Kamis, 30 November 2017

U.S. Scientists Take Step Toward Creating Artificial Life

U.S. Scientists Take Step Toward Creating Artificial Life


CHICAGO (Reuters) – In a major step toward creating artificial life, U.S. researchers have developed a living organism that incorporates both natural and artificial DNA and is capable of creating entirely new, synthetic proteins.

The work, published online November 29 in Nature, brings scientists closer to the development of designer proteins made to order in a laboratory.

Previous work by Floyd Romesberg, a chemical biologist at the Scripps Research Institute in La Jolla, California, showed that it was possible to expand the genetic alphabet of natural DNA beyond its current four letters: adenine(A), cytosine(C), guanine (G) and thymine(T).

In 2014, Romesberg and colleagues created a strain of E. coli bacteria that contained two unnatural letters, X and Y.

In the latest work, Romesberg’s team has shown that this partially synthetic form of E. coli can take instructions from this hybrid genetic alphabet to make new proteins.

“This is the first time ever a cell has translated a protein using something other than G, C, A or T,” Romesberg said.

Although the actual changes to the organism were small, the feat is significant, he said in a telephone interview. “It’s the first change to life ever made.”

It’s a goal Romesberg has been working toward for the past 20 years. Creating new forms of life, however, is not the main point. Romesberg is interested in using this expanded genetic alphabet to create new types of proteins that can be used to treat disease.

In 2014, he formed a company called Synthorx Inc, which is working on developing new protein-based treatments.

“A lot of proteins that you want to use as drugs get cleared in the kidney very quickly,” Romesberg said. The new system would allow scientists to attach fat molecules to drugs to keep them in the body longer.

Romesberg is aware that the creation of semi-synthetic organisms might raise concerns of hybrid life forms spreading beyond the lab, but the system they used makes such an escape unlikely.

For example, in natural DNA, base pairs are attracted to each other through the bonding of hydrogen atoms. Romesberg’s X and Y bases are attracted through an entirely different process, which prevents them from accidentally bonding with natural bases.

And because cells cannot make their own X and Y without the addition of certain chemicals, the semi-synthetic organisms cannot live outside of a laboratory.

“They can’t escape,” Romesberg said. “There’s no ‘Jurassic Park’ scenario.”

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

Nature 2017.



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Risk of Death Very High in Kids With Untreated HIV and Suspected TB

Risk of Death Very High in Kids With Untreated HIV and Suspected TB


NEW YORK (Reuters Health) – Antiretroviral therapy (ART)-naive children with HIV infection and suspected tuberculosis (TB) have an “extremely high” early mortality risk, new findings show.

“Improved access to ART with early diagnosis and ART initiation before presentation with presumptive tuberculosis is needed to prevent many cases of tuberculosis and related mortality,” Dr. Olivier Marcy of the University of Bordeaux in France and his colleagues write in their report, online November 23 in The Lancet HIV.

Estimates suggest that 5% of children in countries with a high TB burden have HIV infection, while prevalence is above 25% for children with TB in South Africa and Zimbabwe, the authors note. World Health Organization (WHO) guidelines recommend that HIV-positive children with poor weight gain, fever, current cough or past contact with a TB patient be investigated for TB, they add, but it is rarely possible to confirm a TB diagnosis in these patients.

“Tuberculosis treatment decisions are generally based on clinical characteristics such as fever, asthenia, weight loss, chronic cough and radiological features, which show poor specificity in the context of advanced immunosuppression,” they explain. “In resource-constrained settings, chest CT and other elaborate tests or technologies are often unavailable.”

WHO guidelines, which are based on studies in adults, recommend starting ART two to eight weeks after anti-TB treatment begins, they add.

To better understand mortality in children with HIV and suspected TB, Dr. Marcy and colleagues looked at 266 children from Burkina Faso, Cambodia, Cameroon and Vietnam who were 13 or younger, ART-naive, and followed for up to six months.

The researchers retrospectively classified study participants into three groups: 40 with confirmed TB, 119 with unconfirmed TB, and 107 with unlikely TB. Fifty-eight percent started anti-TB treatment and 80% started ART. Fifty children (19%) died.

By six months, 14 children with confirmed TB had died, for a two-month survival rate of 65%. Two-month survival was 83.5% for both the unconfirmed and the unlikely TB groups. Children with either confirmed or unconfirmed TB who started anti-TB treatment had a lower mortality risk.

ART initiation during the first month of follow-up was independently associated with lower mortality risk (hazard ratio, 0.08). Higher mortality risk was associated with confirmed TB (HR, 6.33), age younger than 2 years (HR, 5.90), CD4 below 10% (HR, 2.63), miliary features (HR, 4.08) and elevated serum transaminases (HR, 4.40).

“Suspected tuberculosis remains a common and challenging situation in HIV-infected children,” the authors write. “Despite the relatively low proportion of bacteriological confirmation, same-day Xpert MTB/RIF testing could lead to immediate treatment initiation in children most at risk of dying. Optimized algorithms for empirical tuberculosis treatment decision in those without smear-positive or Xpert MTV/RIF confirmed tuberculosis are needed to reduce mortality and accelerate initiation with ART.”

For children at high risk of death, Dr. Marcy and his team conclude, “concomitant initiation of ART and anti-tuberculosis treatment under cautious monitoring should be considered.”

One of the main reasons for delaying ART in TB patients is to help prevent TB immune reconstitution syndrome (IRIS), Dr. Hafsah Deepa Tootla and Dr. Mark Patric Nicol of the National Health Laboratory Service in Cape Town, South Africa, note in an editorial accompanying the study.

However, they add, IRIS may occur less frequently in children. “If paradoxical tuberculosis IRIS in children is uncommon, early concomitant ART and tuberculosis therapy might be beneficial to reduce mortality,” they write.

Dr. Marcy was not available for an interview by press time.

SOURCES: http://bit.ly/2zQbaSI and http://bit.ly/2jwt1mz

Lancet HIV 2017.



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Bodybuilding Products Sold Online May Be Mislabeled or Unsafe

Bodybuilding Products Sold Online May Be Mislabeled or Unsafe


(Reuters Health) – Many bodybuilding products sold online are mislabeled and contain unapproved drugs and other ingredients that may not be safe, a new study suggests.

Researchers tested 44 products they bought online that were marketed as nonsteroidal selective androgen receptor modulators (SARMs), which mimic the effect of testosterone and help build muscle.

Overall, only about half of these items actually contained SARMs, the study found. One in four products contained ingredients that weren’t on the label, including potentially dangerous drugs, and 59% had more or less than the advertised amounts of certain ingredients.

“Our findings show that people should be extremely careful about using these unapproved drugs purchased over the internet not only because these drugs can have harmful effects on their health, but also because the labels cannot be trusted and many products may contain other chemicals not listed on the label whose safety is unknown,” said study co-author Dr. Shalender Bhasin of Harvard Medical School Brigham and Women’s Hospital in Boston.

Anabolic steroids are among the most frequently abused appearance- and performance-enhancing drugs, researchers note online November 28 in JAMA. Use of these drugs was once mostly limited to athletes, but they’ve gained in popularity among men seeking to build muscle and appear more fit.

SARMs are designed to have effects similar to steroids, and several companies are developing SARMs as potential treatment for functional limitations associated with aging and muscle-wasting disorders.

The U.S. Food and Drug Administration hasn’t approved any SARMs to treat these medical problems. These unapproved drugs are marketed as dietary supplements even though they haven’t been reviewed for safety or effectiveness, the FDA has warned.

Consumers shouldn’t use SARMs in bodybuilding products because they can have life-threatening side effects such as heart attacks, strokes and severe liver damage, the FDA has warned.

SARMS, like anabolic steroids, are among the substances athletes aren’t allowed to use under rules outlined by the World Anti-Doping Agency.

For the study, researchers searched online for suppliers selling SARMs and bought all of the items they found that were in stock and possible to purchase.

Then, the study team had all of the products they bought tested using protocols followed by the World Anti-Doping Agency.

Some products were found to contain a drug that increases growth hormone and other substances that are also banned by that agency, the study found. Four products were found to contain the breast cancer drug tamoxifen.

Most undisclosed substances found in the tested products were themselves experimental. Some of the compounds – Ostarine, Andarine, LGD-4033 and ibutamoren – have been tested in humans even though they have not yet won approval by the FDA.

Development of another compound found in tested products, GW-501516, was halted because of safety concerns.

Another compound discovered in the products, SR9009, has been through some preliminary clinical trials but hasn’t yet been tested in humans.

“But people do spend millions of dollars on unregulated drugs every day – and at their peril,” said Dr. Richard Auchus, author of an accompanying editorial and a researcher at the University of Michigan in Ann Arbor.

Vitamin D and calcium are the only supplements people should buy, and even then consumers should only shop from legitimate suppliers like the website for a drugstore chain, Auchus advised.

That’s because the current study highlights problems with supplements that go beyond just SARMs, which may lure a subset of the bodybuilding community with a distrust of medical professionals and a penchant for risk-taking behavior, Anchus said by email.

“This is one of many warnings about such supplements that scam and endanger the public,” Auchus added.

SOURCES: http://bit.ly/2i0NxLN and http://bit.ly/2AngOva

JAMA 2017.



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Insecticide Resistance Spreads in Africa, Threatens Malaria Progress

Insecticide Resistance Spreads in Africa, Threatens Malaria Progress


LONDON (Reuters) – The largest genetic study of mosquitoes has found their ability to resist insecticides is evolving rapidly and spreading across Africa, putting millions of people at higher risk of contracting malaria.

British scientists who led the work said mosquitoes’ growing resistance to control tools such as insecticide-treated bed nets and insecticide spraying, which have helped cut malaria cases since 2000, now threatens “to derail malaria control” in Africa.

