Selasa, 22 Mei 2018

Lung Cancer Screening Rates Only 2% Across US

Lung Cancer Screening Rates Only 2% Across US


Very few of the heavy smokers who are eligible for lung cancer screening in the United States have undergone such screening, a nationwide analysis has found.

The US Preventive Services Task Force (USPSTF) recommended in 2013 that all individuals aged 55 to 80 years who have a smoking history of 30 pack-years or longer and who currently smoke or have quit within the past 15 years should be screened annually for lung cancer with low-dose CT (LDCT).

There are an estimated 7 million such individuals in the United States.

In 2016, fewer than 2% of those eligible underwent LDCT at one of the nearly 1800 screening centers across the country.

The findings, which will be presented at the forthcoming American Society of Clinical Oncology (ASCO) 2018 annual meeting on June 3 (abstract 6504), were highlighted at a press briefing held ahead of the meeting.

They follow the publishing of recent data, reported by Medscape Medical News, that the majority of patients who are referred to lung cancer screening live close to the screening site, suggesting that underserved populations living in remote areas are being left out.

This very low rate of lung cancer screening is particularly stark when compared with screening rates for breast cancer. About 65% of women aged 40 or older underwent a mammogram in 2015, commented lead author Danh Pham, MD, a medical oncologist at the James Graham Brown Cancer Center, University of Louisville, Kentucky.

“This ultimately begs the question of the root of the disparity,” he said at the press briefing.

“Are physicians not referring enough? Or perhaps are eligible patients not wanting screening, even if they knew a test was available?” he continued.

Although it is “still speculation at this point,” he wondered whether there may be a stigma associated with screening for lung cancer, a disease that is “attributed to a modifiable risk factor through heavy smoking, and the at-risk population may be deterred from wanting screening if diagnosing cancer will result in confirming a poor lifestyle choice.”

This has been described as the “ostrich effect,” a term recently coined to describe frightened patients who, when faced with a major health problem, want to “stick their heads in the sand” and make it all go away.

Pham emphasized that, whatever the reason, the findings are “a call to action on everyone’s part to increase much-needed screening, whether it’s through increasing awareness or conducting additional research to urgently increase the screening of the number one cancer killer in America.”

Bruce E. Johnson, MD, president of ASCO, agreed that the low rates of lung cancer screening are “very disappointing.”

He underlined that previous estimates for lung cancer screening suggested that it saves 12,000 lives every year. By comparison, the findings of the current study indicate that 250 lives are saved each year.

However, Johnson also pointed out that, given that reimbursement for screening was only approved by the Centers for Medicare & Medicaid (CMS) in 2015 and that the analysis was conducted in 2016, the results show what happened in “the first year, so this is a measure not of a steady-state situation.”

Approached for comment, Daniel Oh, MD, clinical assistant professor of surgery at Keck School of Medicine of the University of California (USC), Los Angeles, and cofounder of the USC/Norris Lung Cancer Program, agreed that the history of lung cancer screening should be taken into account when interpreting the results.

Results from the landmark National Lung Screening Trial, which showed that screening could save lives, were published in June 2011. The USPSTF recommended screening in 2013, but it was not until February 2015 that coverage of costs by CMS was approved. “There had been concerns among clinicians that CMS was not going to approve it, which placed many physicians in limbo about whether or not to offer LDCT, due to insurance coverage concerns,” he said.

He also pointed out that, when CMS finally approved LDCT screening, “they stipulated that screening centers must report to a CMS-approved registry, which is essentially the American College of Radiology [ACR] Lung Cancer Screening Registry.”

His center was “among the first applicants for entry into the ACR registry, and we still did not become a participant until July 2015,” he said. “Taking into consideration logistics and the resolution of coverage issues, 2016 is a more accurate baseline measurement of lung cancer screening,” he noted.

The study illustrates that our nation still has not embraced lung cancer screening in earnest. Dr Daniel Oh

“That said, the study illustrates that our nation still has not embraced lung cancer screening in earnest, and we need to raise awareness among primary care physicians to improve adoption of LDCT,” he commented.

“When you consider that 60% of eligible patients receive colonoscopies, which are far more unpleasant than an LDCT, it is clear that we need to do better,” he added.

