The cutting edge technique is still a few years away from the marketplace, but it could have the potential to greatly expand the applications for prescription drugs and the way they are delivered.
University of Michigan researchers are working on a technology that can print pure, precise doses of prescription drugs onto various surfaces, which the developers believe could enable on-site printing of custom-dose medications at pharmacies, hospitals, and physicians’ offices.
The technique can print multiple medications into a single dose on a dissolvable strip, microneedle patch or other dosing device. Researchers believe it could make life easier for patients who must now take multiple medications every day.
Max Shtein, professor of materials science and engineering at U of M, is leading the research. He spoke with HealthLeaders Media about the potential for the new technology. The following is a slightly edited transcript.
HLM: How soon will we see this technology in the market place?
Shtein: We think that possibly within five years you might be able to see some applications of this technology. There are different bottlenecks associated with Food and Drug Administration approval, depending on the medications and the indications and the conditions you are trying to treat.
Normally FDA approval for any new medication or process for making a medication takes a while. There are certain conditions for which very few treatments are effective and those gets fast-tracked through the process. There are some possibilities for things to go a little faster. There are also possibilities for using this technology in research in the drug discovery and validation stages. We think that it’s going to be finding applications pretty soon, within five years.
HLM: Are you looking to focus on a particular field of study?
Shtein: Oncology is a very interesting area in part because the medicines can be quite expensive, the treatments can be quite complex, and oftentimes there are certain characteristics of the medication for treating cancer that make it difficult to get the medicine to the cancer, to maintain a regime that people are going to be willing to go through.
There are a lot of possibilities in treating cancers locally, but there is no way to deliver the medication locally, aside from painful injections and even that is an issue because the medicine doesn’t dissolve well. We have worked with a couple of compounds that are used for treating cancer, and we showed that we can enhance these solutions. Toxic solvents aren’t needed for getting it into the system. We demonstrated in a petri dish and there is a lot of promise, but you won’t know how it will work in a living system until you do those studies.
HLM: Does this technology have the potential to disrupt how pharmaceuticals are delivered?
Shtein: We don’t aim to disrupt. That is not our goal. What want to provide a better way of doing things and hope there is a more natural migration of interest from the old crummy way of doing it into this new better way of doing it.
From a standpoint of a person needing something that is uniquely tuned to their body, metabolism, genetic condition or whatever, it is going to be super easy to do that. If you have a course of action that requires a dozen different drugs or compounds and you have to take a dozen pills on a complicated daily schedule, and for half of the drugs the amount is too large and for the other half it is too small, that’s pretty hard.
With our techniques you should sidestep all of that. You print exactly what the person needs. You can do it in a pharmacy or maybe at a doctor’s office or maybe distributed manufacturing thing going on to make that possible. Thinking about it in those terms, all of a sudden it opens possibilities for prescribing medicines in a totally different way.
HLM: Should the shareholders at CVS or Walgreens be nervous?
Shtein: This could be an opportunity for them too. They might have a bunch of people in back now who are counting pills and mixing solutions when they could be providing a lot more value if they could personalize the medicine even further.
There is a big trade off in the pharmaceutical industry and healthcare that personalization is expensive and completely at odds with manufacturability and scalability. If you want to make something cheap it has to be all the same. That goes against the idea of personalization. With this approach you break this trade-off. There is no dilemma. There is no longer an either/or situation. You can get personalization and ease of manufacturing.
HLM: Who owns the rights to this?
Shtein: The University of Michigan has the rights to the technology, but we are in conversations to see what the best way to proceed would be.
HLM: What should we be looking for as this technology progresses?
Shtein: We need input from people who are out there working with specific ailments and conditions who are developing treatments. In particular, folks are working to develop data bases based on electronic medical records that allow a very intelligence physician or a deep-learning algorithm to learn what each patient needs and translate that to formulations.
We want to find conditions that are very difficult to treat using existing techniques where people could look at our study and get inspired to say ‘Could you help us with this compound delivered in this particular way to treat this condition?’ if we could work with those people we could get a cure to that population sooner.
HLM: Can this technology be used remotely?
Shtein: When you need something specific you can have a set of instructions and a cartridge or series of cartridges and this thing makes it on demand. Rather than transporting boxes of pills all over the place, it is a much more elegant way to do it.
