Tag: 2018 News

Scientists at the Salk Institute have developed a technique to directly convert the cells in an open wound into new skin cells. The approach relies on reprogramming the cells to a stem-cell-like state and could be useful for healing skin damage, countering the effects of aging and helping us to better understand skin cancer.

“Our observations constitute an initial proof of principle for in vivo regeneration of an entire three-dimensional tissue like the skin, not just individual cell types as previously shown,” says Salk Professor Juan Carlos Izpisua Belmonte, holder of the Roger Guillemin Chair and senior author of the new paper, published in the journal Nature on September 5, 2018. “This knowledge might not only be useful for enhancing skin repair but could also serve to guide in vivo regenerative strategies in other human pathological situations, as well as during aging, in which tissue repair is impaired.”

Cutaneous ulcers — wounds that can extend through multiple layers of the skin — are typically treated surgically, by transplanting existing skin to cover the wound. However, when the ulcer is especially large, it can be difficult for surgeons to graft enough skin. In these cases, researchers are able to isolate skin stem cells from a patient, grow them in the lab and transplant them back into the patient. However, such a procedure requires an extensive amount of time, which may put the patient’s life at risk and is sometimes not effective.

Izpisua Belmonte and Salk Research Associate Masakazu Kurita, who has a background in plastic surgery, knew that a critical step in wound recovery was the migration — or transplantation — of basal keratinocytes into wounds. These stem-cell-like cells act as precursors to the different types of skin cells. But large, severe wounds that have lost multiple layers of skin no longer have any basal keratinocytes. And even as these wounds heal, the cells multiplying in the area are mainly involved in wound closure and inflammation, rather than rebuilding healthy skin.

Izpisua Belmonte and Kurita wanted to directly convert these other cells into basal keratinocytes — without ever taking them out of the body. “We set out to make skin where there was no skin to start with,” says Kurita.

The researchers first compared the levels of different proteins of the two cell types (inflammation and keratinocytes) to get a sense of what they’d need to change to reprogram the cells’ identities. They pinpointed 55 “reprogramming factors” (proteins and RNA molecules) that were potentially involved in defining the distinct identity of the basal keratinocytes. Then, through trial and error and further experiments on each potential reprogramming factor, they narrowed the list down to four factors that could mediate the conversion to basal keratinocytes.

When the team topically treated skin ulcers on mice with the four factors, the ulcers grew healthy skin (known as epithelia) within 18 days. Over time, the epithelia expanded and connected to the surrounding skin, even in large ulcers. At three and six months later, the generated cells behaved like healthy skin cells in a number of molecular, genetic and cellular tests.

The researchers are planning more studies to optimize the technique and begin testing it in additional ulcer models. “Before going to the clinic, we have to do more studies on the long-term safety of our approach and enhance the efficiency as much as possible,” says Kurita.

A former president of Purdue Pharma, the controversial drug manufacturer widely considered to have ignited the opioid epidemic through its aggressive marketing of OxyContin, has been awarded a patent for a new opioid addiction treatment. Dr. Richard Sackler is one of the six individuals on the patent issued in January, the Financial Times first reported Friday.

Critics expressed concern that Sackler, whose family is worth an estimated $13 billion largely from Purdue’s sale of opioid painkillers, now stands to profit further from medication that treats addiction to the very drugs peddled by his family.

The patent covers a new formulation of buprenorphine in a wafer form. The medication is shown to help people struggling with opioid addiction, and the Food and Drug Administration has already approved the drug in tablet and film form.

Sackler, who served as Purdue’s president from 1999 to 2003, was instrumental in pushing OxyContin’s sales through one of the largest pharmaceutical marketing campaigns in history. The campaign worked: Doctors previously averse to prescribing opioids for pain management due to their addictiveness were convinced by Purdue’s aggressive tactics that OxyContin was safe to prescribe.

Purdue later admitted that its marketing campaign was a sham.

The company was ordered to pay $635 million after it and three top executives pleaded guilty to misleading doctors about the addictiveness of OxyContin and its potential for abuse between 1996 and 2001. Put into perspective, the fine represents less than one-quarter of the sales revenue OxyContin generated for the Sacklers during that six-year period.

