Increase Seen in Cryptosporidiosis Outbreaks From 2007 to 2019

Exposure to treated recreational water accounted for 35.1 percent of outbreaks, 56.7 percent of cases

From 2009 to 2017, there was an increase in the annual number of reported cryptosporidiosis outbreaks in the United States, according to a study published online June 27 in Morbidity and Mortality Weekly Report.

Radhika Gharpure, D.V.M., from the U.S. Centers for Disease Control and Prevention in Atlanta, and colleagues examined outbreaks of cryptosporidiosis for 2009 to 2017 for 40 states and Puerto Rico.

The researchers identified reports of 444 cryptosporidiosis outbreaks resulting in 7,465 cases. Overall, 35.1 percent of outbreaks, resulting in 56.7 percent of cases, were associated with exposure to treated recreational water (for example, in pools and water playgrounds). Contact with cattle (14.6 percent of outbreaks) and contact with infected persons in child care settings (12.8 percent of outbreaks) were also predominant outbreak exposures. Over time, there was an average increase of almost 13 percent in the annual number of reported cryptosporidiosis outbreaks.

“Reversing the increasing trends in annual numbers of reported cryptosporidiosis outbreaks overall and those associated with treated recreational water, contact with cattle, or contact with infected persons in child care settings will require implementing effective prevention measures,” the authors write.

Abstract/Full Text (subscription or payment may be required)

https://www.physiciansbriefing.com/infectious-disease-8/gastrointestinal-problems-news-330/increase-seen-in-cryptosporidiosis-outbreaks-from-2007-to-2019-747850.html

FDA fast-tracks Lilly/Boehringer’s Jardiance for heart failure

Eli Lilly and Boehringer Ingelheim’s Jardiance was the first diabetes drug to lower the risk of cardiovascular disease in a clinical trial, and is now on course to be the first to have a chronic heart failure (CHF) claim on the label.

The FDA has just agreed to fast-track its review of the SGLT2 inhibitor for the reduction of the risk of cardiovascular death and hospitalisation for heart failure in people with CHF, based on the ongoing EMPEROR trials programme which started in 2017.

As their names suggest, EMPEROR-Reduced and EMPEROR-Preserved split the CHF population into those with reduced or preserved ejection fraction, and are due to generate results in 2020. They are massive trials, collectively enrolling almost 9,000 patients including subjects both with and without diabetes.

Boehringer and Lilly are also running another pair of trials, called EMPERIAL, which are investigating the possible benefits of Jardiance on exercise capacity and heart failure symptoms and are due to read out before the end of this year.

It’s an indication of the pressing need for new therapies for CHF that the FDA has already awarded the fast-track status for Jardiance (empagliflozin), well ahead of the trials readout. There are around 6.5 million people with CHF in the US alone and 26 million worldwide, and around half of all those who develop the condition are dead within five years.

“Heart failure contributes to one in nine deaths and is a leading cause of hospitalisation in the US, yet there are limited treatment options for people living with this debilitating disease,” said Mohamed Eid, Boehringer’s head of clinical development.

“We look forward to working closely with the FDA as we explore the potential for [Jardiance] to improve outcomes for adults with CHF.”

Jardiance has become the top-selling drug in the SGLT2 inhibitor class with sales of around $2 billion last year, helped by side-effect problems that have afflicted Johnson & Johnson’s first-to-market Invokana (canagliflozin).

The shift into cardiovascular risk reduction has been another big factor in its success, spurred by the EMPA-REG trial in 2015 which showed that the drug reduced major cardiovascular events (MACE) in diabetic patients by 14% compared to placebo.

J&J and other SGLT2 inhibitor developers like AstraZeneca with Farxiga (dapagliflozin) have tried to follow Jardiance down the cardiovascular outcomes path, and both companies now have data showing they can reduce MACE in diabetic patients. J&J got approval for a cardiovascular outcomes claim for Invokana from the FDA last October.

Analysts at Evercore ISI have suggested that Jardiance could hit sales of $4 billion at its peak, and the cardiovascular outcomes data that could extend its use beyond diabetes is expected to be a big factor in that growth.

FDA fast-tracks Lilly/Boehringer’s Jardiance for heart failure

Blood Test for Alzheimer’s Disease One Step Closer?

An accurate, fully automated blood test for Alzheimer’s disease (AD) that can be used in primary care settings may be one step closer, results of a large prospective study suggest.