HLM: What other uses do you foresee for this technology?
Shtein: Doing diagnostics to help people avoid acute conditions and reduce the cost of healthcare. This technique may help with that. We can deliver so many different compounds on a small area extremely precisely. That can be used for diagnostics.
For example, let’s say you’re allergic to something but you don’t know what. Right now the best you can do is go to a hospital or an allergist who is going to stick pins in your skin with all these different allergens. They do it on a grid and see how you react. You have to kill your entire day to find out. Well, if we can do the same test on an area that was smaller than one-inch, we could do it mail a patch to you that you put on and then the patch gets the information automatically, I just saved you a whole day.
That’s worth a lot. You reduce the inconvenience, you increase the precision with which it is done, and in a smaller area you can test a lot more allergens. You have to release these things in very small quantities because otherwise you can trigger a bad reaction. Well, this technique allows you to put a lot of different compounds into a small area and release small amounts. It’s compact and you can easily ship them. There is that potential.
HLM: What’s next?
Shtein: Our main thing is developing technologies that are ultimately going to help people. We are not just playing in the sandbox in isolation, so the faster we can do it the better.
Despite the slowing rate, rising drug costs and potential changes to Medicare 340B payments for outpatient drugs would further reduce hospitals' margins.
Inpatient drug costs will continue to rise for not-for-profit hospitals, but the pace will slow under growing scrutiny of drug makers' pricing practices, Moody's Investors Service said in a new report.
Drug costs have outpaced hospital revenue growth in recent years. Moody's said the median growth rate for supply costs, which include drugs, slowed between 2015 and 2016. But the gap between how fast supply costs grew versus revenues grew widened.
"Price increases in recent years were extraordinarily high for certain branded hospital inpatient drugs, but drug manufacturers are pulling back on these increases," said Diana Lee, a Moody's Vice President. "On the generic drug side, we expect that some of the pressure will ease as the U.S. Food and Drug Administration approves more generic drugs for the first time."
The proposed reduction of Medicare Part B outpatient drug reimbursement to 340B hospitals by roughly 30% would represent another headwind for hospitals already facing pressure.
"Hospitals and health systems of varying size and across the rating spectrum have noted anecdotally that they have benefited from cost savings from this discount drug program," Lee said.
"In some instances, the savings and income gained from this program can be meaningful relative to total operating cash flow,” she said. “While about half of hospitals in the nation are 340B providers, those that have limited financial flexibility would be most exposed to possible changes to the 340B program."
The National Institutes of Health has created a primer for artificial intelligence that will help computers learn to read chest x-rays, with the hope of providing more sophisticated and consistent diagnoses.
More than 100,000 chest x-rays from a data set of 30,000 patients have been released to the scientific community as part of an effort to teach computers how to detect and diagnose disease, the NIH Clinical Data Center announced.
The images were taken with the permission of patients at the NIH Clinical Center, and will be freely shared with researchers working to improve artificial intelligence diagnoses. The dataset was screened to remove patients’ personally identifiable information.
“By using this free dataset, the hope is that academic and research institutions across the country will be able to teach a computer to read and process extremely large amounts of scans, to confirm the results radiologists have found and potentially identify other findings that may have been overlooked,” NIH said.
Consistent automated readings of chest X-rays can be complicated by a number of factors including knowledge of anatomical principles, physiology and pathology. Ultimately, it is hoped that AI can lead to clinicians making better diagnostic decisions for patients, NIH said.
In addition, this advanced computer technology may also be able to:
Identify slow changes occurring over the course of multiple chest x-rays that might otherwise be overlooked
Benefit patients in developing countries that do not have access to radiologists to read their chest x-rays
Create a virtual radiology resident that can later be taught to read more complex images such as CT and MRI
NIH will release a large dataset of CT scans in the coming months.
Prescriptions for commercially insured patients from the ED were 44% less likely to exceed a three-day supply than those written elsewhere. Those patients were also 38% less likely to exceed a daily dose of 50 milligrams of morphine equivalent.
Emergency department prescriptions for opioids are written for shorter duration and smaller doses than those written by other providers, a new study has found.
