlos) treatment for all postmenopausal women in the ACTIVE trial and its extension phase also were seen among the oldest members of the study cohort (ages ≥80), a post-hoc analysis found.
The Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial was an international randomized study that compared subcutaneous injections of abaloparatide, 80 µg daily, with subcutaneous teriparatide, 20 µg daily, and placebo for 18 months in almost 2,500 postmenopausal women. In the ACTIVExtend phase, all patients received alendronate 70 mg weekly through month 43.
“Efficacy and safety information on pharmacological treatments to prevent fractures is sparse in older patients, who are often excluded from clinical trials. Thus, it is important to understand the efficacy and safety of osteoporosis treatments in this population,” said Felicia Cosman, MD, of Columbia University in New York City, during a poster session at the American Society for Bone and Mineral Research annual meeting.
“Fractures are particularly common among older women, and the consequences take away from the quality and quantity of life in this group,” she told MedPage Today.
Abaloparatide is a selective activator of the parathyroid 1 receptor signaling pathway that is associated with increased bone formation. It was approved by the FDA in April 2017 for the treatment of postmenopausal osteoporosis.
A previous post-hoc analysis of ACTIVE participants in the placebo-controlled phase found that the efficacy and safety of abaloparatide among women, ages ≥80, were similar to what was seen in the overall study population.
The current analysis followed those 56 women whose mean age was 81.8 at baseline through an additional 24 months, during which all received alendronate, 70 mg weekly.
Among those who had initially been randomized to receive placebo, 18.5% had at least one prior nonvertebral fracture within the previous 5 years, as did 17.2% of those initially given abaloparatide. For prevalent vertebral fractures at baseline, the corresponding numbers were 18.5% and 41.4%, respectively.
During the 24-month follow-up phase when all patients were receiving only alendronate, the fracture rates among the age >80 subgroup were low. Among those who had initially received placebo or abaloparatide, respectively, the rates subsequent fractures were:
  • New vertebral fracture: 4% vs 0%
  • Nonvertebral fractures: 7.4% vs 4.2%
  • Clinical fractures: 7.4% vs 4.2%
  • Major osteoporotic fractures: 3.7% vs 0%
BMD at the total hip, femoral neck, and lumbar spine increased significantly more in the group that had initially received abaloparatide at all time points except for total hip at month 6 and femoral neck at month 12.
During the extension phase, 81.5% of the 27 age >80 patients who had initially received placebo reported any adverse event, as did 78.6% of those who had initially been given abaloparatide. For serious adverse events, the numbers were 11% and 14.3%, and for adverse events leading to discontinuation, the numbers were 7.4% and 3.6%. No adverse events resulted in death.
The specific adverse events in the placebo versus abaloparatide groups included arthralgias (11.1% vs 7.1%), back pain (7.4% vs 10.7%), dizziness (11.1% vs 3.6%), dyspepsia (3.7% vs 10.7%), and hypertension (11.1% vs 3.6%).
“Now we have data to suggest that when treating older patients with a drug like Tymlos, we should expect to get very good results,” Cosman concluded.
The study was funded by Radius Health. Some co-authors are company employees.
Cosman dislcosed no relevant relationships with industry. Some co-authors disclosed relevant relationships with the NIH, Radius Health, Amgen, Eli Lilly, Merck, and Tarsa.

HHS funds further research of a wearable device that could warn of early illness


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It’s a device the size of a key fob that measures breathing, heart rate, sleep, and movement. It can be attached to clothing such as undergarments, requires no recharging, and will survive cycles through the washer and dryer.
The U.S. Department of Health and Human Services (HHS) is hoping that one day this easy-to-use monitor will issue early warnings that the individual wearing it is about to become sick. The implications for health systems managing population and chronic health initiatives is obvious: early detection and treatment of illnesses such as the flu could prevent hospitalizations, improve outcomes, and lower costs.
San Francisco-based Spire received a $62,200 grant from HHS to further gather data from these devices and discover, through artificial intelligence, if patterns exist that can predict the onset of illness. The total cost of the project is $88,860, with Spire providing the retaining funds.
The product, Health Tag, is already commercially available for consumer health and wellness use to monitor sleep, stress, and activity. Currently available in a variety of package sizes, with a heavy adhesive for each unit that does not loosen during laundering, individuals using the sytem can attach the monitors to frequently worn clothing and never have to check them again to download information or change batteries. Collectively, an 8-pack lasts about 18 months, says Jonathan Palley, CEO and co-founder of Spire.
The device can send messages to the user’s cell phone to report findings and alert the wearer to real-time bio-signals, like heart-rate and breathing variability, stress levels, and other changes in the user’s unique health signature.
One reason Palley believes Health Tag offers advantages over other such devices on the market is that it requires minimal interaction to operate.
“It really solves the adherence problem,” Palley says. Ideally, data from such monitors needs to be collected continuously, but If constant interaction is required, compliance drops, he explains.
The grant to Spire was awarded through the Division of Research, Innovation and Ventures (DRIVe), a division of the Biomedical Advanced Research and Development Authority(BARDA) in the HHS Office of the Assistant Secretary for Preparedness and Response. One expected outcome from this venture, says Palley, is that BARDA will be able to accelerate development toward Food and Drug Administration 510K clearance.
Palley says he was not aware of opportunities to work with BARDA before the agency approached his company. DRIVe is spurring innovation in the way the government prevents, detects, and responds to major health security threats. The grant was awarded as part of DRIVe’s Early Notification to Act Control and Treat (ENACT) portfolio to develop products that will let people know they are sick before the first symptom appears.
A news release from DRIVe further explains the organization’s interest, “Innovative technologies like wearable ENACT products hold the potential to also strengthen the nation’s ability to protect Americans from health security threats and to save lives.”
In July, BARDA granted funding to two California-based biotech companies for development of at-home flu tests. In September it announced an award to EnLiSense to accelerate development of a wearable device that detects infections in a person’s sweat. The division also has an initiative related to prevention and early detection of sepsis.