Details of the Analysis

For the current analysis, Pharm and colleagues gathered data from the Lung Cancer Screening Registry of the ACR on all LDCTs performed at all 1796 accredited radiographic screening sites in the United States in 2016.

They then used data from the 2015 National Health Interview Survey to estimate the number of eligible smokers who could have been screened on the basis of USPSTF recommendations.

The data were compiled for four US census regions, the Northeast, the South, the Midwest, and the West. The researchers calculated the screening rate by dividing the number of LDCT scans by the number of smokers eligible for screening per USPSTF recommendations.

Overall, the team calculated that an estimated 7,612,975 smokers across the United States were eligible for screening. They found that 14,080 LDCT screens were performed in the 1796 centers nationwide. From these data, they calculated the overall lung cancer screening rate to be just 1.9%.

The South had the highest number of accredited centers, at 663, as well as the highest estimated number of eligible smokers, at 3,072,095, but that region had the second lowest screening rate, at just 1.6%.

The West had the lowest screening rate, at 1.0%. There were 232 accredited centers in the West, and an estimated 1,368,694 eligible smokers.

The screening rate in the Midwest, which had 497 screening centers and an estimated 2,020,045 eligible smokers, was 1.9%.

The highest screening rate was seen in the Northeast, which had a rate of 3.5%. There, there were 404 accredited centers and an estimated 1,152,141 eligible smokers.

How to Improve Lung Cancer Screening Rates?

Discussing how screening rates could be increased, Pham said: “I think the most radical thing that we could suggest based on our study so far would potentially be making lung cancer screening a national quality health measure, just the way that CMS made breast cancer and colonoscopies a national area of improvement in 2008.”

Richard Schilsky, MD, chief medical officer at ASCO, said that “could be an effective strategy, particularly since physicians are increasingly being required to report on quality measures to optimize their reimbursement.”

Schilsky emphasized that screening for cancer is typically carried out by primary care physicians, rather than oncologists. “So one of the things that we also need to do is to be sure primary care physicians are well aware of the screening data and the importance of referring the appropriate patients for screening, and that they are aware of screening centers are available in their communities.”

For Oh, the focus should be on the patients themselves. “I think individuals simply need to be aware that screening for lung cancer exists,” he said.

“People these days are very proactive about their health, but this is a topic that is not getting a lot of attention. For example, we all see numerous commercials on TV every day telling patients to ask their doctor about a new drug, but we do not see anything analogous for lung screening awareness,” he said.

Oh nevertheless agreed with Schilsky about the importance of educating primary care physicians and the need to “clarify for them the requirements for screening and ease the workflow that is involved.

“Ultimately, I think an automated reminder in patients’ electronic health records needs to be implemented, but this will take some time,” Oh commented.

“”Surprisingly, one of the biggest obstacles for this has been the lack of an accurate smoking history in patients’ records, which often goes back to the stigma of smoking,” he said.

Another solution to the low lung cancer screening rates may come from the United Kingdom, where a pilot screening program in a supermarket parking lot quadrupled detection rates of early lung cancer.

As reported by Medscape Medical News, the pilot project, which was funded by a UK charity, used LDCT to screen current and former smokers identified from general practices. Through the program, 80% of lung cancer cases were detected while the disease was at stage I or II.

Another study that was reported by Medscape Medical News suggested that the majority of patients referred to lung cancer screening live close to the screening site, leaving out remote and underserved populations.

One other issue with lung cancer screening concerns the risk-benefit ratio. LDCT screening finds many nodules in the lung that are not cancer. As reported by Medscape Medical News, in a recent study conducted by the Veterans Health Administration, 2000 high-risk individuals were screened for lung cancer. Of those patients, 1.5% were found to have lung cancer, and around 60% of patients had positive results on screening, including one or more nodules that needed to be tracked. Incidental findings were reported in around 40% of patients. The authors concluded that lung cancer screening “benefits few, but may harm many.”

This study received funding from the Bristol-Myers Squibb Foundation. Dr OH has disclosed no relevant financial relationships, but several coauthors have reported financial relationships with pharmaceutical companies, as detailed in the abstract.