“There are a few things that many people assume about opioids, and one is that, in the ED, they give them out like candy,” Jeffery said in remarks accompanying the study. “This idea didn't really fit with the clinical experience of the ED physicians at Mayo Clinic, but there wasn't much information out there to know what's going on nationally.”
The study examined 5.2 million opioid prescriptions written for acute – or new-onset – pain across the nation between 2009 and 2015. None of the patients in the study had received an opioid prescription for the previous six months. This made it easier to compare doses by eliminating patients who built up a tolerance to the drugs.
Prescriptions for commercially insured patients from the ED were 44% less likely to exceed a three-day supply than those written elsewhere. Those patients were also 38% less likely to exceed a daily dose of 50 milligrams of morphine equivalent, which is almost seven pills of five-milligram oxycodone per day. They were 46% less likely to progress to long-term opioid use.
The results were similar for Medicare patients.
An opioid prescribing guideline from the Centers for Disease Control and Prevention issued in 2016 cautions against exceeding a three-day supply or 50 milligrams of morphine equivalent per day for acute pain.
The Mayo researchers said they were surprised to see the high numbers of prescriptions that exceeded 50 milligrams of morphine equivalent per day. One-in-five commercially insured patients in a non-ED setting received a dose exceeding the CDC guideline. People receiving prescriptions exceeding CDC recommendations – regardless of where they were written – were three times more likely to progress to long-term use.
In the last 15 years, the number of Americans receiving an opioid prescription and the number of deaths involving overdoses have roughly quadrupled, according to the CDC. More than 41 people per day died from a prescription opioid overdose in 2015.
On a positive note, the research also found that the proportion of prescriptions progressing to long-term use dropped over the study’s period.
Bond raters say the Graham-Cassidy repeal bill would hurt the U.S. economy, states, health insurers, not-for-profit healthcare providers, and cost about 580,000 jobs.
Ahead of the much-anticipated Congressional Budget Office assessment of the Graham-Cassidy bill, S&P Global Ratings has taken a look at the latest Republican effort to repeal the Affordable Care Act, and found something for everyone to dislike.
In an issues brief released Monday afternoon, S&P highlighted several areas of concern, including:
Insured levels: Lower level of insured initially in the 133%-400% of federal poverty line as repeal’s funding allocation focuses on the lower FPL levels; gradually over the longer term in the traditional Medicaid ranks as some states are unable to maintain current eligibility levels with a lower share of Medicaid federal funding.
Macro-economy: 580,000 lost jobs and $240 billion in lost economic activity by 2027, ensuring that the GDP growth remains stuck in low gear of around 2% at best in the next decade.
States: Increased flexibility comes with fewer federal dollars, creating increased fiscal and operational burdens on the states. S&P expects greater disparity among states in terms of rules for the insurance markets and uninsured levels.
Insurance industry: Increased uncertainty in the short term with repeal of mandate and lack of clarity around cost-sharing reductions. In the longer term, likely return of medical underwriting will make premium pricing more varied by morbidity.
Medicaid was the largest single outlay of federal dollars to states in 2016, accounting for $330 billion.
S&P notes that under the Graham-Cassidy bill, states will have greater flexibility in how they manage their Medicaid program including benefits, rate setting, eligibility and handling of pre-existing conditions, as well as determining a plan's ability to exclude basic healthcare services from coverage, such as maternity care. That also means that enrollees could be charged more if they have a pre-existing condition.
S&P notes that, while the Congressional Budget Office hasn't been able to complete its assessment of this bill, overall funding reductions appear to be harsher in states that have expanded Medicaid. In prior bill assessments, the CBO estimated that overall more than 20 million people would lose their health care coverage or would find it unaffordable.
“For providers, we would expect a rising number of uninsured patients with growth in unreimbursed costs and a sharp rise in charity care and bad debt,” S&P said. “In short, revenue would likely decline for providers in most states. In addition, we would expect this would contribute to a re-emergence of inpatient volume declines.”
Budget pressures on states would also lead to tougher rate negotiations with providers. “These factors, taken together, suggest the broad impact is very likely to lead to further drops in operating income for many providers,” S&P said.