Using a commercially available automated immunoassay, investigators found plasma levels of amyloid proteins Aβ42 and Aβ40 aligned with clinical stage of cognitive impairment and distinguished individuals with mild cognitive impairment (MCI) or AD from their unaffected counterparts.

Dr Sebastian Palmqvist

“This potentially can be a much needed contribution to the otherwise limited diagnostic tools available in primary care,” lead author Sebastian Palmqvist, MD, PhD, associate professor of neurology at Lund University and an investigator at the Clinical Memory Research Unit, Skåne University Hospital, Sweden, told Medscape Medical News.

“In the last one to two decades, we have seen major improvements in the diagnostic evaluation at highly specialized centers — using regional MRI measures, cerebrospinal fluid analyses, FDG-PET, amyloid PET, tau PET, etc. But in most cases, primary care centers still use the same tools as 30 years ago,” he said.

The study was published online June 24 in JAMA Neurology.

Promise of Greater Accuracy

Previous attempts to identify and develop a blood biomarker for AD have fallen short in replication studies. The most promising candidates to date include tau protein, neurofilament light chain levels, Aβ42 and Aβ40.

However, the recent development of fully automated immunoassays — with improved reliability and precision in testing for AD biomarkers — are offering the hope of greater diagnostic accuracy.

To determine the precision of this new technology in detecting Aβ42, Aβ40, and tau, the investigators tested one of the commercially available, fully automated systems (Elecsys Immunoassays, Roche Diagnostics) in a cohort of 842 individuals enrolled in the Swedish BioFINDER study.

They also assessed a separate validation cohort of 237 people from a German study. Each group included participants who were cognitively normal or who had MCI or AD dementia.

The researchers found 44% of the overall BioFINDER cohort was positive for amyloid beta. This result included 29% of the cognitively unaffected group, 60% of the MCI patients, and 100% of the 64 individuals diagnosed with AD dementia.

The amyloid-beta 42/40 ratio predicted amyloid beta positivity with an area under the curve (AUC) correlation of 0.77 in a logistic regression analysis. Assessing Aβ42 and Aβ40 markers individually increased the accuracy (AUC, 0.80).

Interestingly, adding tau protein to the plasma assays did not significantly increase the accuracy of predicting amyloid-beta positivity (AUC, 0.81).

Palmqvist said he was “not really” surprised that tau levels added little to the sensitivity. Previous studies on total tau (T-tau) in plasma, the type of tau measured in the present study, “have shown very modest accuracies,” he said. “On the other hand, ongoing studies on phosphorylated tau (P-tau) in plasma show very promising results, and we plan to publish this soon.”

Adding plasma neurofilament light chain or plasma neurofilament heavy chain levels did not significantly improve the predictability of the assays.

In contrast, adding APOE genotype data to the amyloid-beta individual marker results significantly improved the sensitivity (AUC, 0.85; 95% confidence interval [CI], 0.82 – 0.88; P < .001).

Results were similar in the validation cohort analyses. For example, individual markers Aβ42 and Aβ40 in plasma also predicted amyloid positivity (AUC, 0.86). Addition of tau protein levels actually decreased the sensitivity slightly (AUC, 0.84). Plasma neurofilament light chain, neurofilament heavy chain and APOE status were not available in the validation population.&

In addition to the clinical promise of developing a sensitive blood marker for early detection of AD pathology, the findings could help identify and classify study participants for future AD studies while reducing the need for lumbar punctures or costly imaging.

However, the investigators added a caveat to their findings, noting that the accuracies of “Aβ42 and Aβ40 assays are not sufficient to be used on their own as a clinical test of Aβ positivity.”

“Additional assay development is needed before this can be recommended, possibly together with other blood biomarkers and screening tools in diagnostic algorithms,” they note.

The investigators are currently conducting a large, prospective study known as ADetect, which aims to determine the accuracy using these immunoassays in primary care settings.

“Within 3 to 4 years we will get the results, and hopefully that will be enough to implement it in clinical practice, perhaps together with other measures such as APOE genotype and brief cognitive tests,” Palmqvist said.

“A Solid Foundation”

In an accompanying editorial, Sid E. O’Bryant, PhD, of the Institute for Translational Research at the University of North Texas Health Science Center in Fort Worth, writes that the study provides “preliminary evidence for a test with the specific context of use of screening for amyloid positivity, which the authors suggest may have utility in primary care settings.”

