Hospital Room Lighting May Worsen Your Mood and Pain.


Story at-a-glance

  • Hospital patients are exposed to insufficient levels of light, disrupting both their circadian rhythms and sleep cycles
  • Light-deprived patients had fragmented and low levels of sleep, and those with the lowest exposures to light during the day reported more depressed mood and fatigue
  • Inadequate bright-light exposure has a far-reaching impact on your most critical bodily functions, including your ability to heal
  • Exposure to night-time light may also hinder the production of the hormone melatonin, which is very important for immune health
  • If you or a loved one is confined to a hospital room, move to areas with brighter natural light as much as possible, or bring in some full-spectrum light bulbs, and wear an eye mask at night to block night-time artificial light exposures

Hopefully you have never spent much time in a hospital, but if you have you likely experienced frequent disruptions to your sleep.

Aside from the beeping machines and nightly checks from hospital staff, your room was probably dimly lit with artificial light both day and night — a major impediment to proper sleep and well-being.

As a new study in the Journal of Advanced Nursing1 revealed, the lighting in many hospital rooms may be so bad that it actually worsens patients’ sleep, mood and pain levels.

Hospital-Room Lighting May Lead to Disrupted Sleep Cycles, Increased Pain and Fatigue

The study found that, on average, hospital patients in the study were exposed to about 105 lux (a measure of light emission) daily. This is a very low level of light; for comparison, an office would generally provide about 500 lux and being outdoors on a sunny day could provide 100,000 lux.2

The rooms were so dimly lit that many hospital patients had trouble sleeping. Your body requires a minimum of 1,500 lux for 15 minutes a day just to maintain a normal sleep-wake cycle, but ideally it should be closer to 4,000 for healthful sleep.3

Not surprisingly, the researchers found that the patients’ sleep time was “fragmented and low,” with most averaging just four hours of sleep a night.

Those with the lowest exposures to light during the day also reported more depressed mood and fatigue than those exposed to more light. The researchers noted:4 “Low light exposure significantly predicted fatigue and total mood disturbance.”

Why You Need Exposure to Bright Light During the Day

When full-spectrum light enters your eyes, it not only goes to your visual centers enabling you to see, it also goes to your brain’s hypothalamus where it affects your entire body.

Your hypothalamus controls body temperature, hunger and thirst, water balance and blood pressure. Additionally, it controls your body’s master gland, the pituitary, which secretes many essential hormones, including those that influence your mood.

Exposure to full-spectrum lighting is actually one effective therapy used for treating depression, infection, and much more – so it’s not surprising that hospital patients deprived of such exposures had poorer moods and fatigue.

Studies have also shown that poor lighting in the workplace triggers headaches, stress, fatigue and strained watery eyes, not to mention inferior work production.

Conversely, companies that have switched to full-spectrum lights report improved employee morale, greater productivity, reduced errors and decreased absenteeism. Some experts even believe that “malillumination” is to light what malnutrition is to food.

In a hospital setting, this has serious ramifications, as patients are already under profound stress due to illness and may be further stressed by a lack of natural bright light.

Your ‘body clock’ is also housed in tiny centers located in your hypothalamus, controlling your body’s circadian rhythm. This light-sensitive rhythm is dependent on Mother Nature, with its natural cycles of light and darkness, to function optimally.

Consequently, anything that disrupts these rhythms, like inadequate sunlight exposure to your body (including your eyes), has a far-reaching impact on your body’s ability to function and, certainly, also on its ability to heal.

Nighttime Light Exposure is Also Detrimental

While the featured study didn’t focus specifically on hospital patients’ nighttime light exposures, they’re likely to be significant. Most hospital room doors remain ajar all night, allowing artificial light from the hall to flood the room. There are also lights on medical equipment and monitors, and if your room is not private you may also be exposed to light from a roommates’ television or bathroom trips.

This is important because just as your body requires bright-light exposure during the day, it requires pitch-blackness at night to function optimally – which is all the more critical in the case of a hospital stay when bodily self-healing is most needed.

When you turn on a light at night, you immediately send your brain misinformation about the light-dark cycle. The only thing your brain interprets light to be is day. Believing daytime has arrived, your biological clock instructs your pineal gland to immediately cease its production of the hormone melatonin – a significant blow to your health, especially if you’re ill, as melatonin produces a number of health benefits in terms of your immune system. It’s a powerful antioxidant and free radical scavenger that helps combat inflammation.