The Arizona Republican says he 'cannot in good conscience' support the latest attempt by his GOP colleagues to ram through an Obamacare repeal that bypasses the budget scoring and committee process and makes no effort at bipartisan consensus.
The latest attempt to repeal Obamacare suffered a critical blow on Friday when Sen. John McCain (R-AZ) announced that he could not support the legislation.
“I believe we could do better working together, Republicans and Democrats, and have not yet really tried. Nor could I support it without knowing how much it will cost, how it will affect insurance premiums, and how many people will be helped or hurt by it,” McCain said. “Without a full CBO score, which won’t be available by the end of the month, we won’t have reliable answers to any of those questions.”
McCain’s vote is seen a crucial for the success of the bill, and it’s not clear if Senate Republicans have the votes to proceed without his support as a Sept. 30 deadline for the bill nears. Sens. Rand Paul (R-KY), Susan Collins (R-ME) and Lisa Murkowski (R-AK) have indicated that they will vote against the bill.
It’s the second time in two months that McCain, who has brain cancer, has broken ranks with his Republican colleagues and rejected their efforts to repeal Obamacare. On July 28, McCain shocked colleagues when he voted against the so-called “skinny repeal.”
Sen. Lindsey Graham (R-SC), who is good friends with McCain, issued a statement saying “I respectfully disagree” with McCain’s decision. “Obamacare is collapsing in Arizona, South Carolina, and across the nation - driving up premiums and reducing choices," Graham said. "I feel an obligation to fix this disaster and intend to push forward for state-centric health care versus Washington-knows-best healthcare.”
A federal audit shows that Medicare could have saved nearly $100 million since 2006 if system edits that were supposed to prevent or detect the errors were functioning.
Medicare mistakenly paid acute-care hospitals $51.6 million for outpatient services that were provided to inpatients at other hospitals, according to an audit by the Department of Health and Human Services’ Office of the Inspector General.
In addition, Medicare beneficiaries paid unnecessary deductibles and coinsurance of $14.4 million to the hospitals for outpatient services over the three-year period examined in the audit.
Medicare is not supposed to pay an acute-care hospital for outpatient services provided to an inpatient at another hospital, such as a long-term-care hospital. Those services should be provided under arrangements between the two hospitals, and Medicare should pay the inpatient hospital for all services provided to beneficiaries as part of the hospital's inpatient payment rate.
OIG blamed the snafu on failed systems edits that did not prevent or detect the overpayments during the audit review period between 2013-2016.
“If the system edits had been working properly since 2006, Medicare could have saved almost $100 million, and beneficiaries could have saved $28.9 million in deductibles and coinsurance that may have been incorrectly collected from them or someone on their behalf,” OIG said.
The audit recommended that Centers for Medicare & Medicaid Services direct the Medicare contractors to:
Recover the $51.6 million in improper payments to acute-care hospitals in accordance with CMS's policies and procedures;
Instruct the acute-care hospitals to refund beneficiaries up to $14.4 million in deductible and coinsurance amounts that may have been incorrectly collected from them or from someone on their behalf;
Identify and recover any improper payments to acute-care hospitals after our audit period, which ended on August 31, 2016.
“We also recommended that CMS correct the system edits to prevent overpayments to acute-care hospitals and instruct the Medicare contractors to more effectively educate acute-care hospitals not to bill Medicare for outpatient services they provided to beneficiaries who were inpatients of other facilities, but rather to provide those services under arrangements and look to the inpatient facilities for payment,” OIG said.
When adjusting for differences in injury severity, patients with gunshot or stabbing injuries were 62% less likely to die when transported by private vehicle compared to EMS.
Gunshot and stabbing victims’ odds for survival improve significantly if they’re taken to a trauma center by a private car instead of waiting for an ambulance, a new study shows.
The report, published today in JAMA Surgery, highlights the importance of studying the effects of transport, EMS services and other prehospital interventions by specific injury type.
“Time is truly of the essence when it comes to certain kinds of injuries and our analysis suggests that, for penetrating injuries such as knife and gun wounds, it might be better to just get to a trauma center as soon as possible in whatever way possible,” says Elliott Haut, MD, an associate professor of surgery and emergency medicine at the Johns Hopkins University School of Medicine and the paper’s senior author.
