Kamis, 31 Agustus 2017

Telehealth Firms Waive Fees During Harvey Emergency

Telehealth Firms Waive Fees During Harvey Emergency


Several telehealth companies are offering free virtual care services via phone or video to people affected by Hurricane Harvey in Texas and Louisiana. The free services from American Well, Doctor on Demand, HealthTap, MDLive, and Teladoc started early this week and will continue through into mid-September. A Teladoc news release did not put an end date on the provision of free virtual visits.

It is unclear how many people in the affected areas know that they can use their smartphones to obtain free medical care. But Mary Modahl, chief marketing officer for American Well, told Medscape Medical News that there has been strong demand for her company’s service since it became free on Monday.

Until recently, it was illegal for Texas physicians to remotely diagnose and treat patients with whom they did not have a preexisting relationship. But in May, the Texas legislature passed a bill that allows doctors licensed in Texas to conduct virtual visits with patients whom they have not met in person. The telehealth visit must be audiovisual or use store-and-forward technology in conjunction with an audio-only interaction.

Teladoc, a Texas-based firm, was a key player in the controversy surrounding telehealth before the bill was passed. In the press release about the company’s offer of free virtual visits, Lewis Levy, MD, chief medical officer of Teladoc, said, “As hundreds of thousands of Americans are facing a time of need, Teladoc is working to make sure that they can count on readily available access to high quality care, 24/7. Our call center reps and board-certified and state-licensed physicians are standing by to help those families who have been displaced from their doctors and regular routines, but who still need non-emergency medical care.”

Among the medical conditions that can be effectively diagnosed and treated remotely, Teladoc said, are sinus problems, respiratory infection, allergies, cold and flu symptoms, and other nonemergency illnesses.

American Well is offering free psychological counseling as well as medical care. Most of the early calls from consumers have been about medical conditions, Modahl said, but she expects more demand for psychological help as the stress and trauma of the disaster sink into the population.

“Defining Moment”

It is also possible, as experts pointed out in a recent New York Times article, that contaminants in the flood waters will lead to many waterborne illnesses and even epidemics in coming weeks.

“This is a situation that is unfolding, and at least for the moment, we’re waiving our fees for people who are affected through September 15,” Modahl said. “If it’s needed for us to address [waterborne illnesses] then, we will.”

While the Texas law requires physicians to make their best effort to obtain patients’ medical records when they treat them remotely, Modahl said she doubts that will be possible in many cases during the Harvey emergency. However, she said, patients can fill out medical history forms online, and American Well physicians also have access to prescription records via Surescripts.

When Hurricane Katrina swept through New Orleans, Louisiana, in 2005, many paper medical records were destroyed, making it difficult to treat patients. Much has changed since then, Modahl noted. Not only do most healthcare providers now have electronic health records and backup systems, she says, but telehealth has emerged as an industry on the back of the smartphone revolution that started after Katrina.

In her view, the aftermath of Hurricane Harvey is a “defining moment for telehealth. This disaster has shown that when people are trapped in their homes and surrounded by water, they can’t travel to care, and local health systems are struggling, if they need to see a medical professional or a psychological counselor, telehealth can really help them.”

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Dancing Keeps Older Brains on the Ball

Dancing Keeps Older Brains on the Ball


Dancing can counteract age-related decline in physical and mental abilities, new research shows.

Investigators at the German Center for Neurodegenerative Diseases in Magdeburg, Germany, found that older people who routinely partake in physical exercise can reverse the signs of aging in the brain, but it’s dancing that has the most profound effect.

“The results of our study suggest that participating in a long-term dance program that requires constant cognitive and motor learning is superior to engaging in repetitive physical exercises in inducing neuroplasticity in the brains of seniors,” study author Patrick Müller, a PhD candidate at the German Center for Neurodegenerative Diseases, told Medscape Medical News.

“Therefore, dance is highly promising in its potential to counteract age-related gray matter decline,” he said.

The study was published online June 15 in Frontiers in Human Neuroscience.

Advantage Dance

For the study, the investigators compared an 18-month dance training program to 18 months of endurance and flexibility training in improving hippocampal volume and balance in healthy senior volunteers (aged 63 to 80 years).

The researchers studied the hippocampus (HC) because it is associated with learning, memory, and balance and also is the site of adult neuroplasticity in the brain.

Both groups showed increases in hippocampal volume. However, the dancers also showed increases in regions most strongly associated with neuroplasticity. In addition, only the dancers displayed significant improvement in balance.

The HC “is affected not only by pathological aging such as in Alzheimer’s disease but also by the normal aging process resulting in deficits in memory, learning, and spatial navigation at old age,” the authors write.

Although MRI studies demonstrate that the HC atrophies with each decade and that the process “accelerates in very old age,” other research suggests that the HC “counts among the few brain regions with the ability to generate new neurons throughout the lifespan.”

Aerobic fitness and training have been shown to improve hippocampal volume, which may contribute to better memory function. However, the mechanism of this association and the role of cardiorespiratory fitness in modulating hippocampal gray matter volume are “still under debate.”

The HC is also involved in spatial navigation and motor sequence consolidation, “suggesting that motor skill learning and motor fitness can have an impact on hippocampal volume without any cardiorespiratory change,” the authors note.

Previous research suggests that motor skill training and balance training can lead to “morphological alterations” in the brain and increases in hippocampal gray matter.

“These findings highlight the behavioral relevance of structural brain plasticity in the HC for the learning process,” they note.

Dancing involves the “integration of sensory information from multiple channels (auditory, vestibular, visual, somatosensory)” and “fine-grained motor control of the whole body.”

Mambo, Grapevine, Cha-Cha-Cha

Previous studies have provided evidence of improved performance on balance and memory tasks in elderly dancers, but the underlying neural mechanisms “have not been addressed comprehensively so far.”

“We know from animal research that combining physical activity with sensory enrichment has stronger and longer-lasting effects on the brain than either treatment alone,” said Müller.

The current study was designed to investigate that theory, he said, noting that it built on previous research conducted by his group suggesting that the effect is mediated by brain-derived neurotrophic factor.

The authors conducted a prospective, randomized, longitudinal trial in healthy seniors that compared a specially designed dance program that required participants to continually learn new choreography and a traditional fitness program consisting of repetitive exercises, such as cycling on an ergometer or Nordic walking.

The researchers used voxel-based morphometry to conduct whole-brain analyses in the precentral and parahippocampal gyrus. They noted that the hippocampus is not homoegeneous but consists of specialized subfields, including the subiculum, cornu ammonis (CA) 1 – 4, and the dentate gyrus (DG).

They investigated these regions because the subiculum is involved in working memory and spatial relations, CA3 and DG are involved in memory and early retrieval, and CA1 is involved in late retrieval, consolidation, and recognition. Although all of these regions are interconnected, the DG is one of the few regions of the adult brain in which neurogenesis occurs.

They also assessed the effects of the interventions on balancing capabilities and their relationship to hippocampal subfield volumes, because the hippocampus is also known to be involved with balance.

The first 6 months of training consisted of twice-weekly 90-min dancing or fitness classes. From months 6 through 12, the number of sessions was reduced to one per week.

Dance classes involved constantly changing choreographies, which participants were required to memorize accurately. Single-leg stances, skips and hops, steps used in chasseé, mambo, cha-cha, grapevine, and jazz square were designed to “challenge the balance system.” Also included were patterns in which participants moved their arms away from the center of pressure.

The dance group’s routines in the different genres were changed every second week to keep particpants engaged in a constant learning process. They were required to recall the routines under pressure of time and without cues from the instructor.

The traditional fitness-training program included mostly repetitive sequences of endurance training, strength-endurance training, and flexibility training (stretching and mobility exercises). During the first 6 months, participants engaged in a bicycle activity. During the second period of the study (12 months), the participants completed a Nordic walking program.

The researchers used MRI and voxel-based morphometry with hippocampal mask and analyzed volume changes in five subfields of the HP: the CM (CA1-CA3), DG (including CA4), and subiculum.

Thwarting a Major Health Risk

Postural control was assessed using the Sensory Organization Test, which provides information about the contribution of the visual, somatosensory, and vestibular systems in the maintenance of balance.

Of the participants, 14 members of the dance group (aged 67.21 ± 3.78 years, seven women), and 12 members of the fitness group (aged 68.67 ± 2.57 years, five women) participated for the entire 18-month study period.

There were no group differences at baseline.

To explore changes in hippocampal gray matter volume during the intervention, the researchers used repeated comparisons of baseline and posttest values. They found a significant interaction effect in the right hippocampus (MNI-coordinates: x = 28, y = −16, z D = −23; P [FDR] = 0.049, F + 17.03]). But post hoc paired t-tests showed significant increases in right hippocampal volume only in the dance group (MNI-coordinates: x = 29, y = −16, z D = −27; P [FDR] = 0.001, t = 6.10]).

There were no group differences at baseline. However, repeated measurement of hippocampal subfield volumes showed a main effect of time in the left CA1, the left CA2, the left and right subiculum, and the left CA4/DG.

Although there were no significant interactions by group, paired t -tests showed significant volume increases for the dancers in the left CA1, the left CA2, the left CA4, the DG, and the left and right subiculum. For the exercise group,volume increases were observed in the left CA1, the left CA2, and the left subiculum.

On the composite equilibrium score, repeated measurement of balance data showed an interaction effect with group. In particular, there was a “main effect of time” in the somatosensory and vestibular contribution, but no significant time × group interaction effects after 18 months of fitness training.