American Society of Clinical Oncology (ASCO) 2018. Abstract 6504, to be presented June 1, 2018.

For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc



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FDA OKs Asthma Inhaler Arnuity Ellipta for Kids as Young as 5

FDA Approves Denosumab for Steroid-Induced Osteoporosis

FDA Approves Denosumab for Steroid-Induced Osteoporosis


The US Food and Drug Administration (FDA) has approved denosumab (Prolia, Amgen) for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk of fracture, defined as defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. 

Denosumab is the first approved therapy for osteoporosis that specifically targets RANK ligand, an essential regulator of bone-removing cells (osteoclasts).

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) also recently adopted a positive opinion for the marketing of denosumab in the European Union for the treatment of bone loss associated with long-term systemic glucocorticoid therapy in adults at increased risk of fracture.

This is the fifth indication for denosumab, which is already approved in the United States for the treatment of postmenopausal women with osteoporosis at high risk for fracture; men with osteoporosis at high risk for fracture; women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer; and men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer.

How Long to Give Denosumab for Steroid-Induced Osteoporosis?

Both the US approval and EU positive opinion were based on data from a phase 3 study that showed patients on glucocorticoid therapy who received denosumab had greater gains in bone mineral density (BMD) compared with those who received active comparator, the bisphosphonate risedronate.

The results of this study were recently published in Lancet Diabetes & Endocrinology, as reported by Medscape Medical News.

“Patients on long-term systemic glucocorticoid medications can experience a rapid reduction in BMD within a few months of beginning treatment,” said study lead Kenneth F. Saag, MD, professor of medicine at the University of Alabama at Birmingham School of Medicine in an Amgen press release. “With this approval, patients who receive treatment with glucocorticoids now have a new option to help improve their BMD.”

In an editorial accompanying the publication of the Phase 3 study, Elena Tsourdi, MD, PhD, and Lorenz Hofbauer, MD, PhD, of Technische Universitat Dresden Medical Center, Germany agreed that denosumab “is an important step towards improved treatment options for glucocorticoid-induced osteoporosis.”

But they pointed out that BMD “is not the ideal surrogate for trials in patients with glucocorticoid-induced osteoporosis, because it underestimates fracture risk in view of the extraskeletal adverse effects of glucocorticoids on muscle function and falls.”

And physicians still don’t know how long to continue treatment with denosumab, as investigators in this trial were only able to report results out to 12 months, they noted, adding that discontinuation of denosumab has been shown to lead to a rapid decrease in BMD, at least among postmenopausal women.

And because many patients require long-term, if not life-long, glucocorticoid therapy, they consequently also need concomitant long-term bone-protective therapy, they explained.

Follow Lisa Nainggolan on Twitter: @lisanainggolan1. For more diabetes and endocrinology news, follow us on Twitter and on Facebook.



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Trastuzumab for 6 Months Instead of 1 Year?

Trastuzumab for 6 Months Instead of 1 Year?


When the first human epidermal growth factor receptor 2 (HER2)–targeted agent, trastuzumab (Herceptin, Genentech/Roche), was approved back in 2005, it went on to transform the treatment of early breast cancer for the 12% to 15% of women with tumors that are HER2 positive.

However, its use for 1 year following surgery — as is the standard of care — was arrived at empirically. Early trials compared 1 year to 2 years of therapy.

Now, a new trial suggests that 6 months of trastuzumab has a similar efficacy but halves the incidence of cardiotoxicity that can occur as an adverse event.

This would also halve the cost of the treatment.

“We are confident that this will mark the first steps towards a reduction of the duration of trastuzumab treatment to 6 months in many women with HER2-positive breast cancer,” said lead author Helena Earl, MBBS, PhD, professor of clinical cancer medicine at the University of Cambridge in the United Kingdom.

“But we need to be very careful and cautious about saying at this point that 6 months is enough,” she added, pointing out that this is a first glimpse of the results. 

Earl was speaking at a presscast held ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where she will present these results, from the PERSEPHONE trial, on June 4 (abstract 506).

The trial, conducted in 4088 women, showed noninferiority between the two durations of therapy, said Earl. The disease-free survival rate at 4 years was 89.4% with 6 months of therapy and 89.8% with 12 months of therapy.

