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Tuesday, August 28, 2018

Fed Panel: Prevent Perinatal Depression With Counseling


Healthcare providers should refer pregnant and postpartum women at increased risk for depression to counseling services, according to the U.S. Preventive Service Task Force (USPSTF).
In the draft recommendation statement posted to the USPSTF website, the group found “convincing evidence” (Level B) that referring these women to counseling services, including cognitive behavioral therapy and interpersonal therapy, will have a “moderate net benefit” in helping prevent perinatal depression among women who are at increased risk.
The recommendation applies to pregnant women and women who have given birth less than 1 year ago, without a current depression diagnosis but considered at risk because of factors such unplanned/unwanted pregnancy or as a history of physical or sexual abuse.
“For the first time, the Task Force is recommending counseling to prevent perinatal depression in high-risk women,” explained USPSTF member Aaron Caughey, MD, PhD, of the Oregon Health & Science University in Portland, in a statement. “Clinicians should use patient history and risk factors to identify women who are most likely to benefit.”
This was echoed by fellow member Karina Davidson, PhD, of Columbia University Medical Center in New York, who added that the responsibility falls largely on primary care providers to initiate the conversation. “Perinatal depression is a serious condition that negatively affects mothers, babies, and families,” she said in the statement. “Fortunately, effective counseling interventions can help prevent perinatal depression before it develops, and primary care clinicians can provide or connect women with these services.”
No current guidelines address measures to prevent perinatal depression, explained the USPSTF in the draft. However, they referenced guidelines from the American College of Obstetricians and Gynecologists (ACOG) recommending women with current depression, anxiety, or a history or risk factors for of perinatal mood disorders be screened, as well as recommendations for all postpartum women to be screened for anxiety and depression.
Although there “no accurate screening tool available” for identifying at-risk women for perinatal depression — which the USPSTF called a gap that must be addressed through future research efforts — the statement listed clinical risk factors for clinicians to look for.
These included:
  • Personal or family history of depression
  • Unplanned or unwanted pregnancy
  • History of physical or sexual abuse
  • Stressful life events
  • Gestational diabetes
  • Pregnancy complications
  • Low socioeconomic status
  • Lack of financial or social support
With “adequate evidence” that the benefits of counseling interventions outweigh the potential harms, the USPSTF recommended either cognitive behavioral therapy or interpersonal therapy as a first-line intervention for these at-risk women.
Cognitive behavior therapy “focuses on the concept that positive changes in mood and behavior can be achieved by addressing and managing negative thoughts, beliefs, and attitudes and by increasing positive events and activities,” the USPSTF explained. Common techniques with this intervention include setting goals, modifying thought patterns, patient education, and behavioral activation.
Interpersonal therapy “focuses on treating interpersonal issues that are thought to contribute to the development or maintenance of psychological disorders” through the use of exploratory questioning, decision analysis, role playing, and communication analysis. The USPSTF did not indicate which types of patients would do best with one intervention versus the other.
On average, the duration of this counseling can vary greatly — lasting between four to 70 weeks — depending on patient needs, although sessions are typically initiated during pregnancy.
Besides counseling interventions, the draft also touched upon a lack of definitive evidence on the benefits of other interventions including antidepressants and supplements, such as selenium and vitamin D, for the prevention of perinatal depression. However, they also mentioned a few small trials suggesting benefit from other types of interventions such as exercise, infant sleep education, in-hospital perinatal education, and peer counseling for preventing depression in this population, although additional research is still needed.
Beyond treatment for at-risk pregnant and postpartum women, the USPSTF’s draft also highlighted a previous guideline recommending screening for depression among adolescents between 12-18 years of age (Level B), but found insufficient evidence to screening in children younger than 12 (I statement).
Public comment on the new draft recommendation statement will be accepted through Sept. 24.
None of the authors reported conflicts of interest.

