Tuesday, October 2, 2018
Common Diabetes Meds May Raise Odds of Amputation
People with type 2 diabetes who are taking common drugs called diuretics may be at a significantly increased risk of losing a foot or leg, according to a new French study.
Researchers found that taking a diuretic raised the odds of having an amputation, or requiring an angioplasty or bypass, by 75 percent or more, compared with those not using the medicines.
Based on the findings, “diuretics should be used cautiously in patients with type 2 diabetes at risk of amputations,” concluded a team led by diabetes specialist Dr. Louis Potier, of Bichat Hospital in Paris.
But one U.S. expert said that restricting the use of diuretics puts diabetic patients “between a rock and a hard place.”
As Dr. Gerald Bernstein explained, diuretics are used to help “get rid of extra salt and water” in the blood, thereby helping patients control blood sugar and blood pressure.
In turn, that could help ward off a major killer: congestive heart failure.
So, the challenge is to “select the right drugs to prevent worsening of heart failure in order to prevent increased risk for amputations,” said Bernstein, coordinator for the Friedman Diabetes Program at Lenox Hill Hospital in New York City.
As Bernstein explained, “type 2 diabetes is a disease heavily associated with cardiovascular complications, in particular the big arteries from the heart to the rest of the body. When these arteries and the heart are diseased there is abnormal blood flow to all the organs but the lower extremities can be affected most because of how long that artery is.”
When circulation issues to the leg and foot become severe, amputation is often the only option.
How much might particular diabetes medicines affect the odds of needing an amputation?
To help find out, Potier’s team tracked outcomes for nearly 1,500 people with type 2 diabetes. The study specifically focused on amputations, as well as procedures such as angioplasty or the bypassing of blocked or damaged blood vessels. Those procedures are used to improve circulation and prevent leg or foot amputations.
Participants were followed until they had a leg procedure or died. Nearly 700 of the study participants were taking a diuretic drug.
Over a follow-up of about seven years, 13 percent of those taking a diuretic had an amputation or other procedure on their lower leg, compared with just 7 percent of those not taking a diuretic.
Said another way, this meant that taking a diuretic increased the risk of having an amputation or an angioplasty/bypass by 75 percent or more, compared with those not using one.
Most of this increase involved amputations, which nearly doubled for those taking a diuretic.
The results of the study were presented Monday at the meeting of the European Association for the Study of Diabetes, in Berlin.
It’s important to note the study was observational in nature, meaning that while it could point to an association between diuretics and amputation rates, it could not prove cause and effect, and other factors might be at play. Furthermore, research presented at medical meetings is typically considered preliminary until published in a peer-reviewed journal.
According to Bernstein, the take-home message here is not to immediately discontinue the use of diuretics, but to keep in mind that “the patient and physician must be very careful not to overtreat and be very selective” in which drugs are used to fight diabetes.
Diabetes specialist Dr. Robert Courgi agreed. Reviewing the findings, he said that while more study is needed to confirm the results, “if a patient is at risk for amputation then perhaps diuretics should be avoided for other equally effective options.” Courgi is an endocrinologist at Southside Hospital in Bay Shore, N.Y.
More information
For more on type 2 diabetes, visit the American Diabetes Association.
SOURCES: Gerald Bernstein, M.D., endocrinologist and coordinator, Friedman Diabetes Program, Lenox Hill Hospital, New York City; Robert Courgi, M.D., endocrinologist, Southside Hospital, Bay Shore, N.Y.; Oct. 1, 2018, press release, European Association for the Study of Diabetes
J&J California Talc Cancer Trial Ends With Deadlocked Jury
A Los Angeles jury weighing claims by a retired computer salesman that Johnson & Johnson’s iconic baby powder is laced with cancer-causing asbestos failed to reach a verdict, resulting in a mistrial.
Kirk Von Salzen said J&J was responsible for causing his mesothelioma, a cancer linked to asbestos exposure. He sought more than $12 million in damages. The jury deliberated for several days before a state judge decided the panel was hopelessly deadlocked.