At the same time, only 4% of women in the 6-month group stopped trastuzumab early because of cardiac problems, compared with 8% in the 12-month group, she reported.  

Experts not involved in the study cautioned that longer-term data are needed.

“We need time for the data to mature,” commented Richard Schilsky, MD, chief medical officer at ASCO. “There are no data yet on overall survival as yet,” he pointed out. Also, these results show an average for the patient population as a whole, and there are undoubtedly women who may not do as well, he commented. The researchers are now undertaking translational work to see if they can find biomarkers that would identify women who could benefit from longer therapy.

Nevertheless, Schilsky said he found the data so far to be “quite compelling,” and he predicted that they “will signal a shift towards a shorter duration of trastuzumab adjuvant therapy.”

ASCO President Bruce Johnson, MD, from the Dana-Farber Cancer Center in Boston, Massachusetts, said the cardiotoxicity benefit is clear, but as far as efficacy is concerned, he agreed that longer-term follow-up is needed. “At this point, less than 10% of the patients have died and only 12% have relapsed…so it may be a bit early to call for a definite change in practice.”

“In my opinion, efficacy drives most of the therapeutic decision-making,” Johnson commented. “Once you are very convinced of the data, then you take into account” other considerations, such as reducing adverse events. In this case, “in order to be convinced of the data, we probably need a bit more time and a few more events,” he said.    

Approached for comment, Darcy Spicer, MD, division chief, oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, said, The shortened duration of therapy is quite significant, remembering that the original 2-year standard of adjuvant systemic chemotherapy was shortened to today’s 1-year standard following years of subsequent clinical trials.”

“We look forward to the abstract’s presentation to determine whether or not there are patient subsets for whom shortened duration or longer duration may be more appropriate,” he added.

In addition, several more HER2-targeted drugs are now available. Therefore, Spicer said, “placing this information into an evolving treatment platform for HER2-positive patients employing other anti-HER2 therapies will be an important next step.” 

This study was funded by the National Institute for Health Research (NIHR) in the United Kingdom.  Earl reports a consulting or advisory role with Celgene, Pfizer, Roche, and AstraZeneca; expenses from Pfizer, Daiichi Sankyo, Amgen, and AstraZeneca; honoraria from AstraZeneca, Pfizer, Daiichi Sankyo, and Amgen; and research funding from Roche and Sanofi. Many coauthors also report financial relationships with pharmaceutical companies.

American Society of Clinical Oncology (ASCO) 2018. Abstract 506. To be presented June 4, 2018.

For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc



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Senin, 21 Mei 2018

Proposed Restrictions on Title X Funds Stirs Up Hornet's Nest

Proposed Restrictions on Title X Funds Stirs Up Hornet's Nest


Although it has not yet been officially released, a Trump administration proposal that would prohibit federal Title X family planning funds from being awarded to clinics that provide abortion services is generating comments about its potential impact from clinician groups on both sides of the abortion debate.

Under current law, funds for Title X — a program established in 1970 to provide family planning and preventive healthcare to low-income Americans — cannot be used to provide abortion or promote abortion as a method of family planning. In practice, many clinics that receive the funds — such as Planned Parenthood facilities — provide abortion services. But those services are funded by private money.

The new rule — which is under review at the White House before being formally published — would block those clinics that receive Title X money from performing abortions.

The White House has not made the proposal available to the public. One media outlet — The Hill — reported on Friday that the White House unveiled the proposal in a telephone call to groups opposed to abortion rights. The Hill said that under the rule, Title X recipients could not be co-located with abortion clinics, and they would no longer be required to tell patients that abortion is an option.

“Gag Rule” Under Scrutiny

That last point is of concern to women’s healthcare providers.

Hal Lawrence, MD, executive vice president and CEO of the American Congress of Obstetricians and Gynecologists, said in a statement emailed to Medscape Medical News, “The anticipated changes to Title X issue an ultimatum to qualified health care providers, forcing them to not only stop offering abortion in order to continue being eligible for Title X grants, but to altogether cease inclusion of abortion care in discussion of women’s reproductive health choices, thereby turning back the clock on women’s health.”

