Brain MRI Evidence of Carbon Monoxide Poisoning May Show Up Late

Brain MRI Evidence of Carbon Monoxide Poisoning May Show Up Late

NEW YORK (Reuters Health) – Acute brain lesions on MRI are associated with an increased risk of delayed neurological sequelae after carbon monoxide (CO) poisoning, researchers from Korea report.

Neurological symptoms of CO poisoning can appear as late as 6 weeks after successful resuscitation. Diffusion-weighted imaging (DWI) can identify acute brain lesions in CO poisoning, but it remains unclear how these might be related to the development of delayed neurological sequelae .

Dr. Won Young Kim and colleagues from University of Ulsan College of Medicine, Seoul, South Korea, investigated the prevalence and characteristics of such acute brain lesions on DWI and whether their presence is related to the development of delayed neurological sequelae in 387 patients with acute CO poisoning. Their findings were reported online January 29 in JAMA Neurology.

Just over a quarter of patients (26.9%) had acute brain lesions on DWI, most commonly in the globus pallidus. Delayed neurological sequelae followed CO poisoning in 26.1% of patients.

Although the pattern, region, and location of acute brain lesions on DWI did not differ between patients who developed delayed sequelae and those who did not, their presence was independently associated with nearly a 14-fold increased risk of delayed neurological sequelae.

The presence of acute brain lesions on DWI had 75.2% sensitivity and 90.2% specificity for predicting delayed neurological sequelae, with a positive predictive value of 73.1% and a negative predictive value of 91.2%.

Other factors independently associated with the development of delayed neurological sequelae included altered mental status and longer duration of CO exposure.

“Diffusion-weighted imaging during the acute phase of CO poisoning may therefore help identify patients at risk of developing these debilitating sequelae,” the researchers conclude. “Further studies are needed to validate our findings.”

Dr. Marco Varrassi from S. Salvatore Hospital, L’Aquila, Italy, who recently reviewed the neuroimaging of CO poisoning, told Reuters Health by email, “MRI should always be performed in the acute phase, because it provides an excellent tool to predict the long-term prognosis of these patients.”

He said that it is also essential to follow these patients “for quite a long time even if clinical conditions are good at discharge.”

Dr. Varrassi added, “It would be very important to find a correlation, if it exists, between therapeutic strategy in the acute phase and future development of delayed neurological sequelae, since this condition can be very debilitating.”

Dr. Kim did not respond to a request for comment.

SOURCE: http://bit.ly/2DUKph9

JAMA Neurol 2018.

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No Evidence of CNS Infection With Lyme Encephalopathy

No Evidence of CNS Infection With Lyme Encephalopathy

NEW YORK (Reuters Health) – There is no evidence of central nervous system (CNS) infection in patients with neurobehavioral symptoms of Lyme disease, researchers report.

“The cognitive, memory, and concentration difficulties often attributed to Lyme disease are not caused by brain infection or immune activation within the nervous system, nor do they appear to be specific to Lyme disease,” Dr. John J. Halperin from Overlook Medical Center, Atlantic Health System, Summit, New Jersey, told Reuters Health by email. “There may be systemic immune activation (i.e., not related to the nervous system) causing these symptoms; understanding this better may lead to insights and useful therapeutic interventions.”

Lyme encephalopathy manifests as objective cognitive abnormalities on mental status testing, but it remains unclear what mechanisms underlie this phenomenon.

Dr. Halperin’s team performed multiplex immunoassays to measure cytokines and chemokines in cerebrospinal fluid (CSF) samples from 74 patients who underwent lumbar puncture for possible Lyme neuroborreliosis (LNB).

Several inflammatory markers were elevated in the CSF of patients with definite LNB and non-Lyme neuroinflammation, but not in patients with Lyme or non-Lyme encephalopathy.

CSF CXCL13 proved to be a sensitive and specific marker of LNB in patients with specific intrathecal antibodies to Borrelia burgdorferi, according to the January 11 online report in Clinical Infectious Diseases.

“This is important, first, because it has been proposed as a useful marker of active CNS infection, one that drops after successful treatment,” Dr. Halperin said. “Second, it’s reassuring to find that mechanisms of disease are similar in U.S. and European patients, as the responsible spirochetes are slightly different. Knowing that mechanisms are the same enhances our ability to apply lessons learned in Europe as we try to understand mechanisms of disease in U.S. patients.”

Serum levels of the T-cell growth factor IL-7 were elevated in patients experiencing neurobehavioral symptoms, regardless of their history of Lyme disease.

Moreover, encephalopathy and headache patients, with or without a history of Lyme disease, showed elevations in serum cytokine levels indicative of a Th17-type immune response.

None of the cytokines analyzed in the study was elevated in CSF of patients with headache or encephalopathy, compared with measurements from 50 control patients with non-neuroinflammatory disorders.

These findings “should be reassuring to patients and their physicians – the presence of this symptom complex in no way implies there is a difficult-to-eradicate brain infection,” Dr. Halperin said. “Intriguingly it suggests that this state may, regardless of the specific circumstances, reflect a particular pattern of ongoing immune activation – having nothing to do with the nervous system, or for that matter Lyme disease per se. Understanding this better could lead to better therapeutic interventions in these patients, for many of whom the symptoms are quite disabling.”

SOURCE: http://bit.ly/2DLNiNS

Clin Infect Dis 2018.

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Lower Risk of Some Cancers With Oral Contraceptives Applies Across Lifestyles

Lower Risk of Some Cancers With Oral Contraceptives Applies Across Lifestyles

(Reuters Health) – Women who use oral contraceptives for at least a decade may be less likely to develop ovarian or endometrial malignancies, and this benefit doesn’t seem to be diminished by other lifestyle risk factors, a U.S. study suggests.

In fact, the risk-lowering effect of long-term birth control pill use was greatest for endometrial cancers among women who had other lifestyle risk factors like obesity, smoking and lack of exercise, researchers report online January 18 in JAMA Oncology.

Compared to women who used oral contraceptives for a year or less, women who took the Pill for at least 10 years were 40% less likely to develop ovarian cancer and 35% less likely to develop endometrial tumors, the study found. Among smokers, the endometrial cancer risk was 53% lower, among obese women it was 64% lower and among those who rarely exercised it was 60% lower with long-term Pill use.

“Our study demonstrates that oral contraceptive use is beneficial for the prevention of ovarian and endometrial cancers for women with different underlying risks for these diseases,” said lead study author Kara Michels, a researcher at the National Cancer Institute in Bethesda, Maryland.

While some previous research has linked oral contraceptives to a lower risk of ovarian, endometrial and colorectal tumors, the strength of this evidence has been mixed and left an incomplete picture of how other factors like smoking, drinking, inactivity or obesity might influence this connection, the study authors note.

For the current study, they examined data on 118,144 women who never used oral contraceptives as well as 34,866 women who took them for 1 to 4 years; 25,564 women who used them for 5 to 9 years; and 18,962 who were on the Pill for at least a decade.

Half of the women were at least 62 years old when they joined the study, and most of them had already gone through menopause and no longer required contraception, but they reported any previous contraceptive use.

Compared with women who used birth control pills for a year or less, long-term users were more likely to be younger and premenopausal, to have completed more years of education and to drink alcohol. Long-term birth control users were also less likely to be overweight or obese, which can independently increase the risk of certain cancers.

Overall, the study included 149,504 women who didn’t get ovarian cancer and 1,241 women who did.

Among non-smokers, long-term birth control users were 45% less likely to get ovarian cancer than women who used these contraceptives for less than a year. For current smokers, however, long-term use of birth control pills was associated with 56% lower odds of ovarian cancer.

Long-term birth control users who were a healthy weight had a 45% lower risk of ovarian cancer than women only on the Pill briefly, if ever. Obese women who took the pill for at least a decade had 36% lower odds of developing ovarian tumors.

Overall, the study didn’t find an increased risk of breast cancer associated with birth control pills, except among women who were current smokers or regular drinkers and took oral contraceptives for at least a decade.

The study also found no connection between colorectal cancer and oral contraceptives.

Even so, the results provide fresh evidence that the potential for birth control pills to offer long-lasting protection against certain cancers, said Victoria Cortessis, a researcher at the Keck School of Medicine at the University of Southern California in Los Angeles.

“Women can continue to have confidence in earlier studies – and there are many – reporting that occurrence of both ovarian cancer and endometrial cancer has been lower in groups of women who used oral contraceptives, compared to groups who did not,” Cortessis, who wasn’t involved in the study, said by email.

“Earlier research showed that this apparent benefit likely endures even after women stop taking the pills,” Cortessis added. “What remains to be learned is which specific women are likely to benefit in this way if they use oral contraceptives.”

SOURCE: http://bit.ly/2E04MJL

JAMA Oncol 2018.

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Global Cancer Survival Rates Improve, but Wide Gaps Remain

Global Cancer Survival Rates Improve, but Wide Gaps Remain

LONDON (Reuters) – Cancer patients’ survival prospects are improving, even for some of the deadliest types such as lung cancer, but there are huge disparities between countries, particularly for children, according to a study published on Wednesday.

In the most up-to-date study of cancer survival trends – between 2010 and 2014 – covering countries that are home to two-thirds of the world’s people, researchers found some significant progress, but also wide variations.

While brain tumor survival in children has improved in many countries, the study showed that for children diagnosed as recently as 2014, five-year survival is twice as high in Denmark and Sweden, at around 80%, as it is in Mexico and Brazil, at less than 40%.

This gap was most likely due to variations in the availability and quality of cancer diagnosis and treatment services, the researchers said.

“Despite improvements in awareness, services and treatments, cancer still kills more than 100,000 children every year worldwide,” said Michel Coleman, a professor at the London School of Hygiene & Tropical Medicine who co-led the research.

“If we are to ensure that more children survive cancer for longer, we need reliable data on the cost and effectiveness of health services in all countries, to compare the impact of strategies in managing childhood cancer.”

BREAST CANCER

For the research, known as the CONCORD-3 study and published online January 30 in The Lancet, the scientists analysed patient records from 322 cancer registries in 71 countries and territories, comparing five-year survival rates for 18 common cancers for more than 37.5 million adults and children.