In fact, melatonin is so integral to your immune system that a lack of it causes your thymus gland, a critically important part of your immune system, to atrophy.5 In addition, melatonin helps you fall asleep and bestows a feeling of overall comfort and well being, and it has proven to have an impressive array of anti-cancer benefits.6 So unnaturally suppressing this essential hormone is the last thing that a recovering hospital patient needs.

If a Loved One is In the Hospital, Let the Daylight Shine In

The best way to get exposure to healthy full-spectrum light is to do it the way nature intended, by going out in the sun with your bare skin – and ‘bare’ eyes — exposed on a regular basis. If you or a loved one is confined to a hospital room, however, the next best option is to move to areas with brighter natural light as much as possible, or alternatively bring in some full-spectrum light bulbs.

At night, the opposite holds true. You should turn off lights as much as possible, keep the door closed and close the blinds on the window. Wearing an eye mask is another simple trick that can help to keep unwanted light exposures to a minimum if you’re spending the night in a hospital. Taken together, these are simple ways to boost mood and improve sleep and fatigue levels among hospitalized patients.

The Other Major Risk of Spending Time in a Hospital

No matter how important it is, poor lighting may be the least of your worries if you find yourself hospitalized, as once you’re hospitalized you’re immediately at risk for medical errors, which is actually a leading cause of death in the US. According to the most recent research7 into the cost of medical mistakes in terms of lives lost, 210,000 Americans are killed by preventable hospital errors each year.

When deaths related to diagnostic errors, errors of omission, and failure to follow guidelines are included, the number skyrockets to an estimated 440,000 preventable hospital deaths each year!

One of the best safeguards is to have someone there with you. Dr. Andrew Saul has written an entire book on the issue of safeguarding your health while hospitalized. Frequently, you’re going to be relatively debilitated, especially post-op when you’re under the influence of anesthesia, and you won’t have the opportunity to see clearly the types of processes that are going on.

For every medication given in the hospital, ask, “What is this medication? What is it for? What’s the dose?” Take notes. Ask questions. Building a relationship with the nurses can go a long way. Also, when they realize they’re going to be questioned, they’re more likely to go through that extra step of due diligence to make sure they’re getting it right—that’s human nature. Of course, knowing how to prevent disease so you can avoid hospitals in the first place is clearly your best bet. One of the best strategies on that end is to optimize your diet. You can get up to speed on that by reviewing my comprehensive Nutrition Plan.

It’s Important for Virtually Everyone to Optimize Light Exposure: 5 Top Tips

Getting back to the issue of lighting, this isn’t only an issue for hospital patients. Virtually everyone requires exposure to bright light during the day and darkness at night for optimal health. Toward that end, here are my top tips to optimize your light exposure on a daily (and nightly) basis:

1.    Get some sun in the morning, if possible. Your circadian system needs bright light to reset itself. Ten to 15 minutes of morning sunlight will send a strong message to your internal clock that day has arrived, making it less likely to be confused by weaker light signals during the night. More sunlight exposure is required as you age.

2.    Make sure you get BRIGHT sun exposure regularly. Remember, your pineal gland produces melatonin roughly in approximation to the contrast of bright sun exposure in the day and complete darkness at night. If you work indoors, make a point to get outdoors during your breaks.

3.    Avoid watching TV or using your computer in the evening, at least an hour or so before going to bed.These devices emit blue light, which tricks your brain into thinking it’s still daytime. Normally your brain starts secreting melatonin between 9 and 10 pm, and these devices emit light that may stifle that process.

4.    Sleep in complete darkness, or as close to it as possible. Even the slightest bit of light in your bedroom can disrupt your biological clock and your pineal gland’s melatonin production. This means that even the tiny glow from your clock radio could be interfering with your sleep, so cover your alarm clock up at night or get rid of it altogether. You may want to cover your windows with drapes or blackout shades, or wear an eye mask while you sleep.

5.    Install a low-wattage yellow, orange or red light bulb if you need a source of light for navigation at night.Light in these bandwidths does not shut down melatonin production in the way that white and blue bandwidth light does. Salt lamps are handy for this purpose.

 

 

 

 

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Candy Crush Saga: The Science Behind Our Addiction.


A year after the game’s mobile launch, we still can’t stop playing. The app’s designer and psychology experts weigh in on exactly what makes it so irresistible

If you haven’t heard of Candy Crush, it’s the mobile game that’s so addictive, players say they have left their children stranded at school, abandoned housework and even injured themselves as they try to reach new levels of the game.