Restricting access to Title X funding “is likely to shutter health centers or dramatically narrow the scope of care health centers are able to provide,” he added.

“This ‘gag rule’ is not only unconscionable, but it undermines medical ethics by forcing health care professionals to withhold accurate and timely medical information from patients,” said Jenn Conti, MD, a fellow with Physicians for Reproductive Health, in a statement.

“If I can’t mention the word ‘abortion,’ then I am not providing my pregnant patients who want to know all of their options with complete, accurate, unbiased medical information,” she said.

The White House said the rule would not include a strict prohibition on abortion discussions. “Contrary to recent media reports, [the US Department of Health and Human Services’ (HHS’)] proposal does not include the so-called ‘gag rule’ on counseling about abortion that was part of the Reagan Administration’s Title X rule,” said an unnamed White House press secretary in a statement.

The proposal “would ensure compliance with the program’s existing statutory prohibition on funding programs in which abortion is a method of family planning. The new proposed rule would not cut funds from the Title X program. Instead, it would ensure that taxpayers do not indirectly fund abortions,” said the statement.

Many groups that oppose abortion rights said they were pleased. “The American Association of Pro-Life Obstetricians and Gynecologists (AAPLOG) applauds President Trump’s common sense clarification of the original purpose of Title X, which explicitly did not support pushing abortion as a method of family planning,” said Donna Harrison, MD, executive director of AAPLOG, in a statement emailed to Medscape Medical News.

The Susan B. Anthony (SBA) List, an organization that had lobbied for the rule, called it a “major victory.” SBA List President Marjorie Dannenfelser said in a statement, “President Trump has shown decisive leadership, delivering on a key promise to pro-life voters who worked so hard to elect him.”

The rule “doesn’t cut a single dime from family planning. It instead directs tax dollars to Title X centers that do not promote or perform abortions, such as the growing number of community and rural health centers that far outnumber Planned Parenthood facilities,” she added.

The SBA List said that Planned Parenthood receives $50 million to $60 million a year from Title X. The Title X program was allocated $286 million in 2018, according to the group.

“Family planning at Planned Parenthood means access to abortion,” said Christina Francis, MD, chairman of the AAPLOG board of directors, in the statement sent to Medscape Medical News. Francis added, “President Trump’s proposed Protect Life rule recognizes that women don’t need abortion. Title X dollars aren’t being cut, but simply redirected to abortion-free providers.”

Legal Challenges Expected

A group of Democratic senators who had urged against the rule estimated that Planned Parenthood serves 40% of Title X patients. About 4000 Title X–funded centers provide preventive healthcare — such as Pap smears, HIV testing, and breast examinations — to some 4 million men, women, and adolescents. Of those patients, two thirds have incomes below the federal poverty level, and 43% are uninsured, said the senators in a Politico article.

The concern is that the proposal will revive a rule issued by President Ronald Reagan’s administration in 1988. At the time, multiple organizations filed suit the same day to block the rule, which kept it from going into effect. The case went to the US Supreme Court, which in 1991 determined that the so-called gag rule was legal. When HHS attempted to put the rule back into effect, physician organizations, including the National Family Planning and Reproductive Health Association, sued again. Eventually, the gag rule went into effect — for just a month, until President Bill Clinton rescinded it by executive order in 1993.

The rules governing Title X that have been in effect since 2000 require financial, but not physical, separation of Title X and non–Title X activities and allow healthcare providers to counsel patients about abortion.

Legal challenges to the new Trump rule — when issued — are expected.

In early May, Planned Parenthood of Wisconsin, Planned Parenthood of Greater Ohio, and Planned Parenthood Association of Utah filed suit, along with the National Family Planning & Reproductive Health Association, against the Trump administration in federal district court in Washington, DC, alleging that a February call for Title X grant applications was illegal because it was “changing the program so that it no longer focuses on either birth control or reproductive health care and instead pushes patients toward abstinence and tries to keep patients from coming to Planned Parenthood,” said the group in a statement.

The Title X statute and regulations make it clear that the program “is meant to provide comprehensive, evidence-based contraception and reproductive health services,” they said.