Purdue’s legal woes are far from over. The company is currently facing over 400 lawsuits from cities across the country in addition to 26 lawsuits by state attorneys general for downplaying the risks of OxyContin as part of an allegedly fraudulent marketing scheme to boost sales of OxyContin

Purdue has denied the allegations in the lawsuits and has recently taken steps to address the opioid crisis it helped create. The company has backed safer prescribing practices and announced Wednesday it’s contributing $3.4 million to a company developing a low-cost emergency medication for suspected opioid overdoses.

A former Oakland orthopedic surgeon, and once popular AME, John D. Warbritton, III, was sentenced to 7 years in prison for transportation of child pornography.

Warbritton was a graduate of Harvard Medical School in 1980, and had an office at Frank Ogawa Plaza in Oakland. He surrendered his medical license on April 7, 2017, after the California Medical Board accused him of sexually harassing two of his workers’ compensation patients.

The DWC said Warbritton was one of 20 medical providers it recently suspended from participating in the workers’ compensation system.

The criminal indictment, which was filed on Oct. 13, 2016, alleges that Warbritton violated federal law by knowingly transporting child pornography. He was initially released on an unsecured bond.

But, after the United States Pretrial Services officer reported a violation of his conditions of release (possessing child pornography images on a mobile phone), the Honorable Magistrate Judge Elizabeth D. Laporte held a bail review hearing on January 17, 2017, and detained Dr. Warbritton. He was placed in the Santa Rita Jail.

Last May, he filed a Motion to Reopen his Detention Hearing. His lawyers claimed that “At the time of the alleged offense conduct and the subsequent pretrial release violation in this matter, Dr. Warbritton was suffering from both opioid use disorder and sexual impulsivity disorder.” They claim he subsequently began treatment with Carolyn Ann Schuman, M.D. for his opioid addiction, and that “his incarceration ultimately allowed him to “dry out” from the use of opioids and allowed the Suboxone treatment employed by Dr. Schuman to take effect.”

Prosecutors opposed the Motion claiming “defendant has been a hands-on offender because the defendant was arrested after returning to the United States from Thailand, where he admitted to agents he has spent long periods of time for the last several years” And among the child pornography taken from him by authorities, “one photo collage depicted the defendant along with an Asian female aged 8-10 years old. ….This photograph collage also raises concerns about whether the defendant may be a hands-on offender or someone who was preparing to do so.”

Prosecutors concluding by saying there are no conditions of release that could reasonably assure the safety of the community. Warbritton remains in custody awaiting trial.

Warbritton ultimately pleaded guilty to the child pornography charge on May 16, 2018. According to his plea agreement, in 2016, Warbritton traveled from Bangkok, Thailand, to San Francisco International Airport with electronic devices containing child pornography. Specifically, Warbritton was traveling with a laptop and a cellular telephone, both of which contained images depicting children under the age of 12 engaged in sexually explicit conduct.

The plea agreement describes some of the images that were on the devices, including depictions of grown men engaged in sexual acts with girls under the age of 12. Warbritton stipulated that between 150 and 300 images of child pornography were on his electronic devices as he traveled to SFO.

In addition to the prison term, Judge Breyer also ordered Warbritton to serve a seven-year term of supervised release to begin after the prison term ends.

The WCIRB has released its quarterly update on California statewide insurer experience valued as of March 31, 2018. Highlights of the report include:

California written premium for the first calendar quarter of 2018 is $5.0 billion, which is consistent with the written premium reported for the first calendar quarter of 2017. The decrease in 2017 following 7 consecutive years of increases is primarily driven by decreases in insurer charged rates.

The projected industry average charged rate per $100 of payroll for policies incepting between January 1, 2018 and March 31, 2018 is $2.38, which is 6% below the average rate charged for policies incepting in 2017. The July 1, 2018 approved advisory pure premium rates are on average 37% below those for January 1, 2015.

The projected combined ratio for 2017 is 5 points higher than 2016 as premium levels have lowered while average claim severities increased moderately. Despite the recent increase, combined ratios for 2014 to 2017 remain the lowest since the 2004 through 2006 period.The WCIRB projects the ultimate accident year combined loss and expense ratio for 2017 to be four points above that for accident year 2016, driven by higher medical severities for 2017 and lower premium rates.