The mistrial is the second straight in lawsuits attempting to link the company’s talc products to cancer. A Pasadena, California, jury also deadlocked a little over a week ago, in a lawsuit brought by a school counselor who blamed her mesothelioma on asbestos in J&J talc.
In the last case to end conclusively, a jury in Missouri awarded $4.69 billion in July to more than 20 women with ovarian cancer who alleged asbestos in the company’s baby powder and Shower to Shower products caused their illnesses.
Natural product Fisetin cuts level of damaged cells in body caused by aging
Previous research published earlier this year in Nature Medicine involving University of Minnesota Medical School faculty Paul D. Robbins and Laura J. Niedernhofer and Mayo Clinic investigators James L. Kirkland and Tamara Tchkonia, showed it was possible to reduce the burden of damaged cells, termed senescent cells, and extend lifespan and improve health, even when treatment was initiated late in life. They now have shown that treatment of aged mice with the natural product Fisetin, found in many fruits and vegetables, also has significant positive effects on health and lifespan.
As people age, they accumulate damaged cells. When the cells get to a certain level of damage they go through an aging process of their own, called cellular senescence. The cells also release inflammatory factors that tell the immune system to clear those damaged cells. A younger person’s immune system is healthy and is able to clear the damaged cells. But as people age, they aren’t cleared as effectively. Thus they begin to accumulate, cause low level inflammation and release enzymes that can degrade the tissue.
Robbins and fellow researchers found a natural product, called Fisetin, reduces the level of these damaged cells in the body. They found this by treating mice towards the end of life with this compound and see improvement in health and lifespan. The paper, “Fisetin is a senotherapeutic that extends health and lifespan,” was recently published in EBioMedicine.
“These results suggest that we can extend the period of health, termed healthspan, even towards the end of life,” said Robbins. “But there are still many questions to address, including the right dosage, for example.”
One question they can now answer, however, is why haven’t they done this before? There were always key limitations when it came to figuring out how a drug will act on different tissues, different cells in an aging body. Researchers didn’t have a way to identify if a treatment was actually attacking the particular cells that are senescent, until now.
Under the guidance of Edgar Arriaga, a professor in the Department of Chemistry in the College of Science and Engineering at the University of Minnesota, the team used mass cytometry, or CyTOF, technology and applied it for the first time in aging research, which is unique to the University of Minnesota.
“In addition to showing that the drug works, this is the first demonstration that shows the effects of the drug on specific subsets of these damaged cells within a given tissue.” Robbins said.
Story Source:
Materials provided by University of Minnesota Medical School. Note: Content may be edited for style and length.
Journal Reference:
- Matthew J. Yousefzadeh, Yi Zhu, Sara J. McGowan, Luise Angelini, Heike Fuhrmann-Stroissnigg, Ming Xu, Yuan Yuan Ling, Kendra I. Melos, Tamar Pirtskhalava, Christina L. Inman, Collin McGuckian, Erin A. Wade, Jonathon I. Kato, Diego Grassi, Mark Wentworth, Christin E. Burd, Edgar A. Arriaga, Warren L. Ladiges, Tamara Tchkonia, James L. Kirkland, Paul D. Robbins, Laura J. Niedernhofer. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine, 2018; DOI: 10.1016/j.ebiom.2018.09.015
Why health systems should worry about Walgreens, CVS
There’s a building threat from the nation’s two retail drugstore giants to hospitals and health systems as providers move toward value-based care and lower-cost outpatient services.
Even with Amazon threatening to compete with retail drugstore chains CVS Health and Walgreens with its own online pharmacy, these retailers aren’t giving up on brick-and-mortar as a way to attract more patients into their stores.
And that’s bad news for the nation’s hospitals and health systems.
There’s a building threat from the nation’s two retail drugstore giants to hospitals and health systems as medical care providers move away from fee-for-service medicine to value-based care and lower-cost outpatient services.
Walgreens and CVS are looking to healthcare as a way to keep customers coming into their stores, particularly in an era where consumers are fleeing brick-and-mortar to shop online via Amazon.
As front-end retail sales have fallen in recent years, CVS and Walgreens are moving more rapidly into healthcare from simply their historic role of filling prescriptions beyond the pharmacy counter and treating routine maladies with nurse practitioners in their retail centers to more services.