For most cancers over the past 15 years, survival is highest in just a few wealthy countries – the United States, Canada, Australia, New Zealand, Finland, Norway, Iceland and Sweden.

For women diagnosed with breast cancer in Australia and the United States between 2010 and 2014 for example, five-year survival is 90%. That compares to 66% for women diagnosed in India.

Within Europe, five-year breast cancer survival increased to at least 85% in 16 countries including Britain, compared with 71% in Eastern Europe.

The researchers noted that in some parts of the world, estimation of survival is limited by incomplete data and by legal or administrative obstacles to updating the cancer records with a patient’s date of death. In Africa, they said, as many as 40% of patient records did not have full follow-up data, so survival trends could not be systematically assessed.

SOURCE: http://bit.ly/2FvsElZ

Lancet 2018.

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Bellicum's Cancer Drug Trials on Clinical Hold, Shares Tumble

Medical Community Has Sparse Reaction to State of the Union

Medical Community Has Sparse Reaction to State of the Union

President Donald J. Trump’s first State of the Union speech since taking office has drawn little comment from the medical community, despite his vows to lower drug prices and take on the opioid epidemic.

He did not take the opportunity to address any other science- or health-related topics, including questions over budget issues at the National Institutes of Health, or the ongoing effort to allow states to impose work requirements for Medicaid recipients.

At press time, few organizations had issued any statements on the address, and several contacted by Medscape Medical News for comment had not responded.

On drug prices, Trump said reducing the cost for Americans would be a top priority for his administration this year. “And prices will come down substantially. Watch.”

This is not brand new. In January 2017, when he was still president-elect, Trump vowed to go after drug prices. John J. Leppard, senior editor and healthcare analyst of Washington Analysis, said he doesn’t see the president being able to follow through on his promise.

The government might require some givebacks from pharmacy benefit managers (PBMs), he said in a note to clients, but “We are skeptical that this will result in the sweeping actions that would substantially inhibit the pricing discretion of manufacturers and business practices of supply chain members to bring down prices for consumers to the extent implied by the president last night.”

Leppard said PBMs, not drug makers, will likely feel the brunt of any Trump administration pushback. “We do not expect to see a direct assault on the pricing practices of manufacturers,” he said.

Michael Munger, MD, president of the American Academy of Family Physicians, said in a statement that the organization “welcomes the Administration’s continued attention to high drug prices.” AAFP wants to see some movement, said Dr Munger. “We urge the administration to move beyond rhetoric and take action that ensures patients can afford the medications their physicians prescribe,” he said.

Funding Still Needed for Opioid Programs

The president said that his administration would tackle the opioid epidemic by increasing law enforcement efforts and making sure more treatment was available. But he did not urge Congress to take action — despite having issued two public health emergency declarations — and did not offer up any funding or call on lawmakers to provide appropriations to address the epidemic.

Mike Fraser, PhD, executive director of the Association of State and Territorial Health Organizations (ASTHO), told Medscape Medical News that ASTHO was gratified that the opioid epidemic had been mentioned in the speech. But more emphasis on prevention is needed, he said. Treatment is important, “but you can’t treat your way out of an Ebola epidemic,” said Dr Fraser, adding that the same was true for the opioid epidemic. More needs to be done to understand the drivers of substance use and addiction, he said.

It is irrelevant who asks for — or provides — the funding, said Dr Fraser. The most important issue is to allocate money for the epidemic, he said. “Someone needs to act soon,” he said, adding, “We’ve got programs we know that work that need to be scaled up. We need new dollars to do that.”

A joint statement from the Infectious Diseases Society of America and the HIV Medicine Association also stressed the need for increased funding.

“Mention of America’s opioid crisis during the State of the Union address last night must be followed by increased funding and evidence-based policies that go beyond law enforcement if we are to end this epidemic and prevent the co-occurring epidemics of HIV and hepatitis C,” they said.

After the speech, new Health and Human Services Secretary Alex Azar said Trump “deserves tremendous credit for his leadership in addressing the opioid crisis that’s hitting communities all across America.” Azar cited several administration accomplishments, including declaring the public health emergency, handing out $800 million in grants, approving new Medicaid waivers for two states to expand access to substance abuse treatment, proposing a streamlined process for more such approvals, and clarifying privacy regulations to inform hospitals and doctors that they can share information with patients’ families during crisis situations, such as opioid overdoses.

The administration also delinked patient scores of hospital pain management from Medicare reimbursement, said Azar.

On the morning of the State of the Union speech, Attorney General Jeff Sessions went to the US Attorney’s Office in Louisville, Kentucky, to launch a new Drug Enforcement Administration (DEA) effort against healthcare providers who are illegally prescribing or selling opioids. “I am announcing today that, over the next 45 days, DEA will surge Special Agents, Diversion Investigators, and Intelligence Research Specialists to focus on pharmacies and prescribers who are dispensing unusual or disproportionate amounts of drugs,” he said.

The agency will analyze information in the 80 million transaction reports it receives each year from drug manufacturers and distributors to determine outliers “and put them into targeting packages,” said Sessions.

The move is not unexpected, as the Department of Justice announced in August 2017  that it was creating an Opioid Fraud and Abuse Detection Unit to focus on opioid-related healthcare fraud.

Congress will begin holding another series of hearings on the opioids crisis, beginning with a February 26 meeting of the House Energy and Commerce Committee.

Right to Try Controversy

Trump called on Congress to enact a federal right-to-try law to give Americans the ability to access experimental therapies that have not been approved by the US Food and Drug Administration (FDA). Both Trump and Vice President Mike Pence have made such legislation a priority.

The Goldwater Institute, a Phoenix, Arizona–based conservative think tank, supports right-to-try laws, says that 38 states have passed such legislation. The Senate passed a right-to-try bill in August 2017, but the House has not taken up the legislation.

Those opposed to such laws say that they aren’t likely to offer the same protections to patients as those afforded in clinical trials. And, under the proposal making its way through Congress, drug companies would be able to charge patients for therapy.

In a recent opinion piece in JAMA Internal Medicine, two New York University researchers said the Senate proposal lets patients access investigational drugs that have completed phase 1 studies, grants companies and physicians broad immunity from liability, and “largely blinds the FDA to safety or efficacy data from these therapeutic attempts.”

A federal law “would upend the agency’s expanded access program, which has worked successfully for decades to provide patients who are seriously ill and without therapeutic options access to investigational drugs and still assure the safety and efficacy of new drugs before these products gain marketing approval,” said Alison Bateman-House, PhD, and Christopher T. Robertson, PhD, in the article.

They said that a review of a decade’s worth of requests to the FDA expanded-access program in the Center for Drug Evaluation and Research found that 99% of the 1000 or so applications submitted each year are approved and are done so within days or hours.

The American Society of Clinical Oncology said in April 2017 that it has many concerns about right-to-try laws on the books, including that they don’t protect patients as well as clinical trials do and may interfere with the FDA’s efforts to improve its compassionate- and expanded-use protocols.

After the Trump speech, the Men’s Health Network said that it supported the option to access developmental drugs that have not gotten FDA approval but have shown some life-saving potential. “The right to access should include protections for patients, health care providers and institutions while enhancing and supporting the scientific and regulatory process in such a way as to contribute to marketing approval for these important treatments,” said Sal G. Giorgianni, PharmD, Men’s Health Network senior science advisor, in a statement emailed to Medscape Medical News.

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Menopause May Hasten RA-Associated Functional Decline

Menopause May Hasten RA-Associated Functional Decline

Women with rheumatoid arthritis (RA) experience a worsening in the speed and degree of functional decline when they enter menopause, data from a large, observational study suggest.

The findings “indicate that menopause has a significant impact on the level and rate of functional decline in women with RA,” the study authors write.

A clinical relationship between hormonal status and RA disease activity has already been observed in female patients, Elizabeth Mollard, PhD, from the University of Nebraska Medical Center College of Nursing-Lincoln Division, and colleagues write in an article published online January 29 in Rheumatology. For example, RA symptoms subside during pregnancy, and early menopause is associated with a greater risk of developing RA compared with normal or late menopause.

Given these observations, the authors studied the relationship between menopause and functional status in women with RA. They used data from the National Data Bank for Rheumatic Diseases, which is composed of patient self-reports and is the largest such databank in the United States.

Participants in the National Data Bank for Rheumatic Diseases complete a survey on entry, and then follow-up questionnaires every 6 months. These include the Health Assessment Questionnaire (HAQ), which measures pain and disability patients experience while conducting ordinary activities such as dressing, eating, and walking, as well as medication adverse effects and costs related to their illness. Positive scores on the HAQ indicate worsening functional status and greater functional decline, whereas negative scores reflect less functional decline and better functional status.

To be eligible for this study, women had to have received an RA diagnosis before menopause and to have completed at least two questionnaires between 2003 and 2017. Of the 8189 patients who met the inclusion criteria, 2005 (24.5%) were premenopausal at enrollment, 611 (7.5%) entered menopause during the study, and 5573 (68.1%) were postmenopausal. The mean age of each group was 39.7 years (standard deviation [SD], 7.8), 50.7 years (SD, 3.4), and 61.8 years (SD, 9.8), respectively.

The authors performed univariate and multivariable analyses that accounted for potential confounding variables including age, income level, length of reproductive life, RA duration, and use of tobacco, hormone replacement therapy, and oral contraceptives.

They found that “women who were pre-menopausal had a better HAQ score by −0.50 (95% [confidence interval]: −0.55, −0.19) compared with women who were post-menopausal [with interaction term with age of 0.01 (0.00; 0.01)], indicating that pre-menopausal women had less functional decline than post-menopausal women.” Other factors associated with less functional decline included ever use of hormone replacement therapy, a history of at least one pregnancy, and longer duration of reproductive life.

The findings suggest that not only is menopause associated with greater functional decline among women with RA, but also, milder decline may be related to the greater hormonal exposure, implied by a longer reproductive life, the authors write. “Additional study on RA symptoms and functional status throughout the menstrual cycle and other hormonal life events are indicated in understanding hormonal involvement in RA disease status.”