Early Parkinson’s patients waiting too long to seek medical evaluation


Early Parkinson’s patients waiting too long to seek medical evaluation
Figure 1. Relationship between time of diagnosis, need for symptomatic therapy and the opportunity for a patient to participate in an early PD disease modifying therapy trial. Credit: University of South Florida
The time between diagnosis and the institution of symptomatic treatment is critical in the effort to find a cure for Parkinson’s Disease (PD). A paper published in Nature Partner Journal: Parkinson’s Disease notes too many early PD patients wait too long before seeking medical attention, or start taking symptomatic medications before they are required, thereby dramatically shrinking the pool of candidates for clinical trials.
Parkinson’s disease is a disorder of the central nervous system that affects . Symptoms include tremors, stiffness, and slow and small movement. The pace of progression varies among patients, making the months following diagnosis crucial to researchers studying the disease’s progression.
“The critical time of about one year from when the patient can be diagnosed with early PD based on mild classic motor features until they truly require symptomatic therapy can be considered the Golden Year,” said lead author Robert A. Hauser, MD, director of the Parkinson’s & Movement Disorder Center at the University of South Florida. “It is during this early, untreated phase, that progression of clinical symptoms reflects the progression of the underlying disease.”
Hauser says that in order to determine whether or not a potential disease slowing therapy is actually working, they must be able to compare the therapy to a placebo without interference from symptomatic treatment. Otherwise, they won’t know if the therapy is slowing the disease’s progression or if they are just seeing the effects of symptomatic treatment.
This requires patients to seek assessment soon after they notice the onset of tremor or slow movement. In addition, physicians should consider referring patients to clinical trials soon after diagnosis and delay prescribing symptomatic medication until it’s necessary. If a patient waits until symptomatic  is necessary, the opportunity to participate in these crucial  is lost.
More information: Robert A. Hauser. Help cure Parkinson’s disease: please don’t waste the Golden Year, npj Parkinson’s Disease (2018). DOI: 10.1038/s41531-018-0065-1

Some cancer therapies may avert cardiovascular disease


Existing cancer drugs could be repurposed as treatments for vascular inflammation, according to new research from the University of California San Diego School of Medicine.
Publishing their findings in Cell Reports, the authors describe new insights into the way G-protein-coupled receptors (GPCRs) work within cells to influence inflammation using cellular “waste disposal systems.”
Vascular inflammation (inflammation of the blood vessels) is a significant contributing factorin the early phases of atherosclerosis, a disease whereby plaque builds up inside the arteries and which can lead to heart attack, stroke, or even death.
Cardiovascular disease is the leading cause of death worldwide, so identifying any potential targets for therapies addressing cardiovascular disease or its causes — such as vascular inflammation — is a priority.

GPCR functions ‘not fully understood’

GPCRs are embedded in the membranes of all cells, where they mediate cells’ responses to their external environments. GPCRs change shape when a nutrient or other molecule binds to them.
Part of this shape change involves a G-protein inside the cell docking to the GPCR on the internal side of the membrane, which initiates a series of molecular changes.
Scientists know that GPCRs are important in maintaining many biological functions such as smell, sight, taste, allergic responses, blood pressure, and heart rate.
They also know that when GPCRs malfunction, they can contribute to a range of diseases. However, many of the basic functions of GPCRs are still not fully understood.