“Our study highlights the severe challenges facing public efforts to control mosquitoes and to manage and limit insecticide resistance,” said Martin Donnelly of the Liverpool School of Tropical Medicine, who worked on the study with a team from Britain’s Wellcome Trust Sanger Institute.

Latest World Health Organization (WHO) data show that 216 million people were infected last year with the malaria parasite, which is transmitted by blood-sucking Anopheles mosquitoes.

The disease killed 445,000 people in 2016, the majority of them children in sub-Saharan Africa.

To understand how mosquitoes are evolving, the researchers sequenced the DNA of 765 wild Anopheles mosquitoes taken from 15 locations across eight African countries. Their work, published online November 29 in Nature, created the largest data resource on natural genetic variation for any species of insect.

Analyzing the data, the scientists found that the Anopheles gambiae mosquitoes were extremely genetically diverse compared with most other animal species. This high genetic diversity enables rapid evolution, they said, and helps to explain how mosquitoes develop insecticide resistance so quickly.

The genome data also showed the rapid evolution insecticide resistance appeared to be due to many previously unknown genetic variants within certain genes. The scientists said these genetic variants for insecticide resistance were not only emerging independently in different parts of Africa, but were also being spread across the continent by mosquito migration.

Michael Chew, an infection and immunobiology expert at Britain’s Wellcome Trust global health charity which helped fund the research, said the findings underlined the importance of pushing scientific research ahead to tackle malaria.

“This species is a major transmitter of malaria and the unexpectedly high genetic diversity found by scientists poses fresh questions for those in malaria research and control programmes,” he said in a statement.

“Global efforts to tackle malaria through effective vaccines, insecticides and the best drug combinations require urgent, united action by scientists, drug companies, governments and the WHO.”

SOURCE: http://go.nature.com/2Buy3IJ

Nature 2017.



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Tamsulosin Helps With Expulsion Of Larger Distal Ureteral Stones

Tamsulosin Helps With Expulsion Of Larger Distal Ureteral Stones


NEW YORK (Reuters Health) – Tamsulosin facilitates the passage of larger distal ureteral stones and relieves renal colic, researchers from China report.

Medical expulsive therapy aims to accelerate ureteral stone passage and relieve pain, but several recent studies have questioned the effectiveness of alpha-blockers like tamsulosin for managing ureteral stones.

Dr. Hua Xu from Tongji Medical College, in Wuhan, and colleagues from 30 centers in China evaluated the efficacy and safety of tamsulosin as medical expulsive therapy in their randomized, placebo-controlled trial of 3,450 patients (about two-thirds women).

The stone expulsion rate was modestly though significantly greater with tamsulosin than with placebo (86% vs. 79%), the researchers report in European Urology, online November 11.

In subgroup analyses, tamsulosin was twice as effective as placebo for distal ureteral stones >5 mm, but not effective for smaller stones.

Compared with placebo, tamsulosin was associated with a shorter time to expulsion, less recurrent colic, and fewer analgesics.

Adverse events occurred with similar frequency in the tamsulosin (5.6%) and placebo (5.1%) groups.

“Our findings add to the evidence of tamsulosin as a promising and useful treatment for large distal ureteral stones,” the authors conclude.

Dr. Jason Lee from the University of Toronto, Canada, who recently reviewed evidence for medical expulsive therapy, told Reuters Health by email, “Despite several randomized controlled trials, the jury is still out. There is likely no role for smaller stones (<5 mm), but there might be a benefit in those with larger stones.”

His conclusion: “Tamsulosin should not be given for all patients with distal stones, but perhaps only those with larger stones. Patient selection is important.”

Dr. Oliver J. Wiseman from Cambridge University Hospitals NHS Trust, in Cambridge, UK, who earlier made the case for discontinuing the use of alpha-blockers in this clinical setting, said, “I thought the debate regarding the use of medical expulsive therapy (MET; tamsulosin) for ureteric stones was all over. There were meta-analyses of small randomized studies subject to publication bias recommending the use of MET, and then we published a large study in the UK, SUSPEND, the ‘large randomized study’ which previous meta-analyses had been calling for. However, people didn’t believe SUSPEND, but then we had two further corroborative studies showing that MET was not of benefit in ureteric stones.”

“There are some problems with the current study, which will mean that I won’t be changing my practice away from not using MET for ureteric stones,” he told Reuters Health by email. “For me the issues with this study include the narrow inclusion criteria of stones between 4 and 7 mm, which is very precise and makes we wonder why such tight criteria were chosen, or whether the data underwent some ‘post-study’ analysis and retrospective decision of inclusion criteria. Why would you set out to decide to include stones between 4 and 7 mm?”

Dr. Wiseman also noted, “The exclusion of ‘severe hydronephrosis’ in the current study is difficult to interpret and use in clinical practice. Furthermore, we do need to know about compliance in the study, and this is not mentioned.”

“I don’t want to sound disbelieving about such a large, well-conducted study, a little like people were of SUSPEND, but I won’t be switching back to prescribing alpha-blockers for colic, as there are just too many unanswered questions with this current study,” he concluded.

Astellas Pharma, a maker of tamsulosin, sponsored the study. Dr. Xu did not respond to a request for comment.

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

Eur Urol 2017.



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Epidurals With Fentanyl Not Linked to Lower Odds of Breastfeeding

Epidurals With Fentanyl Not Linked to Lower Odds of Breastfeeding


(Reuters Health) – Women who get epidural pain relief that includes the opioid fentanyl are no less likely to breastfeed their babies than mothers who get epidurals without this drug, a small study suggests.

Epidurals often contain a combination of fentanyl and a local anesthetic such as bupivacaine because using the combination allows doctors to give women lower doses of each drug. Some previous research suggests that fentanyl, particularly in higher doses, may make it harder for newborns to breastfeed because it crosses from mothers to babies through the placenta and can cause sleepiness and feeding difficulties for the infants.

For the current study, researchers tested different epidural solutions in 345 pregnant women who had successfully breastfed at least one baby before. The participants were randomly assigned to receive bupivacaine alone or bupivacaine combined with either 1 or 2 micrograms per milliliter of fentanyl.

After six weeks, 97% of babies in the bupivacaine-only group were breastfeeding, as were 98% of infants with the lower dose of fentanyl and 94% of newborns with the higher fentanyl dose.

These differences were too small to rule out the possibility that they were due to chance, researchers report online November 8 in Anesthesiology.

“We studied women that had previously breastfed and were highly motivated to breastfeed with their current infant,” said study co-author Robert McCarthy, an anesthesiology researcher at Northwestern University Feinberg School of Medicine in Chicago.

“Therefore it is not surprising that the success rate is high,” McCarthy said by email.

It’s possible the results would be different for first-time mothers without any previous experience breastfeeding, or with higher doses of fentanyl, McCarthy added. The study was also done at a so-called “baby friendly” hospital with extra services to support breastfeeding.

“This is a group of mothers that was headed for success,” said Dr. Lydia Furman a researcher at Case Western Reserve University and University Hospitals Rainbow Babies and Children’s Hospital in Cleveland, Ohio.

“Whether this is clearly generalizable to all mothers is not completely clear to me though the results are encouraging in that with good support there is no reason to avoid fentanyl among those intending to breastfeed,” Furman, who wasn’t involved in the study, said by email.

Pediatricians recommend that mothers exclusively breastfeed infants until they’re at least 6 months of age because it can reduce babies’ risk of sudden infant death syndrome (SIDS) as well as ear and respiratory infections, allergies, childhood obesity and diabetes.

Mothers can benefit too, with longer periods of breastfeeding linked to lower risks of depression, bone deterioration and certain cancers.

Many women still choose not to breastfeed or stop nursing their babies much sooner, often due to time constraints, returning to work, or being unable to afford breast pumps and other equipment needed to express milk.

The majority of the women in the current study had previously nursed a baby for at least six months, and less than 10% of them had stopped nursing before three months.

With a larger group of women, it’s possible that the differences in breastfeeding success based on fentanyl doses in the epidurals might have been big enough to be statistically and clinically meaningful, said Yukiko Washio, a researcher at the University of Delaware in Newark who wasn’t involved in the study.

“As a scientist, it seems that not enough evidence shows that epidural fentanyl is adversely impacting the initiation and duration of breastfeeding among women who are highly motivated to breastfeed with previous breastfeeding experiences at this point,” Washio said by email.

“However, replications of this type of study with more power in a similar cohort and with different cohorts of women are required to confirm that for longer-term breastfeeding outcomes to make any definite recommendation as the standard guideline for patients,” Washio added.

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

Anesthesiology 2017.



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Doctor, 84, Who Doesn't Use Computer Won't Get License Back

Doctor, 84, Who Doesn't Use Computer Won't Get License Back


An 84-year-old physician who doesn’t use a computer has been denied reinstatement of her medical license by a New Hampshire judge.

Anna Konopka, MD, from New London, New Hampshire, had surrendered her license in September after 46 years in private practice in advance of a disciplinary hearing before the New Hampshire Board of Medicine.

However, she subsequently asked in a court hearing that it be reinstated, claiming that she had been pressured to relinquish it. Merrimack County Superior Court Judge John Kissinger denied the request on November 15.

Dr Konopka told Medscape Medical News that she filed a new motion November 22 asking for reversal of the latest decision, this time attaching notarized letters from about 30 patients who attested to the quality of her practice. She is awaiting a ruling on that motion.

She does not have a computer in her office or a secretary or nurse, and keeps handwritten records — she was treating about 20 patients a week — in file drawers.

“Electronic medicine has no place in medicine at all,” she said. “It’s good for the system, not for the patients.”

The state is concerned about her remedial computer skills, partly because they prevent her from using the state’s mandatory electronic drug monitoring program. The program, which the state launched in 2014, requires prescribers of opioids to register with it as part of an effort to cut down on prescribing.