Rising STD Rates in U.S. Signal ‘Public Health Crisis’


Sexually transmitted disease (STD) diagnoses have increased every year since 2013, with the number of new STD diagnoses the highest ever in 2017, CDC researchers found.
There were 2.3 million cases of chlamydia, gonorrhea, and syphilis diagnosed in 2017, with syphilis diagnoses up by 76% and gonorrhea diagnoses up by 67% since 2013, according to preliminary data released by the CDC at the National STD Prevention Conference in Washington.
At a press briefing, Gail Bolan, MD, director of the CDC division of STD prevention, characterized this as a “continuation of a persistent and troubling trend,” particularly noting that rates of diagnosis for gonorrhea “nearly doubled” among men and increased one-fifth among women, “something we haven’t seen in a long time,” she added.
The CDC reported that chlamydia remained the most common condition reported to the CDC, with more than 1.7 million cases diagnosed in 2017, with a little under half among women ages 15 to 24.
Bolan cited another troubling statistic about the looming threat of antibiotic resistance regarding gonorrhea treatment. The CDC currently recommends a two-dose therapy for gonorrhea consisting of an intramuscular dose of ceftriaxone — the only “highly effective” antibiotic used to treat gonorrhea in the U.S. — and oral azithromycin.
But Bolan reported that a “small, but growing fraction” of lab specimens of gonorrhea are showing “signs of antibiotic resistance.” While she added that there has never been a “confirmed treatment failure” when using this recommended treatment, the worry is there may eventually be a strain of gonorrhea that does not respond to ceftriaxone.
“Our nation urgently needs new treatment options for gonorrhea,” Bolan said. “But CDC alone cannot turn the tide on rising STDs. It requires new commitment from the healthcare sector, scientists, industry, state and local health departments.”
“Commitment” usually means “money,” and state and local health officials spoke candidly about the country’s “eroding public health infrastructure” that they felt contributed to the tremendous increase in STDs. Specifically, officials cited years of cutbacks in funding for STD prevention, with state and local health departments who rely on federal funding to support their STD programs, working with budgets that are half of what they were 15 years ago.
“We maintain our bridges and roads, and we see them on TV when they crumble. You don’t always see a crumbling public health infrastructure,” said Michael Fraser, PhD, executive director, Association of State and Territorial Health Officials (ASTHO). “We know what works with STD prevention. We just don’t want to pay for all of it.”
David C. Harney, MSW, executive director, National Coalition of STD Directors, called for an additional $70 million in funding to “immediately arm state and local health programs to combat this crisis.” He said that treatment for STDs costs more than $16 billion a year.
“It is time that President Trump and Secretary Azar declare STDs in America a public health crisis,” adding that emergency access to funding is also needed to bring these rates down.
In addition to cutbacks in federal and state funding, Harney cited other factors for the rise of STDs in America, namely the “extreme lack of awareness and education about STDs and sexual health.” But he also said providers and patients played a significant role as “doctors are not screening and testing for STDs and patients don’t know they need to ask for screening and treatment.”
Bolan added that screening needs to be “routine care” and that providers and patients need to be having that conversation about testing.
Harvey added a plea to Congress for more funding for provider training, through the CDC STD Prevention Training Centers, where funding has also been cut over the last 20 years.
But Fraser pointed out that the solution to the rising STD problem is not going to be “treating our way out of it,” and that a solid public health infrastructure is also needed. He specifically noted that cuts in funding have affected programs that support “disease investigators,” who meet with individuals, talk about their sexual behavior, do contact tracing, and try to prevent future infections.
“Expecting a physician in an already hurried day-to-day practice to do a slew of [recommended STD testing] is probably not realistic, given the way physicians practice,” he said. “Public health can take some of the pressure off the clinical system. You don’t need a medical degree to prevent an STD — you need to talk with people about using condoms.”
Bolan said that the full 2017 STD surveillance report is expected to be released in late September.