Post hoc tests revealed that the dancers improved in the use of the sensory, visual, and vestibular systems (P = .004, P = .027, and P = .007, respectively). The exercise group improved in the use of the somatosensory and vestibular systems (P = .006 and P = .004, respectively) but not in the visual system.

“We know from animal research that combining physical activity with sensory enrichment has stronger and longer-lasting effects on the brain than either treatment alone,” Müller noted.

“For humans, dancing has been suggested to be analogous to such training, and we presume that the advantage is related to the multimodal nature of dancing, which combines physical, cognitive, and coordinative challenges,” he explained.

The authors add that balancing is “an important everyday function crucial, for example, for social mobility” and that impaired balance leads to falls, which constitute a “major health risk factor and consequences both on morbidity (and even mortality) and health care costs.”

The authors note that the lack of an inactive control group, the small sample size, and the relatively small change in the overall score limit their findings.

“Promising” Evidence

Commenting on the study for Medscape Medical News, Madeleine E. Hackney, PhD, assistant professor of medicine, Division of General Medicine and Geriatrics, Emory School of Medicine, Atlanta, Georgia, said the study “provides promising initial evidence that multimodal physical activity, which is both mentally and physically challenging, may directly alter the central nervous system specifically in areas involved in memory operations.”

The findings “will justify future larger trials that may or may not confirm these findings,” said Dr Hackney, who was not involved with the study.

She noted study limitations beyond those cited by the authors. The control group switched from ergometer cycling during the first 6 months to the Nordic walking program during the remaining 12 months, and the cycling “would not be expected to benefit balance,” although walking might have done so.

Additionally, the authors state that they “avoided combined arm and leg movement” in the control group so as to minimize coordinative demands, “but that is hard to imagine in a Nordic walking program.”

Nevertheless, “the results are compelling and the methods the researchers employed seem to be vigorous,” she said.

The study has important take-home messages for practicing clinicians, she emphasized.

“Exercise is good for you, and certainly traditional cardiovascular/resistance training has its place. However, dance typically will engage more cognitive resources and may be ultimately more functional because movements are trained, not just specific muscles.”

Müller stressed that the study can fill an important gap in approaches to dementia prevention in that there is a “demographically induced increase in the prevalence of dementia on the one hand and a lack of causal pharmacologic therapies on the other hand.” Preventing dementia by modifying lifestyle factors is therefore of increasing importance.

“Our study results suggest that ‘social enrichment’ and a combination of physical and cognitive activities influences neuroprotection best,” he said.

He added that beyond dancing, “a healthy lifestyle and physical exercise in general can help the brain stay young.”

The authors and Dr Hackney have disclosed no relevant financial relationships.

Front Hum Neurosci. Published online June 15, 2017. Full text



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Flame Retardants Linked to Infertility in Women

Flame Retardants Linked to Infertility in Women


(Reuters Health) – Women with high concentrations of common flame retardants in their urine may have a hard time getting pregnant and carrying a baby to term, a recent study suggests.

The chemicals – known as PFRs, or organophosphate flame retardants – can be used to make clothing or upholstery fire-resistant and may also be found in nail polish, yoga mats and car seats.

For the study, researchers examined data on 211 women who went to a fertility clinic in Massachusetts to be evaluated for in vitro fertilization. Lab tests showed high urinary levels of metabolites, or byproducts, of three flame retardants: diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and isopropylphenyl phenyl phosphate (ip-PPP).

Compared to women with the lowest levels of two of these chemicals – DPHP and ip-PPP – in their urine, women with the highest levels were 10% less likely to have a successful fertilization, 31% less likely to have an embryo implant in the uterus, 41% less likely to have a viable pregnancy, and 38% less likely to have a live birth.

“These findings suggest that exposure to PFRs may be one of many risk factors for lower reproductive success,” said lead study author Courtney Carignan, who did the research at the Harvard T.H. Chan School of Public Health in Boston.

“They also add to the body of evidence indicating a need to reduce the use of these flame retardants and identify safer alternatives,” Carignan, now at the Center for Research on Ingredient Safety at Michigan State University in East Lansing, said by email.

Flame retardants added to a wide range of products aren’t chemically bound, which means they’re continuously released into the air and dust, Carignan said.

“We all ingest a little bit of dust every day because small amounts easily stick to our hands,” Carignan added. “Couples wishing to reduce their exposure to flame retardants may benefit from washing their hands several times throughout the day, particularly before eating, as previous studies have shown that people who wash their hands more frequently have lower levels of these chemicals in their bodies.”

One in six couples struggles with infertility – a proportion likely to rise as increasing numbers of people in developed countries delay childbearing, researchers note in Environmental Health Perspectives, online August 25.

Previous studies have linked exposure to products containing hormone-disrupting chemicals, such as pesticides and phthalates, to infertility and poorer reproductive success. PFRs have been found to cause hormone disruption in animal studies.

In the current study, 87% of the women had BDCIPP in their urine, 94% had DPHP, and 80% had ip-PPP. Just 14% had the flame retardant tert-butylphenyl phenyl phosphate (tp-PPP), and none had bis(1-chloro-2-propyl) phosphate (BCIPP).

The study wasn’t a controlled experiment designed to prove whether or how flame retardants might impact women’s fertility.

Another limitation of the study is that researchers didn’t consider male partners’ exposure to flame retardants, the authors note. Because the study participants were 35 years old on average and seeking care at a fertility clinic, it’s possible the results might not reflect what would happen for younger women or all women trying to conceive.

“Since this is the first study to examine the effects of organophosphate flame retardants on female reproduction, it is unclear how these findings would apply to the general population of reproductive-aged women,” said Ami Zota, an environmental and occupational health researcher at the Milken Institute School of Public Health at George Washington University.

While more research is needed to confirm the study findings in a larger population, women may still take precautions, Zota, who wasn’t involved in the study, said by email.

“Women may be able to reduce their chemical exposures in the indoor environment by washing their hands frequently, especially prior to eating, as well as buying flame-retardant-free furniture,” Zota advised.

SOURCE: http://bit.ly/2wTg67x

Environ Health Persp 2017.



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Earlier Drinking by Teens Linked to Earlier Sex

Earlier Drinking by Teens Linked to Earlier Sex


(Reuters Health) – Teens who start drinking at younger ages are more likely to have their first sexual encounter earlier than others, according to a new study.

Although the pattern held true for both genders, the effects were more pronounced for younger females.

“Adolescents who engage in early sex have higher risks for sexually transmitted infections or unplanned pregnancies,” lead study author Dr. Kelly Ann Doran of Indiana University in Bloomington told Reuters Health by phone. “Although the U.S. has seen a drop in pregnancy rates, we still have one of the highest in the Western industrialized world. It’s a big issue, and it’s important to find the risk factors that lead to risky sex.”

Doran and colleagues analyzed survey data from 4,079 males and 4,059 females who participated in the National Longitudinal Study of Youth 1997. Data collection started when participants were between ages 12 and 16, and it continued periodically until they were 25 to 31 years old.

On average, boys and girls both had their first drinks before their 15th birthday. The average age for first sexual encounter was 16 for both genders, the study authors wrote in the Journal of Adolescent Health, online August 19.

Onset of drinking before age 14 more than doubled the odds that adolescents of either gender would have earlier sexual encounters. For females who had their first drink at 13 or younger, the likelihood of early sexual initiation quadrupled.

“The association is strong for both males and females,” Doran said. “It still holds (regardless of) socioeconomic status or poor parental monitoring, which could mean we see a unique risk with early drinking.”

“With research, we sometimes think about all of these different risks as separate and have separate programs for alcohol use or teen pregnancy, but many of these behaviors are interconnected,” said Dr. Arielle Deutsch of Sanford Research in Sioux Falls, South Dakota. Deutsch, who wasn’t involved with this study, has researched the link between substance use and sexual intercourse among teens. [

“We have to really think about all of these behaviors and what adolescents may be going through during this time in their lives,” she told Reuters Health by phone.

Future studies should look at the reasons why early drinking may be linked to earlier sex, such as lowered inhibitions, impaired decision-making, and peer pressure among social groups, Doran said.

“Impairment from alcohol increases the likelihood of being victimized or victimizing other people,” she said. “We’d like to do more research to see if there is any difference for voluntary or involuntary sex as well.”

The emotional and social context around the first-time sex experience is important, too, Deutsch added.

“It’s about the relationship between two people and how individuals think about what they’re doing,” she said. “How do teens think about planning their first sexual experience?”

“When teens talk about things like drinking, sex, hanging out with their friends, and partying, it’s all interconnected, especially with parenting approaches,” Deutsch said. “We should be talking to teens about how to make good choices overall and have the experiences they want in life.”

SOURCE: http://bit.ly/2wT9O7X

J Adolesc Health 2017.



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Otonomy Pulls Plug on Ear Drug, Shares Nosedive

Otonomy Pulls Plug on Ear Drug, Shares Nosedive


(Reuters) – Otonomy Inc said on Wednesday it suspended developing its drug for Meniere’s disease, a chronic disorder of the inner ear, after it failed a late-stage trial, sending the drugmaker’s shares plummeting in premarket trade.

San Diego-based Otonomy’s stock fell 81.5 percent to $3.85 in trading before the bell.

Meniere’s typically affects one ear, causing vertigo, a persistent ringing in the ear, and ultimately, permanent loss of hearing. The disease affects about 600,000 Americans.