The state had also challenged Dr Konopka’s record keeping, prescribing, and some medical decisions.

Allegations against Dr Konopka started with a complaint about her treatment of a 7-year-old patient with asthma, according to court documents filed May 3, 2017.

She was accused of improper recording practices, leaving dosing of one medication up to the parents, and not treating with daily inhaled steroids. Dr Konopka said she never harmed the patient and that the boy’s mother disregarded her instructions, but agreed to a reprimand.

Four more complaints have since been filed against Dr Konopka, the Associated Press reports.

Dr Konopka says she provided medical services for people without other options, many of whom have multiple complications. She charged a flat fee of $50 for an office visit, which was all that most of her patients could afford. She stopped accepting insurance about 3 years ago because of electronic reporting requirements and because “they were trying to control my practice.”

“War on the Private Physician”

She describes demands for what she calls electronic medicine as a “war on the private physician” and says she practices “a traditional kind of medical art.” She said she was working to teach herself enough basic skills to be able to participate in the drug monitoring registry. But she says she has no interest in changing over to electronic records or looking for diagnostic support from the Internet.

According to a spokesperson for the American Academy of Family Physicians (AAFP), the AAFP supports implementation and use of prescription drug monitoring programs.

She cited policy that also states  that the AAFP “believes that every family physician should leverage health information technology, which includes electronic health records and related technologies needed to support the patient-centered medical home (PCMH). These capabilities can support and enable optimal care coordination, continuity, and patient centeredness, resulting in safe, high quality care and optimal health of patients, families, and communities.”

Patients Search for New Care

Meanwhile, in the small town of 4400, Dr Konopka fears what leaving her patients, many of whom are taking pain medications, will mean for them.

“All my patients are waiting for me. They are desperate,” she said. “They are having difficulty finding someone to take care of them.”

Superior Court documents denying her request to reinstate her license also acknowledged her commitment to her patients.

“The court has admiration for Dr. Konopka’s devotion to her patients,” the judgment states. “Several of her patients were in attendance at the hearing. It is clear to the court that Dr. Konopka has spent her career helping people in her medical practice and has a genuine commitment to address the needs of those not able to afford medical care elsewhere.”

As Medscape Medical News was talking with Dr Konopka, she received a knock at her office door and put the phone down. The son of a former patient who had since passed away had stopped by to say hello.

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New PPI Use Not Tied to Excess Risk of Heart Attack

New PPI Use Not Tied to Excess Risk of Heart Attack


NEW YORK (Reuters Health) – Privately insured patients who take newly prescribed proton pump inhibitors (PPIs) are no more likely than their peers on prescription histamine-2 receptor antagonists (H2RAs) to have a myocardial infarction (MI) over the next three years, according to new findings.

Safety concerns have been raised about PPIs – for example, that they may increase the risk of Clostridium difficile infection or fracture, Suzanne Landi, a PhD student at the University of North Carolina at Chapel Hill, and her colleagues report in Gastroenterology, online November 6. In 2009, the U.S. Food and Drug Administration warned that omeprazole could reduce the effectiveness of clopidogrel, thereby increasing the risk of cardiovascular events.

The few epidemiological studies of PPIs and MI risk have had mixed results, Landi and her team add. While it is plausible that the drugs could harm coronary blood vessels by increasing asymmetrical dimethylarginine (ADMA), they say, studies showing this effect were done in animals and ex vivo human tissue.

To investigate whether PPIs were independently associated with MI risk, the researchers looked at 2001-2014 administrative claims data from commercial insurers and Medicare Supplemental plans on more than 5 million people who started using prescription PPIs or H2RAs.

The commercial claims cohort included close to 3.7 million PPI initiators and more than 800,000 patients starting H2RAs. In the PPI group, 29.4% had a recorded ICD-9 code for gastroesophageal reflux disease (GERD) in the past year, compared to 15% of the H2RA group.

The Medicare Supplemental group included nearly 900,000 PPI initiators and close to 200,000 patients starting H2RAs, 21.1% and 14.4% of whom had GERD diagnoses, respectively.

The overall annual weighted risk of MI was 2 per 1,000 for the commercial plan enrollees and 8 per 1,000 for those on Medicare Supplemental plans.

There was no overall difference in MI risk between the patients on PPIs and those on H2RAs. When Dr. Landi and her colleagues analyzed commercial and Medicare Supplemental patients separately, they found that PPIs were not associated with an increased MI risk in the younger patients (compared to H2RAs), while PPIs were linked to reduced MI risk in patients age 65 or older, although the absolute risk reduction was small.

Most patients taking prescription PPIs or H2RAs did not have an ICD-9 code referring to GERD, Landi noted in an interview with Reuters Health.

“This suggests that proton pump inhibitors and histamine-2 receptor antagonists are frequently used outside their typical indications,” she said. “This does mean that these medications may be prescribed without a clear medical indication, and they are used widely.”

“We recommend more biological research focused on how proton pump inhibitors work in the body,” she said. “This line of research could help inform future efforts.”

SOURCE: http://bit.ly/2ijaU75

Gastroenterology 2017.



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FDA Approves AliveCor Personal ECG Monitor for Apple Watch

FDA Approves AliveCor Personal ECG Monitor for Apple Watch


MOUNTAIN VIEW, CA —The Food and Drug Administration has approved a wrist-worn version of the groundbreaking KardiaMobile from AliveCor, the company has announced. It’s the next step in AliveCor’s bid to do for the Apple Watch what it did for the iPhone: turn it into a single-channel ECG monitor[1].

The new AliveCor product, KardiaBand, is a wristband for the Apple Watch equipped with a sensor the user presses with a thumb. Via the company’s Kardia mobile app, the ECG and heart rate are soon displayed on the watch’s screen.

“This is a paradigm shift for cardiac care as well as an important advance in healthcare,” Dr Ronald P Karlsberg (David Geffen School of Medicine, University of California, Los Angeles) is quoted as saying in the company announcement. “With an [ECG] device on the wrist, afib can be detected wherever the patient is, 24 hours a day.”

Users must subscribe to a $99/year service to use the KardiaBand system, the company notes in its announcement. That allows the user to email ECG recordings, among other things.

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.



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Smartphone Pics May Be Sharp Enough for Dermatology Diagnosis

Smartphone Pics May Be Sharp Enough for Dermatology Diagnosis


(Reuters Health) – With a few exceptions, a dermatologist was just as accurate in diagnosing children’s skin conditions from smartphone photos taken by parents as the doctors who saw the kids in person, a small U.S. study found.

Along with some basic clinical information, a high-quality photo taken with a modern smartphone can be a reliable way to get an accurate dermatologic diagnosis, the study team argues in JAMA Dermatology, online November 15.

Two categories of skin conditions could be more difficult to diagnose remotely: hair disorders, such as alopecia, and deeper skin lesions, including nodules and cysts, senior study author Dr. Patrick McMahon of the Children’s Hospital of Philadelphia said by email.

“We have also found that we cannot make specific diagnoses on some images, but those images can be helpful in deciding if urgent office visits are necessary,” said Dr. Lawrence Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego, who wasn’t involved in the study.

Despite the increasing popularity of telemedicine as a way to reduce costs, improve time efficiencies and tackle geographic barriers to care, adoption of this kind of remote care has been slowed by barriers to reimbursement, cross-state licensing requirements and uncertainty about privacy regulations, the authors and other experts said.

In the current study, a dermatologist assessed 87 images from 40 parent-patient pairs who also were seen in person by a different dermatologist. Overall, the doctor who viewed photos and the doctors who saw the same patients in person came to the same diagnosis 83% of the time.

“While the authors did not test the usefulness of complete teledermatology visits, which would include treatment plans, prescribing medications, and giving patient educational materials, they strongly showed diagnostic consistency within limits,” Eichenfield said.

The greatest number of incorrect diagnoses occurred in cases of alopecia, but since one of the in-person clinicians specializes in pediatric hair conditions, the study included an above-average proportion of such cases, the researchers note. Such diagnoses can also be difficult to differentiate without dermoscopy and a thorough case history, they add.

Prior studies of adults have found that so-called store-and-forward teledermatology generates accurate diagnoses, improves access to specialty care and reduces time to treatment, McMahon and colleagues point out. Pediatric dermatologists are also in short supply, with “fewer than 300 board-certified physicians serving the nearly 75 million children in the United States,” they write.

The authors acknowledge that the small trial simulated, rather than performed, an actual teledermatology encounter. Another limitation is that the study was conducted in a setting that was urban, academic and clinic-based, and used a solitary pediatric dermatologist to provide remote diagnoses.

“The patient population was very small to base any real conclusions so it was more of a pilot study,” Dr. Bruce A. Brod, clinical professor of dermatology at University of Pennsylvania Perelman School of Medicine in Philadelphia, said by email. “The pediatric dermatologists at CHOP function at the highest level, so the question is whether this translates at the community level,” said Brod, who wasn’t involved in the study.

McMahon said he was confident the study could be reproduced on a larger scale, and if they decided to exclude certain conditions like hair disorders and nodules, “we could exceed 90 percent in our diagnostic accuracy.”

A study published in 2016 in the same journal raised concerns about direct-to-consumer teledermatology websites, including the risk for incorrect diagnoses, inappropriate treatments, a lack of information about possible side-effects and a lack of transparency about a doctor’s credentials (bit.ly/1srMuYU).

“I think more work needs to be done to assess the accuracy of teledermatology and to determine the optimal type of care episodes where this can be best utilized,” Brod said.

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

JAMA Dermatol 2017.



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High Levels of Burnout Among Oncology Physician Assistants

High Levels of Burnout Among Oncology Physician Assistants


Over one third of physician assistants (PAs) working in oncology in the United States report fairly high levels of burnout even though they are generally happy with their career and choice of specialty, the first national survey of its kind suggests.