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Amyloid in Cognitively Normal Predicts Later MCI, Dementia

Amyloid in Cognitively Normal Predicts Later MCI, Dementia


Elevated brain amyloid in individuals without dementia is associated with a dramatically higher risk for subsequent amnestic mild cognitive impairment (aMCI) and clinically diagnosed Alzheimer’s disease (AD), new research shows.

Investigators studied a sample of community-dwelling adults drawn from the total community in Olmsted County, Minnesota, and found that among those without cognitive impairment, amyloid-positive people were more than twice as likely as amyloid-negative people to develop aMCI.

Those with MCI and amyloid positivity were almost twice as likely to develop AD dementia as those with MCI who were amyloid negative, and the dementia risk of amyloid-positive participants with no cognitive impairment or with aMCI was 2.6-fold higher.

“This is the first large-scale, community-based trial on cognitively unimpaired people and we are confident that from within this population, the people who agreed to imaging were pretty representative of the whole population,” study author Ronald Petersen, MD, PhD, professor of neurology, Mayo Clinic College of Medicine and director, Mayo Clinic Alzheimer’s Disease Research Center, Rochester, Minnesota, told Medscape Medical News.

“Our estimates of the progression from nonimpairment to amnestic mild cognitive impairment in amyloid-positive people may provide reliable and vital data to inform future research and, from a public health perspective, provide necessary information for the government regarding how many people have these characteristics, so that if an amyloid-based therapy for AD is developed, the magnitude of cost of Medicare/Medicaid coverage can be taken into account,” he said.

The study was published online April 30 in JAMA Neurology.

Complete Capture

Elevated brain amyloid is considered to be a “key biomarker for AD pathology,” the authors note.

Analyzing the prevalence of amyloid positivity in a population without dementia “provides reliable and valid estimates of the burden of AD pathology, which are useful for sample size estimations in designing primary and secondary AD prevention trials in persons without dementia,” they write.

The researchers’ “first objective” was to “estimate the prevalence of amyloid positivity in a population without dementia,” and the second was “to estimate outcomes of amyloid positivity in a large, prospective, population-based cohort.”

In 2004, the researchers established the Mayo Clinic Study of Aging (MCSA) cohort to identify risk factors for MCI and dementia (Neuroepidemiology. 2008;30:58-69; Neurology. 2010;75:889-997) and enumerated the 70- to 89-year-olds in Olmsted County.

Participants were selected for the study by using an age- and sex-stratified sample scheme; patients with terminal illness, hospice admission, or dementia were excluded.

Beginning in 2012, the study recruited people age 50 to 69 years to “determine the timing of onset of brain pathology and cognitive impairment,” and people with dementia were recruited beginning in 2014.

Participants underwent a battery of cognitive and neurologic tests, diagnostic assessments to determine potential MCI and dementia, and measurement of covariates, such as weight, height, and apolipoprotein E (ApoE) ε4 status.

Participants also underwent amyloid positron emission tomography (PET) imaging, which was initiated in 2008 and used carbon-11 Pittsburgh compound B.

The researchers compared characteristics of participants of both sexes and several age groups who were amyloid positive or amyloid negative and who had or did not have cognitive impairment.

Logistic regression models were used to adjust for nonparticipation bias in the MCSA cohort, and a series of statistical tests were conducted to apply findings in the study sample to the findings in the population who did not participate in the study.

“One of the advantages of this study is that it is truly population-based, as compared to virtually all the good work done on amyloid imaging, which has been in a referral clinic, university, or multicenter setting,” Petersen said.

Because Olmsted has only two medical facilities that provide care to the community, “we have a unique opportunity to have complete capture of everyone who lives in this community,” he said.

Age and Sex

Of 3894 participants (mean [SD], 71.3 [9.8] years; 53.4% male), 1671 underwent PET imaging and were included in the study.

Compared with participants who underwent amyloid imaging, nonparticipants were older, were more frequently female, had fewer mean years of education, had higher rates of hypertension and strokes, and had lower global cognitive z scores.

Of the participants, 10.7% (n = 179) had prevalent MCI and 28.3% (n = 470) were ApoE ε4 carriers.

