Australian Physician/Diver Played Key Role in Thai Cave Rescue

Australian anesthetist and world-renowned cave diver Richard Harris, MBBS, played a key role in rescuing the 12 youth soccer team members and their coach trapped in a cave in Thailand since June 23, according to the New York Post.

The last four boys and the coach were removed from the cave this morning, ending an 18-day ordeal.

Harris, 53, known as “Harry,” from Adelaide, works for the South Australian Ambulance Service’s aeromedical evacuation service MedStar and has 30 years’ experience as a diver.

He joined Thai medical and diving experts in the rescue from the flooded Tham Luang cave complex and entered a chamber deep inside the complex to check on the boys early Sunday, the Post reported.

After assessing their fitness, Harris recommended that the weakest boys be rescued first, which changed the initial strategy of taking the strongest first, the newspaper reported.

In a press conference  on Sunday, Harris’s boss at MedStar, clinical director Andrew Pearce, said that Harris had been headed for vacation when British officials asked for his help.

“Harry is selfless,” Pearce told reporters. “He is extremely thoughtful. He’s a quiet person. He’s the type of guy who will give of his all. He was actually meant to be on holiday and gave up his holiday to be part of this.”

In addition to his skills as a doctor, Pearce said, “He happens to have this amazing ability to do what no one else does in diving into very dark, tight spaces with not a lot of equipment.”

A Doctor in Demand

Harris’s work biography says, “His love of underwater exploration has led him to work on National Geographic documentaries, feature films and with various teams worldwide in the role of diver, underwater cameraman and of course medical support. He is a member of the Explorers Club of New York and recently received an Australian award for ‘Outstanding Contributions to Cave Exploration.”

This was not the first cave retrieval mission for Harris.

According to the publication The Australian,  Harris helped recover the body of his friend Agnes Milowka, 29, in 2011. Milowka died after running  out of oxygen in Tank Cave near Mount Gambier in South Australia.

Medical Concerns

CNN, citing information from the Mayo Clinic, said medical providers will likely check the team for signs of histoplasmosis, or “cave disease,” caused by breathing in spores of a fungus often found in bird and bat droppings. The CNN report said the team — currently quarantined — is likely to stay in a hospital for a week because of their weakened immune systems.

The New York Times has reported that at least two of the first eight boys recovered may have pneumonia, and according to Thailand’s permanent secretary for public health, Jesada Chokedamrongsuk, all are being treated with antibiotics and being vaccinated for tetanus and rabies.

Multiple media reports also cite experts discussing the high risk among the boys — ranging in age from 11 to 16  — and their coach, 25, for post-traumatic stress disorder.

https://wb.md/2unCG4v

Israeli non-opiate painkiller could compete with Heron med candidate

Israeli pharmaceuticals company PainReform has received approval from the U.S. Food and Drug Administration (FDA) to begin late-stage clinical studies for a pain relief drug that is a departure from opiate-based narcotics, it said on Tuesday.

Many patients today dealing with pain after surgery are prescribed opioids, which can be highly addictive and are at the heart of a costly health crisis in the United States.

PainReform said the FDA had given it a green light to carry out two Phase 3 trials on its product PRF-110, which prolongs the action of a local analgesic, or painkiller, called ropivacaine. The studies will focus on post-operative pain relief in soft and hard tissue.

The drug is administered during surgery, before the wound is sutured. An earlier study showed PRF-110 was able to relieve pain for up to 72 hours – 10 times longer than the current standard of care, PainReform said.

SPONSORED

This is a crucial period when pain is maximal and opioids are often given, said Chief Executive Eli Hazum.

“This kind of drug can help delay or prevent the prescription of opiates,” he told Reuters.

PainReform estimates the market potential for such treatment at $5 billion.

FDA Commissioner Scott Gottlieb said in a statement on Monday the agency “remains focused on striking the right balance between reducing the rate of new addiction by decreasing exposure to opioids and rationalizing prescribing, while still enabling appropriate access to those patients who have legitimate medical need for these medicines”.

Opioids were involved in more than 42,000 deaths in the United States in 2016, more than any previous year on record, according to the Centers for Disease Control and Prevention.

There are prescription versions of opioids, like oxycodone, and illegal ones, like heroin. About 40 percent of the opioid overdose deaths involved prescription drugs.

Should PainReform’s treatment pass its trials, results for which Hazum estimated could come within a year after they start, it would compete with other non-opiate drugs like Heron Therapeutics’ HTX-011, which just finished Phase 3 studies.

“This market will not depend on a single drug,” Hazum said.

The company has raised $12 million and is looking for an additional $15 million before beginning the trials, which focus on bunion and hernia operations.