“Physician assistants are in most cases satisfied with the work they are doing — they find it challenging, yet very rewarding,” lead author, Eric Daniel Tetzlaff, MHS, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a statement.

“Our research suggests, however, that there are several gaps we need to address to strengthen team relationships, better define roles and responsibilities and reduce burnout,” he added.

“By understanding the personal and professional characteristics associated with burnout, meaningful changes and modifications in team-based care design can be implemented to lead to more effective care delivery,” Tetzlaff suggested.

The study was published online November 30 in the Journal of Oncology Practice.

For the survey, the researchers used the membership database of the Association of Physician Assistants in Oncology as well as registration data from the 18th annual APO continuing medical education conference to identify participants.

Of 855 members contacted, 250 responded to the survey. To assess the level of burnout, researchers used the standard 22-item Maslach Burnout Inventory (MBI), a well-recognized questionnaire designed to measure professional burnout.

All respondents were currently in some form of oncology practice in the United States. Almost all were female, and most were married. The mean age of respondents was 41.8 years.

“On average, participants had been a PA in oncology for 9.6 years,” the study authors note.

“Overall, 34.8% of oncology PAs had MBI scores that indicated professional burnout (ie, high scores on either the emotional exhaustion and/or depersonalization subscales),” the researchers report.

Specifically, on different subscales, 30.4% of respondents indicated they were experiencing high levels of emotional exhaustion.

Another 17.6% reported feeling high levels of depersonalization, while almost 20% reported feeling a low sense of personal accomplishment.

The degree to which PAs engaged in different professional activities also affected the risk for burnout, with direct patient care being associated with a significantly lower risk compared with indirect patient care, such as phone calls, reviewing laboratory results, and charting.

Table. PA Engagement in Different Professional Activities

Activity PAs With Burnout (%) PAs Without Burnout (%) P Value
Direct patient care 60 70 .005
Indirect patient care 25 20 <.001

 

Whether participants felt they were “fairly compensated” also affected burnout risk. Fewer than 20% of PAs who felt compensation was fair reported burnout, whereas among those who “strongly disagreed” that they were being fairly compensated, the percentage rose to 65% (P < .001).

In contrast, “there were no significant differences in the reporting of burnout for PAs with respect to sex, relationship status, years as a PA in oncology, compensation model, and practice settings,” the researchers observe.

Noteworthy was the finding that over 86% of respondents indicated they were satisfied with their career, and almost 89% indicated that they were satisfied with their choice of specialty.

Furthermore, only 3.6% of survey respondents indicated they planned to switch careers or specialty over the next 2 years and only 2% indicated they planned to retire within the same time interval.

Burnout Risk

The relationship between a PA and their collaborating physician (CP) also affected burnout risk.

For example, “PAs who did not feel valued by their collaborating physician, did not feel encouraged to achieve professional goals, or whose contributions to the practice were not acknowledged by their CP were more likely to be burned out,” the authors observe.

How well a PA felt the CP could provide leadership guidance also significantly affected the risk for burnout as well.

“It is recognized that using PAs results in increased efficiency and productivity for the practice,” study authors observe.

“[But] the rate of burnout is of significant concern because the wellness of providers has been associated with quality of care and patients’ safety,” they add.

 

[I]f burnout is not addressed, the impact of PAs to help meet the demand for oncology care may be hindered.
Tetzlaff et al

 

“[I]f burnout is not addressed, the impact of PAs to help meet the demand for oncology care may be hindered,” the researchers conclude.

Study authors stress that strategies to improve collaboration between members of the oncology team might help reduce the risk for burnout.

“Supportive relationships lead to less burnout and represent an important modifiable factor than can strengthen the oncology workforce,” Tetzlaff emphasized.

Commenting in a statement on the survey findings, Robin Zon, MD, an expert spokesperson from the American Society of Clinical Oncology, felt that survey findings can provide important guidance for the specialty as the number of PAs working in oncology increases with growing demand.

“While it is reassuring that PAs in oncology report high levels of satisfaction in their profession, they also experience high rates of burnout in a manner similar to oncologists,” Dr Zon said.

“The collaboration of an entire team — from the front desk to the PAs to the institutional leaders — is critical to patient and provider satisfaction,” she added.

A study published in 2014 found that almost 45% of oncologists surveyed in the United States reported feelings of burnout.

Mr Tetzlaff and Dr Zon have disclosed no relevant financial relationships.

J Oncol Pract. Published online November 30, 2017. Abstract

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CGRP Antagonists the Next Frontier for Migraine Prevention

CGRP Antagonists the Next Frontier for Migraine Prevention


Two investigational monoclonal antibodies that target calcitonin gene-related peptide (CGRP) proved safe and effective for migraine prevention in separate randomized placebo-controlled phase 3 studies published November 30 in the New England Journal of Medicine.

One is erenumab (AMG334, Amgen/Novartis), a fully human monoclonal antibody targeting CGRP receptor, and the other is fremanezumab (TEV-48125, Teva Pharmaceuticals), a humanized monoclonal antibody targeting CGRP itself.

Mechanism-Specific Treatment

CGRP is a neuropeptide believed to be directly involved in the pathophysiologic processes underlying migraine.  Targeting CGRP is a “new distinct treatment and what we call a mechanism-specific treatment in the sense that CGRP may be the mechanism of migraine,” Stephen Silberstein, MD, from the Jefferson Headache Center at Thomas Jefferson University in Philadelphia, Pennsylvania, noted in an interview with Medscape Medical News.

In the fremanezumab trial,  Dr Silberstein and colleagues enrolled 1130 patients with chronic migraine (defined as headache of any duration or severity on 15 or more days per month and migraine on 8 days or more per month). Patients were randomly allocated to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8; n = 376), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8; n = 379), or matching placebo (n = 375). Both fremanezumab and placebo were given by subcutaneous injection.

Baseline demographic and clinical characteristics were similar among the three groups; the mean number of baseline headache days per month was 13.2 in the fremanezumab-quarterly group, 12.8 in the fremanezumab-monthly group, and 13.3 in the placebo group.

Results showed a significant benefit of fremanezumab over placebo with regard to the average number of headache days per month, which was reduced by 4.3 days with fremanezumab quarterly and 4.6 days with fremanezumab monthly, vs 2.5 days with placebo (P < .001 for both comparisons with placebo).

There was also a significantly larger reduction in the average number of migraine days per month with fremanezumab quarterly (by 4.9 days) and monthly (by 5.0 days) than with placebo (by 3.2 days; P < .001 for both comparisons with placebo).

In addition, significantly more patients who received fremanezumab had a reduction of at least 50% in the average number of headache days per month (38% with the quarterly regimen and 41% with the monthly regimen) than did patients who received placebo (18%) (P < .001 for both comparisons with placebo).

Fremanezumab “has a lasting effect that starts immediately, within a couple days,” Dr Silberstein told Medscape Medical News. “And when patients respond they often respond extraordinarily well.  So it works quickly and it’s effective and has no more side effects than placebo except that it hurts at the site of injection,” he noted. 

In the erenumab trial,  Peter Goadsby, MD, PhD, from King’s College London, United Kingdom, and colleagues randomly assigned 955 patients with episodic migraine to receive a subcutaneous injection of erenumab 70 mg (n = 317) or 140 mg (n = 319) or placebo (n = 319) monthly for 6 months.

At baseline, the average number of migraine days per month was 8.3 in the overall population. By months 4 through 6, the number was reduced by 3.2 days in the 70-mg erenumab group and by 3.7 days in the 140-mg erenumab group, compared with 1.8 days in the placebo group (P < .001 for each dose vs placebo).

A 50% or greater reduction in the average number of migraine days per month was achieved for 43.3% of patients in the 70-mg erenumab group and 50.0% of patients in the 140-mg erenumab group, as compared with 26.6% in the placebo group (P < .001 for each dose vs placebo).

In addition, the number of days of use of acute migraine-specific medication was reduced by 1.1 days in the 70-mg erenumab group and by 1.6 days in the 140-mg erenumab group, as compared with 0.2 days in the placebo group (P < .001 for each dose vs placebo).

Patients receiving erenumab reported reduced physical impairment and improved ability to participate in daily activities, according to a validated patient-reported outcome tool. Rates of adverse events were similar between erenumab and placebo.

Important Advance in Migraine

Both erenumab and fremanezumab have been submitted to the US Food and Drug Administration for approval. Two other antibodies targeting the CGRP pathway for migraine prevention are also in development. They are eptinezumab (Alder Biopharmaceuticals) and galcanezumab (Eli Lilly & Co).

“With the ongoing development of four different antibodies targeting the CGRP pathway, it will be difficult to determine whether unique patient populations will have a response to a specific drug or whether one agent is superior to others,” Andrew Hershey, MD, PhD, from University of Cincinnati College of Medicine in Ohio, writes in an editorial.

“Furthermore, many patients will probably still have a response to standard multidisciplinary treatment that is less costly in patient and provider time and dollars. It is of interest that these agents worked rapidly and that a number of patients became completely headache-free. Thus, these drugs may find a specific role in the treatment of patients who have migraines that are refractory to treatment or who are severely disabled by headaches,” he notes.

Dr Hershey says it will also be important to determine whether the beneficial effects are sustained after discontinuation or whether continued treatment will be necessary.

“A migraine-specific preventive treatment that is directed toward a suspected underlying pathophysiological mechanism is an important advance for patients with migraine. As mechanisms of migraine are revealed by advances in neuroimaging, biomarker identification, and genomic analysis, one may expect new compounds to bring a brighter future to our patients who have migraine,” Dr Hershey concludes.