They are partnering more closely with health insurance companies that will work harder to funnel more patients to outpatient healthcare services inside the stores that will make them direct competitors of U.S. hospitals and health systems.
CVS has more than 1,100 retail MinuteClinics compared to 800 five years ago and 400 a decade ago.
CVS was opening 100 clinics per year 10 years ago, and that has slowed because they are now focusing on expanding healthcare services in the clinics as well as their stores generally. The same goes for Walgreens.
Walgreens has increased the services in its retail clinics, advertising the ability of nurse practitioners to conduct routine exams and student physicals and has been aggressively lobbying states across the country to change scope-of-practice laws to allow pharmacists to administer an array of vaccines.
“Why not use those locations as a strategy for healthcare?” Walgreens Chief Medical Officer Dr. Patrick Carroll says of the drugstore chain’s nearly 10,000 locations across the country. “We have the space. We should use it.”
To be sure, Walgreens is looking to provide more physician services like x-rays and procedures by partnering with UnitedHealth Group’s Optum to connect its MedExpress brand urgent care centers to an adjacent Walgreens. Like most retailers, Walgreens’ sales of general merchandise in the front end of the store is falling just as pharmacy sales, personal healthcare, and wellness revenues rise.
In the first such ventures, the Walgreens store and the MedExpress center each have their own entrance with a door inside connecting the urgent care center with the drugstore. It’s designed for a medical provider to guide a patient to either facility depending on their prescription or other needs.
For now, there are 15 locations in six states that have MedExpress urgent care centers connected to Walgreens stores as part of the pilot. The markets include Las Vegas; Dallas; Minneapolis; Omaha, Nebraska; two cities in West Virginia; and Martinsville, Virginia.
“We’re working closely with a number of partners in the healthcare community to bring services closer to our customers,” Carroll said. “With our stores serving as more of a neighborhood health destination, we can best meet the changing needs of our customers, while also complementing our expanded pharmacy services.”
Meanwhile, CVS plans to offer more healthcare services inside its stores after its merger with Aetna closes. CVS executives say they aren’t ruling out developing urgent care centers as well.
CVS’ network of nearly 10,000 pharmacies and over 1,000 retail clinics, and Optum’s growing network of ambulatory facilities like the MedExpress urgent care centers are emerging as a model health insurers want to do business with as fee-for-service medicine gives way to value-based care that keeps patients out of the hospital.
And in CVS’ case, the pharmacy will soon own Aetna, a health plan with more than 20 million members. That combination, which is currently wending its way through the regulatory process, is expected to lead to more narrow network health plans that encourage patients to use providers in the Aetna-CVS network over other health systems’ facilities.
Health systems should be concerned, healthcare analysts say.
“CVS and Aetna, in their own words, are promising to reinvent the front door of American healthcare,” says Kenneth Kaufman, managing director and chair of the consulting firm Kaufman Hall. “That promise should be of serious concern for legacy hospital providers since those providers have occupied that front door for the past 75 years.”
CVS Health President and CEO Larry Merlo is beginning to offer some details to their strategies.
While cautioning that it’s “very early” in the development of new programs the combined company will develop, Merlo has said the larger company plans to first focus on three primary patient populations: those patients with any of five chronic diseases: diabetes, hypertension, hyperlipidemia, asthma, and depression.
CVS and Aetna will also focus on “patients undergoing transitions in care,” and a third “broader focus on managing high-risk patients,” Merlo told analysts on the company’s second quarter earnings call in May.
“By extending our new health care model more broadly in the marketplace, patients will benefit from earlier interventions and better connected care leading to improved health outcomes,” Merlo said on September 20 at a CVS Health town hall meeting in Los Angeles.
“Think again about that senior leaving the hospital, knowing that the care plan prescribed by her doctor is being seamlessly coordinated by CVS and her caregiver. By fully integrating Aetna’s medical information and analytics with CVS Health’s pharmacy data and our 10,000 community locations, we can enable more effective treatment of the whole patient,” he says.