Study limitations include the inability to establish a directional relationship between functional decline and menopausal status, or to account for all potential confounding variables. Also, the National Data Bank for Rheumatic Diseases database and the HAQ rely on patient self-reports, which may not necessarily match objective clinical measures.

Nevertheless, these findings “suggest that menopause is associated with worse functional decline in women with RA. Further study is needed to understand this relationship,” the authors conclude.

One author reports receiving grant funding from Pfizer and the Rheumatology Research Foundation. The remaining authors have disclosed no relevant financial relationships.

Rheumatology. Published online January 29, 2018. Abstract

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Health Investors Roll Out Unwelcome Mat for Amazon's Arrival

Health Investors Roll Out Unwelcome Mat for Amazon's Arrival

NEW YORK (Reuters) – As press releases go, it was vague and brief – six paragraphs, 394 words in all. In general terms, it described the beginnings of an effort by three big U.S. companies to team up to improve their employees’ healthcare services and save money.

But it delivered a $69 billion body blow to stocks across the healthcare sector, driven in large part because of the first word: “Amazon.”

The day long feared by executives and investors alike in the $3.47 trillion U.S. healthcare sector had arrived. And with an unsettling lack of specificity.

“Everyone is still terrified of Amazon,” said Jeff Jonas, a portfolio manager focusing on healthcare for Gabelli Funds.

Earlier on Tuesday, Amazon.com Inc, Berkshire Hathaway and JPMorgan Chase & Co announced they will form a healthcare company aimed at cutting costs for their more than 500,000 U.S. employees.

Investors for months have fretted over a potential Amazon entry into healthcare delivery, particularly selling prescription drugs, with stocks periodically selling off on headlines anticipating a move by the massive online retailer.

But Tuesday’s news was short on details, creating the potential for the uncertainty over Amazon’s healthcare aims to linger over the sector.

“The release that we have today is very cryptic and broad,” said John Schroer, U.S. healthcare sector head for Allianz Global Investors in San Francisco.

“This is just one move amongst perhaps many more that Amazon could take in moving into the retail chain of drug delivery. I doubt it’s the only thing they are going to do,” he said.

Among stocks in the drug supply chain, pharmacy benefit manager Express Scripts Holding Co was down 3.3% in midafternoon, drug-store chain CVS Health Corp was down 4.1% and pharmaceutical distributor McKesson Corp was down 3%.

Health insurers, which had been relatively immune from previous Amazon-related jitters, were clobbered. Cigna Corp was down 7.2%, Anthem Inc slumped 5.3% and UnitedHealth Group declined 4.2%, making it the biggest single drag on the blue-chip Dow Jones Industrial Average.

The news sent the S&P 500 healthcare sector down 2% in Tuesday afternoon trading, putting the group on pace for its biggest single-day decline since October 2016 and blunting the sector’s strong momentum to start the year.

Through Monday, healthcare had risen 10.5% already in 2018, the best performance among all major sectors and well ahead of the 6.7% rise for the overall S&P 500.

“Healthcare had been outperforming the market, at least year to date,” Jonas said. “It’s always a good excuse to sell and take some profit.”

Jonas and others pointed to reasons the healthcare sector should be able to move past the Amazon threat, including a healthy climate for dealmaking that has particularly boosted biotech shares, benefits from U.S. tax reform, and a solid economy leading to use of medical services.

Others shrugged off the Amazon announcement. RBC Capital Markets analyst George Hill, who covers drug distributors, said the initiative at first glance seems to have little market clout to impact healthcare costs and did not seem to be able to displace established players.

“If this was the Amazon announcement drug supply chain investors have been fearing since early 2017,” Hill wrote in a research note, “consider us relieved.”

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Could a 'Hard' Brexit Disrupt Drug Supply?

Could a 'Hard' Brexit Disrupt Drug Supply?

Patients could face delays accessing medicines they need when the UK leaves the EU, a coalition of health professionals, NHS employers and pharmaceutical companies is warning.

A briefing paper from the Brexit Health Alliance says a shared regulatory framework across the EU has provided patients with faster access to treatments. But it cautions that no deal, or one between the UK and the EU that does not address future cooperation on medicines and medical technologies could put public health at risk.

A Complex Regulatory Framework

It says current regulations for medicines and medical devices are complex and warns that changes to the current regime may have an impact on supplies across Europe, as well as to the UK.

“It is critical that UK and EU patients do not lose out on the best treatments and medical devices as the UK leaves the EU,” says Niall Dickson, the Alliance’s co-chair in a statement. “We want to make sure that patients continue to benefit from early access to new health technologies and cutting-edge medicines, and that includes being able to take part in international clinical trials.”

According to the Brexit Health Alliance, a report by the Office of Health Economics found that depending on the final outcome of the negotiations to leave the bloc, the potential impact on the UK means:

• The average lag of new marketing submissions for drugs and medical technologies could be 2 to 3 months

• 5% to 15% of applications could be submitted more than a year later

• Some products may never be marketed in the UK

Despite bilateral trade agreements with the EU, it is estimated that Switzerland gains access to new medicines on average 157 days later than the EU, the paper says.

Drugs for Prostate Cancer

In a case study, supplies of a prostate cancer medicine, made in a sophisticated process in the UK and used in 80 countries including all of Europe, could be disrupted in the event of a ‘no deal’ Brexit.

The paper says a possible need for duplication of quality testing and release facilities by the manufacturer to another EU country could seriously affect the supply of this cancer medication to patients, including up to 120,000 in Europe each year, as well as jeopardising skilled UK jobs.

It also warns that the future of research into new medicines and medical technologies could also be affected with many UK-led clinical trials hanging in the balance.

The Alliance says disruption has already begun while leave talks are still in progress. As a result of the relocation of the European Medicines Agency (EMA) from London to Amsterdam, the agency has already had to slow down some of its work on child and public health issues, including in the fields of anti-microbial resistance and flu pandemics.

Future Cooperation Between the UK and the EU

The Alliance makes a number of recommendations including establishing close regulatory cooperation between the EU and the UK and an extension of the 2 year implementation period for Brexit.

“What patients need is maximum co-operation and alignment between the EU and the UK on the regulation of medicines and medical devices and we very much welcome the UK Government’s commitment to close collaboration with our European partners,” says Niall Dickson. “Let’s put patients first. Both the UK Government and European Commission must make this cooperation [a] priority in the interests of UK and EU patients.”

Aisling Burnand, chief executive of the Association of Medical Research Charities, adds: “It is vital that the health of patients is prioritised in the second phase of negotiations. If not, patients in the UK and the EU could face delays in accessing potentially life-saving treatments.

“Officials on both sides of the negotiating table must have patients’ best interests at heart and ensure safety considerations are paramount.”

A spokesperson for the Department of Health and Social Care says in an emailed statement: “We are committed to ensuring patients in the UK continue to access the best and most innovative medicines.

“Patient safety is our priority, and we will protect it through ongoing co-operation and a strong regulatory framework.”

SOURCES:

Brexit and the impact on patient access to medicines and medical technologies, Brexit Health Alliance

Department of Health and Social Care

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PRISMS: No Benefit of tPA in Mild Stroke Without Disability

PRISMS: No Benefit of tPA in Mild Stroke Without Disability

LOS ANGELES — Data from the first randomized trial of thrombolysis in patients with mild ischemic stroke and no clear disabling deficit show no evidence of benefit of tissue plasminogen activator (tPA) and an increased risk for symptomatic intracerebral hemorrhage in this population.

“Although the results of the PRISMS trial are not reliable as the study was stopped early due to slow recruitment and so was underpowered, based on the data we do have it appears unlikely that the benefits of tPA extend to those stroke patients without clearly disabling deficits at presentation,” lead investigator, Pooja Khatri, MD, University of Cincinnati, Ohio, told Medscape Medical News.

“This is a big disappointment,” she added. “We had hoped that tPA would be beneficial in patients with just a very mild neurological deficit, but we are now a step closer to making an informed decision about this.”

She estimated that the PRISMS trial population reflected about one third of ischemic stroke patients. “So we are talking about a large group, and it is important to have evidence-based information on tPA in this group.”

Dr Khatri stressed that it was important to understand that this trial excluded patients with a clear disability deficit. “This trial included patients who were still deemed able to carry out basic activities of daily living, such as walking, bathing/dressing, toileting, and eating, and be able to return to work if appropriate. They had some neurological deficit, but this could have been very mild, such as a little facial droop or subtle weakness in the arm. The investigator with the patient’s input had to make a clinical judgment on this based on presenting symptoms.”

The results do not apply to patients with a mild stroke who are judged to have a disabling deficit that would affect their basic activities of daily living, she noted. “These patients should receive thrombolysis as this has been shown beneficial in previous studies.”

The trial was presented here at the International Stroke Conference (ISC) 2018.

Chair of the ISC 2018 session at which the PRISM trial was presented, Bo Norrving, MD, Lund University, Sweden, said, “By stopping early, the study was underpowered for any firm conclusions, and the confidence intervals were very large, so it’s difficult to draw definitive conclusions. Earlier studies have showed benefit if the patient has mild stroke with symptoms that are disabling. This study included patients with mild symptoms that were not disabling — so, a different cohort — and the results do not support use of tPA in such patients.” 

He added, however, that these results were preliminary. “It will be important to have more details about what symptoms these patients had,” Dr Norrving said. “An issue is also the reliability of determining in the very acute case if symptoms are disabling or not. It would be good to have more data on the precision of this.”

In her presentation, Dr Khatri explained that more than half of all ischemic stroke patients present with mild stroke, defined as National Institutes of Health Stroke Scale (NIHSS) scores of 0 to 5.

Evidence from previous studies supports treating patients with mild stroke who have a clear disability deficit, but exactly which patients with mild strokes to treat “is somewhat of a gray area as different trials have excluded different types of mild stroke,” she said.