“For certain types of injury, it might be best to call the police, Uber or a cab — however you can get to the trauma center fastest,” he said.
Haut and colleagues examined American College of Surgeons data on 103,029 patients at least 16 years old who entered a trauma center between 2010 and 2012 for a gunshot or stab wound and were transported to the trauma center by ground ambulance or private vehicle. The data were gathered from 298 level I and level II trauma centers within the 100 most populous metro areas.
Approximately 16.4% of all patients were transported by private vehicle. The analysis found an overall 2.2% mortality rate for patients transported via private vehicle, compared to 11.6% for ground EMS.
Gunshot victims transported by private vehicle saw a lower mortality rate (4.5% versus 19.3%), as did stab victims (0.2% versus 2.9%). When adjusting for differences in injury severity, patients with penetrating injuries were 62% less likely to die when transported by private vehicle compared to EMS.
“Unlike CPR and defibrillation for heart attacks, the type of damage done in penetrating trauma often can’t be reversed in a prehospital setting. This study supports other studies that prehospital interventions can actually result in less favorable outcomes for certain types of injuries,” says Michael W. Wandling, MD, an American College of Surgeons Clinical Scholar in Residence, general surgery resident at the Northwestern University Feinberg School of Medicine and the study’s first author.
Vaccinations are urged, but the source of the outbreak is still unknown, as public health agencies in Los Angeles, Santa Cruz and San Diego counties take measures to combat the highly contagious virus.
Three counties in Southern California are dealing with a hepatitis A outbreak, with the majority of cases afflicting homeless people, drug addicts and the people who provide services for them.
“Public Health has been proactively preparing for an outbreak for some time and is working diligently to prevent spread in local communities. Our priorities are to keep all our residents both safe and well informed of the situation,” Jeffrey Gunzenhauser, MD, MPH, Interim Health Officer, Los Angeles County, said in a media release this week.
“Vaccination is the best protection against Hepatitis A. With this in mind, our outreach teams and clinics are offering free vaccine to persons who are homeless, active drug users, and those who provide services and support to those individuals,” Gunzenhauser said.
Hepatitis A outbreaks are also ongoing in San Diego and Santa Cruz counties. Officials have confirmed 10 total cases of the highly contagious virus among high-risk people in Los Angeles County. Four of the infected people had been in San Diego and one had been in Santa Cruz during their exposure period.
Three secondary cases occurred in a healthcare facility in Los Angeles County. Two most-recent cases appear to have acquired their infection locally within Los Angeles County, officials said.
Hepatitis A can be acquired through contact with an infected person’s feces through contaminated food or objects. Officials have all but ruled out contaminated food as the source of this outbreak.
The hepatitis A virus can spread when a person does not properly wash their hands after going to the bathroom or changing diapers. The virus can cause acute liver disease.
Other modes of transmission include certain sexual practices, sharing equipment related to illicit drug use, and consumption of food or water contaminated with the virus. People who are homeless are at higher risk because they face challenges to maintaining good hygiene, officials said.
Symptoms of acute hepatitis A include fever, malaise, dark urine, lack of appetite, nausea, and stomach pain, followed by jaundice. Symptoms generally last for less than two months although some persons may have prolonged or more severe illness. Infection can be prevented in close contacts of patients by vaccination or administration of immune globulin within two-weeks following exposure.
San Diego County
Public health officials in San Diego County have been grappling for several months with the outbreak of hepatitis A, which is blamed for at least eight deaths, with all of the victims weakened by underlying medical conditions.
Nick Yphantides, MD, with the San Diego County Health & Human Services Agency, said this week that “the outbreak is not from a contaminated food source. It is caused by person-to-person transmission.”
“One of the challenges of this virus is the long incubation period,” Yphantides said. “With this virus the average incubation period is 28 days, but the range of the incubation period can be anywhere from 15 to 50 days, which is quite a long incubation period.”
“Another complicating factor, medically speaking, is that individuals can be infected and can be transmitting the virus for up to two weeks prior to them having any symptoms,” he said.
The county’s Public Health Division says an investigation is ongoing and challenging because of the long incubation period and the difficulty contacting people sickened with the illness who are homeless and/or illicit drug users.