Compared with those who were amyloid negative, those who were amyloid positive more frequently had the ApoE ε4 allele, regardless of the absence or presence of MCI and regardless of age.

Among study participants without dementia, the prevalence of amyloid positivity increased with age, both in those without cognitive impairment (from

2.7% in the 50- to 59-year-old age group to 41.3% in participants aged 80 to 89 years) and in those with MCI (from 0% in the 50- to 59-year-old group to 16.4% at age 80 to 89 years).

The total prevalence of amyloid positivity across all ages was 22.0% (18.9% to 30.5%), with a higher total prevalence of amyloid positivity in women (25.6%; 95% CI, 20.8% – 30.5%) vs men (17.8%; 95% CI, 14.2% – 21.4%).

In models adjusted by age, sex, and education, the hazard ratios were 2.26 (95% CI, 1.52 – 3.35; P < .001) for both sexes combined, 1.96 (95% CI, 1.05 – 3.67; P = .04) for women, and 2.42 (95% CI, 1.46 – 4.04; P < .001) for men.

A Question of Magnitude

For amyloid-positive participants with MCI vs amyloid-negative participants with MCI, the risk for AD dementia was 1.86 (95% CI, 0.89 – 3.88; P = .10), while for amyloid-positive participants vs amyloid-negative participants with aMCI, the risk was 1.63 (95% CI, 0.78 – 3.41; P = .20).

Amyloid-positive vs amyloid-negative participants who were cognitively unimpaired or who had aMCI had a risk of 2.56 (95% CI, 1.35 – 4.88; P = .004).

In amyloid-positive people, global cognitive and memory domain z scores declined significantly during follow-up from baseline to incident aMCI and from aMCI to incident AD dementia (mean [SD] follow-up time, 3.7 [1.9] years and 3.8 [2.0] years, respectively).

“These findings are consistent with amyloid as a biomarker of AD dementia,” the authors note.

During this period, a higher proportion of deaths occurred in amyloid-positive vs amyloid-negative participants.

“This study addresses the critical question from a scientific but also a public health perspective — if we found an amyloid therapy or amyloid antibody, what is the magnitude of the audience, what is the age range, and what does amyloid positivity mean in the general population?” Petersen said.

He noted that a limitation of the study was that most older participants were white, although younger participants tended to be more racially and ethnically diverse, and the findings may not be generalizable to other groups.

“We are currently establishing a population-based sister study in Jackson, Mississippi, which will be equally weighted with African Americans and Caucasians,” he reported.

Setting the Stage

Commenting on the study for Medscape Medical News, William Klunk, MD, PhD, distinguished professor of psychiatry, University of Pittsburgh School of Medicine, Pennsylvania, who was not involved with the study, called it the “largest study to date that defines the consequences of being amyloid-positive prior to having dementia.”

He noted that early studies of amyloid positivity have led to treatment trials, such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study,  “even before definitive proof that amyloid positivity carries a big enough risk of clinically significant cognitive decline to warrant expensive, risky therapy.”

The data from this study “gives us better information upon which we can design trials that follow A4 and are also intended to ‘prevent’ AD,” he added.

Petersen emphasized that he is “not recommending that cognitively unimpaired people should have an amyloid imaging because we do not yet know what the results might mean for each individual, and the psychological impact of that scan on individuals might be variable.”

However, “we are setting the stage for how to interpret amyloid-related findings,” he said.

Petersen reports receiving personal fees as a consultant for Roche Inc. The other authors’ disclosures are listed on the original study. Klunk is the coinventor of the Pittsburgh Compound B that was used to identify amyloid positivity in this study.

JAMA Neurol. Published online April 30, 2018.  Abstract

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RF Ablation Significantly Reduces Thyroid Nodules in Biggest Study

RF Ablation Significantly Reduces Thyroid Nodules in Biggest Study


Monopolar radiofrequency ablation (RFA) shows high efficacy and safety in reducing the volume of benign thyroid nodules while avoiding the need for invasive surgery in a new study.

The authors conclude that “a single treatment course with monopolar RFA is both safe and highly effective in terms of nodule volume reduction, relief of local symptoms, and, in patients with hyperthyroidism, restoration of euthyroid function,” say Harald Dobnig, MD, of the Thyroid, Endocrine and Osteoporosis Institute Dobnig, Graz, Austria, and colleagues.