The U.S. Food and Drug Administration (FDA) has so far not approved any specific drug for Meniere’s, but compounded steroids are routinely used to treat patients.

These steroids, however, often require many repeat injections. Patients are also restricted from moving or swallowing for up to thirty minutes once the steroid is taken, to ensure the drug stays in the inner ear.

Otonomy’s drug, Otividex, is a formulation of an existing steroid designed to become a viscous gel upon injection, allowing for a quicker, five-minute procedure.

Otividex missed the trial’s main goal of significantly reducing the number and severity of vertigo episodes over a three-month period when compared with a placebo.

The drug also failed to meet the study’s key secondary goals, Otonomy said.

“At this point, we have no explanation for the unequivocal negative result,” the company said on a call with analysts, adding it planned to further analyze the data to investigate what went wrong.

Otonomy said it would also suspend its ongoing European trial in Meniere’s disease patients.

Before Wednesday’s trial results, analysts had largely believed both trials would succeed.

Cowen and Co analyst Ken Cacciatore said on Tuesday that if approved, Otividex could account for a $500 million market opportunity in the United States alone.

The delivery technology used by Otividex is already used by Otonomy’s FDA-approved antibiotic for an ear infection that generated about $300,000 in second-quarter sales.

Otonomy also withdrew its annual operating costs forecast, pending an internal review of its product pipeline.

The company had estimated adjusted operating expenses of $80 million to $85 million for 2017.



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US Obesity Rates Leveling Off, No Time to Be Complacent

US Obesity Rates Leveling Off, No Time to Be Complacent


Adult obesity rates are showing signs of leveling off for the second year in a row, following years of rapid increases, according to a new report from Trust for America’s Health (TFAH) and the Robert Wood Johnson Foundation (RWJF).

But the report warns that progress could be eroded if antiobesity programs are cut and policies are weakened.

“Obesity rates are still far too high, but the progress we’ve seen in recent years is real and it’s encouraging,” Richard E Besser, MD, president and chief executive officer of RWJF, said in a statement. “That progress could be easily undermined if leaders and policy makers at all levels don’t continue to prioritize efforts that help all Americans lead healthier lives.”

Nationally, nearly 38% of adults are obese and nearly 8% are extremely obese, according to the 14th annual “State of Obesity: Better Policies for a Healthier America” report.

Between 2015 and 2016, adult obesity rates decreased in one state (Kansas), increased in four (Colorado, Minnesota, Washington, and West Virginia), and remained steady in the rest.

“This supports trends that show steadying levels in recent years,” the report notes.

Last year was the first time the annual report found any declines in adult obesity rates, with four states experiencing declines, and, over time, increases have started to slow. In 2006, obesity rates increased in 31 states; in 2010 rates increased in 16 states.

Other major findings in this year’s report:

  • In all 50 states, more than one in five adults (20%) are obese.

  • Adult obesity rates exceed 35% in five states (Alabama, Arkansas, Louisiana, Mississippi, and West Virginia) and top 30% in 25 states. West Virginia has the highest obesity rate (37.7%).

  • Hawaii, Massachusetts, the District of Columbia, and Colorado have the lowest obesity rates (below 25%). Colorado has the lowest adult obesity rate (22.3%).

  • The South has the highest prevalence of obesity (32.0%) followed by the Midwest (31.4%), the Northeast (26.9%), and the West (26.0%).

  • Adult obesity rates have “striking” racial and ethnic inequities, with rates above 40% for blacks in 15 states and rates at or above 35% among Latinos in nine states. In contrast, in only one state are adult obesity rates above 35% among whites.

  • Adults with more education were less likely to be obese. Obesity rates are 35.5% in adults without a high school education, 32.3% in high school graduates, 31% in those with some college, and 22.2% in college graduates.

  • One in four young adults who try to join the military are ineligible due to fitness and weight concerns.

The report also notes that, based on several federal government data sources, the national childhood obesity rate has leveled off, after increasing steadily for decades, but remains “alarmingly high” compared with a generation ago.

A Critical Juncture

To accelerate progress in addressing obesity, the report urges policy makers to invest in prevention at the federal, state, and local levels, including early childhood programs such as Head Start, school-based programs that emphasize healthy food choices, and community-based policies and programs, including those that support physical activity.

The report also supports fully implementing menu-labeling rules and the updated Nutrition Facts label, as well as continued and expanded Medicare and Medicaid coverage of obesity prevention, treatment, and management services.

“It’s clear that the progress we’ve made in fighting obesity is fragile — and that we’re at a critical juncture where continuation of the policies that show promise and increased support and resources could truly help bend the rising tide of obesity rates,” John Auerbach, president and CEO of TFAH, said in a statement.

“We’re far from out of the woods when it comes to obesity. But we have many reasons to be optimistic, thanks to parents, educators, business owners, health officials, and other local leaders. Our nation’s policy makers must follow their example to build a culture of health.”

The State of Obesity report with state rankings and interactive maps, charts, and graphs is available online. This year, the report contains a new feature that tracks the status of each state’s efforts on more than two dozen policies aimed at preventing obesity and supporting health.

The obesity rate analyses are based on the US Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System (BRFSS).

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Could a Cancer Drug Someday Be Used to Reverse HIV-1 Latency?

Could a Cancer Drug Someday Be Used to Reverse HIV-1 Latency?


NEW YORK (Reuters Health) – The short isoform of the BET protein BRD4 promotes HIV-1 latency, which can be overcome by treatment with one of the new chemotherapeutic BET protein inhibitors, researchers report.

“BET inhibitors are potent reactivators of latent HIV and could serve as part of a future ‘show and kill’ clinical strategy,” Dr. Melanie Ott from University of California, San Francisco, told Reuters Health by email. “BET inhibitor treatment could lead to significant reactivation of endogenous retroelements and retroviruses, a process that should be monitored also in current early phase clinical trial testing BET inhibitors in conditions like cancer.”

Bromodomain and extraterminal domain (BET) proteins commonly activate cellular gene expression, but inhibiting their recruitment reactivates latent HIV-1 transcription.

Dr. Ott and colleagues investigated the functional contributions of the long (BRD4L) and short (BRD4S) isoforms of BRD protein to the enforcement of HIV-1 latency.

BRD4S emerged as a corepressor of HIV-1 transcription and a relevant target of the BET inhibitor JQ1, which affected T-cell reactivation in the presence of BRD4S, less so in the presence of BRD4L, and not at all in their absence.

BRD4S was enriched in the chromatin fraction of latently infected T cells, and cytoplasmic levels of both BRD4 isoforms increased significantly in the presence of JQ1, according to the August 24 Molecular Cell online report.

JQ1 exposure led to reversal of HIV-1 latency by way of marked nucleosome remodeling at the latent HIV-1 promoter, which was dependent on the activity of BRG1-associated factors (BAFs), an SWI/SNF chromatin-remodeling complex with known repressive functions in HIV-1 transcription.

BRD4S directly bound BRG1, a catalytic subunit of BAF, via its bromodomain and extraterminal (ET) domain, and it was necessary for BRG1 recruitment to the latent HIV-1 promoter.

The researchers propose that JQ1-mediated release of BRD4S-BRG1 is a critical early derepressive step required to overcome HIV-1 latency.

“Multiple clinical trials with various BET inhibitors are currently in early stages specifically for applications in cancer,” they note. “In addition, combinatorial treatment with BET inhibitors and low-dose protein kinase C agonists is currently the most effective way to reactivate latent HIV from CD4+ T cells isolated from aviremic HIV+ individuals, rendering BET inhibitors attractive candidates in future clinical trials targeting HIV-1 latency.”

“We anticipate that our data in the context of previous literature will inform future studies into the pleiotropic functions of this epigenetic regulator, not only in HIV biology but also in various noninfectious pathological conditions,” the researchers conclude.

“HIV latency is complex, and important molecular mechanisms are still to be discovered that will inform clinical trials in the future,” Dr. Ott said.

Dr. Jian Zhu from the University of Rochester’s Center for AIDS Research, Rochester, New York, told Reuters Health by email, “The most interesting finding of this paper is that they identified a short version of BRD4 that may execute the suppressive function to maintain the silence of latent HIV.”

“To eliminate the HIV latent reservoirs, a BET inhibitor like JQ1 could be a useful latency-reversing agent that would initially ‘shock and kill’ those ‘reactivatable’ HIV proviruses, followed by the administration of other latency-reinforcing agents to permanently silence the rest of the latent HIV,” he suggested.

Dr. Zhu added, “Although JQ1 targets BRD4, its indirect effect is to remove the suppressive BRG1-associated factors (BAFs), an SWI/SNF chromatin-remodeling complex, from latent HIV promoter. It is also an interesting discovery. Therefore, theoretically the BRG1 ATPase could be a new target for development of its small-molecule inhibitors to eliminate latent HIV.”

SOURCE: http://bit.ly/2wiyk0F

Mol Cell 2017.



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Spain Hires More Staff at Drug Agency to Prepare for Brexit Disruption

Spain Hires More Staff at Drug Agency to Prepare for Brexit Disruption


MADRID (Reuters) – Spain posted 40 vacancies at its National Drug Agency on Wednesday to reinforce evaluation and monitoring of medicines ahead of Britain’s exit from the European Union which will likely lead to the European regulator leaving London.

The European Union wants the European Medicines Agency (EMA), which is a one-stop shop for approving and monitoring the safety of drugs across Europe, to leave London after Brexit.