In the subset of patients with deficits judged as nondisabling, the benefit of thrombolysis is unclear. Few such patients were enrolled in major randomized trials, and guidelines reflect community equipoise for this subset, with a class IIb recommendation (level of evidence C).  

In the PRISMS trial, investigators focused on these patients with NIHSS scores of 0 to 5 and no clear disability deficit. “Previous data have suggested that patients who are thought not to have a disability deficit when they first present can often turn out to have such a disabling deficit later on. So it was thought there could be some benefit to treatment in this group.”

In the trial, such patients presenting within 3 hours of last known well were randomly assigned to standard dose of tPA (alteplase, Genentech) or oral aspirin (325 mg) as the control.

The trial was stopped early by the sponsor, Genentech, because the prespecified recruitment targets were not being met. 

“We had enrolled 313 of 948 planned patients by 32 months,” Dr Khatri commented. “We don’t know the reasons for the slow recruitment. It is possible that doctors were reluctant to enroll patients as there is a trend to treat these patients, even though there is no good evidence for this.”

The intention-to-treat analysis included 154 patients in the tPA group and 153 in the control group.

The primary endpoint — a good functional outcome of 0 to 1 on the modified Rankin Scale (mRS) at 90 days — was seen in 78.2% of the alteplase group vs 81.5% of the controls, giving an adjusted risk difference of –1.10% (95% confidence interval, –9.44% to 7.25%).

Dr Khatri said the 90-day mRS 0 to 1 outcome was better than expected in the control group, with prior literature suggesting this would be nearer 70% than the 81% seen in this trial. 

The primary safety endpoint, symptomatic intracerebral hemorrhage (ICH) within 36 hours, occurred in 5 patients in the tPA group (3.2%) vs 0 in the control group, although there was no associated increase in mortality. Any ICH occurred in 11 tPA patients (7.1%) vs 5 control patients (3.3%).  

“So we appear to be seeing a harm without any suggestion of benefit,” Dr Khatri noted. 

 Almost all other secondary or exploratory outcomes were also unfavorable.

For clinical interpretation and future trial planning purposes, the researchers conducted a Bayesian analysis in which the PRISMS unadjusted outcome proportions were added to an uninformative prior. This suggested the likelihood of tPA having any benefit in this population was 23%, and the chances of an absolute benefit of more than 6% (in achieving mRS scores of 0 to 1) was just 1.9%.

Dr Khatri noted the trial had several limitations, the major one being early termination and resulting low power. There was also a relatively high rate of missing 90-day outcomes, but she added that 30-day mRS score is known to permit robust imputation.

She said that there is still a possibility that tPA may be of benefit in higher-risk subsets of the mild stroke population, such as those with a large-vessel occlusion. This is being studied in another ongoing trial known as TEMPO-2.

The PRISMS trial was sponsored by Genentech. The University of Cincinnati Department of Neurology received funds from Genentech towards conduct of the study.

 International Stroke Conference (ISC) 2018. Abstract LB 9. Presented January 25, 2018. 

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Continuous Glucose Monitoring Provides Real-world Benefits to Diabetes Patients

Continuous Glucose Monitoring Provides Real-world Benefits to Diabetes Patients

NEW YORK (Reuters Health) – Real-time continuous glucose monitoring (RT-CGM) provides numerous clinical benefits and improves quality of life, researchers from Belgium report.

“Here, within a strict budget, diabetes specialists of one of the 17 specialized centers were free in selecting any patient with type 1 diabetes on continuous subcutaneous insulin infusion (CSII),” Dr. Pieter Gillard from University Hospitals Leuven, in Belgium, told Reuters Health by email. “This made it possible to select motivated patients who they believed would benefit the most from RT-CGM. It shows that CGM reimbursement in the right patient population (using RT-CGM more than 70% of the time) has positive effects on glycemic control, quality of life, hospital admissions for acute diabetes complications, and work absenteeism.”

The Belgian healthcare authority authorized the reimbursement, starting in September 2014, of RT-CGM for type 1 diabetes patients using CSII and treated in selected specialized diabetes centers.

Dr. Gillard and colleagues in the RESCUE trial investigated the effect of RT-CGM reimbursement on hemoglobin A1c, admissions for acute diabetes complications, quality of life (QOL), and hypoglycemia under real-world conditions in the first two years of the program.

The analysis, published online January 12 in the Journal of Clinical Endocrinology and Metabolism, involved 515 patients with type 1 diabetes and CSII who benefited from the new RT-CGM reimbursement authorization.

Mean HbA1c was significantly lower at 12 months (7.4%) than at baseline (7.7%), and the percentage of patients who achieved HbA1c <7% increased from 23% at baseline to 33% at 12 months.

Acute hospitalization rates for severe hypoglycemia and/or ketoacidosis declined from 16% the year before RT-CGM initiation to 4% during the year in the program, a significant change.

The average number of days of diabetes-related hospital admissions per 100 patient-years declined significantly from 54 at baseline to 18 after introduction of RT-CGM reimbursement, and fewer patients reported diabetes-related work absenteeism with fewer absenteeism days.

All but one general QOL measure improved significantly after 12 months of reimbursement, and QOL improvements were greatest in patients who had problems with hypoglycemia and less substantial in patients with insufficient and variable glycemic control as their indications for implementing RT-CGM.

“In this single, largest prospective real-world study, we show that patients with type 1 diabetes using RT-CGM have a clear health benefit,” Dr. Gillard concluded. “Our findings thus support the use of RT-CGM under real-world conditions.”

He added, “Since the introduction and reimbursement of the FreeStyle Libre (FSL; Abbott Diabetes Care, Alameda, CA), more and more patients with type 1 diabetes switched to this system. Since studies investigated RT-CGM in comparison with SMBG, it is currently not known if RT-CGM offers the same benefits compared to FSL. Comparative studies are therefore required to understand which system (i.e., FSL or RT-CGM) offers the most benefit to which patients.”

SOURCE: http://bit.ly/2GgNsPf

J Clin Endocrinol Metabol 2018.

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Treating Domestic Violence as a Medical Problem

Treating Domestic Violence as a Medical Problem

Fanny Ortiz, a mother of five who lives just east of downtown Los Angeles, spent nearly a decade married to a man who controlled her and frequently threatened her. Then, she said, his abuse escalated. “He would physically hit me in the face, throw me on the wall,” she recalled.

Ortiz, 43, eventually left the marriage, taking her children with her. A few years later, she learned that the East Los Angeles Women’s Center offered domestic violence services at the Los Angeles County-USC Medical Center, near her home. Now she goes to the hospital campus for weekly therapy sessions, which she said have helped stop her suicidal thoughts.

“I was afraid to talk,” Ortiz said. “Now I am more open to talk about things that I was holding in.”

Nearly 1 in 4 women have experienced serious physical violence at the hands of a partner. They often end up in the emergency room or the doctor’s office. But they don’t typically volunteer the reason for their injuries, and doctors don’t always ask about abuse in the home. That failure of communication means the patients may miss out on the help they need.

Yet a growing number of health providers and anti-abuse agencies in California and around the country are collaborating to identify victims and get them help. More doctors now screen their patients for signs of abuse and more agencies place victims’ advocates inside health centers. Education and counseling for people experiencing violence is also more widely available in clinics and hospitals.

About four years ago, the East Los Angeles Women’s Center opened offices on the campus of L.A. County-USC, a busy public hospital. Since then, center staff members have trained more than 2,500 doctors, nurses, social workers and others to identify victims of domestic violence. They also respond quickly to calls from the medical center’s emergency room, inpatient hospital and outpatient facilities to help patients in crisis.

Today, the women’s center has embarked on an innovative approach: In February, it plans to open a short-term shelter for abuse victims on the medical center grounds. The 10-bed shelter fills a serious need, said Deirdre Anglin, an emergency room physician at L.A. County-USC.

“We sometimes have patients in the emergency department who don’t have a place to go, and in the evenings and nights all the shelters in L.A. will be filled,” Anglin said.

Victims of abuse can suffer long-term health problems, including chronic pain, frequent headaches, depression, diabetes and asthma. And they have higher health costs than people who have not experienced abuse. So “it makes complete sense to have the health care providers acting as allies and partners in treating domestic violence,” said Peter Long, CEO of the Blue Shield of California Foundation. (The foundation provides support for Kaiser Health News coverage in California.)

The foundation has funded 19 partnerships between health centers and domestic violence agencies around the state, including the L.A. County-USC office of the East Los Angeles Women’s Center. Similar partnerships operate in Illinois, Maryland and other states.

Last year, the East Los Angeles Women’s Center served 600 victims of domestic violence at the L.A. County-USC hospital campus. Nearly one-third were homeless or couldn’t go back home for safety reasons.

Advocates say that hospitals and clinics are ideal settings to respond to the needs of abused women.

The East Los Angeles Women’s Center is opening a domestic violence shelter on the Los Angeles County-USC Medical Center campus. The proximity makes it easier for doctors to ask patients about violence, said Rebeca Melendez, director of wellness at the center’s hospital office. Anna Gorman/KHN

In the San Gabriel Valley, the YWCA sponsors domestic violence support groups at a community clinic, while the clinic offers health education for survivors of abuse at the YWCA. In Sacramento, a Native American health center works closely with a domestic violence group a few blocks away.

Doctors have an “unprecedented opportunity to promote prevention and to respond because they are seeing patients that may not ever reach out to a domestic violence agency or police for help,” said Lisa James, director of health for Futures Without Violence, which runs a national resource center dedicated to improving the response of medical professionals to domestic violence. “They can provide this critical lifesaving intervention.”

The proximity of the East Los Angeles Women’s Center to the hospital and clinic buildings on the L.A. County-USC campus makes it easier for doctors to ask their patients about violence, said Rebeca Melendez, director of programs for the center’s office at the medical center. The medical providers know where to turn for guidance – and that the help is nearby.

“They don’t need to know all the answers,” she said. “They just need to call us.”

This growing collaboration between the medical profession and anti-abuse agencies is driven in part by the Affordable Care Act, which requires that health plans cover domestic violence screening and counseling.