Cowen: 10 biotechs set to shake up the industry’s top ranks
While some of the biggest biotechs have recently struggled with continuing their impressive paths to success, investment bank Cowen & Co. took a future look at the industry and predicted 10 biotechs its analysts believe will grow to lead the industry.
“Stalled products, high-profile clinical failures, management dysfunction, dry pipelines, and overly conservative business development have made some [large-cap biotechs] look more big pharma than even some big pharmas,” the Cowen report stated, citing examples such as Amgen, Celgene and Gilead.
The Sept. 28 report emphasized four key factors in making the picks: (1) a business with low clinical development risk and high sales potential; (2) a de-risked mid- to late-stage pipeline; (3) a proven scientific or business strategy to drive long-term growth; (4) “credible management that can reliably drive execution of the pipeline and strategy.”
Here are the 10 mid-sized biotechs that Cowen believes will become the next generation’s top biotechs. Order is alphabetical.
Agios
Market capitalization: $4.5 billionApproved drug(s): Idhifa (enasidenib) and Tibsovo (ivosidenib)Top pipeline prospect(s): Mitapivat, a PKR activator in two pivotal studiesReasons for optimism: Cowen sees Agios’ base business peaking at $1 billion in revenue with an additional boost from Celgene-provided royalties for Idhifa. Their analysts highlighted the company’s embrace of personalized medicine, where the focus is on drugs with available biomarkers.Reasons for caution: While its outgoing CEO will become executive chairman, it will be worth watching how the company transitions to its new leader, Jacqualyn Fouse, a former Celgene executive. And, as with all biotechs, the transition from R&D promise to commercial reality can be a challenge. How quickly Agios can turn its recent approvals into profit will be a key test.Alnylam
Market capitalization: $8.9 billionApproved drug(s): Onpattro (patisiran)Top pipeline prospect(s): Givosiran, for acute hepatic porphyrias; and fitusiran, for hemophilia and bleeding disordersReasons for optimism: Alnylam stands out for its work in RNA interference, which led to the landmark approval of Onpattro in August. Cowen views RNAi as “not just a prolific engine of drug candidate generation, but also capable of addressing diseases that are otherwise undruggable.”Reasons for caution: While the approval of Onpattro was unquestionably a scientific breakthrough, commercial success is still a question. Ionis and Pfizer could bring rival drugs to market and pricing will be an area to watch as well. The influential watchdog group ICER recently found Onpattro “far exceeds” its cost-effectiveness thresholds.BioMarin
Market capitalization: $17.5 billionApproved drug(s): Palynziq (pegvaliase), Brineura (cerliponase alfa), Vimizin (elosulfase alfa), Kuvan (sapropterin dihydrochloride), Aldurazyme (laronidase) and Nagalzyme (galsulfase)Top pipeline prospect(s): Valoctocogene roxaparvovec, in Phase 3 for hemophilia A; and Vosoritide, in Phase 3 for anchondroplasiaReasons for optimism: Cowen praised BioMarin’s pipeline as “the deepest, most mature pipeline of rare disease therapies of any company currently.” The biotech already brought seven products to market and has several more in various stages of development.Reasons for caution: While securing approval for seven drugs is no easy feat, few of BioMarin’s products are seen as blockbusters-to-be. Much of the recent excitement around the company is concentrated on its hemophilia gene therapy, which has clear promise but a number of clinical hurdles to meet yet.Bluebird bio
Market capitalization: $7.8 billionApproved drug(s): NoneTop pipeline prospect(s): Lenti-D, in Phase 2/3 for cerebral adrenoleukodystrophy; bb2121, in Phase 3 testing for multiple myeloma; and LentiGlobin, for transfusion-dependent beta-thalassemia)Reasons for optimism: Bluebird said earlier this year they plan to file three therapies for approval by the end of 2019. Recent data released in September reinforced Lenti-D’s strength in efficacy and safety and the company is among the leaders in BCMA-targeting CAR-T therapy.Reasons for caution: Gene therapy is as promising as it is risky, with numerous challenges in manufacturing, pricing and potential commercialization. The required time and cost to bring products to market may test investor’s faith, making setbacks all the more damaging. Rivals in CAR-T could also upset Bluebird and partner Celgene’s plans.Incyte