“Overall, the performance of the assay was excellent. This study suggests that the field is one step closer to the actual application of blood based biomarkers with specific [use] in AD,” he adds.

However, O’Bryant also said the findings “certainly leave room for improvement. The primary concern is the scalability of the methods.”

He added that the Aβ42/Aβ40 ratio yielded a sensitivity of 0.70 and specificity of 0.73 when applied to the validation cohort.

“If applied to the expected base rates found in a primary care setting (in other words, 10% to 12%) the negative predictive power would be greater than 0.90; however, the positive predictive power would be 0.22,” he writes.

“Overall, the findings of Palmqvist et al are promising and demonstrate that the field is rapidly moving from ‘if’ blood biomarkers can be used in AD to ‘how’ they can be used,” writes O’Bryant. “This work demonstrates the superiority of automated technologies, and the findings provide a solid foundation on which to build.”

The European Research Council, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Marianne and Marcus Wallenberg Foundation, the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s disease) at Lund University, the Swedish Alzheimer Association, the Swedish Brain Foundation, The Parkinson Foundation of Sweden, The Parkinson Research Foundation, the Skåne University Hospital Foundation, and the Swedish federal government under the ALF agreement support work at the authors’ research center.

Palmqvist has disclosed no relevant financial relationships. O’Bryant reported grants from the National Institute on Aging during the conduct of the study and personal fees and other support from Roche outside the submitted work; has served on an advisory board for Roche Diagnostics; and is founding scientist of Cx Precision Medicine.

JAMA Neurol. Published online June 24, 2019. Abstract, Editorial

https://www.medscape.com/viewarticle/915026#vp_1

Reducing Cancer Patients’ Risk of Opioid Addiction, Harm

Eric Roeland, MD, of Massachusetts General Hospital in Boston, explains how oncologists can seek balance when prescribing opioids to patients with cancer and how to mitigate risks of addiction and other opioid-related harms.

Following is a transcript of his remarks:

We had the opportunity to discuss the use of opioids at ASCO this year. Given the high aberrancy of opioid use across the United States, this is a very important topic for oncologists to be aware of. I think the first thing that we all need to be focused on is maintaining access to opioids for our cancer patients, those who are most at risk and who need access to these very important drugs. At the same time, it’s very important that we now recognize the importance of assessing risk, risk of aberrant use.

For the busy oncologist, it might feel overwhelming to add yet another thing that they need to do day-to-day in their busy clinical practice, but there’s some real simple things that you can do to assess opioid aberrancy risk. The first is to complete a prescription drug monitoring program report. This is now available in most states across the United States and even available online. In some institutions, like mine, it’s integrated into the electronic medical record. Prior to prescribing any opioid or benzodiazepine, it’s important to see the number of other prescribers and pharmacies that a patient is having those medications filled and to really engage the patient and ask if there’s anything that’s unclear.

The second thing I think we all need to make sure that we’re doing is having discussions about safety and safe storage of opioids because even a patient who has legitimate cancer pain at home might have relatives or loved ones that may be taking these medications and using them inappropriately. There’s just some of us out there that are at higher risk of using or misusing opioids for inappropriate reasons.

Then the last is to really start thinking about universal precautions. In the same way that we look at the prevention of spreading infectious diseases in the hospital, we also need to start thinking of universal ways that we can prevent yet another issue for our patients in terms of developing addiction to opioids. Balancing and seeking, and ensuring that we have access to opioids for our cancer patients, but we’re assessing risk, and then instituting practices in our day-to-day clinical care to ensure that we’re not causing more issues or problems for the patient and/or their family.

https://www.medpagetoday.com/meetingcoverage/ascovideopearls/80768

American Pain Society files for bankruptcy

Saying it is beleaguered by legal debt fighting lawsuits alleging that its policies contributed to the nation’s opioid crisis, the American Pain Society has voted to cease operations and on Friday, filed for bankruptcy protection under Chapter 7.

Numerous legal filings have accused the organization, along with other companies and associations, of acting as “front groups” for opioid drugmakers because many of them regularly contributed significant financial support to professional groups such as the APS.

In a statement emailed Friday afternoon, the 42-year-old organization said it had been “named a defendant in numerous spurious lawsuits related to opioids prescribing and abuse. The organization’s financial health has deteriorated as a result of the litigation” that constituted “a perfect storm” for the organization’s demise.