Candy Crush

Candy Crush has been played 151 billion times since it launched as an app on mobile devices exactly year ago. And it’s the first game to ever be No. 1 on iOS, Android and Facebook at the same time. Candy Crush’s creator, King, a Stockholm-based company, says 1 in every 23 Facebook users plays it. And while Candy Crush is free, the in-game purchases that some players choose to make add up. Think Gaming, which releases gaming analytics, estimates that it takes in $875,382 per day. (By comparison, another insanely popular mobile game, Angry Birds, takes in an estimated $6,381 daily.)

All that adds up to some seriously distracted users. A survey by Ask Your Target Market polled 1,000 players and found that 32% of them ignored friends or family to play the game, 28% played during work, 10% got into arguments with significant others over how long they played, and 30% said they were “addicted.”

But there are lots of amusing games out there, so what’s so addictive about this one?

We asked Tommy Palm, one of the game’s designers, what the King team did to get us hooked. We also called a few psychology experts and players to understand the backstory on why their tactics worked so well. Here are the nine reasons they say Candy Crush is so irresistible:

1. It Makes You Wait

Perhaps the most genius element of Candy Crush is its ability to make you long for it. You get five chances (lives) to line up the requisite number of candy icons. Once you run out of lives, you have to wait in 30-minute increments to continue play. Or, if you’re impatient, you can pay to get back in the game — which is why it’s bringing in so much revenue. “You can’t just play all the time. You run out of lives,” says Andy Jarc, 22, one of the few players to reach level 440 in the game. “So the fact that they kind of constrain you — the whole mantra, ‘You always want what you can’t have.’ I can’t have more lives and I want them.”

“I think it makes the game more fun long term,” says designer Palm. “If you have a game that consumes a lot of mental bandwidth, you will continue playing it without noticing that you’re hungry or need to go to the bathroom. But then you binge and eventually you stop playing. It’s much better from an entertainment point of view to create a more balanced experience where you have natural breaks.”

2. We’re All Suckers for Sweet Talk

You flick four candies in a row, and they zap away. Candies above begin to cascade down, making even more matches. At the end words pop up on your screen, accompanied by a voice that says “Sweet” or “Delicious.” This feedback is essential for player immersion. “Positive rewards are the main reason people become addicted to things,” says Dr. Kimberly Young, a pioneering expert on Internet and gaming addiction who treats those addicted to the cyberworld. “When you play the game, you feel better about yourself.”

3. You Can Play With One Hand 

According to Palm, the icons and setup were created so players could multitask. You can play Candy Crush while carrying a drink, toting a purse or bag, clinging to a subway pole, or hiding your phone under the table. That’s a huge advantage and makes this game perfect for a train ride, a distraction while you’re waiting to see a doctor, or something to get you through boring meetings. Plus, you can play offline as well — so even if you’re stuck in a tunnel, you can be “crushing.”

4. There’s Always More

According to Palm, the Candy Crush team updates the game constantly and creates new levels every two weeks. Right now there are 544 levels. “Just three years ago, a game with 30 levels would be astonishing,” King says. “And now with this game, it has raised the bar with how much content a mobile game should and will have.”

Plus, on any single level, there’s no way to fail. If you run out of options on a board — and that happens once in a blue moon — the board immediately resets. You never get stuck. You can’t lose. “I believe this is part of the reinforcing pattern which keeps you playing,” says Dr. Dinah Miller, a psychiatrist who has written about the addicting elements of another popular game, Angry Birds. The game only ends when you’ve run out of your allotted number of moves “and you can end that frustration by buying your way out.”

5. You Don’t Have to Pay – but if You Want to, It’s Easy

King reports that of all the players on its last level — 544 — more than 60% of them didn’t pay a cent to buy extra lives or chances to get there. But if you want to pay, it’s easy. Connected to Facebook or the app store? Just click to pay.

6. It Taps Into Our Inner Child

“Many people have had a very positive feeling about candy since they were kids,” says Palm. “And it makes for a really nice visual game board with a lot of color and interesting shapes.” In fact, when you play you feel as if you’re transported into an entire Candy Land experience. The game pieces are candy, and the homepage for the game looks like the traditional Candy Land board, with your Facebook friends’ pictures displayed as pieces on that board, sitting at whatever level they’re stuck on.

7. It’s Social

Social games — any game that allows you to connect with your friends through a social-media platform like Facebook — have taken off. Whether it’s Words With Friends, Kingdoms of Camelot or Candy Crush, the ability to play with, or compete against, friends is irresistible. “Look, nobody’s coming to me because they have a clinical addiction to Candy Crush,” says Young. “It’s more of a social addiction, if you will.”