The health ministry plans to hire 40 staff this year to reinforce the 493 employees who monitor medicines in Spain, it said. More staff would also allow Barcelona to better compete as one of 19 European cities that have lodged official applications to host the EMA, the ministry added.

Spain’s decision to boost staff at a national level comes after the European agency initiated a business continuity plan earlier this month to deal with the uncertainty and workload implications linked to Britain’s withdrawal from the EU.

The European Commission will assess the European city candidates to host the EMA by September but the final decision rests with EU leaders who will try to reach a consensus deal at their next summit in October. The winner is expected to be announced the following month.

The EMA is a prized asset for the host country, employing nearly 900 staff with an annual budget of $360 million. It attracts 36,000 experts a year to London for meetings.



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'Reprogrammed' Stem Cells Fight Parkinson's Disease in Monkeys

'Reprogrammed' Stem Cells Fight Parkinson's Disease in Monkeys


LONDON (Reuters) – Scientists have successfully used “reprogrammed” stem cells to restore functioning brain cells in monkeys, raising hopes the technique could be used in future to help patients with Parkinson’s disease.

Since Parkinson’s is caused by a lack of dopamine made by brain cells, researchers have long hoped to use stem cells to restore normal production of the neurotransmitter chemical.

Now, for the first time, Japanese researchers have shown that human induced pluripotent stem cells (iPS) can be administered safely and effectively to treat primates with symptoms of the debilitating disease.

Human iPS cells are made by removing mature cells from an individual – often from the skin – and reprogramming them to behave like embryonic stem cells. They can then be coaxed into dopamine-producing brain cells.

The scientists from Kyoto University, a world-leader in iPS technology, said their experiment indicated that this approach could potentially be used for the clinical treatment of human patients with Parkinson’s.

In addition to boosting dopamine production, the tests showed improved movement in affected monkeys and no tumours in their brains for at least two years.

The human iPS cells used in the experiment worked whether they came from healthy individuals or Parkinson’s disease patients, the Japanese team reported in the journal Nature online August 30.

“This is extremely promising research demonstrating that a safe and highly effective cell therapy for Parkinson’s can be produced in the lab,” said Tilo Kunath of the MRC Centre for Regenerative Medicine, University of Edinburgh, who was not involved in the research.

The next step will be to test the treatment in a first-in-human clinical trial, which Jun Takahashi of Kyoto University told Reuters he hoped to start by the end of 2018.

Any widespread use of the new therapy is still many years away, but the research has significantly reduced previous uncertainties about iPS-derived cell grafts.

The fact that this research uses iPS cells rather human embryonic stem cells means the treatment would be acceptable in countries such as Ireland and much of Latin America, where embryonic cells are banned.

Excitement about the promise of stem cells has led to hundreds of medical centers springing up around the world claiming to be able to repair damaged tissue in conditions such as multiple sclerosis and Parkinson’s.

While some treatments for cancer and skin grafts have been approved by regulators, many other potential therapies are only in early-stage development, prompting a warning last month by health experts about the dangers of “stem-cell tourism”.

SOURCE: http://go.nature.com/2xN4LT5

Nature 2017.



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Pathologists Take Aim at Inappropriate Testing

Pathologists Take Aim at Inappropriate Testing


CHICAGO — Pathologists and laboratory medicine professionals will be taking a cold, hard look at all the tests physicians order, and why they order them, as part of their Choosing Wisely effort to cut down on unnecessary and even harmful orders that continue to burden patients and payers alike.

The fourth list of recommendations for the Choosing Wisely campaign — currently undergoing review — will be discussed at the upcoming American Society for Clinical Pathology (ASCP) 2017 Annual Meeting.



Dr William Schreiber

“We want to make sure that doctors do not order tests that are wasteful or inappropriate and generate more tests down the road,” ASCP President William Schreiber, MD, told Medscape Medical News.

During a special Choosing Wisely workshop at the meeting, the goal will be to continue to identify which tests are useful, which tests might be considered an alternative to standard tests, and, most important, which tests should be avoided.

Pathologists and laboratory scientists see examples of inappropriate testing every day.

“Pathologists and laboratory scientists see examples of inappropriate testing every day,” said James Wisecarver, MD, PhD, who is president-elect of the ASCP and chair of the workshop.

For example, even if a test for a disease that is not prevalent in the general population “has a relatively high specificity — meaning that a positive test is highly likely to mean the patient actually has the disease — there will still be more false-positive test results than true positives,” Dr Wisecarver told Medscape Medical News.

These false positives are likely to trigger a series of other medical work-ups that will only serve to prove that the patient does not, in fact, have the disease in question. “All of the expense, physician time, patient time and inconvenience, as well as patient concern about health, are wasted,” he explained. “All of the problems associated with overutilization and inappropriate utilization are exactly what I and my copresenters are going to discuss at our workshop.”

More resourceful approaches to testing are sprinkled throughout the program. One salient example, which will be addressed by researchers from Stony Brook University Hospital in New York, is the cost of fundic gland polyp biopsy. The number of fundic gland polyps typically identified as an incidental finding during routine esophagogastroduodenoscopy has increased dramatically over the years, but so, too, has the cost of handling these benign entities.

With virtually no malignant potential, researchers argue that biopsy of these polyps can be effectively eliminated without compromising patient care. Similarly, rates of prostate-specific antigen (PSA) testing, although lower now than at their peak in the early 1990s, as reported by Medscape Medical News, are still unacceptably high.

During one presentation, researchers will be asking why consensus recommendations, at least those from the US Preventive Services Task Force (which discourages PSA screening in men of any age), are not being followed; rates of screening are still high in the United States, especially in men 50 to 59 years of age.

And the use of serum antigen testing for the initial detection of histoplasmosis, after urinary antigen testing, will be addressed by researchers from the Cleveland Clinic.

Changes in the Wind

Changes in the regulatory environment are bound to be implemented as payers vow to reduce out-of-control healthcare costs, and pathologists and laboratory medicine specialists will not escape their effects.

“What’s happening now is that governmental organizations that pay for healthcare are expecting to see evidence that what’s being done is being done in a cost-efficient manner, and there are going to be penalties for not providing evidence that we are doing things in a quality manner,” Dr Schreiber reported.

To help practitioners arrive at the “right” diagnosis, delegates will be walked through the convoluted realm of advanced analytics involved in the transition from volume- to value-based healthcare by the team of Michael Caligiuri, MD, director of the Comprehensive Cancer Center at the Ohio State University in Columbus, and Colin Pritchard, MD, PhD, director of the genetics and solid tumors laboratory at the University of Washington Medical Center in Seattle.

“Tools are needed that can gather all aspects of a patient’s current disease state — clinical, imaging, laboratory, histology, sequencing — to produce the best pathway for patient care,” said Dan Milner, MD, chief medical officer for the ASCP.

“Pathologists must be at the forefront of this process and lead the teams to create the best possible outcomes for our patients,” he told Medscape Medical News. The ASCP recently created, for specialists who want to learn how to better deal with big data, an online opportunity to go through a certificate program in informatics.

And changes are in the wind. During her Michele D. Raible Lecture for Residents, Elaine Jaffe, MD, head of the hematopathology section at the National Cancer Institute in Bethesda, Maryland, will explain that only people who are prepared for the changing healthcare climate will succeed.

New Technologies

The considerable buzz about new technologies — one of which is digital pathology — will surely be audible, at least in the corridors, at the meeting.

“Digital pathology makes it possible to take a glass slide with tissue on it and scan it to create a computer file that can then be sent over the internet or archived,” Dr Schreiber explained.

This means that pathologists will eventually be able to review cases and make diagnoses from remote locations, he pointed out.

And the breakthrough technology of selective whole-genome sequencing will eventually allow pathologists and laboratory scientists to look at hundreds of genes at a time.

“This will allow us to read the genetic code and look for abnormalities that may be important in terms of the development of cancer, genetic disorders, or even multifactorial disorders, like heart disease, in which many genes may play a role,” Dr Schreiber explained.

Global efforts in pathology will also garner attention. The headline speaker at the general scientific session — Ambassador Deborah Birx, MD, the US global AIDS coordinator for the President’s Emergency Plan for AIDS Relief — will address the role that ASCP members, who work in the thousands of laboratories around the world, have played in improving the diagnosis and treatment of HIV.



Dr Zubair Baloch

Pathologists have also assumed a leadership role in shaping the diagnosis of certain malignancies. For example, removal of the “carcinoma” designation from a thyroid neoplasm because it is largely indolent and rarely metastasizes will be discussed by Zubair Baloch, MD, PhD, from the Hospital of the University of Pennsylvania in Philadelphia, who is chair of the meeting education committee and a member of the panel of pathologists and clinicians that made the recommendation.

“Before this change, most patients with this neoplasm were being overtreated,” Dr Baloch told Medscape Medical News.

An emphasis on leadership is also evident in the numerous learning tracks structured into the meeting in which delegates interested in taking a proactive, professional stance can learn what it takes to be a good leader.

“Pathologists are always considered nerds; we’re the guys who are sitting behind a microscope,” Dr Baloch joked. “But this leadership track will teach many techniques that go well beyond traditional pathology education.”

Arguably, the real value of attending any annual meeting lies in the personal aspects.

“What our meeting does best is bring together the latest developments in pathology and laboratory medicine to provide a variety of educational experiences and social opportunities for people to really talk to one another so that they get a sense of where pathology and laboratory medicine are really at today,” Dr Schreiber pointed out.