The U.S. Preventive Services Task Force recommends doctors routinely question women about violence in the home and refer them to services if needed. The task force concluded in 2013 that intervention could reduce violence and abuse as well as mental and physical health problems.

Organizations such as the American Congress of Obstetricians and Gynecologists and the American Medical Association also recommend routine screening and counseling for domestic violence.

In the past, patients would go to health centers with such problems, but providers did not feel comfortable asking questions about abuse at home, said Long, of the Blue Shield of California Foundation.

“They didn’t feel they had the time and they didn’t feel they had the resources to do something about it,” he said. Nor did they always have a place to send patients who were abuse victims.

Treating patients who are in abusive relationships is “very challenging,” said Anglin, the ER physician. “There is no pill to give.” But asking about violence needs to be part of a physician’s job, she said.

“Part of what we need to do is try to identify patients who may be in a dangerous situation … so we are not just sending these patients back to the same situation they were in only to come back worse off another time.”

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Hospital HF Case Volumes Predict Care Quality, Not Outcomes

Hospital HF Case Volumes Predict Care Quality, Not Outcomes

DALLAS — Lower HF case volumes tended to predict less adherence to HF quality-of-care measures, especially use of device therapies, yet their association with 30-day and 6-month clinical outcomes was weak at best, a new analysis shows.^[1]

For example, hospitals with the lowest case volume were less likely than highest-volume centers to discharge HF patients with atrial fibrillation (AF) on oral anticoagulants, to put in or prescribe an implantable defibrillator (ICD), or measure LV ejection fraction with echocardiography, but nevertheless they didn’t have significantly higher mortality or readmissions at 30 days or 6 months.  

The findings, based on 125,595 patients admitted with HF at 342 hospitals participating in the Get With The Guidelines (GWTG) Heart Failure program, were published January 29 in Circulation, with lead author Dr Dharam J Kumbhani (University of Texas Southwestern Medical Center, Dallas).

Although some guidelines and reimbursement schemes continue to consider case volume to be an index of care quality that translates into improved outcomes, Kumbhani told theheart.org | Medscape Cardiology, the current analysis suggests that the relationship between volume and outcomes is more complex.

“The real emphasis should be on understanding what the things are that higher-volume hospitals do better” and then “implementing them in other hospitals even if they are lower volume,” he said.

“This is not to say that there is absolutely zero relationship between higher volume and outcomes, but I think the relationship is very modest.”

Even among the GWTG hospitals in the current analysis, “there were clearly certain process measures that higher-volume hospitals did better than lower-volume hospitals.” And higher volume, Kumbhani observed, probably does correlate with better HF care quality for some interventions, such as some device therapies, PCI, and surgical procedures.

“Extremely Powerful”

The current study suggests that “among hospitals that have joined a quality-improvement initiative, volume doesn’t seem to matter as much as it does in the absence of a quality-improvement initiative,” Dr Karen Joynt Maddox (Washington University School of Medicine, St Louis, MO) said in an interview.

“That, I think, is extremely powerful. That tells me that quality-improvement initiatives may particularly help low-volume centers,” said Joynt Maddox, who isn’t connected with the analysis.

For LV assist device management or complex surgeries, for example, “there is no doubt that volume is important,” she said. But “measuring volume is a surrogate for quality. And if we can measure quality, we should just measure quality, because I would rather go to a high-quality low-volume center than a low-quality high-volume center.”

Joynt Maddox also noted that HF case volume in the current study did correlate with some quality measures, such as use of ICDs and cardiac resynchronization therapy (CRT). That’s not surprising, but such treatments would take time to confer better outcomes.

“The expectation that those quality measures would translate into outcomes at 30 or 90 days, or even a year? That’s not how they work,” she said.

“Those process measures matter because they influence people’s 2-, 5-, and 10-year survival.” So quality measures can matter “even if you don’t you don’t see any difference in short-term outcomes.”

GWTG centers in the current analysis covering 2005 to 2014 had a mean annual HF case volume of 89; the median was 77.3. Those with volumes in the lowest quartile (5 to 38 cases) compared with the highest quartile (123 to 457 cases) generally were less likely to meet care-quality measures.

Table 1. Odds Ratio for Meeting Quality Measures by HF Case Volume, First (Lowest) vs Fourth (Highest) Quartile

Care Quality Measure	Odds Ratio (95% CI)a Q1 vs Q4	P Value
ACE inhibitors or ARBs at Discharge	0.67 (0.47–0.95)	0.025
β-Blocker at discharge	0.60 (0.43–0.83)	0.002
Aldosterone antagonist at discharge	0.81 (0.62–1.06)	0.13
Anticoagulation for AF	0.59 (0.47–0.74)	<0.001
LV function measured	0.26 (0.17–0.41)	<0.001
ICD implanted or prescribed	0.41 (0.28–0.58)	<0.001
CRT device implanted or prescribed	0.42 (0.23–0.78)	0.006
Appropriate discharge instructions	0.58 (0.39–0.87)	0.008
ARB = angiotensin receptor blocker; Q1 = first quartile; Q4 = fourth quartile. aAdjusted for sociodemographic and demographic features, medical history (anemia, ischemic disease, cerebrovascular events, diabetes, hyperlipidemia, hypertension, chronic obstructive pulmonary disease or asthma, peripheral vascular disease, and renal insufficiency), smoking, features at baseline (systolic blood pressure, heart rate, serum sodium, serum urea nitrogen, and ejection fraction), and hospital characteristics (region and teaching vs nonteaching hospital).

 

In an analysis treating case volume as a continuous variable rather than by quartiles, volume was slightly but significantly related to 6-month outcomes. The odds of 6-month readmission from any cause was 0.98 (95% CI, 0.97–1.00; P=0.025) and for 6-month mortality was 0.98 (95% CI, 0.97–0.99; P=0.001) for every increase of 50 HF cases per year.

But analysis of case volume by quartiles showed no such significant effect.

Table 2. Odds Ratio for Outcomes 1st (Lowest) vs 4th (Highest) Heart-Failure Case Volume Quartile

Outcome	Odds Ratio (95% CI)a Q1 vs Q4	P Value
In-hospital mortality	1.15 (0.92–1.43)	0.23
30-d readmission	1.04 (0.94–1.15)	0.47
30-d mortality	1.05 (0.92–1.19)	0.45
6-mo readmission	1.04 (0.96–1.12)	0.38
6-mo mortality	1.06 (0.99–1.14)	0.11
Q1 = first quartile; Q4 = fourth quartile a30-day and 6-month outcomes apply to patients discharged (hospital survivors). Adjusted for sociodemographic and demographic features, medical history (anemia, ischemic disease, cerebrovascular events, diabetes, hyperlipidemia, hypertension, chronic obstructive pulmonary disease or asthma, peripheral vascular disease, and renal insufficiency), smoking, features at baseline (systolic blood pressure, heart rate, serum sodium, serum urea nitrogen, and ejection fraction), and hospital characteristics (region and teaching vs nonteaching hospital).

 

“If you just focus on volume, you’re missing the bigger picture: that you have the ability to deliver outstanding care, quality care, at low- and medium-volume hospitals,” Kumbhani said. Once the differences between low- and high-volume centers are understood, you can then select the “highest-yield” care processes and improve them at the lower-volume centers.

Circulation is the flagship journal of the American Heart Association (AHA), which also launched the GWTG initiative. GWTG has been supported by Amgen Cardiovascular, Medtronic, GlaxoSmithKline, Ortho-McNeil, and the AHA Pharmaceutical Roundtable. Kumbhani reports receiving honoraria from the American College of Cardiology and consulting for Somahlution; disclosures for the other authors are in the report. Joynt Maddox reports that she has no relevant financial relationships.

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Frequency of Breast Biopsies After Surgery? Finally, Answers

Frequency of Breast Biopsies After Surgery? Finally, Answers

After surgery for invasive breast cancer, how often will patients need biopsies during follow-up? Remarkably, the medical literature has been unclear about the answer to this basic question.

Now, a first-of-its-kind study reveals that the 5- and 10-year overall incidence of breast biopsy was under 15% after a lumpectomy and 24% after unilateral mastectomy, with even lower percentages for older women.

A “key message” for patients from the findings is that having a biopsy is the exception, not the rule, said study senior author, Henry Kuerer, MD, PhD, executive director of breast programs, MD Anderson Cancer Network, Houston, Texas.

“Patients may believe they are going to be getting biopsies regularly,” he told Medscape Medical News.

The study is published online January 31 in JAMA Surgery.

The investigators, who are all from the University of Texas MD Anderson Cancer Center in Houston, reviewed records on 80,369 older patients by using the Surveillance, Epidemiology, and End Results–Medicare database (age ≥ 66 years) and on 41,510 younger patients in MarketScan, a private insurance database, (age ≤ 64 years).

The study is the first comprehensive nationwide population-based study of breast biopsies in women with breast cancer, the researchers note.

The 5- and 10-year overall incidence of breast biopsy was 11.8% after lumpectomy and 14.9% after unilateral mastectomy in the cohort of older women and 14.7% and 23.4%, respectively, in the cohort of younger women.  

Adjuvant chemotherapy use, patient age, and endocrine therapy were independently associated with biopsy in both cohorts.

The 160,000-plus patients had stage I to III disease and were diagnosed between 2000 and 2011. Patients had breast-conserving surgery (with or without radiation) or unilateral mastectomy; diagnosis and procedural codes were used to identify biopsies during follow-up.

Breast-conserving surgery and mastectomy are the two main options for surgical management of breast cancer, points out Cheng-Har Yip, MD, a surgeon at the University of Malaysia in Kuala Lumpur, writing in an accompanying editorial.

Overall survival does not differ between these two approaches after 20 years, as shown in a major randomized clinical trial (N Engl J Med. 2002;347:1233-1241), Dr Yip comments.

Follow-up is different for patients based on their initial treatment, he points out: “Women who have received a unilateral mastectomy need an annual mammography on the intact breast, and those who have undergone BCS [breast-conserving surgery] require bilateral mammography.”