Indemnity claim frequency increased by 11% from accident year 2009 to accident year 2014, but has decreased by 5% from accident year 2014 through the first three months of accident year 2018. Indemnity claims continue to settle quicker, steadily improving over the last 5 years. Frequency increases since 2011 have largely been attributed to increases in cumulative injury claims and claims from the Los Angeles Basin area.

Cumulative trauma (CT) claim rates continue to be at high levels in 2016 and the ratio of CT claims to all indemnity claims has increased by over 65% since 2005. The sharp increase in CT claims since 2012 is in the Los Angeles and San Diego areas, as CT claims in other regions of CA have decreased. The WCIRB will be publishing a study of CT claim patterns later this year.

Projected claim severity for 2017 is 2.5% higher than that for 2016, following several years of relatively flat severities. Severity growth over the last several years has been relatively modest as increases in average indemnity and ALAE costs have been in part offset by declines in average medical costs.

Indemnity severity increases in 2014 are largely attributable to SB 863 increases to PD benefits. Indemnity severity growth since 2014 has been relatively modest and generally consistent with wage inflation.

Decreases in medical severities from 2011 to 2015 were driven by the medical cost savings arising from SB 863. It is unclear whether the projected 2017 medical severity increase of 3% will develop downward like other recent years or if it represents a return the more typical rates of post-reform medical inflation.

Pharmaceutical costs per claim decreased 70% from 2012 to 2017. These reductions have been driven by SB 863’s IMR & IBR, reduced utilization of opioids, and changes to Medi- Cal reimbursement rates. The new drug formulary effective in 2018 is expected to further reduce pharmaceutical cost levels.

SB 1160 and AB 1244 made changes to lien filings effective 1/1/2017. Some of the lien activity in the fourth quarter of 2016 through the first quarter of 2017 may be impacted by the transition to the reforms. The number of liens filed since the first quarter of 2017 are 40% below pre-SB 1160 and AB 1244 levels.

The full report is available in the Research section of the WCIRB website (wcirb.com) and linked below:

U.S. drug prices fell again in the second quarter of 2018, likely due to a new tactic insurers are using to limit financial assistance drugmakers provide directly to consumers, according to research firm Sector and Sovereign Research (SSR).

Reuters reports that real U.S. drug prices, which includes discounts and rebates drugmakers provide to insurers and pharmacy benefit managers (PBMs), fell 5.8 percent in the quarter, compared with a 0.7 percent increase a year earlier, SSR analyst Richard Evans said in a research note on Tuesday. That is in line with how far prices fell in the first quarter, he said.

But lower “real” drug prices means drugmakers are receiving less revenue on sales, but does not necessarily translate into savings for patients as employers and payers are more likely to reap the benefit.

Evans believes “copay accumulator” programs, which effectively force drug companies to continue to assist patients with their copays, were to blame for the declining real drug prices.

“Unless manufacturers adapt their copay support programs fairly drastically, net price declines may worsen in 2019,” Evans said.

Gilead Sciences Inc, Eli Lilly and Co, Novo Nordisk and GlaxoSmithKline Plc made the largest contribution to the real drug price decline in the quarter, according to the report.

In recent years, insurers have tried to guide patients toward less expensive treatments by making them pay a higher portion of a drug’s costs. Drugmakers responded by raising the financial aid they offer in the form of “copay assistance” cards – similar to a debit card – that reduce consumer costs at the pharmacy.

PBMs, which manage prescription drug coverage for large U.S. employers, say these payments shield consumers from drug costs, making it easier for manufacturers to raise prices. Insurers have to make up the difference.

Many PBMs introduced the copay accumulator approach for their corporate customers this year. The programs prevent copay card funds from counting toward a patient’s required out-of-pocket spending before insurance kicks in on expensive specialty drugs.

Major pharmaceutical companies are trying to limit the damage from the tactic. Still, most large drug companies did not address the issue of copay accumulators during conference calls to review second quarter results. Amgen Inc and Eli Lilly played down the effect the programs were having their own bottom lines.

Evans said he believes more employers will add the programs next year. A recent survey of large corporate employers by the National Business Group on Health showed that around 25 percent of respondents already had copay accumulator programs in place, and another 3 percent will be adding them next year. An additional 21 percent is considering the programs for 2020 or 2021, the survey found.