Pathologists are always considered nerds; we’re the guys who are sitting behind a microscope.

The intangibles of an annual meeting — opportunities to reconnect with colleagues from across the country and around the world, renew old friendships, and see what is going on elsewhere — make attendance worthwhile, Dr Baloch explained.

“By coming to the ASCP, people get a more holistic approach to pathology. It’s not just academic pathology or just diagnostic pathology, the meeting goes way beyond that,” he said.

“I want our meeting to provide that holistic approach by offering sessions that help you to become a better pathologist, a better leader, a better communicator, and to be a real part of this entire machinery,” Dr Baloch said.

The meeting will come to a rocking close with a performance by a band of top-notch pathologists known as Lost in Processing.

Dr Schreiber, Dr Wisecarver, Dr Baloch, and Dr Milner have disclosed no relevant financial relationships.

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Rabu, 30 Agustus 2017

FDA OKs Vabomere, New Antibacterial for Complicated UTI

FDA OKs Vabomere, New Antibacterial for Complicated UTI


The US Food and Drug Administration (FDA) has approved (Vabomere, Medicines Company) for adults aged 18 years and older with complicated urinary tract infections (cUTIs), including pyelonephritis, caused by designated susceptible Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex).

Vabomere combines the carbapenem antibacterial agent meropenem with vaborbactam, which inhibits certain types of resistance mechanisms used by bacteria.

“Carbapenem antibiotics have been the preferred drugs for treating serious infections, such as cUTI, due to Enterobacteriaceae-producing, extended-spectrum beta-lactamases. With the dissemination of the KPC [Klebsiella pneumoniae carbapenemase] enzyme, new drugs that address this resistance mechanism to carbapenems are a welcome addition to our armamentarium,” Cornelius Clancy, MD, chief of infectious diseases at the Veterans Affairs Pittsburgh Health System, said in a company news release.

Vabomere received priority review and is expected to be available in the fourth quarter of this year.

“The FDA is committed to making new safe and effective antibacterial drugs available. This approval provides an additional treatment option for patients with cUTI,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in an FDA news release. 

The safety and efficacy of Vabomere were evaluated in more than 500 adults with cUTI, including those with pyelonephritis. At the end of intravenous treatment, about 98% of patients treated with Vabomere had cure or improvement in symptoms and a negative urine culture, compared with about 94% of patients treated with piperacillin–tazobactam, according to the FDA.

Approximately 7 days after completing treatment, about 77% of patients treated with Vabomere had resolved symptoms and a negative urine culture, compared with about 73% of patients treated with piperacillin–tazobactam.

The recommended dosage of Vabomere is 4 g (meropenem 2 g and vaborbactam 2 g) administered as a 3-hour intravenous infusion every 8 hours in patients 18 years of age and older with an estimated glomerular filtration rate of 50 mL/min per 1.73 m2 or greater. The duration of treatment is up to 14 days.

“To reduce the development of drug-resistant bacteria and maintain the effectiveness of antibacterial drugs, Vabomere should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria,” the FDA advises.

The most common adverse reactions seen with Vabomere were headache, infusion site reactions, and diarrhea. Vabomere is associated with serious risks, including allergic reactions and seizures. It is contraindicated in patients with known hypersensitivity to meropenem or vaborbactam, or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to β-lactam antibacterial drugs.

Full prescribing information is available online.

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FDA Okays Clinical Trial Testing of Psychedelic Drug for PTSD

FDA Okays Clinical Trial Testing of Psychedelic Drug for PTSD


The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to MDMA (3,4-methylenedioxymethamphetamine) as an adjunct to psychotherapy for adults with posttraumatic stress disorder (PTSD).

According to the Multidisciplinary Association for Psychedelic Studies (MAPS), the FDA has agreed on the design of two upcoming phase 3 trials of the drug, also known as ecstasy, in patients with severe PTSD.

This agreement was reached under the FDA’s Special Protocol Assessment Process and “confirms that the protocol design, clinical endpoints, planned conduct, and statistical analyses for the phase 3 trials…are acceptable to support regulatory approval,” MAPS notes in a press release.

The organization reports that the first of these trials, known as MAPP1, is set to start enrollment in spring 2018. However, an open-label lead-in training study will begin this fall.

“For the first time ever, psychedelic-assisted psychotherapy will be evaluated in phase 3 trials for possible prescription use,” Rick Doblin, PhD, founder and executive director of MAPS, said in the release.

“Now that we have agreement with FDA, we are ready to start negotiations with the European Medicines Agency,” he added.

Promising Phase 2 Results

Breakthrough therapy designation from the FDA means that a treatment has a “meaningful advantage” compared with existing medications in treating serious or life-threatening conditions. Also, previous yet preliminary research must show substantial improvement for the novel treatment over those that are currently available.

Completed phase 2 trials from MAPS included 107 patients with treatment-resistant PTSD (mean duration, 17.8 years). Combined results showed that after three sessions of MDMA-assisted psychotherapy, 61% of the participants no longer met PTSD criteria 2 months post treatment. This number increased to 68% 1 year post treatment. Full data from these trials are expected to be published soon.

The upcoming, randomized, phase 3 MAPP1 trial will evaluate 100 to 150 patients with PTSD at centers in the United States, Canada, and Israel. The primary outcome measure will be improvement in scores on the Clinician Administered PTSD Scale, which is known as the CAPS-5.

If the results of this and the phase 3 MAPP2 trial show significant efficacy and safety, the organization said MDMA-assisted psychotherapy “is on track for FDA approval by 2021.”

Although MDMA, in a dose-dependent manner, has been found to transiently increase blood pressure, heart rate, and body temperature, this was “generally not problematic for physically healthy individuals,” according to MAPS.

Follow Deborah Brauser on Twitter: @MedscapeDeb . For more Medscape Psychiatry news, join us on Facebook  and Twitter .



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Convicted German Nurse May Have Killed at Least 86 Patients

Convicted German Nurse May Have Killed at Least 86 Patients


Niels Högel, a former German nurse serving a life sentence for killing two of his patients, is now believed to have murdered at least 84 other patients in his care, according to media reports.

“The realization of what we were able to learn is horrifying,” Johan Kühme, chief of police in Oldenburg, Germany, told The New York Times. “It defies any scope of the imagination.”

Högel was sentenced to life in prison in February 2015 after confessing to the two murders, and a court in Oldenburg found him guilty of the crimes.



A picture taken December 19, 2014, shows former nurse Niels Högel in handcuffs, covering his face with a folder next to a clerk and his lawyer. (Source: AFP/Getty Images)

In court, he admitted to intentionally inducing cardiac arrest in dozens of patients by administering lethal injections of heart medication, including sotalol, lidocaine, amiodarone, and calcium chloride.

He said he liked trying to revive the patients, but sometimes failed, the Times reported. It appears Högel chose his victims at random.

His court confession prompted authorities to investigate other patients who had died while in Högel’s care at clinics in Delmenhorst and Oldenburg. They combed through more than 500 patient files and performed toxicology tests on the remains of 134 possible victims who were exhumed. Toxicology reports for 41 of these cases are pending. The exact number of patients Högel murdered may never be known, as some of his former patients were cremated.

“The death toll is unique in the history of the German republic,” the chief police investigator, Arne Schmidt, said, according to The Guardian , noting that there was “evidence for at least 90 murders, and at least as many [suspected] cases again that can no longer be proven.” 

There is also evidence that coworkers of Högel’s who became suspicious failed to say anything about it.

“Six employees of the Delmenhorst clinic have been charged with manslaughter through failure to render assistance, while an investigation into neglect at the Oldenburg hospital is continuing,” The Guardian reported.

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Nurse Guilty of Killing Eight in Canadian Nursing Homes

Nurse Guilty of Killing Eight in Canadian Nursing Homes


A former nurse has pleaded guilty to first-degree murder in the deaths of eight nursing home residents in Ontario, Canada, the Associated Press (AP) reports.

Elizabeth Wettlaufer, 49, also pleaded guilty June 1 to four counts of attempted murder and two counts of aggravated assault in a Woodstock, Ontario, courtroom.

She told the judge that while she was working as a registered nurse between 2007 and 2014 she injected the victims with insulin without medical reason.



Convicted nurse Elizabeth Wettlaufer. (Source: Jesse Winter/Toronto Star/Getty Images)

 

In a taped interview with a Toronto police officer conducted on October 5, 2016, which was made public and posted to media websites, Wettlaufer said about one of the murders, “I knew the difference between right and wrong, but I thought this was something God, or whoever, wanted me to do. But I was starting at that point to doubt that it was God.”

She also described some of the victims as “feisty” and hard to handle, and she reported feeling a “red surge” come over her before each killing.

The AP reported that she was a registered nurse from August 1995 until she resigned on September 30, 2016.

The incidents reportedly occurred in three Ontario long-term care facilities and at a private home. According to a CBC report, Wettlaufer worked at homes in the Ontario communities of Woodstock, Paris, and London and often was in charge of the nightshifts.

The eight people killed were Maurice Granat, 84; Arpad Horvath, 75; Helen Matheson, 95; Gladys Millard, 87; Maureen Pickering, 79; James Silcox, 84; Helen Young, 90; and Mary Zurawinski, 96.

” ‘I’m Sorry’ Isn’t Enough”

In the taped interview, the officer asks what she would say to the families.

“What can you say to them that would matter? ‘I’m sorry’ isn’t enough,” she says. “I should have gotten help sooner. I took something from you that was precious and was taken too soon.”