Oppenheimer Starts Weight Watchers (WTW) at Outperform

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Karyopharm presents Phase 2 myeloma data


— Oral Selinexor Achieves 25.4% Overall Response Rate and DOR of 4.4 Months in Overall Study Population —
— Median Survival of 8.6 Months in All Patients; Median Survival of Responders not yet Reached —
— New Drug Application Submitted to FDA; On Track to Submit MAA in Q1 2019 —
Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today announced that clinical data from the Phase 2b STORM study evaluating the Company’s lead, oral Selective Inhibitor of Nuclear Export (SINE) compound selinexor in heavily pretreated patients with refractory multiple myeloma, has been selected for oral presentation at the Society of Hematologic Oncology (SOHO) 2018 Annual Meeting, taking place September 12-15, 2018 in Houston.
“The clinical results from the STORM study further support selinexor’s potential role in advancing the treatment options available to patients with refractory multiple myeloma. In addition to the 25.4% overall response rate (ORR), including two patients who achieved stringent complete responses (sCRs) with minimum residual disease (MRD) negativity, patients treated with oral selinexor and dexamethasone (dex; Sd) also achieved median duration of response (DOR) of 4.4 months and median overall survival (OS) of 8.6 months,” said Sundar Jagannath, MD, Director of the Multiple Myeloma Program, Professor of Medicine (Hematology and Medical Oncology) at Tisch Cancer Institute at Mount Sinai School of Medicine, and principal investigator of the STORM study. “The importance of achieving MRD negativity and extending overall survival rates in this heavily pretreated patient population is very encouraging. Notably, patients with any response to Sd, including minimal, partial, very good partial and complete responses, experienced significantly prolonged OS compared to patients who did not respond, and the median OS had not yet been reached in this population.”
“Despite recent advances in myeloma treatment, an increasing number of patients will require additional therapeutic options for this progressive and fatal disease,” said Sharon Shacham, PhD, Founder, President and Chief Scientific Officer of Karyopharm. “The 27.3% ORR observed in patients who had previously received Darzalex® in combination regimens is particularly compelling as these patients are especially difficult to treat. Additionally, we are increasingly encouraged by the improvement in overall survival demonstrated in patients who had a response of stable disease or better. We look forward to presenting additional data from what is covered in the abstract at the SOHO 2018 Annual Meeting in mid-September. Finally, we remain tremendously excited by the recent submission of our first New Drug Application to the U.S. Food and Drug Administration seeking accelerated approved for selinexor in patients with penta-refractory myeloma, and we look forward to submitting a Marketing Authorization Application (MAA) with the EMA in the first quarter of 2019.”

Doctor, hospital groups organize to oppose single-payer in Calif.