Until now, there has been “little” information about the rate of biopsies for suspected malignancies that inevitably arise from these mammograms, Dr Yip adds.

Subsequent biopsy rates are seldom discussed with women at the time of surgical decision making.
Dr Cheng-Har Yip

“Subsequent biopsy rates are seldom discussed with women at the time of surgical decision making but may affect the women’s decision and lead to an increasing number of women who opt for bilateral mastectomy,” he adds. 

How Will New Data Be Used in Clinic?

Dr Kuerer says the new data on biopsy rates can be added into patients’ decision-making process about treatment for early-stage, invasive breast cancer..

“Many feel very anxious over the future need for biopsies and the potential of another diagnosis,” he said in a press statement. “Women will often choose a mastectomy rather than have the fear and stress associated with future biopsies or another cancer diagnosis.”

In the new study, having a unilateral mastectomy in one breast did, in fact, result in a lower rate of subsequent biopsy. The estimated 5-year breast biopsy rates for the remaining breast were 7.8% and 10.4% and in the SEER-Medicare and MarketScan and cohorts, respectively.

Whether you remove both breasts, one breast or have a lumpectomy, we are going to need to follow you forever.
Dr Henry Kuerer

 

However, Dr Kuerer explained that, regardless of what type of treatment a patient chooses — including double mastectomy — both distant and local recurrences are a possibility. Long-term monitoring is needed for all patients.

“Whether you remove both breasts, one breast or have a lumpectomy, we are going to need to follow you forever. You have to get comfortable with this as part of your life,” he said.

Furthermore, the new study also shows that only 23.2% of the women in the SEER-Medicare cohort and 29.8% of the women in the MarketScan cohort eventually underwent subsequent cancer treatment after a biopsy. Hence, most biopsies produced benign results, he added.

But clinicians who encourage lumpectomy are swimming against a tide, Dr Kuerer also suggested.

He commented that in almost all breast surgery settings, patients “increasingly” want a mastectomy or double mastectomy in the event of any breast cancer diagnosis. Unfortunately, the decisions are being made soon after the “trauma” of a breast cancer diagnosis, he said.  

The study was funded by the Dutch Cancer Society Clinical KWF Fellowship, the PH and Fay Etta Robinson Distinguished Professorship in Cancer Research Endowment, the National Institutes of Health, and the MD Anderson Clinical Research Funding Award Program. Dr Kuerer reports publishing patents, royalties, and other intellectual property from the New England Journal of Medicine Group and McGraw-Hill Publishing, serving on the speaker’s bureau for PER, and former research funding from Genomic Health. Dr Yip has disclosed no relevant financial relationships.

JAMA Surg. Published online January 31, 2018. Abstract, Editorial

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Prominent Endocrinologist Killed in Philippines Van Crash

Prominent Endocrinologist Killed in Philippines Van Crash

Colleagues and friends are remembering Nunilo Rubio, MD, in memorials and prayer services this week after the well-known Chicago endocrinologist and six others were killed in a van crash just before a medical mission in the Philippines.

He and his wife, Elenita Rubio, MD, a Chicago internist, both 74, were among 10 passengers in the van on a sightseeing tour of Alegria in Cebu province, the Philippines, on January 20, before starting a 3-day medical mission in Camiguin Island to help bring surgical, medical, and optical services to the poor.

A report published in the Chicago Tribune said the driver told police he had fallen asleep at the wheel just before the van crashed into a tree. The newspaper reported he was taken into custody.

Sons Have Flown to Be With Their Mother

Elenita was seriously injured in the crash, and her three sons flew to be with her as she begins recovery in a Philippines hospital after multiple fractures and two hip replacements, according to the husband of Elenita’s sister, Noel Lasala, MD, a family physician in Chicago.

Drs Nunilo and Elenita Rubio

Dr Lasala is affiliated with Presence Saints Mary and Elizabeth Medical Center, Chicago, Illinois, where Dr Nunilo Rubio served as medical director for more than 25 years until his retirement in 2015.

Dr Lasala told Medscape Medical News that Dr Elenita Rubio would be moved to Manila the end of this week to begin rehabilitation while her sons — Nunilo Rubio Jr, MD, Noel Rubio, MD, and Nathaniel Rubio, an occupational therapist — attend a memorial service for their father in the town of Bacoor in Cavite province, where both their parents were born and began dating. Dr Lasala said his wife had also flown to be with her sister.

Drs Nunilo and Elenita Rubio were “practically inseparable,” Dr Lasala said, even before their marriage 47 years ago. “They were living happily for so many years,” he said.

They also shared a passion for giving back, he said, especially helping those in the Filipino community in Chicago and in poor, rural areas in the Philippines, even after retirement.

The couple had just traveled to Australia and New Zealand before the mission and were planning to extend their stay in the Philippines and return to the United States in spring, he noted.

“This was a tragedy not just for family, but for friends, loved ones, and patients. They were enjoying life to the fullest.”

Doctor’s Gift Helped Open Diabetes Center

Jim O’Connell, communications director at Presence Saints Mary and Elizabeth Medical Center, told Medscape Medical News that one of the greatest physical legacies Dr Rubio leaves is his contribution to the Center for Diabetes and Endocrine Care at the center, which opened last year.

“It was in large part due to a financial gift Dr Rubio made at his retirement that gave us the funds to create that clinic,” he said.

O’Connell noted that the west Chicago region the clinic serves has one of the highest rates of diabetes in the United States. In addition to full clinical services, it offers educational and dietary classes for the public in a community room that bears Dr Rubio’s name.

He said a mass would be held for employees this week.

A statement from Presence said, “Dr Nunilo Rubio was a beloved member of our community and the Presence Saints Mary and Elizabeth family. His generosity, compassion, and commitment to our patients, hospital staff, and his fellow clinicians was truly special.”

According to the Philippine Medical Association in Chicago (PMAC), Dr Rubio received his medical degree from Far Eastern University, Manila, the Philippines, in 1967 and completed his residency and fellowship at Edward Hines Jr Veterans Affairs Hospital and Loyola Stritch School of Medicine in Chicago, Illinois. He is a diplomate of the American Board of Internal Medicine and American Board of Endocrinology.

Both Leaders in the Philippine Medical Association of Chicago

Dr Elenita Rubio is the incoming president of PMAC and Nunilo was president in 1984–1985.

Both were well-known lecturers, according to Chicago pediatrician Nida Blankas-Hernaez, MD, past PMAC president.

They both loved to teach, Dr Blankas-Hernaez said, and Dr Nunilo Rubio often lectured to alumni at Far Eastern.

Additionally, he was a clinical associate professor of medicine at Loyola Stritch School of Medicine.

The husband and wife regularly served on annual mission trips, Dr Blankas-Hernaez said. On these trips volunteers paid their own way and brought supplies to treat indigent patients who needed diabetes, dental, and optical care, and surgeries, among other services.

According to PMAC, the couple donated 5 acres of land with Dr and Mrs Ben Alibudbud to build the Jose Rizal Community Center in Jacksonville, Florida and in Cavite they donated a water tank and well to the Trece Martires Psychiatric Hospital, and a classroom and bathroom to a local public school.

Dr Blankas-Hernaez said of Dr Rubio, “He was a philanthropic man. He was a service man and humanitarian, who was soft-spoken. His heart was full of generosity.”

She had known the couple, who moved to Chicago 50 years ago, for the past 10 years.

“They loved each other. They were never separated. They were very close,” she said.

Nearly 50 people were part of the group on this year’s mission, and they continued the work without their colleagues, Dr Blankas-Hernaez said.

She stressed the mission trips will continue, adding that for some impoverished people these volunteers represent their only hope of getting certain procedures. Teams often see 1000 patients a day, she noted.

“We need to continue the work. We need to help these people.”

The six other volunteers killed were Aurora M Gagni, from Orland Park, Illinois; husband and wife Reynaldo J and Diane I Pascual, of White Plains, New York; Joseph and Juvela Huang; and Berenice Roxas, New York City, according to INQUIRER.net.

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Severe, Unusual Cases of Memory Loss Tied to Fentanyl Abuse

Severe, Unusual Cases of Memory Loss Tied to Fentanyl Abuse

Survivors of a fentanyl overdose may have cheated death in the short term, but they may end up with long-term memory loss.

Researchers in West Virginia have identified another case of an unusual amnestic syndrome in a man who used fentanyl and cocaine.

The syndrome was documented in 14 patients from Massachusetts between 2012 and 2016.

“We want to make people aware that survivors of overdoses where fentanyl is involved may develop significant memory problems,” Marc W. Haut, PhD, West Virginia University School of Medicine, Morgantown, told Medscape Medical News.

“There is a lot of talk about the folks who are not surviving a fentanyl overdose, but there are those who do survive for whatever reason. If you have someone with a chronic relapsing disease such as addiction, and then you add on cognitive and memory problems, managing them becomes even more difficult,” Dr Haut said.

Dr Marc Haut

“We would like to find out how common this amnestic syndrome is, and if others are finding that it is specific to fentanyl plus stimulants,” he said.

The case report was published online January 29 in the Annals of Internal Medicine.

Brain Imaging

The case involves a 30-year-old man with a history of heroin use who had recently been discharged from a residential addiction treatment program and had been abstinent from drugs for more than a month.

“The family recounted that he returned home late one night, and when they went into his room the next morning, he was difficult to arouse. As he became more alert, the family noticed that he kept on asking the same questions. Because of this, they brought him to the local hospital,” Dr Haut said.

There, results of a serum toxicology screen were positive for cocaine, but results of a urine toxicology screen were negative for fentanyl.

“When you do urine drug screening, some things, like fentanyl and its by-products, don’t show up unless you specifically test for them,” Dr Haut noted.

A CT scan of his brain showed bilateral, symmetrical hypodensities in the hippocampi and basal ganglia.

Additionally, serum aspartate and alanine aminotransferase levels were slightly elevated.

Because the memory impairment persisted, the patient was transferred to the J. W. Ruby Memorial Hospital in Morgantown. There, an MRI of the brain found diffusion-weighted hyperintensities involving all of both hippocampi, as well as the fornices, mammillary bodies, and globus pallidus.