It would consider an initial public offering in New York after the trials are finished, or even at the time of interim results, which could be after about six months, Hazum said.

https://reut.rs/2m8BCh1

Extended Tamoxifen May Double Endometrial Cancer Risk

There was a twofold increase in the risk of endometrial cancer following extended versus standard adjuvant tamoxifen therapy in patients with breast cancer, a meta-analysis found.

The systematic review of four randomized controlled trials showed that the absolute risk of endometrial cancer in patients receiving adjuvant tamoxifen for 10 years was 3.2% compared with 1.5% in patients receiving 5-year standard therapy (cumulative risk ratio [RR] 2.29, 1.60 to 3.28, P<0.001), reported Christina A. Fleming, MBBCh, of St. Vincent’s Hospital Group in Dublin, and colleagues.

Most tamoxifen-related uterine cancers occurred in patients who were postmenopausal and symptomatic, but diagnosed at an early stage and with a low grade, and carried a mortality risk of less than 1%, the authors wrote in the British Journal of Surgery.

“There is a paucity of clear evidence on how we should best manage endometrial cancer risk in extended tamoxifen therapy,” said Fleming in a statement. “This is a research area that requires immediate focus with expansion of extended tamoxifen therapy regimes.”

Few studies have data on endometrial surveillance in patients on adjuvant tamoxifen, the most recent of which (2003) was part of this review and did not find any benefit for routine endometrial surveillance in patients receiving tamoxifen for 5 years. Guidelinespublished by the American College of Obstetricians and Gynecologists, plus those from the Australian and New Zealand group do not recommend routine surveillance in asymptomatic patients receiving tamoxifen.

“Although it is difficult to make clear evidence-based recommendations on endometrial surveillance in the setting of extended therapy because of the sparsity of robust results, a practical approach may be to screen all patients using endometrial ultrasonography after 5 years on tamoxifen,” they wrote. “The validity of this approach should be assessed prospectively.”

Regarding breast cancer outcomes, Fleming’s group observed a non-significant reduction in breast cancer-specific mortality in patients receiving tamoxifen for 10 years, from 11.6% to 10.1% (RR 0.94, P=0.58). Likewise, the overall reduction in local recurrence, from 19.1% to 17.1% (RR 1.03, P = 0.76), and 1.7% reduction in overall mortality with 10-year tamoxifen were not significant (RR 0.93, P = 0.14).

These data would not preclude the use of extended tamoxifen in women who are deemed appropriate, Hatem Soliman, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, told MedPage Today. He added that there are “many factors to consider in choosing endocrine therapy,” including menopausal status, risk of breast cancer recurrence, bone health, other comorbid conditions, and tolerance of estrogen deprivation.

Soliman, who was not affiliated with the study, noted that the absolute increase in endometrial cancer rates was very small. Also, it was seen predominantly in postmenopausal women who had baseline endometrial abnormalities. “The majority of these endometrial cancers are treatable if patients are followed and counseled appropriately,” he pointed out.

“In general, higher risk women who are or have become postmenopausal during their first 5 years of tamoxifen should be counseled to try switching to an aromatase inhibitor if they have no contraindications to doing so,” advised Soliman.

When asked to comment, Marissa Weiss, MD, of Lankenau Medical Center in Philadelphia, told MedPage Today: “There are a lot of issues here that impact clinical practice, including compliance.”

Weiss, who was not affiliated with the research, noted that in one study in the meta-analysis, 17% of patients randomized to extended tamoxifen therapy didn’t finish the first 5 years, while in a second study, 40% didn’t complete extended tamoxifen therapy. Even in patients randomized to standard treatment, there was a fall-off in the number who continued taking adjuvant tamoxifen because of side effects such as vaginal bleeding.

The study confirms that premenopausal women with serious disease still derive the most benefit from taking tamoxifen for an extended period of time, Weiss said. Like Soliman, she emphasized that patients need to be assessed individually, and said the pros and cons of adjuvant tamoxifen therapy must be discussed regularly.

“This is not just one conversation,” she said. “At the time of prescription renewal, you always have a repeat conversation about tamoxifen therapy and ask the patient how it’s going.” This is also the time to revisit the increased risk of endometrial cancer and to ask your patient about signs of abnormal bleeding and so on, Weiss said.

The four randomized controlled trials included in the meta-analysis enrolled 21,361 patients from 1978 to 2005. Of these, 7,652 (35.8%) received 10 years of 20-mg oral tamoxifen daily. Follow-up ranged from a median of 7 to 10 years.

Three studies compared 10 years of adjuvant tamoxifen therapy in patients with estrogen receptor–positive breast cancer with standard 5-year therapy with or without placebo.