A group of influential, deep-pocketed business and health care organizations that have long helped shape the legislative agenda in California have joined forces to oppose any future effort to craft a universal, single-payer health care system for the nation’s largest state.
The main focus of the coalition, called “Californians against the costly disruption of our health care,” is to kill any single-payer health care bill in the state Legislature, said Ned Wigglesworth, a political strategist for the coalition.
“As long as proponents plan to bring this back time and again, we think it’s important to have a strong, unified presence to oppose it,” Wigglesworth said, referring to Senate Bill 562, the 2017 single-payer bill pushed by the California Nurses Association that was shelvedlast year by Assembly Speaker Anthony Rendon.
The anti-single payer coalition includes powerful groups representing the interests in Sacramento of doctors, hospitals, insurers and businesses. Instead of single-payer, the coalition is expected to press for alternatives, which could include several legislative proposals on health care that failed this year and some under discussion, including expanding state insurance subsidies, allowing undocumented adults to sign up for Medi-Cal and creating a state-based individual mandate for everyone to have coverage.
Nurses, acknowledging their high-profile effort to create a government-financed single-payer system is dead (the end of the two-year session is Friday), said the union plans to introduce another single-payer bill next year. They say anything short of that is insufficient.
“We are working on a bill,” said Stephanie Roberson, chief legislative director for the nurses association. “The California Nurses Association is in no way backing off pursuing legislation to achieve ‘Medicare for all’ next year. Speaker Rendon’s act of shelving the bill last spring only strengthened our resolve.”
She said the nurses are talking to various lawmakers about legislation heading into the new two-year term, but they don’t yet have an author. She said she expects Lt. Gov. Gavin Newsom, the frontrunner in the California governor’s race, to play a prominent role, should he be elected in November.
“We welcome the new leadership of our future governor, Gavin Newsom, with his commitment to this issue… We need political leadership and courage.”
Newsom has voiced support for single-payer, but has also said he has concerns about whether California could overcome the steep challenges it would take to create such a system. It would cost an estimated $400 billion per year and, although it would eliminate insurance costs for health care consumers, it would also require large tax increases. It would also likely require voters to approve amendments to the state Constitution, and the state would have to secure several federal waivers from the Trump administration.
Doctors, hospital groups and insurers are gearing up fight back next year against any single-payer bill similar in scope to last year’s proposal.
“I think you’re going to hear our messaging loud and clear,” said Charles Bacchi, president and CEO of the California Association of Health Plans. “It’s going to be really focused around how expensive (single-payer) would be for California to do, and how disruptive it would be for people who currently receive health care coverage.
“The remaining uninsured is what we should address next,” Bacchi said.
Health care industry groups were somewhat blindsided last year by the single-payer bill, authored by state Sens. Ricardo Lara and Toni Atkins, who is now leader of the Senate, representatives of doctor and hospital groups said. They’ve long opposed single-payer, but were not formally organized to push back against the nurses’ single-payer proposal.
“The rapid advancement of SB 562 caught everyone by surprise,” Bacchi said. “We were all individually talking about ways to improve our health care system and in the meantime, a really bad idea was speeding its way through the Legislature.”
Allan Zaremberg, president of the California Chamber of Commerce, said that will be different next year.
“A lot of employers provide health care, and like their employees, they’re satisfied with how health care is delivered,” Zaremberg said. “From a business perspective, I think they’d rather have the administration (of health care) done through the private sector rather than the government.”
Coalition members said they’ll be focusing their early efforts on the Legislature and the next governor, but did not rule out spending on advertising and other public messaging. Key discussions will be focused on alternative potential proposals to contain escalating costs and expand coverage to everyone regardless of immigration status or ability to pay.
Opposing sides have heard what they’ve wanted to hear from Newsom in the gubernatorial race. The nurses see an ally in their fight, while Newsom’s comments lately indicate deep skepticism about the ability to implement single-payer, industry representatives said.
“We have spoken to Mr. Newsom and if he’s elected, we will continue to talk to Mr. Newsom,” said Janus Norman, chief lobbyist for the California Medical Association. “We expressed our concern and he expressed his commitment to getting to a place where everyone is covered… He did it in San Francisco and he is dead-set on doing it as governor.”
Newsom spokesman Nathan Click said in a statement, “As he did as mayor, Gavin Newsom will bring stakeholders of differing perspectives together to achieve a health system that is bold, affordable and works for everyone.”