The AP reported that the daughter of James Silcox, Andrea Silcox, said she was glad there would be no lengthy trial.

“I will forgive her, I have to forgive her…. My father would want that,” she said. “Forget? I’ll never forget what happened.”

Arpad Horvath Jr, however, said about his father’s death, “She took away my best friend and my hero, and I can’t forgive that.”

Wettlaufer will be sentenced at the end of June.

The Canadian Association of Retired Persons (CARP) is calling for a public inquiry into abuse and deaths of older patients in Canada.

“The murder of these eight elderly residents in their long-term care facility puts a disturbing spotlight on long-term care,” Wanda Morris, vice president of advocacy for CARP, said in a statement the day Wettlaufer pleaded guilty. “CARP is very concerned about attitudes and behaviors towards our most vulnerable Canadians in long-term care. A public inquiry is long overdue.”



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Prospective Study Shows Just How Bad TV Can Be

Prospective Study Shows Just How Bad TV Can Be


Those who may be tempted to binge watch the latest episodes of “Game of Thrones” may want to reconsider: A new study suggests time spent watching television is significantly related to subsequent risk for limited mobility among older adults.

In a longitudinal, prospective study involving more than 130,000 people, there was no significant association between sedentary behavior and the risk of walking disability among participants who exercised at least 7 hours a week, lead author Loretta DiPietro, PhD, MPH, and colleagues report in an article published online August 30 in the Journal of Gerontology: Series A. However, time watching television was associated with a dose-dependent increase in risk, regardless of the level of overall physical activity.

“TV viewing is a very potent risk factor for disability in older age,” Dr DiPietro, chair of the Department of Exercise and Nutrition Sciences at the Milken Institute School of Public Health, George Washington University, Washington, DC, said in a press release about the study. “Sitting and watching TV for long periods (especially in the evening) has got to be one of the most dangerous things that older people can do because they are much more susceptible to the damages of physical inactivity.”

The study is one of the first to address the joint associations between sitting time and physical activity with mobility disability: having difficulty walking or being unable to walk at all.

A Prospective, Longitudinal Analysis

The authors analyzed data from the National Institutes of Health–American Association of Retired Persons Diet and Health Study, which began in 1995 to 1996. The study consisted of 566,398 participants aged 50 to 71 years at baseline who answered a questionnaire about their medical history, diet, physical activity, and hours of active and sedentary time. Sedentary behavior was divided into total time engaged in activities such as sitting, napping, and working at the computer, as well as watching television, and just time spent watching television. The questionnaire also asked about hours per week spent in light-intensity activities such as housework or walking, and in activities of moderate to vigorous intensity, such as brisk walking, jogging, or yard work.

A follow-up questionnaire, distributed in 2004 to 2006, assessed mobility status through questions about normal walking pace, ranging from unable to walk or “easy” (less than 2 mph) through “very brisk” (4 mph or more). Mobility disability was defined as unable to walk or an “easy” normal pace.

Only people who completed both questionnaires, were free of chronic illnesses such as cancer or heart disease at baseline, and who had reported their health status as fair or better at baseline were included in the current analysis study. A total of 134,269 participants fit these eligibility criteria.

The cohort included 57,977 women (43.18%) and had an average age at baseline of 61.2 ± 5.3 years. Mean follow-up was 8.6 ± 0.42 years. Of the 38,798 (28.9%) participants reporting a mobility disability at follow-up, 58.00% were women (P < .001). Compared with no disability, mobility disability was associated with lower educational status, poorer health at baseline and follow-up, more smoking, and higher body mass index (P < .001 for all comparisons).

Participants with some mobility disability at follow-up had reported fewer hours per week of both light and moderate to vigorous activity at baseline than their peers. Similarly, hours per day spent watching television at baseline were significantly associated with limited mobility at follow-up (P < .001 for both comparisons.)

On logistic regression analysis, which adjusted for activity level as well as other variables such as race, educational level, and smoking status, sedentary behavior had an “almost negligible” relationship with mobility disability, the authors write.

Television watching showed a different pattern. Compared with 0 to 2 hours a day of television, 3 to 4 hours a day was associated with a 25% increase in risk for mobility disability (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.215 – 1.293). With 5 hours or more of television, risk was increased by 65% (OR, 1.65; 95% CI, 1.587 – 1.713; P < .001 for both comparisons).

Activity level had an inverse effect on the risk for disability, independent of sitting time, television time, or other independent variables. For example, when analyzed in conjunction with sitting time, 4 to 7 hours per week of light activity was associated with a 20% decrease in the risk for disability (OR, 0.80; 95% CI, 0.766 – 0.839; P < .001). In a model using television time as the sole form of sedentary behavior, this level of activity again was associated with a 20% decrease in risk (OR, 0.80; 95% CI, 0.759 – 0.831; P < .001).

Similarly, more than 7 hours per week of moderate to vigorous activity was associated with a 57% decrease in disability risk (OR, 0.43; 95% CI, 0.411 – 0.449) in the first model and a 56% decrease in the second (OR, 0.44; 95% CI, 0.418 – 0.456; P < .001 for both comparisons).

Among people who spent the most time sitting (≥7 hours per day) and the least time in physical activity (≤3 hours a week), the odds of mobility disability were more than doubled (OR, 2.17; 95% CI, 2.03 – 2.32) compared with the least sedentary, most active participants. For people who engaged in the same degree of sedentary behavior but were active 4 to 7 hours a week, the OR was 1.34 (95% CI, 1.25 – 1.43), and “those reporting the highest level of sitting but who were most physically active (>7 h/wk) had excess odds of 11% (OR=1.11; 95% CI=1.02, 1.20),” the authors explain.

When they repeated these analyses using television time, “the results were even stronger,” they add. For example, among people who were active 4 to 7 hours/week, those who watched television for 5 or more hours a day had a 94% increase in the risk for disability (OR, 1.94; 95% CI , 1.82 – 2.08), which was close to that of participants who watched the least television, but who were also the least active (OR, 1.83; 95% CI, 1.73 – 1.94). Overall, the authors observed that more television time “was significantly related to increased disability within all levels of physical activity.”

The structured nature of television viewing may provide a more accurate estimate of sedentary time, which could account for its seemingly pernicious effect, the authors suggest. “Alternatively, people may break up their sitting time more frequently during the day compared with when watching TV in the evening.”

A third possibility is that heavy television watching plus low levels of physical activity may signal an underlying chronic illness; “however, we controlled for self-reported health status at follow-up and still observed excess mobility disability.”

Recommendations for healthy aging should include reducing sedentary time as well as increasing physical activity, they conclude.

Modern life “often includes 14 hours of sitting per day,” Dr DiPietro said in the press release. “Our findings suggest that older people who want to remain fit must ramp up their daily physical activity and reduce the amount of time they spend sitting.”

The authors have disclosed no relevant financial relationships.

J Gerontol A Biol Sci Med Sci. Published online August 30, 2017. Full text

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Surgical Residents Vulnerable to Malpractice Claims

Surgical Residents Vulnerable to Malpractice Claims


Most medical malpractice cases involving surgical residents focus on the perioperative medical knowledge and decision making of the surgical trainees, and junior residents, in particular, are especially vulnerable, a new study shows.

In a review of the US legal literature for malpractice cases involving surgical residents during a 10-year period, Cornelius A. Thiels, DO, from the Mayo Clinic in Rochester, Minnesota, and colleagues identified 87 malpractice cases citing direct involvement of a surgical intern, residents, or fellow, with nearly half of the cases resulting in a jury verdict or settlement in favor of the plaintiff.. The payouts for these cases, the researchers report in an article published online today in JAMA Surgery, range from $1852 to $32 million, with a median of $900,000.

From January 1, 2005, to January 1, 2015, 70% of the US malpractice claims involving surgical trainees (excluding infant-related obstetric and ophthalmologic procedures) arose from elective surgery cases. General surgery was the most common source of claims (54%), followed by orthopedics (21%), gynecologic surgery (13%), urologic surgery (5%), neurosurgery (5%), oral surgery (2%), and otolaryngology (1%).

The outcomes of patients in 67 of the 87 claims identified involved death or permanent disability, the authors report.

More than half (51%) of the claims cited nonoperative decision making errors and injuries, and most of the alleged errors occurred in the postoperative vs preoperative setting (64% vs 36%). Intraoperative errors and injuries were cited in 34 cases (39%), whereas both nonoperative decision-making errors or injuries and intraoperative errors or injuries were cited in 9 cases (10%).

In 10 cases, the malpractice claims alluded to situations in which the surgical resident made a decision or proceeded with care without evaluating the patient in person, including two cases in which residents prescribed or increased the dose of patients’ postoperative pain medication before or instead of examining the patient, according to the authors.

Of the 10 cases involving claims of residents’ failure to evaluate patients in person before making a decision, seven were decided in favor or the plaintiff and had disproportionately high payouts (median, $1,203,000).

Insufficient direct supervision by attending physicians was deemed a contributing factor in 48 of the malpractice claims. In 10 of these cases, “the attending physician’s failure to appropriately supervise part of an operation in person was cited,” the authors write. “Three cases claimed that intraoperative injuries were the result of residents becoming anatomically ‘lost’ without an attending physician present.” All 10 cases resulted in a judgment in favor of the patient, they note.

Issues related to informed consent, documentation errors, and communication lapses were also cited in the claims.