The fremanezumab trial was funded by Teva Pharmaceuticals, and the erenumab trial was funded by Amgen and Novartis. Full disclosures for authors are available with the full text of the articles at NEJM.org.

N Engl J Med. 2017;377:2113-2122, 2123-2132, 2190-2191.  Silberstein et al abstract,  Goadsby et al abstract,  Editorial  

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Fast MRI Improves Breast Cancer Screening

Fast MRI Improves Breast Cancer Screening


Abbreviated MRI protocols could dramatically improve the diagnosis of breast cancer and lead to the earlier diagnosis of a lot more women, especially those with fast-growing cancers, according to an ongoing study.

“Mammograms detect slow-growing cancers but, notoriously, deliver false negatives for rapid-growing cancers,” said Christiane Kuhl, MD, from University of Aachen in Germany.

“We have good reason to search for other methods,” she pointed out.

Traditionally, MRI has only been used to characterize a cancer, to map known disease. “But we are seeing that it’s by far the most accurate imaging method for diagnosis,” she told Medscape Medical News.

“Breast MRI has the sensitivity profile we want to see in screening methods used today,” Dr Kuhl said.

She and her colleagues are conducting the ongoing large-scale phase 2 EA1141 trial to investigate the utility of abbreviated MRI for screening in 1450 women with dense breast tissue who are at average risk for breast cancer (NCT02933489).

At the Radiological Society of North America (RSNA) 2017 Annual Meeting in Chicago, Dr Kuhl discussed the premise for the EA1141 trial.

Mammograms detect slow-growing cancers but, notoriously, deliver false negatives for rapid-growing cancers.

Host-related factors, such as breast tissue density, and tumor-related factors contribute to the failure of mammographic screening to detect biologically relevant breast cancer.

Biologically relevant cancers can exhibit features that render them indistinguishable from normal or benign breast tissue on mammography. “But only a small fraction of women qualify for breast MRI,” she explained.

A typical MRI study takes up to 40 minutes and generates several hundred images. An abbreviated MRI has a 3-minute magnet time and an abridged image interpretation time (about 30 seconds), generates only one precontrast and one postcontrast T1 weighted image set, and uses maximum-intensity projections to fuse the first postcontrast subtracted images into one single high-contrast image.

“The new era is about finding more, earlier, then using targeted therapies to be more efficient,” she said, explaining that her group started publishing studies that showed the advantages of abbreviated MRI in 2014. “Surprisingly, it’s still considered new,” she said.

In an early study, the diagnostic accuracy of abbreviated breast MRI was shown by Dr Kuhl’s team to be equivalent to that of a diagnostic protocol that took 17 minutes (J Clin Oncol. 2014;32:2304-2310). In addition, because women were diagnosed with greater efficiency, the cancer yield increased by 18.2 per 1000 people, as reported by Medscape Medical News.

In a more recent study, the team showed that MRI screening improves the early diagnosis of prognostically relevant breast cancer in women at average risk for breast cancer (Radiology. 2017;283:361-370).

Currently, there are about 16 publications that confirm that abbreviated MRI is the best way to detect breast cancer, Dr Kuhl reported. It is generally agreed, however, that “it’s way too expensive.”

“If it’s just a matter of cost, let’s find other ways,” she said. Maybe with abbreviated MRI “we will change the way we screen for breast cancer in the foreseeable future.”

“It’s been difficult for people to think outside the box,” she said, adding that MRI does not have to be a long process. “Having dedicated magnets optimized for fast patient throughput will be crucial for taking advantage of this approach.”

Benefits of Fast MRI

Fast MRI protocols can also improve the diagnosis of conditions other than breast cancer. Dr Kuhl’s group recently showed that abbreviated biparametric MRI improved the detection of clinically significant prostate cancer in men with elevated levels of prostate-specific antigen (Radiology. 2017;285:493-505).

And in a study also presented at the RSNA meeting, a 5-minute MRI protocol was as accurate as standard knee MRI for the evaluation of internal derangement of the knee.

“The two were diagnostically interchangeable, particularly for our patients who have claustrophobia or pain,” said Erin Alaia, MD, assistant professor of radiology at NYU Langone Health in New York City.

For their study, Dr Alaia and her colleagues assessed patients who underwent MRI at two academic centers from January 2015 to July 2016. Of the 146 patients, 100 underwent 3T MRI (100 scans) and 46 underwent 1.5T MRI (50 scans).

Four musculoskeletal radiologists evaluated menisci, ligaments, cartilage, and bone, and compared five fast multiplanar 2D FSE sequences using parallel imaging with 5 standard sequences.

“We compared and saw the same results,” Dr Alaia reported.

“We just need to get the image quality that’s necessary for the diagnosis,” said her colleague Naveen Subhas, MD, associate professor of radiology at the Cleveland Clinic. “That’s going to take some time for a lot of people to get their heads around.”

“From volume-based to value-based imaging, I think this is a paradigm shift that’s going to happen,” Dr Subhas said.

Dr Khul, Dr Alaia, and Dr Subhas have disclosed no relevant financial relationships.

Radiological Society of North America (RSNA) 2017 Annual Meeting: Abstract SPSH50A, presented November 30, 2017; abstract SSA14-05, presented November 26, 2017.

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Three-Item Juvenile Arthritis Scale Can Guide Anti-TNF Use

Three-Item Juvenile Arthritis Scale Can Guide Anti-TNF Use


A simple modification of the Juvenile Arthritis Disease Activity Score (JADAS) that could be used in routine clinical practice may simplify treat-to-target care for juvenile patients with oligoarticular (OJIA) or polyarticular (PJIA) juvenile idiopathic arthritis, Joost F. Swart, MD, and colleagues report in an article published in the Annals of the Rheumatic Diseases. This tool might help clinicians navigate the complex path between undertreatment of patients with JIA whose underlying disease will not be sufficiently controlled by methotrexate (MTX) by 12 months and unnecessary early use of expensive biologicals in patients whose disease can be expected to respond to MTX.

The clinical JADAS (cJADAS) uses the physician global assessment, the parent/patient Visual Analogue Scale (VAS) of well-being, and the active joint count to calculate a disease activity score. It differs from the full JADAS in omitting erythrocyte sedimentation rate.

“Our key finding was that the three-item cJADAS (without the [erythrocyte sedimentation rate]) could be used to identify JIA patients who should be escalated to anti-TNF therapy after 3 months or 6 months of MTX. Clinicians could be using the cJADAS as guide for treatment; however, the optimal cut-off values for the escalation to anti-TNF need to be validated in a new cohort. This will take place soon. We already display cJADAS graphs in our clinical practice, and patients love it (as do we),” lead author Joost F. Swart, MD, told Medscape Medical News. Dr Swart is pediatric rheumatologist/immunologist, Department of Pediatric Immunology and Rheumatology, UMC Utrecht, Wilhelmina Children’s Hospital, Utrecht, the Netherlands.

The cJADAS score, as defined for JIA by Consolaro et al, combines the physician global assessment of overall disease activity measured on a 0 to 10 VAS, where 0 = no activity and 10 = maximum activity; parent/child ratings of well-being assessed on a 0 to 10 VAS, where 0 = best and 10 = worst; and the active joint count assessed in 71, 27, or 10 joints (cJADAS71, cJADAS27, or cJADAS10). The cJADAS in the Swart study used the active joint count 71-joint count, which yielded a global score of 0 to 91.

The single-center, retrospective cohort study included 39 patients with OJIA and 74 patients with PJIA, all of whom were first starting MTX. Dr Swart pointed out that the study did not include two of the seven JIA subtypes: JIA with enthesitis and systemic JIA.

At 3 and 6 months after MTX start, patients were assessed using the 2011 American College of Rheumatology (ACR) JIA clinical practice guideline, the full JADAS71, and the cJADAS. This comparison was made in part because the clinical practice guideline has not gained wide acceptance, apparently as a result of its complexity for use in daily practice, and the JADAS71 and cJADAS were being tested as possible replacements.

The researchers report, “The cJADAS incorporates the patient perspective, is very user-friendly and does not need waiting for [erythrocyte sedimentation rate] results before a decision can be made. We therefore believe that the cJADAS can be used for treat-to-target therapy in JIA. The cut-off values for cJADAS that we found for the need to escalate to anti-TNF were >5 for OJIA and >7 for PJIA at 3 months and >3 for OJIA and >4 for PJIA at 6 months.”

“In fact, we wondered what the real decisive reasons were for physicians to escalate to anti-TNF or not, but this was not clear-cut. We expected that we were likely to follow the ACR 2011 recommendations for JIA, but this was not the case at all, and would totally change our practice today if we would do so,” Dr Swart told Medscape Medical News.

“We looked for the best way to improve these really important decisions and make them more transparent. This was the reason we chose to look at the composite score of cJADAS as an instrument/tool to predict nonresponse to MTX, and therefore the need to escalate to anti-TNF. We felt that 3 months of nonresponse is different from 6 months of nonresponse. This difference was relevant for the choice of cut-off values: We felt that the risk of overtreatment at 3 months is higher, and we really wished to avoid undertreating, [which is why the cut-off scores are lower at 6 months,]” Dr Swart explained.

He said that he had been “honestly surprised” to discover that the ACR JIA clinical practice guideline was not easy to understand and not really helpful in identifying patients in need of anti-TNF. “I was pleasantly surprised that the cJADAS was able to discriminate in this. I also had not expected…the “voice” of the patient [the parent/patient VAS] to be so critical in this.”

Timothy Beukelman, MD, MSCE, from the Division of Pediatric Rheumatology, University of Alabama at Birmingham, who was lead author for the 2011 ACR Recommendations for the Treatment of JIA, told Medscape Medical News the recommendations were not developed to predict which patients would require initiation of anti-TNF inhibitor therapy to achieve inactive disease 12 months after initiation of methotrexate, the question asked in the current study.