In the first, the National Surgical Adjuvant Breast and Bowel Project (NSABP) trial, the RR of endometrial malignancy was 6.84. However, 75% of participants in that trial were postmenopausal, with most endometrial cancers stage I with good to moderate histological grade, the study authors noted.

Both the 2012 ATLAS (Adjuvant Tamoxifen: Longer Against Shorter) trial, and the 2013 aTTom (Adjuvant Tamoxifen: To Offer More?) trial showed that younger patients with high-risk disease benefitted most from extended tamoxifen therapy.

ATLAS showed that extending tamoxifen to 10 years was associated with a twofold increase in the 15-year endometrial cancer risk and a 0.4% absolute increase in mortality. This was seen almost exclusively in postmenopausal patients. Similar observations were reported in aTTom (RR 2.28) and in the 2001 Scottish trial of adjuvant tamoxifen (RR 3.42).

None of the surveillance studies compared the benefit of routine endometrial surveillance with no surveillance in similar or matched cohorts of patients receiving tamoxifen. “This greatly limits the conclusions that can be drawn from the included studies,” the investigators wrote.

Fleming and co-authors reported having no conflicts of interest.

Weiss is the founder of Breastcancer.org.

• Primary Source

  British Journal of Surgery

  Source Reference: Fleming CA, et al “Meta-analysis of the cumulative risk of endometrial malignancy and systematic review of endometrial surveillance in extended tamoxifen therapy” Br J Surg 2018; DOI: 10.1002/bjs.10899.

https://bit.ly/2KOzQAH

FDA: New Warnings for Fluoroquinolones

Manufacturers of fluoroquinolone antibiotics must update their labeling to warn about mental health issues and potential low blood sugar adverse reactions, the FDA said Tuesday.

The labeling changes come after what the agency described as a “comprehensive review of the FDA’s adverse event reports and case reports published in the medical literature,” the agency said in a Drug Safety Communication.

The FDA stated that these will be class-wide updates, where they previously differed by individual drug. Mental health side effects will now be listed separately and labeled “consistently.” They are set to include “disturbances in attention, disorientation, agitation, nervousness, memory impairment and delirium.” However, the new warnings won’t come with the black border signifying the most serious types of risks.

A warning about nerve damage, specifically peripheral neuropathy, associated with the use of fluoroquinolone antibiotics was previously added in 2013.

Fluoroquinolone antibiotics will also require a separate warning about the risk of hypoglycemic coma added to the Blood Glucose Labeling Subsection, the agency said, citing “instances of hypoglycemic coma where users of fluoroquinolones experienced hypoglycemia.”

However, the FDA said that healthcare providers and patients should continue to “consider the risks and benefits” of fluoroquinolone antibiotics in treatment.

“The use of fluoroquinolones has a place in the treatment of serious bacterial infections — such as certain types of bacterial pneumonia — where the benefits of these drugs outweigh the risks, and they should remain available as a therapeutic option,” said Edward Cox, MD, FDA director of the Office of Antimicrobial Products, in a statement.

Fluoroquinolone antibiotics include levofloxacin (Levaquin), ciprofloxacin (Cipro), ciprofloxacin extended-release tablets, moxifloxacin (Avelox), ofloxacin, gemifloxacin (Factive) and delafloxacin (Baxdela), as well as more than 60 generic versions. This revised warning applies to forms of the drug taken by mouth or given by injection, the FDA said.

This is the latest in a series of escalating warnings about the safety of fluoroquinolones that date back to 2008. The latest came in 2016, when the FDA required a warning about potentially permanent musculoskeletal complications associated with the use of these drugs.

https://bit.ly/2N1rBhh

Cerner sinks $266M into Lumeris deal targeting Medicare Advantage plans

Cerner will become a minority owner in the parent company of the population health services platform Lumeris as part of a 10-year strategic partnership that includes a new value-based technology offering geared towards Medicare Advantage plans.

The deal allows Cerner to tap into an established Medicare Advantage plan in Missouri, operated by Lumeris. The two companies plan to use data and digital processes to help providers “maximize outcomes” for patients enrolled in value-based arrangements, including Medicare Advantage and provider-sponsored plans.

As part of the deal, Cerner subsidiary Cerner Capital will become a minority stakeholder in Lumaris’ parent company, Essence Group Holdings, purchasing $266 million in stock, according to a financial filing. The company also owns Essence Healthcare, a Lumeris-operated Medicare Advantage plan with 65,000 beneficiaries in Missouri.