Combination approach shows promise for beating advanced melanoma


A UCLA-led study has found that a treatment that uses a bacteria-like agent in combination with an immunotherapy drug could help some people with advanced melanoma, an aggressive form of skin cancer, live longer.
The research showed that using the immunotherapy drug pembrolizumab and the experimental agent SD-101, a sequence of nucleic acids that mimics a bacterial infection, altered the microenvironment around the tumor in a way that enabled the immune system to more effectively attack the cancer. The research was an early-stage study, conducted to test the side effects and best dosage of a potential new combined therapy, and the findings were published today in the journal Cancer Discovery.
Pembrolizumab, which is marketed under the brand name Keytruda, works by blocking a protein called PD-1, which interferes with immune system function. Blocking PD-1 with pembrolizumab enables the immune system cells to better attack the cancer. While pembrolizumab has been a significant advancement for treating people with a variety of advanced or metastatic cancers, a majority of metastatic melanoma tumors are still resistant to the drug.
“We have found that the reason patients with metastatic melanoma do not initially respond to immunotherapy with an anti-PD-1 is that their immune system was not ready,” said Dr. Antoni Ribas, the study’s lead author, a professor of medicine at the David Geffen School of Medicine at UCLA and director of the UCLA Jonsson Comprehensive Cancer Center Tumor Immunology Program. “So we thought, ‘What if we change that by injecting the therapy drug into the metastatic lesions and change the microenvironment of the cancer?’
“It’s like having a pile of wood but not having a match to light it. With this new approach, SD-101 is the match that starts the fire.”
The researchers found that SD-101 not only directs T cells to cancer cells, but it also makes the microenvironment more hospitable for the T cells, so that they can better kill the cancer cells.
All 22 people in the study had an advanced stage of inoperable or metastatic melanoma. Nine were receiving an immunotherapy treatment for the first time as part of the study. Seven of those nine had a positive response to the drug combination, including two for whom the tumors disappeared completely.
The other 13 people in the study had previously received a type of immunotherapy before the study. Of them, two had a partial response, meaning parts of the tumors shrank, but the tumors did not go away completely. Five more showed some reduction in the tumors, but the other participants did respond to the therapy.
The results of the study suggest that the combination of pembrolizumab and SD-101 could provide an alternative treatment for people with melanoma whose tumors have not responded or would be unlikely to respond to other therapies.
“For all patients with advanced cancer, immunotherapy using PD-1 inhibitors has really changed the face of cancer treatment. Unfortunately, this therapy still only works in a subset of patients,” said Dr. Deborah Wong, assistant clinical professor of medicine at the Geffen School of Medicine and an oncologist at the Ronald Reagan UCLA Medical Center, who was also an author of the paper.
“This particular combination has been especially gratifying because not only does the SD-101 therapy drug induce tumor shrinkage at the actual site where it’s injected, but it’s working in conjunction with pembrolizumab to shrink tumors outside of the ones we’re directly injecting.”
The study highlights the need for more research into combination therapies like this one, because many people with cancer do not respond to immunotherapy or experience a reoccurrence of their tumors after treatment.
“We are really starting to understand the science of how immunotherapies work in patients,” said Ribas, who is also the director of the Parker Institute for Cancer Immunotherapy Center at UCLA. “By understanding that, we can find more ways to make that therapy more active. One way is by combining the therapy with another agent that can overcome the resistance that some cancers have to these therapies.”
The study was funded by Dynavax Technologies Corp., which provided SD-101. Merck & Co. provided pembrolizumab. Ribas’ research is funded by the Parker Institute for Cancer Immunotherapy and the National Institutes of Health.
Story Source:
Materials provided by University of California – Los Angeles Health SciencesNote: Content may be edited for style and length.

Journal Reference:
  1. Antoni Ribas, Theresa Medina, Shivaani Kummar, Asim Amin, Anusha Kalbasi, Joseph J. Drabick, Minal Barve, Gregory A. Daniels, Deborah J. Wong, Emmett V. Schmidt, Albert F. Candia, Robert L. Coffman, Abraham C.F. Leung, Robert S. Janssen. SD-101 in Combination with Pembrolizumab in Advanced Melanoma: Results of a Phase 1b, Multicenter StudyCancer Discovery, 2018; CD-18-0280 DOI: 10.1158/2159-8290.CD-18-0280