8. It’s an Escape

“When you read the research about gaming,” Young says, “you’re often looking at people who are distracting themselves from something in their lives.” The relaxing exercise of lining up candies to the tune of upbeat music is a perfect stress reliever.

9.  It Grows on You

This isn’t your average “line up three” game. “I started playing, and at first I was like whatever, it’s just bejeweled,” says Jarc. “But as I played more and more, it became addicting.”

King’s high-level of attentiveness toward updating gameplay has made it better quality than most casual games that are out there. When players took to Facebook to express their frustration with level 65 — notoriously one of the hardest levels in the game — King went into the game and altered the level to make it easier (though not too easy) multiple times.

 

 

Playing Pop and Rock Music Boosts Performance of Solar Cells.


Playing pop and rock music improves the performance of solar cells, according to new research from scientists at Queen Mary University of London and Imperial College London.

The high frequencies and pitch found in pop and rock music cause vibrations that enhanced energy generation in solar cells containing a cluster of ‘nanorods’, leading to a 40 per cent increase in efficiency of the solar cells.

The study has implications for improving energy generation from sunlight, particularly for the development of new, lower cost, printed solar cells.

The researchers grew billions of tiny rods (nanorods) made from zinc oxide, then covered them with an active polymer to form a device that converts sunlight into electricity.

Using the special properties of the zinc oxide material, the team was able to show that sound levels as low as 75 decibels (equivalent to a typical roadside noise or a printer in an office) could significantly improve the solar cell performance.

“After investigating systems for converting vibrations into electricity this is a really exciting development that shows a similar set of physical properties can also enhance the performance of a photovoltaic,” said Dr Steve Dunn, Reader in Nanoscale Materials from Queen Mary’s School of Engineering and Materials Science and co-author of the paper.

Scientists had previously shown that applying pressure or strain to zinc oxide materials could result in voltage outputs, known as the piezoelectric effect. However, the effect of these piezoelectric voltages on solar cell efficiency had not received significant attention before.

“We thought the soundwaves, which produce random fluctuations, would cancel each other out and so didn’t expect to see any significant overall effect on the power output,” said James Durrant, Professor of Photochemistry at Imperial College London, who co-led the study.

“We tried playing music instead of dull flat sounds, as this helped us explore the effect of different pitches. The biggest difference we found was when we played pop music rather than classical, which we now realise is because our acoustic solar cells respond best to the higher pitched sounds present in pop music,” he concluded.

The discovery could be used to power devices that are exposed to acoustic vibrations, such as air conditioning units or within cars and other vehicles.

Co-author Dr Joe Briscoe also from Queen Mary’s School of Engineering and Materials Science, commented: “The whole device extremely simple and inexpensive to produce as the zinc oxide was grown using a simple, chemical solution technique and the polymer was also deposited from a solution.”

Dr Dunn added: “The work highlights the benefits of collaboration to develop new and interesting systems and scientific understanding.”

Major Bleed Risk Falls with Bivalirudin vs Heparin en Route to PCI for STEMI: EUROMAX.


The 30-day risk of death or major bleeding fell significantly in ST-elevation MI (STEMI) patients treated with bivalirudin (Angiomax, the Medicines Company) compared with heparin-based management, both initiated prior to arrival at a hospital for primary PCI, in a large randomized but open-label study[1].

The bivalirudin benefit for that composite end point in the European Ambulance Acute Coronary Syndrome Angiography(EUROMAX) trial was driven by a significant drop in major bleeding, the definition of which excluded bleeding related to CABG surgery.

The heparin-based strategy consisted of either unfractionated heparin (UFH) or the low-molecular-weight heparin enoxaparin(Lovenox, Sanofi). Both groups could receive a GP IIb/IIIa inhibitor provisionally.

EUROMAX was published today in the New England Journal of Medicine with lead author Dr Philippe Gabriel Steg (Hôpital Bichat, Paris, France) to coincide with his presentation of the trial here at TCT 2013 .

http://img.medscape.com/news/2013/ih_131030_Steg_Philippe_Gabriel_TCT2013_120x156.jpg

Dr Philippe Gabriel Steg

Bivalirudin’s 40% primary-end-point relative risk reduction included a >50% drop in risk for non-CABG major bleeding. On the other hand, the relative risk of stent thrombosis with bivalirudin was nearly threefold what was seen in the heparin group, although absolute rates were very low.