The statement added that the organization’s financial health had deteriorated as a result of litigation costs, but that declines in membership, sponsorship revenue, and meeting attendance also contributed to the decision.

“Our resources are being diverted to paying staff to comply with subpoenas and other requests for information and for payment of legal fees instead of funding research grants, sponsoring pain education programs, and public policy advocacy,” APS President William Maixner, DDS, PhD, said.

In late May, the APS board of directors had called for a membership vote to support bankruptcy action, but said it was doing so “with heavy hearts.” Results were supposed to have been announced the following week, but requests for a determination were not forthcoming. A decision required at least 10% of its 1,173 eligible members to vote; the APS statement posted Friday on its website said 93% voted to approve the bankruptcy filing.

APS spokesman Chuck Weber said on Friday the decision was made with only one round of voting, but he said he did not know the reason why the organization delayed announcing the ballot’s result.

The press release quoted several members lamenting the end of the APS.

Roger Fillingim, PhD, an APS past president and professor of psychology, University of Florida School of Dentistry, said the “APS has been advocating for increased investment in research for many years, and it is particularly ironic that APS’s voice will go silent at this critical time in our history, when increased investment in pain research has finally become a reality in an effort to combat the opioid crisis.”

APS President-elect Gary Walco, PhD, also noted the irony that a “professional organization best poised to provide the spectrum of science to improve the prevention and treatment of pain and related substance abuse is defunct.”

Walco, director of pain medicine at Seattle Children’s Hospital, added that “Now, more than ever, our nation needs the collective efforts of leading scientists and clinicians who hold patients’ well-being at the highest premium. The principal focus on punishing those in industry that may have contributed to the problem is shortsighted and far from sufficient.”

The Chicago-based organization said it filed for bankruptcy protection in the U.S. Bankruptcy Court for the Northern District of Illinois.

It is unclear what will happen to its monthly Journal of Pain, although Weber said last month that the journal, as well as numerous research grants, a young investors fund and the group’s annual scientific meeting, would disappear or be taken over by other organizations.

In brief remarks Friday afternoon, Weber said he expected that all of the organization’s endeavors and operations “will be gone,” and that there is no sign that any other organizations are willing to pick up any of its functions.

“The next steps are in the hands of the trustee,” he said. The APS statement also promised more information for members “in the next week or so.”

https://www.medpagetoday.com/primarycare/opioids/80777

Berkshire Hathaway shedding stake in workers’ comp firm

Warren Buffett’s Berkshire Hathaway (BRK.B) (BRK.A) has agreed to sell its majority stake in Applied Underwriters, a workers’ compensation insurer that’s been under a number of regulatory investigations, to United Insurance Co., the New York Post reports, citing a filing with the California Department of Insurance.

UIC is buying the 81 percent stake owned by Berkshire as well as stakes owned by two other executives.

Financial terms weren’t disclosed.

Ex-clients have accused Applied Underwriters of being a “reverse Ponzi scheme” in a civil lawsuit filed in 2016; the company had denied the accusation.

One report in 2007 estimated that Berkshire paid $339M for the Applied Underwriters stake; KBW analyst Meyer Shields told the Post that it could now be worth $1B-$1.2B.

https://seekingalpha.com/news/3474707-berkshire-hathaway-shedding-stake-workers-comp-firm-ny-post

Theranos founder Elizabeth Holmes and top deputy ordered to stand trial in 2020

Theranos founder Elizabeth Holmes and her former second-in-command at the Silicon Valley blood-testing startup were ordered on Friday to stand trial next year on fraud charges stemming from their claims about the company’s technology, court documents show.

During a hearing in federal court in San Jose, California, U.S. District Judge Edward Davila set jury selection to begin in the trial of Holmes, 35, and former Theranos President Ramesh “Sunny” Balwani, on July 28, 2020, according to minutes of the proceedings.

Both have pleaded not guilty.

Davila ordered the trial itself, which was expected to last three months, to begin in August 2020.

Prosecutors have said Holmes and Balwani used advertising and solicitations to encourage doctors and patients to use its blood testing laboratory services, despite knowing the company could not produce accurate and reliable results consistently.

The criminal charges came after Holmes settled civil fraud charges brought by the U.S. Securities and Exchange Commission under which she was barred from serving as an officer or director of a public company for 10 years.

https://www.reuters.com/article/us-crime-theranos/theranos-founder-elizabeth-holmes-and-top-deputy-ordered-to-stand-trial-in-2020-idUSKCN1TU01N