“Nevertheless, this fact does not detract from this important and impactful study that highlights the potential utility of cJADAS for a treat-to-target approach in JIA,” Dr Beukelman said. He explained that at the time when the 2011 ACR Recommendations were being developed, the JADAS was relatively new and still undergoing validation. “The simplicity of the cJADAS is very appealing, making studies that examine its performance in clinical practice very important,” Dr Beukelman explained.

However, Dr Beukelman disagreed with some of the authors’ concerns about potential “overtreatment” of JIA with anti-TNF therapy.

Dr Beukelman said, “The issues with the ACR recommendations aside, I think that ‘over-treatment’ is not easily defined. Achievement of clinical inactive disease at a single arbitrary time-point is not sufficient to assess treatment success. For that we need longer-term outcomes. If the outcome definition used in this study is accepted, then 30% of the patients who did not receive TNF inhibitors were ‘undertreated’ by their physicians because they had persistent disease activity. To me, this is far more worrisome than ‘overtreatment.’ “

Dr Swart’s group currently measures cJADAS for every patient with JIA at each visit, but does not yet use it to guide decisions on anti-TNV therapy, as the cut-off values need to be validated. “The obvious question is, How will cJADAS perform in a new cohort? I believe that soon we will be able to sit down with, for example, a PJIA patient and tell them that we start MTX today, but if 3 months from now the cJADAS is still >7 (if validated in another cohort), we will need to change therapy, or if after 6 months the cJADAS is >4, we will also change. At this moment, only the sequence of the drugs [for treat-to-target therapy] is agreed upon, not the target you and the patient are aiming at for a certain point in time,” Dr Swart said.

The study was supported by Pfizer and by the Dutch Arthritis Foundation (Reumafonds). The authors and Dr Beukelman have disclosed no relevant financial relationships.

Ann Rheum Dis. Published online November 14, 2017. Full text

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Database Studies May Support Supplemental Drug Applications

Database Studies May Support Supplemental Drug Applications


Analysis of database information from patients in routine clinical settings may, in certain circumstances, provide similar results as randomized clinical trials (RCTs), according to a study published online November 20 in JAMA Internal Medicine.

The results suggest that database studies could help support supplemental drug applications for some drugs that are already approved by the US Food and Drug Administration (FDA) for other indications.

The study is one of the largest to analyze real-world data mirroring a large RCT (ONTARGET [Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial]) that had already established the clinical basis for a supplemental drug application. The drugs in question were the blood pressure medications telmisartan and ramipril.

“The fact that our case study bolstered the conclusions of a trial designed to identify a supplemental indication for a marketed medication and was done relatively efficiently using available data sets, rigorous epidemiologic methods, and modern software platforms supports the concept of conducting similar database analyses as part of routine practice for manufacturers submitting applications for supplemental indications to the FDA,” Michael Fralick, MD, from Harvard Medical School, Boston, Massachusetts, and colleagues write.

The researchers reviewed all supplemental applications to the FDA and their accompanying clinical trials between 2005 and 2014 to find a drug whose study population, inclusion and exclusion criteria, and primary clinical trial outcome could be found in Marketscan, a US healthcare database of more than 60 million commercially insured people.

That search identified the angiotensin receptor blocker telmisartan, which was approved for treating high blood pressure in 1998, and gained supplemental approval in 2009 for cardiovascular risk reduction in patients aged 55 years and older who are at high risk for major cardiovascular events but cannot take angiotensin-converting enzyme inhibitors.

Then researchers used similar inclusion and exclusion criteria as ONTARGET to identify a cohort of patients in the Marketscan database. Study patients were aged 55 years and older and were newly started on telmisartan before its supplemental approval, and had a diagnosis of coronary artery disease, peripheral arterial disease, cardiovascular disease, or diabetes. Including only new starts was one technique to decrease confounding and bias in the study.

Finally, the authors used propensity score matching to further minimize confounding and bias by adjusting for 74 patient characteristics, including demographics, comorbid conditions, concurrent medications, and healthcare use.

After propensity score matching, the analysis included 4665 patients newly started on telmisartan (mean age, 69.43 years; 51.7% men) and 4665 patients newly started on ramipril (mean age, 69.36 years; 50.2% men).

Telmisartan and ramipril had similar risk for the primary outcome, a composite of myocardial infarction, stroke, or hospitalization for congestive heart failure (hazard ratio, 0.99; 95% confidence interval, 0.85 – 1.14).

Telmisartan was also linked to much lower risk for angioedema than ramipril (hazard ratio, 0.13; 95% confidence interval, 0.03 – 0.56), suggesting the analysis could find known differences in adverse effects between the two drugs.

About half of drugs approved in the United States later gain additional approval for other indications or for modifications or expanded populations. Such applications usually rely on RCTs, the gold standard for establishing that a drug causes a particular effect. However, RCTs are costly and take a long time. For certain conditions, real-world databases, from insurance claims, registries, or electronic health records, contain much of the same information as RCTs and offer the possibility to establish clinical efficacy more quickly and at reduced cost.

For example, ONTARGET, the pivotal RCT that established that telmisartan had similar efficacy as ramipril in decreasing cardiovascular risk and led to telmisartan’s supplemental approval, took about 7 years to complete and cost tens of millions of dollars. This new database study took 12 weeks and cost a hundredth of the price.

Database studies can also include patients often excluded from RCTs, such as the elderly, pregnant women, and those with many medical conditions. Database studies are sometimes larger and may detect rare adverse events not found in RCTs.

The problem is that database studies are nonrandomized; therefore, the results may not always be valid or reproducible. However, applying new statistical techniques may improve results.

In an invited commentary, Rover M. Califf, MD, from Duke University School of Medicine, Durham, North Carolina, and Verily Life Sciences (Alphabet), South San Francisco, California, and former commissioner of food and drugs, US Food and Drug Administration, writes that the study is “valuable and technically excellent,” but represents only one case.

“Thus, it is open to the criticism that generalizing from 1 positive finding to a vast field of potential treatment comparisons with observational data is analogous to painting the target around the arrow, especially considering the high probability that the telmisartan-ramipril comparison would work,” he explains.

Also, because the study could not account for death, it used a different endpoint (a composite of heart attack, stroke, or heart failure hospitalization) than ONTARGET (a composite of all cardiovascular deaths, heart failure admission, nonfatal myocardial infarction, or nonfatal stroke).

However, he acknowledges that “excessive bureaucracy” may stand in the way of performing rigorous studies for supplemental applications. That, in turn, may encourage drug makers to push off-label use. The result is a research system that fails to answer many questions important to clinical practice.

For that reason, observational studies may have a role, he writes, while emphasizing the primacy of RCTs for establishing the comparative efficacy between drugs.

“In many circumstances, however, observational analyses will supplement RCTs for new indications and provide deeper knowledge about real-world use within labeled indications,” he concludes. “Despite the need for more examples and robust efforts to guide the use of different methods for different circumstances, observational analyses have an important place in the continuum of clinical evidence.”

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, and the Laura and John Arnold Foundation. Dr Fralick was funded by the University of Toronto Clinician Scientist Training Program. One coauthor’s work is also supported by the Engelberg Foundation and the Harvard Program in Therapeutic Science. Dr Califf served as the commissioner of food and drugs, US Food and Drug Administration (FDA), from February 2016 to January 2017. Before being appointed as FDA deputy commissioner for medical products and tobacco in February 2015, he received grant funding and/or consulted for the following: the Patient-Centered Outcomes Research Institute, the National Institutes of Health, the FDA, Amylin, Eli Lilly and Company, Bristol-Myers Squibb, Janssen Research and Development, Merck, Novartis, Amgen, Bayer Healthcare, BMEB Services, Genentech, GlaxoSmithKline, Heart.org–Daiichi Sankyo, Kowa, Les Laboratoires Servier, Medscape/Heart.org, Regado, and Roche. He also holds equity in N30 Pharma and Portola. He currently receives consulting payments from Merck and is employed as a scientific adviser by Verily Life Sciences (Alphabet).

JAMA Intern Med. Published online November 20, 2017. Article full text, Commentary

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When PSA Is 4-10, phi Test Helps With Biopsy Decision

When PSA Is 4-10, phi Test Helps With Biopsy Decision


The Prostate Health Index (phi) (Beckman Coulter) significantly changes urologists’ opinions about whether men with certain results on prostate-specific antigen (PSA) screening should or should not undergo a prostate biopsy to assess for cancer, according to new observational research.

Use of the test affected the physician’s management plan in 73% of the cases in the study, report the authors, led by Jay White, MD, a urologist at Carolina Urology Partners in Huntersville, North Carolina.

The changes included biopsy deferrals when the phi test score was low and biopsy referrals when the score indicated an intermediate or high probability of prostate cancer.

In the study, the most common change in management was to avoida of a biopsy.

The study was published online November 20 in Prostate Cancer and Prostatic Diseases.

For their study, Dr White and colleagues compared 506 men who were prospectively enrolled and who received the phi test, and 683 historical control patients, who did not receive the phi test. Notably, the prospectively enrolled participants and the control patients were from the same four large urology groups (in North Carolina, Maryland, Colorado, and Texas) and were managed by the same physicians.

The men who received the phi test underwent significantly fewer biopsy procedures compared to the historical control group (36.4% vs 60.3%, respectively; P < .0001).

“Physicians were less inclined to do a biopsy on patients receiving a low phi score,” said Dr White in a press statement.

All of the men in the study were at least 50 years old and had undergone digital rectal examinations, the results of which were not suspicious. The patients’ PSA values ranged from 4 to 10 ng/mL.

Other studies have shown that men with PSA values in this range have only about a 30% to 35% chance of being found to have a cancer upon biopsy. This poor diagnostic specificity is one of the leading problems related to PSA testing.