Of 35 cases in which the residents’ level of training was available through the literature search, 24 named a junior resident (postgraduate training year 1 or 2) in the claim and 11 named a senior resident (postgraduate training year 3 or higher). “Cases involving junior residents often heavily emphasized the novice training level of the resident during the testimonial,” the authors write, noting also that most of the lawsuits in which junior residents were named cited issues related to medical decision-making in the claim.

The median time from injury to resolution of the lawsuit was 4 years, with 42 of the cases being decided in favor of the plaintiff. The extended duration “likely profoundly affected the involved surgical trainees in the beginning of their careers,” the authors state.

Given the high number of claims citing medical decision-making errors, especially in the postoperative period, and insufficient supervision by attending physicians as contributing factors to the litigation, the current review “highlights the importance of perioperative management, particularly among junior residents, and appropriate supervision by attending physicians as targets for education on litigation prevention,” Dr Thiels and colleagues continue. “These data should be used to inform surgical training programs on the importance of developing effective methods of faculty supervision and communication between residents and attending physicians in an effort to reduce the number of lawsuits involving trainees.”

The findings also have implications for the emotional well-being of residents. “Physician burnout is independently associated with a recent malpractice suit, even when accounting for all personal and professional characteristics,” the authors write. “Given that 69% of surgical trainees already meet criteria for burnout, it is critical that we better understand legal cases involving surgical trainees and how such cases can be avoided in the future.”

The authors have disclosed no relevant financial relationships.

JAMA Surg. Published online August 30, 2017. Full text

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GLP-1 Analogue Improves Renal Outcomes in Type 2 Diabetes

GLP-1 Analogue Improves Renal Outcomes in Type 2 Diabetes


Liraglutide (Victoza, Novo Nordisk), a glucagonlike peptide 1 (GLP-1) analogue, significantly reduces the risk of adverse renal outcomes compared with placebo in patients with type 2 diabetes receiving usual care, results of a prespecified secondary analysis of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial suggest.

“New-onset persistent macroalbuminuria is an effect that is typically associated with subsequent progressive reductions in the [glomerular filtration rate (GFR)] in patients with type 2 diabetes,” Johannes Mann, MD, KfH Kidney Center, Munich and Friedrich Alexander University of Erlangen, Germany, and colleagues report.

“In this secondary analysis, among patients with type 2 diabetes at high risk for cardiovascular disease who were receiving usual care, liraglutide resulted in a lower risk of the composite renal outcome than placebo, primarily owing to a lower rate of new-onset persistent macroalbuminuria.”

The study was published in the August 31 issue of the New England Journal of Medicine.

LEADER Trial

The LEADER trial randomized a total of 9340 patients with type 2 diabetes at high risk of cardiovascular disease to either active drug or placebo. Of those, 4668 patients were assigned to liraglutide and the remaining 4672 patients received placebo. Patients took the trial medication for a mean of 83% of the study interval. The mean age of patients in the study was 64 years; the mean blood pressure was 136/77 mm Hg, and the mean estimated glomerular filtration rate (eGFR) was 80 mL/min/1.73 m2.

As reported earlier by Medscape Medical News, liraglutide significantly reduced the rates of major adverse cardiovascular events, which was the primary end point, including a 22% relative reduction in the risk of cardiovascular death.

Now, Dr Mann and colleagues report a reduction with liraglutide in a composite renal end point of persistent macroalbuminuria (defined as a urinary albumin excretion rate >300 mg/day); persistent doubling of the serum creatinine level; end-stage renal disease (ESRD); or death from renal disease. At a median follow-up of 3.84 years, 22% fewer patients receiving liraglutide reached the primary composite renal end point compared those receiving placebo (5.7% vs 7.2%; hazard ratio [HR], 0.78; = .003).

Similarly, 26% fewer patients in the active-treatment group developed new-onset persistent macroalbuminuria compared with the placebo group (3.4% vs 4.6%; HR, 0.74, P = .004).

However, “the risks of doubling of the serum creatinine level and end-stage renal disease did not differ significantly between the liraglutide group and the placebo group, possibly owing to the moderate decline in the estimated GFR observed in this cohort and the few patients who had advanced kidney disease at randomization,” Dr Mann and colleagues suggest.

Only a few patients in either group died of renal causes over the follow-up interval—eight in the liraglutide group and five in the placebo group.

Renal Risk at Baseline

When stratified according to baseline renal risks, the benefit of active therapy was seen across the different subgroups. For example, for patients with either microalbuminuria or macroalbuminuria at baseline, 13.7% of patients in the liraglutide group reached a renal end point over during follow-up compared with 16.3% of placebo patients (HR, 0.81, P = .02).

Similarly, among those with a baseline eGFR <60 mL/min/1.73 m2, composite renal end-point rates were seen in 13.1% of the liraglutide group compared with 15% for placebo controls (HR, 0.84, P = .13). And in patients who qualified for both subgroups, 22.5% of those in the study drug arm met the composite renal outcome compared with 25.8% of those in the placebo arm (HR, 0.81, P = .09).

“The estimated GFR declined continuously, but the decline was slightly slower in the liraglutide group than in the placebo group…corresponding to a 2% less decrease with liraglutide,” Dr Mann and colleagues observe.

A similar trend was seen in the urinary albumin-to-creatinine ratio, which despite an overall increase in both arms, was 17% lower at 36 months in liraglutide arm compared with placebo (P < .001). As the study authors point out, the changes observed in albuminuria at 36 months in favor of liraglutide were independent of baseline eGFR levels as well as baseline levels of albuminuria.

The percentage of patients who developed an adverse renal event were also similar in both groups, at 15.1 events per 1000 patient years in the active-treatment arm and 16.5 events per 1000 patient-years in the placebo arm.

Investigators suggest that the effect that liraglutide had on renal outcomes might be the result of intensified glucose control, which itself has been associated with a lower incidence of new-onset macroalbuminuria compared with usual care alone.

Impressive Renal Benefits

In an accompanying editorial, Ian de Boer, MD, associate professor of medicine, nephrology, University of Washington, Seattle, points out that both the GLP-1 agonists and the sodium-glucose cotransporter 2 (SGLT2) inhibitors, including empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) and canagliflozin (Invokana, Janssen Pharmaceuticals), have demonstrated “impressive” renal benefits in patients with type 2 diabetes. These benefits include “markedly lower rates of decline in the estimated GFR in addition to lower rates of albuminuria,” Dr de Boer writes.

The same two drug classes have also been shown to significantly lower the risk of cardiovascular end points in the same patient group independent of the presence or absence of diabetic kidney disease at baseline. “Taken together, these trial results suggest that the use of GLP-1 agonists and SGLT2 inhibitors may ultimately help to reduce the incidence of diabetic kidney disease.

“Overall, the new data on GLP-1 agonists, SGLT2 inhibitors, and kidney outcomes suggest a hopeful change in story line in which, over time, the incidence and progression of diabetic kidney disease may be reduced and its cardiovascular sequelae mitigated,” Dr de Boer concludes.

As reported by Medscape Medical News, Dr Mann and colleagues presented preliminary results from the renal outcomes analysis last year at the European Association for the Study of Diabetes (EASD) 2016 Annual Meeting.

The study was funded by Novo Nordisk. Dr Mann reports receiving personal fees from Novo Nordisk, AstraZeneca, Amgen, Braun, ACI Clinical (a CRO), Fresenius, Gambro, MEDICE, Lanthio Pharma, Sanifit, Relypsa, and ZS Pharma. He has also received grants and personal fees from Celgene, AbbVie, Novo Nordisk, Roche, and Sandoz. Disclosures for the coauthors are listed on the journal website. Dr de Boer reports receiving personal fees from Boehringer Ingelheim, Janssen Global, and Ironwood.

N Engl J Med. 2017;377:839-848. Article, Editorial

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First Results of Biologics for COPD Eagerly Awaited

First Results of Biologics for COPD Eagerly Awaited


MILAN — Biologics, which have shown promise in severe asthma, are now being studied in chronic obstructive pulmonary disease, and early findings will be among the highlights at the upcoming European Respiratory Society (ERS) International Congress 2017.

“We’re looking forward to hearing the results,” said Guy Brusselle, MD, from the Department of Respiratory Medicine at Ghent University Hospital in Belgium, who is chair of the ERS science council.

New guidelines, including recommendations for COPD exacerbations with acute respiratory failure, will be released at the meeting.

This will be “a much-anticipated session,” Dr Brusselle said. “This is a big step forward for a major health concern. We’re expecting this session to be highly attended and we hope the guidelines will be implemented in clinical practice.”

New Guidelines

Other guidelines will be launched throughout the conference. One set will address novel approaches to the prevention of hospital-acquired pneumonia. Another will make recommendations on the detection and treatment of tuberculosis (TB).

Multidrug-resistant TB will be under the microscope at the congress, especially the development of mycobacterial infections resistant to current TB drugs.

“Novel treatments for drug-resistant TB are very expensive, so it’s becoming extremely important to diagnose TB as soon as possible and to treat it properly from beginning,” explained ERS President Guy Joos, MD, from the Department of Respiratory Medicine at Ghent University Hospital.

Otherwise, the risk for drug-resistant strains of TB increase, putting the infected individual and the population at further risk for infection or death. “We have to mitigate this nightmare,” he explained.

Drug resistance — including issues related to the overuse of antibiotics, particularly in patients with asthma — will be a hot topic at the meeting. “This leads to antimicrobial resistance. We’re looking at this on pan-European and world levels,” Dr Joos pointed out.