The findings were published in the April issue of Thyroid.

The study of 277 Austrian patients, the largest prospective cohort of benign thyroid nodules treated with a single monopolar RFA treatment to date, showed mean volume reduction rates after 12 months to be as much as 82%, with more than 81% of nodules showing a volume reduction of 70% or more.

Whereas approximately 90% of thyroid nodules do not increase in size over time, those that do grow can present cosmetic as well as functional problems and are commonly treated with surgery.

Thermoablative alternatives such as RFA — though primarily used by just a few research groups worldwide — offer the potential to avoid surgery and conserve normal thyroid function.

“The results of the current study are consistent with the existing literature and confirm the safety of RFA in general and the efficacy of a single treatment course of monopolar RFA in a large central European cohort,” write Dobnig and colleagues.

“The results also provide some potentially significant data for future discussions regarding possible selection criteria for patients with thyroid nodules that could be treated with RFA,” they add.

Study Included Patients With Larger Thyroid Nodules

In the current study, mean baseline nodule volume (± standard deviation) was 13.8 ± 15 mL, which corresponds to a nodule diameter of 3.0 cm, the authors note. This contrasts with the previous largest study to date, conducted in 200 participants in Asia (AJNR Am J Neuroradiol. 2015;36:1321-1325), which was retrospective and included patients with relatively smaller nodules (mean volume, 5.4 mL).

Almost 300 patients were treated as outpatients at Dobnig’s institute with a single RFA session from April 2014 to June 2017. Nodules were visible in 62.8% of patients and 40% had a symptom score of 4 or higher on a 10-point visual analog scale.

Treatment involved an internally cooled 18G RF electrode used with a free-hand “moving-shot” technique after patients received subcutaneous and local peri-thyroidal anesthesia.

Mean overall rates of nodule volume reduction were 68% ± 16% at 3 months and 82% ± 13% at 12 months (P < .001).

In addition to the 81% of nodules with a volume reduction rate of 70% or higher at 12 months, 10% had volume reductions of 60% to 70%, 6% had reductions of 50% to 60%, and only 2% had reductions of 50% or less.

Most nodules were solid or predominantly solid (74.4%), and these nodules had a mean volume of 13.6 ± 15.9 mL. The rest were mixed (12.1%) or cystic/predominantly cystic (13.5%).

Volume Reduction Rates Higher for Smaller and Cystic Nodules

In a subgroup analysis of nodules based on factors including baseline size (≤ 10  mL or > 30  mL), or nodule composition (solid, mixed or cystic), volume reduction rates were significantly higher for smaller and cystic nodules, at rates of 8.8% and 14.5% higher, respectively, than for the other groups at 12 months post-RFA (P < .001).

Importantly, scores on symptoms as well as cosmetic appearance significantly improved at 3 and 12 months (P < .001).

Specifically, the percentage of nodules that were visible with or without neck extension declined from 62.8% prior to RFA to 17.1% at 3 months post-RFA and 7.1% after 12 months.

In addition, the percentage of patients with significant symptoms (visual analog scale ≥ 4) declined from 38.2% to 0%.

Of 32 hyperthyroid patients who had follow-up data available, 27 (84%) became euthyroid, one (3.1%) developed subclinical hypothyroidism, and four (12.5%) had subclinical hyperthyroidism at their last visit.

Although RFA is currently not endorsed in the United States for the treatment of thyroid nodules, the findings add to increasing interest in the modality.

As reported by Medscape Medical News, a smaller recent study of 14 patients treated with a median of eight RFA cycles at the Mayo Clinic, Rochester, Minnesota, showed a mean nodule reduction of 44.6% at a mean follow-up of 8.6 months, with 8 of 12 patients having compressive symptoms resolved and four patients having reduced symptoms.

The authors of that study noted that skill and patient selection are key factors in RFA treatment, with appropriate candidates including those with poor ultrasonographic visualization of the nodule and poor access to the nodule.

The authors have reported no relevant financial relationships.

Thyroid. 2018;28:472-480. Full text

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