As a result, 65% to 70% of men who undergo PSA testing and whose PSA value is in this range undergo unnecessary biopsies and are exposed to complications, including pain, infection, and costs.

In the new study, in 28.3% of cases, the physician stated that knowing the phi score helped to alleviate patient anxiety.

Test Already Available

The phi test has been available for clinical use for a few years. It was cleared by the US Food and Drug Administration in 2012 to help clinicians distinguish between prostate cancer and other prostatic conditions in men with PSA values in the 4 to 10 ng/mL range. The test combines the results of three immunoassays ― total PSA, free PSA, and p2PSA ― into a single numerical score.

The new study is only the second study in which the clinical utility of the phi test was evaluated in “real world” practice.

In the other study, which was conducted at Johns Hopkins University in Baltimore, Maryland, by academic researchers, the findings were similar (Prostate Cancer Prostatic Dis. 2017;20:228-33).

That study compared a prospective registry of 345 men who received a phi test to a contemporary cohort of 1318 men who did not have the test and who served as control patients. Notably, phi testing reduced the rate of biopsies performed without changing the frequency of higher-grade cancers detected. Overall, 39% of men in their registry underwent a biopsy when the phi test was included in the assessment; this represented a 9% reduction in the rate of prostate biopsies performed compared to the control group (48%; P < .001).

“Both studies show a reduction in rate of biopsy when phi is used,” Jeffrey Tosoian, MD, MPH, a resident at the James Buchanan Brady Urological Institute at Johns Hopkins School of Medicine, commented in an email to Medscape Medical News. Dr Tosoian is the lead author of the Johns Hopkins study.

Both studies show a reduction in rate of biopsy when phi is used.
Dr Jeffrey Tosoian

He noted that Dr White and colleagues administered a two-part questionnaire to the participating physicians, which made their study “more of a true ‘clinical utility’ study, where you assess decision making in the absence and presence of the test,” he added.

The questionnaire allowed physicians to record their recommendations before and after receiving the phi test result. Through use of this tool, 73% of all patient management plans were changed.

Thus, the study from Dr White and colleagues builds on the earlier study from Johns Hopkins by “showing specifically that the information provided by phi impacted the physician’s management plan, providing more direct evidence that phi can aid in the decision-making process,” he commented.

Dr Tosoian also said that urologists at Johns Hopkins have begun in the past 1 to 2 years to use the phi test routinely in cases in which the PSA level is 4 to 10 ng/mL. “Personally, I routinely use phi in cases where deciding whether to biopsy is not clear cut,” he commented.

There are other blood tests, including the 4KScore test (OPKO Diagnostics), that men without prostate cancer who undergo PSA testing and whose result is concerning may choose to have performed. However, the phi test is substantially less expensive. In 2014, Medscape Medical News reported that the 4KScore test cost $395, vs $80 for the phi test.

The study was supported by Beckman Coulter. Dr White has disclosed no relevant financial relationships. Several coauthors are employees of Beckman Coulter, as listed in the original article. Dr Tosoian has disclosed no relevant financial relationships.

Prostate Cancer Prostatic Dis. Published online November 20, 2017. Full text

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Question Relevant to All Oncologists Answered at ASH 2017

Question Relevant to All Oncologists Answered at ASH 2017


A big question relevant to all oncologists that will be answered at the forthcoming American Society of Hematology (ASH) 2017 Annual Meeting concerns the use of newer oral anticoagulants instead of older injectable agents for cancer patients with venous thromboembolism (VTE).

The newer oral drugs have been available for some time, but “hematologists and oncologists have been reluctant to use them in cancer patients, until we have trials done in cancer patients,” commented ASH Secretary Robert A. Brodsky, MD, professor of medicine and oncology and the director of the Division of Hematology at Johns Hopkins School of Medicine in Baltimore, Maryland.

Well, data from clinical trials conducted specifically in cancer patients are now going to be presented.

One set of results comes from the large international Hokusai VTE Cancer Study (abstract LBA-6), which investigated the use of the oral agent edoxaban (Savaysa, Daichi Sankyo Inc). Another set of results come from a smaller British study, Select D (abstract 625) which investigated the use of rivaroxaban (Xarelto, Janssen).

In both studies, the oral agents were found to be similar to dalteparin (Fragmin, Pfizer), a low-molecular-weight heparin product that is administered subcutaneously. It is considered standard of care for the extended treatment and prevention of recurrence of acute venous thrombosis (VTE) in cancer patients.

These new results are “showing that oral anticoagulants are safe to use in patients with cancer, and this is big news,” Dr Brodsky told journalists listening into a meeting preview.

The ASH meeting will take place in Atlanta, Georgia, from December 8-12 and will feature more than 4500 abstracts, of which 1000 will be presented at oral sessions. Many of the others will be presented as posters.

“It is by far the largest hematology conference on the planet,” commented Joseph Mikhael, MD, professor of medicine at Mayo Clinic in Phoenix, Arizona. Dr Mikhael is also deputy director of the Mayo Clinic Cancer Center and is chair of the ASH Committee on Communications. More than 25,000 attendees from around the world are expected.

Practice-Changing Results

Several presentations may result in treatment changes, the experts said.

One such presentations will feature the first results from the MURANO trial (abstract LBA-2), which involved patients with relapsed/refractory chronic lymphocytic leukemia. Standard treatment for this patient population is the chemo/immuno combination of bendamuustine plus rituximab, but these new results ― from the first preplanned interim analysis ― show superior outcomes with a newcomer. The oral agent venetoclax (Venclexa, AbbVie) showed a “profound improvement” in progression-free survival (PFS), the authors report. It also beat the standard of care on every other clinical outcome. This new drug “represents an advance in treatment,” commented Dr Mikhael.

Another potential practice-changing presentation concerns multiple myeloma, with results from the ALCYONE trial (abstract LBA-4). The patients in this trial, who were not eligible for a transplant, were treated with the triplet of bortezomib (Velcade, Millennium), melphalan, and prednisone (VMP), but half of the patients also received the new monoclonal antibody daratumumab (Darzalex, Janssen). The addition of this novel drug to the triplet doubled PFS. The results were driven by the fact that more patients achieved deep responses, the authors report. The four-drug regimen, as used in this trial, is a potential new standard of care, said Dr Mikhael.

More Details on CAR T-Cell Therapy

“Very promising data” will be presented for the novel products with chimeric antigen receptor (CAR) T cells, commented 2017 ASH President Kenneth C. Anderson, MD, of the Lebow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center at Dana-Farber Cancer Institute in Boston, Massachusetts.

Two of these agents have been approved in the past year ― tisagenlecleucel-T (Kymriah, Novartis), which is approved for use in pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) was approved in August 2017, and axicabtagene ciloleucel (Yescarta, Kite Pharma) was approved in October 2017 for patients with relapsed/refractory aggressive B-cell non-Hodgkin’s lymphoma (NHL) who are ineligible for autologous stem cell transplant.

The new long-term data come from two large international trials ― the ZUMA trial of axicabtagene ciloleucel in refractory/relapsed NHL (abstract 578) and the JULIET trial of tisagenlecleucel-T in patients with refractory/relapsed diffuse large B cell lymphoma (abstract 577 ). The updated results from these trials show complete responses in patients who had no other therapeutic options. “These are remarkable data…and they show that novel therapies can be used in the real world,” Dr Anderson commented.

New Targeted Agents

Two new targeted agents will make their debut at the meeting.

Mogamulizumab is a monoclonal antibody directed against chemokine receptor 4, which is overexpressed on malignant T cells. Meeting attendees will hear about the first phase 3 trial conducted specifically in patients with cutaneous T-cell lymphoma (CTCL), a rare form of NHL that causes intractable itching and leaves patients prone to infections. Results from this trial, known as MAVORIC (abstract 817), show that mogamulizumab is a valuable new therapeutic option for these patients, say the trialists.

The other new agent, BLU-285, has shown considerable clinical activity in patients with advanced systemic mastocytosis, which are a group of mast cell neoplasms that are associated with poor prognosis. This drug was designed as a highly potent and highly specific oral inhibitor of KIT activation loop mutants, including D816V, and KIT D816V is a key oncogenic driver in these cancers. Although the results come from a small phase 1 study (abstract 2), this drug showed marked clinical efficacy, and it targets a known defect, commented Dr Brodsky. “This is so exciting, as it is reminiscent of the Gleevec [imatinib] story in chronic myeloid leukemia from 20 years ago,” he said.

For patients with acquired or immune-mediated thrombotic thrombocytopenic purpura (aTTP), a new drug, caplacizumab, looks to be a “potential game changer,” said Dr Brodsky. The results with this new drug come from the placebo-controlled phase 3 Hercules study (abstract LBA-1), which show that it achieved a highly clinically meaningful reduction in aTTP-related death and recurrence of aTTP or a major thromboembolic event during study drug treatment, the authors report. They conclude that caplacizumab, which is under development by Ablynx, represents a novel treatment option for patients with aTTP.

Another abstract to look out for, he said, shows further clinical data with emicizumab (Hemlibra, Roche) in pediatric patients with hemophilia A who have developed inhibitors. This agent was recently approved in the United States on the basis of results from the HAVEN-1 trial. It has “been a game changer” for this patient population, Dr Brodsky commented. Now results from HAVEN-2 (abstract 85), which included 57 pediatric patients and is the largest such study to date, show that emicizumab prevented or substantially reduced bleeding episodes and was well tolerated.

For hemophilia B patients, there are results from early research on a gene therapy (abstract 650) that is “very exciting,” commented Dr Brodsky, because it offers “a potential cure,” he said.

Details on all these presentations at the ASH meeting will be reported by a team of medical journalists heading to Atlanta, so check back to read the news as it breaks.