Market capitalization: $14.8 billionApproved drug(s): Jakafi (ruxolitinib), Iclusig (ponatinib) in the EU, Olumiant (baricitinib)Top pipeline prospect(s): Ruxolitinib, for acute and chronic graft-versus-host disease; itacitinib; and several early-stage cancer drugsReasons for optimism: “Incyte’s expert medical chemists have been prolific in the generation of promising small molecules targeting oncology and immunology targets,” the Cowen report stated. “Despite recent setbacks, management still has an above-average track record of execution, including driving commercial success of Jakafi.”Reasons for caution: The Delaware-based biotech missed on a crucial Phase 3 trial with the IDO inhibitor epacadostat, which essentially ended that candidate’s potential for combination use in cancer treatments.Neurocrine
Market capitalization: $11.2 billionApproved drug(s): Ingrezza (valbenazine) and Orilissa (elagolix)Top pipeline prospect(s): Opicapone, in Phase 3 for Parkinson’s disease; and NBI-74788, in Phase 2 for congenital adrenal hyperplasiaReasons for optimism: Neurocrine strikes Cowen with a solid all-around business, noting a proven drug discovery process that yielded Ingrezza and Orilissa as well as an Ingrezza launch that beat “modest investor expectations.”Reasons for caution: Neuroscience is a notoriously challenging field and, with few wholly owned clinical assets, the biotech could feel the pain of a clinical setback more acutely.Sage
Market capitalization: $6.6 billionApproved drug(s): NoneTop pipeline prospect(s): Brexanolone, in registration phase for postpartum depression; SAGE-217, in Phase 2 and 3 for various indications; and SAGE-324, in Phase 1 for Parkinson’s diseaseReasons for optimism: The main draw for Cowen is “the commercial promise of its late-stage pipeline with $3B+ potential in major depressive disorder and broader PPD alone, not even including other programs in essential tremor and insomnia.” Clinical successes for brexanolone and SAGE-217 have raised investor expectations.Reasons for caution: A lot will be riding on Sage’s bet on an sped-up clinical development pathway for SAGE-217. The FDA signed off on the company’s in June, but future updates will likely be closely watched.Sarepta
Market capitalization: $10.5 billionApproved drug(s): Exondys 51 (eteplirsen)Top pipeline prospect(s): Golodirsen, for certain Duchenne muscular dystrophy patients; casimersen, for DMD; and a micro-dystrophin gene therapyReasons for optimism: As Cowen highlighted, Exondys 51 has found commercial success, with peak sales estimates of more than $700 million despite modest efficacy for Duchenne muscular dystrophy. The biotech’s pipeline, particularly in gene therapy, could make it a key player in DMD down the road as well as in the present.Reasons for caution: The FDA’s OK of Exondys 51 was one of the most controversial approvals in the agency’s recent history. To clear FDA scrutiny with future products, Sarepta may need to see stronger results in the clinic going forward. Recent bullishness around its gene therapy was tied to results in just three patients. Whether that efficacy holds up in a larger group is a critical question.Seattle Genetics
Market capitalization: $12.5 billionApproved drug(s): Adcetris (brentuximab vedotin)Top pipeline prospect(s): Enfortumab vedotin, for solid tumors; tisotumab vedotin, as a tissue factor; and tucatinib, for HER2 breast cancerReasons for optimism: Adcetris could grow to be a blockbuster drug for Seattle Genetics. It already has picked up five approved indications from the FDA and, on Monday, scored positive results in another key Phase 3 study.Reasons for caution: Commercial execution will be key for Seattle Genetics, which hopes to expand the market for Adcetris. The biotech has bet heavily on antibody-drug conjugates. Can it expand into immuno-oncology as well?Ultragenyx
Market capitalization: $3.8 billionApproved drug(s): Crysvita (burosumab-twza) and Mepsevii (vestronidase alfa)Top pipeline prospect(s): Small molecule UX007, for fatty acid oxidation disorders; and gene therapies DTX301 and DTX401Reasons for optimism: Cowen seems sold on Ultragenyx’s leader. The bank’s report stated its “most unique value lies in the experience and company-building strategy driven by its founding CEO, a pediatric geneticist and original CMO of Biomarin.”Reasons for caution: Ultragenyx has yet to turn a profit and expects “significant losses for the forseeable future,” according to its most recent quarterly filing. Its gene therapy candidates, meanwhile, are still early in development.