Urine testing, which was conducted approximately 80 hours after drug exposure, was negative for fentanyl but was positive for its metabolite norfentanyl.

No New Memories

The patient’s amnesia was characterized as anterograde.

“This is not the type of amnesia that you see on a soap opera, where you can’t remember anything about your past. In anterograde amnesia, you cannot lay down new memories going forward. Patients will repeat themselves. They cannot remember what they did yesterday, and they may not even remember what they did earlier in the day,” Dr Haut said.

Whether or not the condition is permanent is difficult to say at present, he added.

“I’m a little hesitant to say that the condition is permanent. We were following this patient for a while, and his memory may have been improving slightly, but then we lost him to follow-up.

“It is very challenging to keep these patients in contact with us. If they still have family involved, it might be easier, but we’re talking about people who have a significant history of drug use, and they may have no family around, so following them is a definite challenge,” Dr Haut said.

He noted that this is the second case of a similar amnestic syndrome that had been seen here.

“The first was in September 2015, and to our knowledge, these two patients constitute the first cluster of this syndrome to be documented outside of Massachusetts. The fact that this syndrome has been identified in different areas of the country means that physicians in other states should be on the lookout for it when they evaluate patients with new-onset amnesia, especially if these patients have a history of substance abuse,” he said.

“We recommend using diffusion-weighted MRI of the head, routine toxicology screening, and neurologic consultation, as well as toxicology tests that are specific for fentanyl, its metabolites, and its analogues.”

Dr Haut has disclosed no relevant financial relationships.

Ann Int Med. Published online January 30, 2018. Abstract

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New Pattern in Gastric Cancer: One Type Increasing in US

New Pattern in Gastric Cancer: One Type Increasing in US

The epidemiology of gastric cancer is changing in the United States, say researchers. Incidence rates of noncardia gastric cancer are rising among individuals younger than 50 years, although it’s falling in older patients. Women will soon be more at risk than men.

The findings were published online January 19 in the Journal of the National Cancer Institute.

The data show “a new pattern in gastric cancer epidemiology,” Martin Blaser, MD, and Yu Chen, MD, New York University School of Medicine in New York City, write in an accompanying editorial.

“This pattern appears to identify a new form of noncardia stomach cancer,” they add.

The rising incidence of noncardia gastric cancers in individuals younger than 50 that is reported in the current study — together with the fact that the largest increase in noncardia gastric cancer involves tumors in the gastric corpus and that women are more at risk of developing corpus cancer than men — suggests that a new type of gastric cancer is taking hold in the United States, defined by the editorialists as “CYF” cancers — corpus-dominant, young age–dominant, female-dominant gastric cancers.

“Gastric cancer has always been more common in men, but these data in women predict an unprecedented reversal,” Dr Blaser and Dr Chen write.

Driven by Infection or Autoimmunity?

“The initial step for noncardia gastric carcinogenesis is atrophic gastritis, driven by either Helicobacter pylori infection or autoimmunity,” note the study authors, led by William Anderson, MD, MPH, National Cancer Institute, Bethesda, Maryland.

However, in recent years, the prevalence of H pylori has declined significantly, not only in the United States but also globally, they note. At the same time, the prevalence of autoimmunity has increased as Western lifestyles change.

These two trends prompted investigators to see whether there has been a shift in the incidence of gastric cancer as well as in the type of gastric cancer manifested in the US population across almost 2 decades.

To track the incidence of gastric cancer, they mined data from 1995 to 2013 in the National Cancer Institute’s Surveillance, Epidemiology, and End Results database and in 45 North American Association of Central Cancer Tumor Registries (NAACCR).

These data represent about 80% of the US population.

“There were 137,447 noncardia cancers in 4.4 billion person-years of observation,” the investigators report.

The majority of the adenocarcinomas recorded in the NAACCR database were found in non-Hispanic whites; people aged 50 years or older at the time of diagnosis; and in counties were rates of poverty were less than 20%, they add.

However, incidence rates varied considerably, depending on ethnicity.

For example, age-standardized rates (ASRs) of noncardia gastric cancer were 2.2 per 100,000 person-years among non-Hispanic whites; 6.2 per 100,000 person-years for non-Hispanic blacks; and 7.7 per 100,000 person-year for non-Hispanic others, primarily Asians.

The sites involved in these cancers — and their incidence rates over the years — also varied considerably, depending on sex and age.

Confining their analysis to non-Hispanic whites — the only race in which significant changes in the epidemiology of noncardia cancer were seen — “12.8% of noncardia cancers were localized to the gastric fundus, 19.8% to the corpus, 35.0% to the antrum, and 5.5% to the pylorus,” the study authors report.

Regarding the estimated annual percentage change (EAPC) in the incidence of these cancers, the researchers found that overall, the incidence for noncardia cancer dropped by 3% per year (95% confidence interval [CI] = -3.3% to -2.7%) between 1995 and 2013.

On the other hand, incidence rates did not drop uniformly between these years, and they were age-dependent.

Table. EAPC for Noncardia Cancers per Year Over Time

Men	-1.7% (95% CI = -2.0 to -1.4%)
Women	-2.3 % (95% CI = -2.6% to -2.0%)
Men and women younger than 50 years	+1.3% (95% CI = 0.6 to 2.1%)
Men and women aged 50 years or older	-2.6% (95% CI = -2.4% to -2.9%)
Women younger than 50 years	+2.6% (95% CI = 1.7% to 3.4%)
Women aged 50 years or older	-2.2% (95% CI = -2.5% to -1.9%)

 

Expected Trends

The researchers also compared current trends of noncardia cancer incidence rates among non-Hispanic whites between 1995 and 2013 and expected rates between 2014 and 2030, again stratified by age and sex.

They observed that in 2005, age-standardized rates for individuals younger than 50 years began to reverse. For a lengthy period before that time, noncardia gastric cancers were predominantly seen in males; since that time, such cancers have been increasingly seen in females.

“By 2020, the long-term falling ASRs for all ages combined are expected to stabilize for men and increase for women,” the authors observe — and by 2025, the researchers anticipate that the incidence of noncardia cancer among women will surpass the incidence in men.

Most importantly, women younger than 50 are expected to experience the greatest increase in tumors localized to the gastric corpus.

For this group of women, researchers anticipate an estimated annual percent change of 6% a year, compared to 3% a year for men.

“In contrast, noncardia incidence trends declined for non-Hispanic blacks and for non-Hispanic others, irrespective of age,” investigators observe.

Poverty and Cancer Incidence

The authors emphasize that the rising incidence rates of noncardia gastric cancer seen predominantly in non-Hispanic whites occurred only in counties where the prevalence of poverty was less than 20%.

Because H pylori colonization rates tend to be lower among more affluent individuals, noncardia gastric cancer incidence rates logically should be higher in poorer counties, not counties where H pylori colonization rates are presumably the lowest.

On this basis, the authors suggest that factors other than H pylori may be responsible for the trends observed between 1995 and 2013 among non-Hispanic whites.

These factors might include a higher prevalence of autoimmune gastritis, which disproportionately affects women and is thought to play an important causal role in corpus-predominant gastritis.

Alternatively, decades of exposure to antibiotics, again disproportionately used by women, may have altered the gut microbiome to such an extent that it, too, might be contributing to autoimmune gastritis and the subsequent promotion of noncardia gastric cancer in women younger than 50.

In their editorial, Dr Blaser and Dr Chen also speculate on what factors might be contributing to this new variant of noncardia gastric cancer.

They also highlight the fact that H pylori has been progressively disappearing everywhere, and suggest that replacement microbes may be particularly injurious to the gastric mucosa.

The editorialists also suggest that the incidence of gastroesophageal junction (GEJ) cancers, which were first seen in the United States around 1970, are really occurring in birth cohorts born after the turn of the 20th century.

“In non-Hispanic whites in the United States, the incidence of GEJ cancers is now higher than the traditional noncardia gastric cancers,” they observe.

“Much evidence shows a strong inverse relationship of H pylori with GEJ cancers,” they add — a confirmation that the observed fall in the incidence of distal gastric cancer in the United States and the concomitant rise in the incidence of GEJ cancers reflect the disappearance of H pylori across the country.

“[I]n cohorts beginning in the early 20th century, the changes [in gastric microecology] fueled the rise of the GEJ adenocarcinomas, Stage III, occurring chiefly in the post-World War II birth cohorts [and are] fueling the CYF cancer increases,” they argue.

“This timing parallels the antibiotic era, possibly reflecting the dysbioses caused by substantial exposures,” Dr Blaser and Dr Chen add.

They also agree with the study authors that increases in CYF noncardia gastric cancer might also involve autoimmunity — “either primary or secondary to microbiota change,” they suggest.

The study was supported by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute. The authors have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online January 19, 2018. Full text, Editorial

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Provider Factors Tied to Unneeded Antibiotic Prescriptions

Provider Factors Tied to Unneeded Antibiotic Prescriptions

Nurse practitioners (NPs) and physician assistants (PAs) are more likely than physicians to prescribe unneeded antibiotics for adult patients compared with physicians, a new study shows.

Monica L Schmidt, PhD, from the Center for Outcomes Research and Evaluation in Charlotte, North Carolina, and colleagues collected electronic medical record data from 448,990 outpatient visits between January 2014 and May 2016 for common upper respiratory conditions that should not need antibiotics. The visits spanned 898 providers and 246 practices in Carolinas HealthCare System urgent care, family medicine, internal medicine, and pediatric practices.

They focused on four conditions that do not usually require antibiotics: acute upper respiratory infection, acute bronchitis, bronchiolitis, and nonsuppurative otitis media. There was no overlap among acute bronchitis, bronchiolitis, and upper respiratory infection.

The overall prescribing rate for antibiotics in these nonindicated conditions was 407 per 1000 visits (95% confidence interval [CI], 405 – 408), the researchers report in an article published online January 30 in Infection Control & Hospital Epidemiology.