AI can deliver specialty-level diagnosis in primary care setting


A system designed by a University of Iowa ophthalmologist that uses artificial intelligence (AI) to detect diabetic retinopathy without a person interpreting the results earned Food and Drug Administration (FDA) authorization in April, following a clinical trial in primary care offices. Results of that study were published Aug. 28 online in Nature Digital Medicine, offering the first look at data that led to FDA clearance for IDx-DR, the first medical device that uses AI for the autonomous detection of diabetic retinopathy.
The clinical trial, which also was the first study to prospectively assess the safety of an autonomous AI system in patient care, compared the performance of IDx-DR to the gold standard diagnostic for diabetic retinopathy, which is the leading cause of vision loss in adults and one of the most severe complications for the 30.3 million Americans living with diabetes.
IDx-DR exceeded all pre-specified superiority endpoints in sensitivity, the ability to correctly identify a patient with disease; specificity, the ability to correctly classify a person as disease-free; and imageability, or the capability to produce quality images of the retina and determine the severity of the disease.
“The AI system’s primary role is to identify those people with diabetes who are likely to have diabetic retinopathy that requires further evaluation by an eye-care provider. The study results demonstrate the safety of autonomous AI systems to bring specialty-level diagnostics to a primary care setting, with the potential to increase access and lower cost,” says Michael Abràmoff, MD, PhD, the Robert C. Watzke Professor of Ophthalmology and Visual Sciences with UI Health Care and principal investigator on the study. He is founder and president of IDx, the company that created the IDx-DR system and funded the study.
Early detection may prevent vision loss
More than 24,000 people in the U.S. lose their sight to diabetic retinopathy each year. Early detection and treatment can reduce the risk of blindness by 95 percent, but less than 50 percent of patients with diabetes schedule regular exams with an eye-care specialist.
In the study, 900 adult patients with diabetes — but no history of diabetic retinopathy — were examined at 10 primary care sites across the U.S. Retinal images of the patients were obtained using a robotic camera, with an AI assisting the operator in getting good quality images. Once the four images were complete, the diagnostic AI then made a clinical diagnosis in 20 seconds. The diagnostic AI detects disease just as expert clinicians do, by having detectors for the lesions characteristic for diabetic retinopathy, including microaneurysms, hemorrhages, and lipoprotein exudates.
Camera operators in the study were existing staff of the primary care clinics, but not physicians or trained photographers.
“This was much more than just a study testing an algorithm on an image. We wanted to test it in the places where it will be used, by the people who will use it, and we compared it to the highest standard in the world,” says Abràmoff, who also holds faculty appointments in the UI College of Engineering.
AI measured against gold standard
Study participants also had retinal images taken at each of the primary care clinics using specialized widefield and 3D imaging equipment without AI operated by experienced retinal photographers certified by the Wisconsin Fundus Photograph Reading Center (FPRC) — the gold standard in grading the severity of diabetic retinopathy.
Complete diagnostic data accomplished by both the AI system and FPRC readers was available for 819 of the original 900 study participants. FPRC readers identified 198 participants with more than mild diabetic retinopathy who should be further examined by a specialist; the AI was able to correctly identify 173 of the 198 participants with disease, resulting in a sensitivity of 87 percent. Among the 621 disease-free participants identified by FPRC readers, AI identified 556 participants, for a specificity of 90 percent. The AI had a 96 percent imageability rate: of the 852 participants who had an FPRC diagnosis, 819 had an AI system diagnostic output.
In June, following FDA clearance, providers at the Diabetes and Endocrinology Center at UI Health Care-Iowa River Landing in Coralville, Iowa, were the first in the nation to begin using IDx-DR to screen patients.
“We are hoping to do this also for early detection of diseases like glaucoma and macular degeneration. We are working on those algorithms already. The goal is to get these specialty diagnostics into primary care and retail, which is where the patients are,” Abràmoff says.
IDx is working with the American Medical Association to ensure that there is clear coding guidance for billing of IDx-DR. Providers, physicians, and suppliers should contact their third-party payers for specific and current information on their coding, coverage, and payment policies. IDx is a licensed distributor of the robotic camera used in the study.
The paper, “Pivotal trial of an autonomous AI-based diagnostic system for detection of diabetic retinopathy in primary care offices,” was co-authored by James Folk, MD, UI professor of ophthalmology and visual sciences and the Donald H. Beisner, MD, Professor of Vitreoretinal Diseases and Surgery, as well as an IDx board member. Also involved in the study were Philip Lavin at Boston Biostatistics Research Foundation, Inc, Michele Birch at University of North Carolina School of Medicine, and Nilay Shah at The Emmes Corporation, Rockville, Md.
Story Source:
Materials provided by University of Iowa Health CareNote: Content may be edited for style and length.

Journal Reference:
  1. Michael D. Abràmoff, Philip T. Lavin, Michele Birch, Nilay Shah, James C. Folk. Pivotal trial of an autonomous AI-based diagnostic system for detection of diabetic retinopathy in primary care officesnpj Digital Medicine, 2018; 1 (1) DOI: 10.1038/s41746-018-0040-6