Southern Diet Called Single Biggest Factor in Hypertension Racial Disparities
Several clinical and social factors have contributed to the higher rates of hypertension among black American adults, but key among them is the “Southern diet,” a prospective cohort study found.
Such a diet — calorie-dense with relatively little fresh fruit and vegetables or whole grains — was the largest statistical mediator of difference in hypertension prevalence between black and whites, accounting for 29.2% of the excess risk among black women and 51.6% of the excess risk among black men, reported George Howard, DrPH, of the University of Alabama at Birmingham, and colleagues in JAMA.
The researchers found a greater number of significant mediating factors among women than men for the racial disparity in hypertension incidence, which “may be partially attributable to an observed stronger association of race with incident hypertension among women than men that would provide greater statistical power to detect mediating factors,” they wrote.
This study provided a look into “some of the unique lifestyle choices that individuals make in terms of diet and exercise and other factors that may be contributing to a more likely development of hypertension and as such it is a non-biased assessment of diet and exercise and alcohol and smoking and all the other factors that we presume contribute to hypertension,” commented Donald Molony, MD, of University of Texas Health Science Center in Houston, in an interview with MedPage Today.
The researchers evaluated 6,897 participants (mean age 62), among whom 26% were black and 55% were women. Over the course of the study, 46% of black participants and 33% of white participants developed hypertension in a follow-up visit 9.4 years later.
Black participants scored higher on the adjusted mean Southern diet scale, which ranges from -4.5 to 8.2 and where higher values are associated with higher intake of fried foods, organ meats, processed meats, eggs, added fats, high-fat dairy, sugar-sweetened beverages, and bread. The researchers found the following average scores:
- Black men: 0.81 (95% CI, 0.72 to 0.90)
- White men: -0.26 (95% CI, -0.31 to -0.21)
- Black women: 0.27 (95% CI, 0.20 to 0.33)
- White women: -0.57 (95% CI, -0.61 to -0.54)
Higher Southern diet scores were significantly linked with incident hypertension for women (OR 1.17 per 1 SD; 95% CI, 1.08-1.28) and for men (1.16 per 1 SD; 95% CI, 1.06 to 1.27).
Among black men, two other factors were significant — a higher dietary ratio of sodium to potassium and an educational level of graduating high school or even less each accounted for 12.3% of the excess hypertension risk compared with white men.
Among black women, the proportion of excess risk mediated by the various risk factors was:
- 18.3% for higher body mass index
- 15.2% for a larger waist
- 11.2% for lower adherence to the Dietary Approaches to Stop Hypertension (DASH) diet
- 9.3% for income level of $35,000 or less
- 6.8% for higher dietary ratio of sodium to potassium
- 4.1% for education level of high school graduate or less
Comment on the study’s findings, Molony noted that there was “little evidence from this cohort that alcohol consumption and lifestyle stresses are contributing significantly to hypertension.”
Perceived stress levels reported by the participants were similar between black and white groups by gender.
However, Molony questioned that finding. “I’m concerned about the stress issue, because I don’t think that the measurements that they used are sensitive enough to look at daily stresses on the development of hypertension. More importantly, if stress is a factor in the development of hypertension in the African American population, then it might be more important in the younger age groups that are excluded from the study,” Molony continued.
The researchers acknowledged the limitations of their work: over half of the cohort did not have a follow-up visit, 16% passed away, and 24% did not complete the study because they withdrew or declined follow-up.
The investigators also noted the potential for measurement error and misclassification of mediating factors. “Such misclassification would generally lead to underestimation of the effects of potential mediating factors, so the reported estimates of the mediating effects could be underestimates,” the investigators wrote.
The study was funded by the National Institute of Neurological Disorders and Stroke.
Howard and Molony did not disclose any relevant financial relationships with industry.
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