NPs, PAs More Likely to Prescribe

After adjusting for practice and patient characteristics, NPs and PAs were 15% more likely to prescribe antibiotics to adult patients compared with physicians (incident risk ratio, 1.15; 95% CI, 1.03 – 1.29). For pediatric patients, however, there was no difference in prescribing rates.

The authors note that their results are in line with previous studies. “Future national stewardship efforts should target education and antimicrobial stewardship interventions for [advance practice providers] as their role in patient care continues to grow,” they write.

Among pediatric visits, older providers (aged 51 – 60 years) were 4 times more likely to prescribe an antibiotic than providers aged 30 years or younger (incident risk ratio, 4.21; 95% CI, 2.96 – 5.97). Moreover, when stratified by indication, the authors found that prescription rates went up with provider age up to age 61 years across all indications.

Patient Factors

The authors also found that patient factors affected the likelihood of prescription. For example, prescribing rates were 36% higher for adults in urban vs rural practice areas, after adjusting for practice and provider factors (incident risk ratio, 1.36; 95% CI, 1.15 – 1.61).

Acute bronchitis had the highest rate for inappropriate prescribing by any provider, at 703 prescriptions per 1000 visits (95% CI, 700 – 706).

Azithromycin was the most common drug prescribed for bronchitis in both adults and children.

“Previous studies and our results suggest that patient and provider education on appropriate prescribing for bronchitis, including guidance on correct use of azithromycin, may be an effective way to reduce prescribing rates,” the authors write.

Also as reported in previous studies, the authors found that white patients were more likely to receive antibiotics vs patients of other ethnicities/races, and people in commercial care plans were more likely to receive them than were patients covered by Medicare or Medicaid.

Evidence for a Targeted Approach

The authors say the findings suggest a more targeted approach to stewardship practices and better supports in outpatient settings.

“At Carolinas HealthCare System, we’ve equipped our outpatient providers with scripts and educational materials to help guide conversations with patients about antibiotics,” coauthor Lisa Davidson, MD, medical director for the Antimicrobial Support Network at Carolinas HealthCare System, said in a news release. “We’ve also given them checklists for over-the-counter medicines, which they can recommend to patients who have viral symptoms.”

The results of the study could be key in reducing inappropriate prescriptions in a setting where they are comparatively high compared with inpatient settings.

“[N]ational data demonstrate that the volume of antibiotics used in the outpatient setting is much greater, with up to 30% of all outpatient antibiotic prescriptions deemed unnecessary and up to 50% inappropriate for the indication,” the authors write.

The authors have disclosed no relevant financial relationships.

Infect Control Hosp Epidemiol. Published online January 30, 2018. Abstract

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Rivaroxaban Plus Aspirin Cuts Stroke Rate in Half

Rivaroxaban Plus Aspirin Cuts Stroke Rate in Half

LOS ANGELES — Combining the anticoagulant rivaroxaban (Xarelto, Bayer) with aspirin cuts the ischemic stroke rate by almost half without significantly increasing the risk for intracerebral hemorrhage (ICH) compared with aspirin alone in patients with stable atherosclerotic vascular disease, new research shows.

The combination was particularly effective for secondary stroke prevention, researchers report. These new results represent a significant advance in stroke prevention, author Mike Sharma, MD, associate professor of medicine (neurology), McMaster University, Hamilton, Ontario, Canada, told Medscape Medical News.

“What we have seen here is an additional benefit on top of aspirin, which essentially doubles the effect,” said Dr Sharma. “If we can increase the effectiveness, have fewer strokes, the better off we’ll be.”

Updated results of the study — Effect of Rivaroxaban with Aspirin on Stroke Outcomes in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) — were presented here at the International Stroke Conference (ISC) 2018.

Patients with established cardiovascular disease have a high rate of additional events, between 5% and 10%, despite modern preventive therapies, said Dr Sharma. Aspirin has long been the standard antithrombotic treatment for prevention.

“We have been stuck with aspirin for decades,” but it’s only modestly effective for stroke prevention, said Dr Sharma. “If you haven’t had an event before, it reduces your risk by about 12%, but even if you have already had a stroke or heart attack, it reduces your risk only by about 19%, so the rest of the risk is untouched.”

Rivaroxaban is a selective direct factor Xa inhibitor. It’s already approved by the US Food and Drug Administration, indicated (at a dose of 15 mg or 20 mg) for prevention of deep-vein thrombosis in the legs and for prevention of stroke in the setting of atrial fibrillation (AF).

COMPASS enrolled 27,395 patients at 602 centers in 32 countries. Participants had coronary artery disease and could have had a myocardial infarction (MI) within 20 years or multivessel disease, or they had peripheral artery disease (PAD), which included those who had surgery for PAD or intermittent claudication with carotid stenosis (where at least 50% were asymptomatic) and carotid revascularization.

Of the total study population, 1032 patients had previously had a stroke. Patients with AF were excluded from the study.

The trial had three treatment groups: aspirin 100 mg a day, rivaroxaban 5 mg twice daily, and a combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg per day.

The study was designed to run up to 4 years but was stopped early at 23 months, after an interim analysis uncovered “overwhelming efficacy” of the combination therapy, said Dr Sharma.

Primary results for a composite endpoint of cardiovascular death, stroke, or MI, were published online August 27 in the New England Journal of Medicine and presented at that time at the European Society of Cardiology meeting.

That analysis showed that event rates were 4.1% for the combination therapy and 5.4% for aspirin (hazard ratio [HR] for combination vs aspirin, 0.76; 95% confidence interval [CI], 0.66 – 0.86; P < .0001), but major bleeding events occurred in more patients in the combination group (3.1% vs 1.9%; HR, 1.70; 95% CI, 1.40 – 2.05; P < .001).

Intracranial or fatal bleeding did not significantly differ between these two groups. Rivaroxaban by itself did not show a benefit over aspirin alone.

The current analysis looked specifically at stroke endpoints and found that for the combined stroke outcome (ischemic and hemorrhagic), there was a significant reduction for the combination therapy compared with aspirin alone (HR, 0.58; 95% CI, 0.44 – 0.76; P < .0001). The HR with rivaroxaban alone was 0.82 (95% CI, 0.65 – 1.05; P = .12)

“As you can see from the Kaplan–Meier curves, there is an early and consistent separation of the combination arm of rivaroxaban plus aspirin over aspirin,” Dr Sharma said at a media briefing.

“Rivaroxaban alone stays very close to the aspirin arm and separates at about 18 months. We’re not sure of the reason for that; it does not show significant benefit.”

For ischemic stroke, the risk was cut almost in half for the combination therapy (HR, 0.51), with a “robust early separation of the curves” for the combination therapy over aspirin, said Dr Sharma.

“Once again, rivaroxaban by itself stays very close to the aspirin arm to 18 months or so and then separates.”

The analysis showed that the rate of hemorrhagic transformation (bleeding into areas of infarct) was reduced in patients taking the combination therapy compared with those taking aspirin (HR, 0.35; 95% CI, 0.13 – 0.99; P = .04).

“We would expect this to be increased with anticoagulation,” commented Dr Sharma.

There was no statistically significant increase in hemorrhagic stroke with the combined approach compared with the aspirin alone (P = .33), However, more hemorrhages occurred with combination than with aspirin therapy (15 vs 10).

“Any time you affect blood coagulation, you’re going to get some bleeding,” said Dr Sharma. “With all factor Xa inhibitors, there is an increase in bleeding in the [gastrointestinal] tract. In this trial, with the combination therapy, we saw a slight increase in bleeding outside the brain but happily no real increase inside the brain.”

The 30-day mortality did not significantly differ between the groups.

As for the chance of being disabled or dead (modified Rankin Scale [mRS] score of 3 to 6) at 7 days or at hospital discharge, the combined therapy again came out on top (HR, 0.58; 95% CI, 0.37 – 0.89; P = .01)

“We think this was due to a reduction in the event rate for strokes altogether,” said Dr Sharma. He noted that there was a similar reduction in the hazard of having a stroke with an mRS score of 0 to 2.

The biggest predictor of having any kind of stroke was having had one in the past (2.6% per year; P = .0001). A previous MI did not significantly increase the risk for stroke. Having carotid stenosis, or having undergone previous carotid surgery or stenting, increased the risk for ischemic stroke but not hemorrhagic stroke.

While an estimated 77% of strokes occur in patients who have never had a stroke, the researchers wanted to look at the risk in those with a history of stroke. In this secondary prevention population, those on aspirin had strokes at a rate of 3.4% per year, but among those with combination therapy, the rate was reduced to 0.7% per year (HR, 0.42; 95% CI, 0.19 – 0.92; P = .03).

The absolute risk reduction was 2.7 percentage points per year, and the number needed to treat was 37.

Dr Sharma stressed that this combination approach is not for every patient. “If you’ve got coronary artery disease, had a previous heart attack, or have peripheral vessel disease or carotid stenosis, then this is absolutely a combination to consider; but if you don’t have those, we’re not sure it will have the same benefit,” he said, adding that this is also true for aspirin alone.

“If you’re a 32-year-old healthy man, I don’t think there’s any benefit,” he added.

Commenting on the study for Medscape Medical News, Larry B. Goldstein, MD, Ruth L Works Professor and  chairman, Department of Neurology, University of Kentucky, Lexington, said he found it somewhat challenging to determine the impact of the combination therapy on secondary stroke prevention because patients with a prior stroke made up only a subpopulation.

“These were mostly patients with coronary heart disease, and the study was evaluating a combined outcome: stroke/MI and death together, so that makes it a little difficult to tease that out.”

The “big concern,” said Dr Goldstein, is that adding any anticoagulant to aspirin will increase the risk for bleeding in those who have had a stroke.

“Almost all these drugs have a narrow potential index between decreasing recurrent ischemic events, decreased blood clots, and causing bleeding.”

The study was funded by Bayer. Dr Sharma reports being a consultant for Bayer, BMS, BI, and Daiichi Sankyo. Dr Goldstein has disclosed no relevant financial relationships.

International Stroke Conference (ISC) 2018. Late-breaking abstract 7. Presented January 25, 2018.

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