With no common source of food, beverage, or other cause identified, the source of the outbreak remains undetermined, county officials said.
Tennessee officials said they approved the proposal after the two systems demonstrated that they would create a public benefit to Northeast Tennessee that would outweigh any downsides of a monopoly of services.
The proposed merger between Mountain States Health Alliance and Wellmont Health System took a big step forward on Tuesday when Tennessee officials approved the health systems’ Certificate of Public Advantage application.
“We believe this merger will result in sustaining high-quality health care for our region, will reduce the growth in costs and will create one of the nation’s leading health systems,” said Mountain States President/CEO Alan Levine, who would be executive chairman and president of the combined systems if the merger is finalized.
The new system, to be called Ballad Health, still requires approval from Virginia, but executives at Johnson City, TN-based Wellmont and Kingsport, TN-based Mountain States said they expect the merger to be approved by the end of the month.
For Tennessee to approve the merger, the systems agreed through the legislative process and in a series of public meetings to demonstrate that their merger would create a public benefitto Northeast Tennessee that would outweigh any downsides of a monopoly of services, Tennessee officials said.
“We appreciated how Wellmont and Mountain States assisted our office and the department during this process and certainly want to acknowledge the commitment of the community leaders to reach this point,” said Tennessee Attorney General Herbert H. Slatery III. “Everyone’s objective is to employ a new idea, a new structure to fundamentally improve the health of the region. We wish them great success.”
According to the terms of the COPA, the systems have 90 days to complete the merger, when they will complete the legal work to form Ballad health. Virginia officials are expected to issue their decision by the end of the month. With approval from Virginia, the merger is expected to be finalized in early 2018.
Ballad Health said it will “make significant investments to improve the health of our region, to advance academics and research, to improve children’s healthcare, and to strengthen and better align rural healthcare offerings.”
Tennessee Department of Health Commission John Dreyzehner, MD, said state officials worked with the healthcare systems to create an index of benchmarks to improving key health outcomes in the region. The index includes recommendations from the COPA Index Advisory Group, which was comprised of 16 people from the region. The group held five listening sessions and subsequent working meetings in the spring of 2016.
FTC Opposition
Tennessee approved the deal despite the longstanding opposition by the Federal Trade Commission, which sees the merger as anti-competitive. In several comments submitted to Virginia and Tennessee, FTC staff have repeatedly stated that “the lost competition from the proposed merger of Mountain States and Wellmont would significantly harm residents of northeast Tennessee and southwest Virginia.
“The staff emphasizes that the two hospital systems have failed to show that the consumer harm from the proposed merger would be outweighed by its purported benefits, or offset by the applicants’ proposed commitments,” the FTC said in a media release.
“FTC staff conclude that the applicants’ consultants’ reports “fail to provide sufficient additional information or analysis to demonstrate by clear and convincing evidence that the purported benefits of this merger would outweigh the serious competitive harm that would likely result from creating a near-monopoly.”
Jay Levine, an anti-trust attorney with Porter Wright Morris & Arthur LLP, said there might not be much the FTC can do to block the deal at this point.
“Depending on how the COPA law and approval process is structured, the parties may be entitled to state action immunity,” Levine said. “In that case, the FTC can’t do anything, even if they think the merger is anticompetitive.”
“Absent an immunity, merely because state officials cleared the merger under one set of regulations, which focus on things that are not necessarily antitrust-related, the FTC can still argue that the merger substantially reduces competition,” he said. “Given state approval, though, the FTC may need a bit more evidence than usual to decide to challenge the merger.”
Wellmont and Mountain States provided this statement when asked Tuesday about the ongoing FTC opposition:
"We have pursued a robust state approval process in Tennessee and Virginia for two and a half years. Should both states approve our applications, both will play an active role in supervising the new health system. Under longstanding U.S. Supreme Court legal doctrine, state approval of the kind obtained in Tennessee and under consideration by Virginia protects the merger from such an FTC challenge."
"The FTC staff submitted written comments to the Tennessee Department of Health on various occasions, urging the Department to deny the parties’ application to merge. We cannot speculate on what the FTC might do. We respect the role they play, but we believe our merger is lawful and we would vigorously defend it if any action is taken to challenge it."