Passionate Debate

There will be a debate about how to treat obstructive sleep apnea and a discussion on whether treatment with nasal continuous positive airway pressure throughout the night is beneficial for obese patients with respect to cardiovascular outcomes.

“A recent study shows negative results, so this is sure to be a lively debate at the symposia covering this dilemma,” Dr Brusselle said.

Diesel fuel will be discussed at length. “Outdoor air pollution from diesel exhaust particles is linked to respiratory morbidity and mortality. This is a very hot topic for all of us, especially in light of the recent Volkswagen Dieselgate scandal,” Dr Brusselle explained.

The car manufacturer admitted to evading emissions regulations and specialists will discuss the problem and evaluate the damage to human health.

For the second time, live endoscopies will be performed during a full-day session. Participants will be able to watch procedures performed in real time, ask questions, and interact with the physicians performing the procedures.

Live Endoscopies to Be Performed

There will be a link between the auditorium and the operating theater where invasive pulmonologists will be working. “The procedure will be explained and experts will show their techniques,” Dr Joos told Medscape Medical News.

There will also be a panel of experts to answer questions. “It’s a live experience, so is really something special,” he said. “It was a well-attended and highly successful session when we did it the first time in Amsterdam in 2015,” he said. “I’m hoping to get to that one myself.”

Dr Joos said he is looking forward to hearing more about real-life adherence to bronchiectasis guideline recommendations when the ERS and EMBARC Bronchiectasis Registry results are presented. “This area does not have a lot of research evidence yet, and is a really important hot topic.”

The ERS has teamed up with the New England Journal of Medicine and the Lancet Respiratory Medicine, where the most important studies will be published, to present lunchtime sessions that are not to be missed, Dr Joos pointed out. The session on lung cancer for the pulmonologist will be chaired Jeff Drazen, MD, editor-in-chief of the New England Journal of Medicine.

“We’re also going to hear the increasing evidence that we need to screen for lung cancer with CT scanning in high-risk patients, including heavy smokers,” he noted. “Researchers know that the screening is necessary, but there are questions as to how, which patients, and how to organize and implement this in clinical practice.”

The treatment of lung cancer with tumor immune checkpoint inhibitors will be discussed during several symposia, including a lunchtime session.

Bringing Together Physicians and the Public

Several health campaigns will be launched during the congress, such as the Healthy Lungs for Life campaign, which continues the 2016 theme of Breathe Clean Air and places special attention on smoking cessation and air quality. There will also be a lung function spirometry testing event for the public at the Piazza Castello in Milan, run by the European Lung Foundation, which was founded by the ERS to bring together patients and the public with respiratory professionals to positively influence lung health.

In addition, congress organizers will be collecting signatures on a petition that asks the World Health Organization to recognize September 25 as World Lung Day.

“The day would be devoted to raising awareness about world lung health, the role of pollution, and cigarette smoke. We want to put lungs on the world stage that day, about a week and a half after the conference, and encourage people to hold their own Healthy Lungs for Life events,” Dr Joos explained. “We look forward to seeing this go through.”

Dr Brusselle reports financial relationships with AstraZeneca, Boehringer-Ingelheim, Chiesi, GSK, Novartis, Sanofi, Teva, and Zambon. Dr Joos reports financial relationships with AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Teva.

Follow Medscape Pulmonary Medicine on Twitter @MedscapeLung and Ingrid Hein @ingridhein



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Retinal Imaging Device May Offer Insight Into Alzheimer's

Retinal Imaging Device May Offer Insight Into Alzheimer's


A noninvasive retinal imaging device that detects changes in the eye that are indicative of brain amyloid may provide new insight into Alzheimer’s disease (AD), new research shows.

The proof-of-concept study showed that the mean retinal amyloid index score in AD patients was elevated compared with that of healthy control persons. Other evidence showed that amyloid beta (Aβ) deposits were distributed in a particular pattern in the retinas of AD patients.

The study was published online August 17 in JCI Insight.

Surrogate Biomarker?

Although accumulation of neurotoxic Aβ protein can be detected with positron-emission tomography (PET) or by analysis of cerebrospinal fluid (CSF), these approaches are invasive, inconvenient, and costly and thus are impractical for routine screening and follow-up evaluation.

The new technology, developed by investigators at Cedars-Sinai Medical Center in Los Angeles, California, and NeuroVision Imaging LLC, addresses these limitations.

“Findings from this study strongly suggest that retinal imaging can serve as a surrogate biomarker to investigate and monitor Alzheimer’s disease,” study investigator Maya Koronyo-Hamaoui, PhD, said in a press release.

The experimental technology involves autofluorescence scanning of the retina using a specialized ophthalmic camera and sophisticated image processing software. The technology was unveiled at the Alzheimer’s Association International Conference in 2014.

Since then, researchers have carried out a number of additional analyses.

The new study included 10 AD patients and six healthy control participants. The researchers sought to demonstrate the feasibility of identifying Aβ in the eye using autofluorescence imaging.

As a contrast medium, investigators used curcumin, the main ingredient in the spice turmeric. Curcumin has several properties that make it a good contrast agent. It binds with high affinity to Aβ, has fluorescent properties that enable amyloid plaques to be imaged in the retina, and is safe.

The researchers also report on AD pathology in the retina from a study involving donated eyes and brains of 37 deceased patients, 23 with confirmed AD and 14 control individuals.

Among key findings, the researchers report a 4.7-fold increase in retinal plaque burden in AD patients compared to control persons. In addition, they provide observations regarding geometric distribution and layer location of amyloid pathology in the retina.

The research provides other new insights into the disease’s manifestations in the retina and information on the optical imaging system. Research highlights include the following:

  • The first histologic quantitative analysis of retinal plaque clusters, or “hot spots,” containing the most toxic forms of Aβ with specific distribution patterns in superior peripheral regions that were previously unexplored

  • A detailed analysis of Aβ deposit types using electron microscopy

  • The first report of certain Alzheimer’s-related pathologies in the retina, including vascular amyloid pathology

  • The demonstration of a significant correlation between retinal and brain plaques, and coexistence of neuronal loss

  • The first feasibility study for noninvasively detecting presumed amyloid deposits in retinas of living patients

  • The demonstration of a fully automated calculation quantifying retinal autofluorescence that showed a 2.1-fold increase in patients with Alzheimer’s, compared with control persons

As a developmental outgrowth of the central nervous system that shares many of the brain’s characteristics, the retina may offer a “unique opportunity” to easily and conveniently detect and monitor Alzheimer’s disease, Keith L. Black, MD, chairman of NeuroVision, chair of the Department of Neurosurgery, and director of the Maxine Dunitz Neurosurgical Institute at Cedars-Sinai, said in a release.

“We know that Alzheimer’s begins as many as 10 or 20 years before cognitive decline becomes evident, and we believe that potential treatments may be more effective if they can be started early in the process. Therefore, screening and early detection may be crucial to our efforts to turn the tide against the growing threat of this devastating disease.”

Cautious Optimism

Commenting on the findings for Medscape Medical News, David Knopman, MD, a neurologist at the Mayo Clinic, Rochester, Minnesota, who is involved in research in late-life cognitive disorders, including dementia, expressed cautious optimistic.

“The Koronyo report offers some exciting but tentative evidence that visualization of amyloid in the eyes of living persons might be predictive of levels of brain amyloid. The authors show pathologically that they can visualize beta amyloid in the retina,” said Dr Knopman.

The article, he added, also provides “very preliminary evidence” for visualizing Aβ in living people using the authors’ proprietary curcumin.

“The ocular pathology was carefully described and is very convincing, and the living human data on the ocular imaging is also excellent.”

However, Dr Knopman stressed that these comparisons are “a long way” from being clinically useful.

He pointed out that in the pathologic demonstration, the authors show differences between normal individuals who are known to be free of evidence of AD and those who died with AD.

“In the case of the antemortem comparisons of controls and persons with clinically diagnosed AD dementia, there were too few subjects, poor age-matching, and inadequate characterization of the AD dementia patients.”

Conclusions from such sources cannot be extrapolated to the clinical setting, in which some elderly normal individuals are known to harbor excess Aβ, said Dr Knopman. “In fact, about 30% of cognitively normal people over age 70 have elevated beta amyloid by PET imaging.”

The weaknesses of a proof-of-concept demonstration such as the current report “are understandable,” and the demonstrations form “a strong rationale” for conducting a fully powered clinical trial, said Dr Knopman.

If ocular imaging could be proved through rigorous clinical testing to correlate well with brain beta-amyloidosis, and if it is less expensive and less burdensome to perform than PET imaging or CSF examinations, “there is genuine value for this technique.”

However, Dr Knopman added, “Ultimately, it is likely to be at best a screening tool for elevated brain beta-amyloid, and like beta-amyloid PET or CSF assays of beta-amyloid, it will not correlate with disease severity, and there will be a large overlap with cognitively normal people.”

He reiterated that elevations in levels of brain Aβ is not synonymous with AD. “Elevated brain beta-amyloid is necessary but not sufficient to make a diagnosis of Alzheimer’s.”

Funding for the study was provided by the National Institutes of Health/National Institute on Aging, the Saban Family Foundation, and the Marciano Family Foundation. Dr Koronyo is a scientist and inventor at NeuroVision. Dr Koronyo-Hamaoui is cofounder, inventor, and scientist at NeuroVision. Dr Knopman has disclosed no relevant financial relationships.

JCI Insight. Published online August 17, 2017. Full text



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