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Rabu, 29 November 2017

Poll: Half of Doctors, Nurses Have Put Off Giving Bad News

Poll: Half of Doctors, Nurses Have Put Off Giving Bad News


Half of physicians (51%) and more than two in five nurses and advance practice nurses (44%) say they have delayed giving bad news to patients, according to a Medscape Medical News poll.

The poll question was one of four pitched to readers September 6 after Medscape contributor and New York University medical ethicist Art Caplan, PhD,  wrote a commentary in which he posed questions about whether physicians should get to decide the best timing for delivering bad health news and whether they should be punished if failure to disclose results in worsening of the condition.

Dr Caplan used the example of a physician who had determined a patient had incurable lung cancer. The doctor also knew the patient was going on a 2-week cruise the next week. He chose to delay telling her and the patient went on the cruise, contracted pneumonia, and died. The family was angry with the doctor and considered his actions paternalistic rather than compassionate.

Respondents to the poll of healthcare professionals and other Medscape members totaled 470; 145 were nurses/advanced practice nurses, and 222 were physicians.

Anxiety Is Top Emotion When Delivering Bad News

Anxiety was the top emotion reported by physicians and nurses in describing their experience when delivering bad health news to a patient. Among physicians, 55% reported that anxiety was the primary emotion. The percentage was even higher among nurses, at 59%.

Next were feelings of failure and frustration. Among physicians, 36% experienced feelings of failure and 32% experienced frustration. For nurses, 32% reported feeling frustration and 27% reported feelings of failure. Some even felt anger (6% of nurses and 9% of physicians.)

Delivering bad news is a common requirement for both groups, although twice as many physicians (50%) as nurses (26%) said they frequently had to deliver bad news to patients. Only 4% of physicians and 10% of nurses/nurse practitioners said they had never had to do it.

Reactions of the patient and patient’s family were drivers in how the professionals reacted, poll responses show.

The patient’s reaction is the biggest influence on the professionals’ reaction; 66% of physicians and 70% of nurses answered that way.

The next biggest influence for both groups was the family or caregiver’s reaction. It was listed by 53% for physicians and 60% of nurses.

Other factors influencing how physicians and nurses deliver bad news included access to a private space, lack of time, communication challenges between healthcare professionals, and lack of training/experience in delivering bad news.

Commenters Say Doctors Should Tell Patients Right Away

Those who posted comments on the poll leaned toward full and immediate disclosure by providers.

A commenter whose occupation was listed as health/business administration said, “Honesty between doctor and patient shouldn’t be an option. Trust is essential.  If I took deductions that could get me in hot water with the IRS I’d expect my accountant to advise me so. If I had a disease that could threaten my life I’d expect my doctor to tell me.”

A critical care/intensive care physician said physicians need more training in communicating difficult news in order to feel comfortable and pointed to a gap in medical training.

“Many effective approaches exist but they have to be more broadly incorporated into the curriculum. That would be a useful topic to include in [maintenance of certification] instead of observing colleagues wash their hands!” the commenter wrote.

Need for more education was echoed in a Baylor University Medical Center survey conducted among 54 participants in the Department of Surgery (17 women and 37 men). The survey found that almost all (93%) of respondents felt that delivering bad news is a very important skill, but only 43% felt that they had the training to effectively do so.

An advanced practice nurse who commented on the Medscape Medical News poll said, “I have found that most people want to know the results as soon as possible following diagnostic testing. Even with an initial emotional outburst they usually want to know more about any options for treatment and palliative care.”

She added, “I have never believed that withholding information from patients is within our right, especially when they have sought out our knowledge and capability to provide answers.”

Dr Caplan took the same view in the case of the patient who went on the cruise: that there should have been full disclosure.

He said while he understood the doctor’s actions, the doctor also took away the patient’s right to decide how to spend the time she had left. That might have included forgoing the cruise and spending time with family or taking the time to get her affairs in order.

“It’s the patient’s choice,” Dr Caplan said, in how to manage bad news when “there’s nothing much medicine has to offer.”

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Diabetes and Adiposity Cause 1 in 20 Cancers Worldwide

Diabetes and Adiposity Cause 1 in 20 Cancers Worldwide


Nearly 6% of cancers, equating to almost 800,000 cases globally, were attributable to type 2 diabetes and overweight/obesity in 2012, new data show, with adiposity being responsible for almost twice as many cases as diabetes.

The study represents the first to estimate the worldwide cancer burden due to diabetes alone and also to diabetes and high body mass index (BMI) combined, say Jonathan Pearson-Stuttard, BMBCh, Imperial College London, United Kingdom, and colleagues in their paper published online November 28 in Lancet Diabetes & Endocrinology.

The new figures highlight the substantial role of diabetes in cancer worldwide, particularly in lower-income countries where rates of people being overweight and diabetes and cancer cases are soaring, they say.

“While obesity has been associated with cancer for some time, the link between diabetes and cancer has only been established quite recently,” stressed Dr Pearson-Stuttard.

“Our study shows that diabetes, either on its own or combined with being overweight, is responsible for hundreds of thousands of cancer cases each year across the world,” he noted in a press release from Imperial College.

He and his coauthors say that if global rates of diabetes and overweight continue to rise, the share of cancers attributable to the combined factors will increase by over 30% in women and by 20% in men by 2035.

“The distinct features of cancer patients are evolving throughout the world,” said Dr Pearson-Stuttard. “In the past, smoking was by far the major risk factor for cancer, but now healthcare professionals should also be aware that patients who have diabetes or are overweight also have an increased risk of cancer.”

Contribution of High BMI and Diabetes to 12 Cancers

Dr Pearson-Stuttard and colleagues estimated population-attributable fractions for 12 cancers by age and sex for 175 countries in 2012.

They selected cancers that the World Cancer Research Fund [WCRF] and the International Agency for Research on Cancer (IARC) have judged to have a causal association with high BMI (defined as >25 kg/m2): colorectal, gallbladder, pancreatic, liver, postmenopausal breast, endometrial, kidney, ovarian, stomach cardia, and thyroid cancer, esophageal adenocarcinoma, and multiple myeloma.

For the diabetes analysis, they included colorectal, gallbladder, pancreatic, liver, breast, and endometrial cancer.

Using comprehensive prevalence estimates of diabetes and BMI categories in 2002 and assuming a 10-year lag between exposure to diabetes or high BMI and incidence of cancer, combined with relative risks from published estimates, they quantified the contribution of diabetes and high BMI to site-specific cancers, individually and combined as independent risk factors and in a conservative scenario in which they assumed full overlap of risk of diabetes and high BMI.

They then used GLOBOCAN cancer incidence data to estimate the number of cancer cases attributable to the two risk factors.

Specifically, 5.6% of all incident cancers (792,600 cases) were attributable to the combined effects of diabetes and high BMI; individually, high BMI was responsible for 3.9% (544,300 cases) vs 2% (280,100 cases) for diabetes.

Variation by Cancer Site, Gender, and Geographic Region

The researchers found substantial variation in the proportion of cancer due to high BMI and diabetes by gender, by cancer site, and by geographical area.

Approximately one in four liver and esophageal adenocarcinomas and 38.4% of endometrial cancers worldwide in 2012 were estimated to be attributable to diabetes and high BMI.

Cancers caused by diabetes and being overweight or obese were almost twice as common in women as men (496,700 cases vs 295,900 in men).

In men, liver cancer was the commonest cancer caused by diabetes and high BMI, accounting for 126,700 cases, or 42.8% of all cancers caused by these two factors. Colorectal cancer was the second commonest, accounting for 63,200 new cancer cases, or 21.4%.

In women, breast cancer was the commonest cancer caused by diabetes and high BMI, accounting for 147,400 cases, or 29.7% of such cancers. Endometrial cancer was the second commonest, accounting for 121,700 new cancer cases, or 24.5%.

And the largest proportion of cancer cases attributable to the increase in prevalence of diabetes and high BMI during this period was in low-income and middle-income countries in Asia and sub-Saharan Africa.

This finding is key, “because these countries are generally less well equipped to manage the burden of complex noncommunicable diseases than high-income countries,” the authors note.

Underestimation of Cancer Burden Due to High BMI and Diabetes?

In an accompanying comment, Yikyung Park, MD, and Graham A Colditz, MD, both from Washington University School of Medicine, St Louis, Missouri, wonder whether the study might have underestimated the burden of cancer because the time lag between exposure and cancer was limited to 10 years, whereas there is emerging evidence that that high BMI in late adolescence/young adulthood is directly related to risk of cancer in old age.

“A focus on adiposity in midlife or later and insufficient consideration of lifetime adiposity could lead to substantial underestimation of the contribution of high BMI to the global burden of cancers,” they note.

 “Both obesity and diabetes are preventable causes of cancer for which intervention is possible at multiple levels — in individuals, communities, healthcare systems, and policy.”

More prompt actions are needed to help people maintain a healthy body weight “throughout the life course, starting at an early age,” they conclude.

Also commenting on the new findings, American Society of Clinical Oncology (ASCO) CEO Clifford Hudis, MD, FACP, FASCO, said they “add another reason for the general public to be concerned about the health risks associated with obesity, which clearly include cancer.” 

A recent survey by ASCO found that fewer than one in three people realize obesity is a risk factor for cancer, even though it is the second leading preventable cause of the disease. 

“Armed with this increasing recognition of its medical risks, we must work together across medical disciplines to help…address this challenge,” he stressed.

Senior author Majid Ezzati reports a charitable grant from the Young Health Programme of AstraZeneca and personal fees from Third Bridge, Scor, and Prudential outside the submitted work. All other authors declare no relevant financial relationships, as do the editorialists.

Lancet Diabetes Endocrinol. Published online November 28, 2017. Article, Editorial

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