How GPCRs influence inflammation

The research team from this latest study investigated how a process called ubiquitination affects GPCR functions in the cells that line blood vessels.
Ubiquitination is when proteins are tagged by enzymes with molecules called ubiquitin, acting as a kind of flag to let the cell know that this protein can be disposed of.
However, the team discovered that in these cells, the GPCR activates the E3 ligase enzyme that initiates ubiquitination, which in turn activates an inflammation-promoting protein called p38. This is a markedly different mechanism to the usual process of ubiquitination.
“We were surprised to discover that GPCRs and inflammation are influenced by ubiquitination — a process that was previously thought to only mark proteins for destruction,” explains senior author JoAnn Trejo. “Instead, we’ve unveiled new insights into both GPCR function and ubiquitination.”
According to Trejo, this is the first time that E3 ligases have been identified as playing a role in vascular inflammation, making it a viable target in developing treatments for this condition.
The good news is that several drugs that are currently used as cancer treatments have already been approved by the Food and Drug Administration (FDA); such drugs inhibit these E3 ubiquitin ligases, and researchers are currently studying more in clinical trials. So, it may be possible to also use these drugs to treat vascular inflammation.
However, Trejo warns that “the field is really in its infancy,” and that “the number of E3-targeting drugs approved or in clinical trials is remarkably small.” This is further complicated by the sheer number of different E3 ligases in the body, thought to be between 600 and 700, and which are associated with a variety of biological functions.
Although vascular inflammation is a known contributor to atherosclerosis, Medical News Todayrecently reported on a study that found inflammation may actually help to keep heart attack and stroke at bay in more advanced cases of the condition.

China HIV/AIDS cases surge by 14%


The number of people living with HIV/AIDS in China has surged by 14 percent, with most cases transmitted through sex rather than blood transfusions, state media said Saturday.
More than 820,000 people had AIDS or were HIV-positive at the end of June, up by 100,000 year-on-year, the official Xinhua news agency said, citing national health officials at an HIV/AIDS conference.
More than 40,000 new HIV/AIDS cases were reported in the second quarter alone, with 93.1 percent having contracted the virus through sex.
The number of HIV infections caused by  transfusions has “essentially been reduced to zero”, according to Xinhua.
China has been hit by blood transfusion scandals in the past.
In the 1990s, rural parts of China—particularly the central province of Henan—endured the country’s most debilitating AIDS epidemic.
It stemmed from a tainted government-backed blood donation programme and infected tens of thousands of people, including entire villages.
In 2015,  reported the case of a five-year-old girl who had contracted HIV through a blood transfusion during an operation for .

New cancer vaccine shows early promise for patients with HER2-positive cancers


Treatment with a HER2-targeted therapeutic cancer vaccine provided clinical benefit to several patients with metastatic HER2-positive cancers who had not previously been treated with a HER2-targeted therapeutic, according to data from a phase I clinical trial presented at the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival, held Sept. 30-Oct. 3.
Among 11 evaluable  who had received more than the lowest dose of the , six (54 percent) had clinical benefit. One patient with ovarian  had a complete response that lasted 89 weeks, one patient with gastroesophageal cancer had a partial response that lasted 16 weeks, and four patients (two with colon cancer, one with prostate cancer, and one with ovarian cancer) had stable disease.
“Immunotherapy marshals the exquisite specificity of the immune system to destroy cancer, and some types may have potentially fewer side effects than traditional chemotherapy,” said Jay A. Berzofsky, MD, Ph.D., chief of the Vaccine Branch at the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. “We are using a  to generate an immune response to HER2, which is found at high levels on and drives the growth of several types of cancer, including breast, ovarian, lung, colorectal, and gastroesophageal cancers.
“Our results suggest that we have a very promising vaccine for HER2-overexpressing cancers,” continued Berzofsky. “We hope that one day the vaccine will provide a new treatment option for patients with these cancers.”
The patients’ vaccines are individually customized by Berzofsky and colleagues using their own immune  isolated from their blood. The blood-derived immune cells are modified in several ways in the laboratory. The final product, which is administered intradermally (between the layers of the skin), comprises patient-derived dendritic cells genetically modified with an adenovirus to produce parts of the HER2 protein.
Preclinical studies, which were previously published in the AACR journal Cancer Research, showed that this type of vaccine could eradicate large, established tumors as well as lung metastases in mice.
In the dose escalation portion of the phase I clinical trial, patients were injected with the vaccine on weeks 0, 4, 8, 16, and 24 after enrollment in the study. Among the six patients who received the lowest dose of the vaccine, 5 million dendritic cells per injection, no clinical benefit was seen. Among the 11 patients who received either 10 million or 20 million dendritic cells per injection, six had clinical benefit.
Adverse reactions were predominantly injection-site reactions that did not require treatment. No cardiotoxicity was seen.
“Based on the current safety and  data, the dose of the vaccine was increased to 40 million  per injection and the trial opened to patients who have previously been treated with a HER2-targeted therapeutic, including patients with breast cancer,” said Berzofsky.
“Moving forward, we would like to investigate whether we can increase the proportion of people who benefit from treatment with the vaccine by combining it with checkpoint inhibitor therapy,” he added.
According to Berzofsky, the main scientific limitation of the study is that it is a relatively small, phase I clinical trial with no placebo control. However, the approach is sufficiently promising to warrant additional trials.