Together, Lumeris and Cerner plan to release an “EHR-agnostic” solution called Maestro Advantage, with deployments expected by the end of the year and broad market implementation in 2019. The companies plan to identify systems “best positioned to succeed with the offering, particularly large organizations pursuing multi-year growth strategies.”

Lumeris will also adopt Cerner’s HealtheIntent population health platform.

“By using data to reduce or eliminate unnecessary costs and ineffective transitions of care, providing doctors and their patients a more complete view of their medical history and a health plan that consistently receives high quality scores from CMS, this collaboration with Lumeris aligns well with our mission and illustrates the potential of Cerner technology to positively impact health care economics and outcomes in deeper, more impactful ways than before,” said Cerner CEO Brent Shafer.

John Doerr, Lumeris board member and chairman of Kleiner Perkins added that the value-based care transition has been “impeded by disjointed technology, cumbersome processes, misaligned incentives and inadequate management of clinical and financial outcomes,” pointing to the partnership’s focus on data transparency and provider empowerment.

The population health management market is expected to grow rapidly over the next decade, reaching $69 billion by 2025, according to Transparency Market Research.

https://bit.ly/2L5qBLS

Analysts Call Verrica A Buy For Vast Molluscum Opportunity

Investors who bought into Verrica Pharmaceuticals Inc VRCA 6.22%at its June 15 IPO are celebrating 13.1-percent returns.

The gains should continue, in the view of two new sell-side bulls.

The Ratings

Bank of America Merrill Lynch analyst Jason Gerberry initiated coverage of Verrica with a Buy rating and $26 price target.

Cowen analyst Ken Cacciatore initiated coverage with an Outperform rating and $35 target.

The Theses

The analysts are bullish on Verrica for its lead candidate, VP-102, which is in Phase 3 trials for the treatment of molluscum.

The therapy — a non-invasive alternative to cryotherapy and surgery — is poised to become the first approved molluscum drug for a potentially underdiagnosed population growing by an estimated 1 million U.S. patents per year.

Bank of America expects dermatologists to be receptive to VP-102 considering the drug’s familiar active ingredient.

“Supportive Phase 2 data suggests VP-102 can achieve high clearance rates, which have made the API popular with dermatologists,” Gerberry said in a Tuesday note. (See the analyst’s track record here.)

BofA forecast a 60-percent possibility of success and anticipates favorable Phase 3 data will boost the likelihood to 85 percent. Cowen’s Cacciatore expressed similar optimism.

“With what we believe will be a very reasonable pricing strategy that should secure broad coverage, combined with FDA guidelines that mandate the discontinuation of compounded versions of approved products — as well as what appears to be limited raw material supplies — we believe that Verrica’s formulation will quickly capture, penetrate, and expand the current treatment market,” the analyst said in a Tuesday note. (See Cacciatore’s track record here.)

Indication expansion into common warts could drive additional upside for Verrica.

https://bit.ly/2KLFWSe

MorphoSys Licensee Janssen Starts Phase 2/3 for Crohn’s Disease Med

MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; NASDAQ: MOR) announced today that its licensee Janssen Research & Development, LLC, part of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), has initiated a pivotal phase 2/3 clinical program to evaluate the efficacy and safety of Tremfya(R) (guselkumab) in the treatment of patients with moderately to severely active Crohn’s disease. Expected to enroll approximately 2,000 patients, the program, which is named GALAXI, consists of three separate studies, a phase 2 study (GALAXI 1), followed by two phase 3 studies (GALAXI 2 and GALAXI 3).

Tremfya(R) is a fully human anti-IL-23 monoclonal antibody developed by Janssen, and was generated utilizing MorphoSys’s proprietary HuCAL antibody technology.

In connection with the start of the GALAXI program, MorphoSys will receive two milestone payments from Janssen. Financial details were not disclosed.

Dr. Markus Enzelberger, Chief Scientific Officer of MorphoSys AG, said: ‘We are very pleased that our licensee Janssen has started a pivotal phase 2/3 development program in Crohn’s disease, a severe illness where significant unmet needs exist despite the availability of some effective therapies. If successful, this could result in a further expansion of the therapeutic range of Tremfya(R).’

Crohn’s disease is a type of inflammatory bowel disease (IBD) affecting any part of the gastrointestinal tract. In addition to the clinical development in Crohn’s disease, Tremfya(R) is currently being investigated in two phase 3 trials in psoriatic arthritis. Tremfya(R) has been approved in the U.S., Canada, the European Union, and several other countries for the treatment of plaque psoriasis and in Japan for the treatment of both psoriasis and psoriatic arthritis.

More information about Tremfya(R) (guselkumab) clinical studies is available on clinicaltrials.gov.

https://bit.ly/2uoALws