At a media briefing on the trial, Steg said the excess stent thromboses with bivalirudin were driven by events in the acute phase, within 24 hours of PCI. And, he observed, they didn’t translate into more reinfarctions or ischemia-driven revascularization.

Still, “acute stent thrombosis . . . while rarely fatal and not outweighing the advantages of bivalirudin, is the only troubling issue with bivalirudin in STEMI, and we do need strategies to reduce this complication,” according to Dr Gregg W Stone (New York-Presbyterian Hospital/Columbia University Medical Center New York, NY), the assigned discussant following Steg’s formal presentation of EUROMAX.

Shades of HORIZONS AMI

The trial’s findings are reminiscent of the HORIZONS AMI trial 30-day outcomes reported about six years ago and covered then by heartwire . That trial, Steg et al observe, preceded some important changes in STEMI management and PCI technique that likely affected bleeding risk, changes that were a part of EUROMAX. These included the expansion of radial-artery PCI access, newer antiplatelet agents, reduced GP-IIb/IIIa-inhibitor use, and progressively earlier initiation of IV anticoagulants.

In the >3600-patient HORIZONS AMI, anticoagulation wasn’t started early during transport. But both it and EUROMAX with its nearly 2200 patients saw a decreased bleeding risk and increased stent-thrombosis risk with bivalirudin compared with heparin. But in contrast to EUROMAX, the earlier trial also showed a reduced risk of cardiac death in bivalirudin patients.

The two studies taken together have more to say than either alone. “I think the results of EUROMAX will heavily impact clinical use of bivalirudin in Europe,” Steg said to heartwire . “The results are very consistent wih HORIZONS AMI, even to the point of the stent-thrombosis signal” and are “reassuring enough to embrace [bivalirudin] in the prehospital setting.” That is, he added, “If you want to. [The EUROMAX results] are not mind-blowing because we don’t see a mortality reduction. But they suggest that the benefits seen in HORIZONS AMI can be extended to the contemporary prehospital setting. “

At the media briefing, Dr Bernard Gersh (Mayo Clinic, Rochester, MN), who wasn’t involved in the trial, said, “It’s not that often that you see trials that really will change clinical practice, and I think this will.”

The Role of Prehospital Diagnosis and Treatment

Gersh also said, “I’ve never seen really anything that suggests that prehospital administration [of anticoagulants] and [STEMI] diagnosis is not beneficial.”

But whether they are achievable in the field varies by country, even within Europe. Interviewed, Steg pointed out that at most participating centers, there were no physicians in the ambulances. It does take some expertise to interpret the ECGs, unless the tracings can be transmitted to a center for remote reading. But, he said, “It’s been shown in other trials if you have good trained paramedics, they do just as well if not better than physicians.”

Also speaking at the briefing as a EUROMAX observer, Dr Philippe Généreux (NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, NY) said prehospital STEMI diagnosis and treatment initiation could make the most difference in countries like Canada, “where there aren’t cath labs on every corner” and it might take 45 to 60 minutes for an ambulance to reach a PCI center.

Prospects for prehospital management in the US seem more remote, observers agreed. Dr James B Hermiller, Jr (St Vincent Hospital/The Heart Center of Indiana, Indianapolis,) said at the briefing, “The barrier to this in the US is very great. It’s difficult just to  get ECGs in the field, let alone administer anticoagulants, but we need to get there because this is very important.”

The Open-Label Randomization

EUROMAX randomized patients at centers in nine European countries presenting within 12 hours of onset of symptoms from electrocardiographically defined STEMI, on an open-label basis, to the bivalirudin or heparin strategies. Treatment was initiated in the ambulance or at a non-PCI hospital with subsequent transport to a PCI center.

For the 1089 patients who received bivalirudin, the drug was started as a 0.75-mg/kg bolus followed by an infusion of 1.75 mg/kg/h continued for at least four hours after PCI. The 1109 control patients received UFH at either 100 IU/g or 60 IU/kg with a GP IIb/IIIa inhibitor or were allowed to have enoxaparin at 0.5 mg/kg. Adjuvant GP IIb/IIIa inhibitors were allowed at physicians’ discretion. All patients received aspirin plus a P2Y12 inhibitor.

Relative Risk (95% CI) for Outcomes, Bivalirudin vs Heparin Strategies for STEMI Initiated During Emergency Transport to Primary PCI

End points

RR (95% CI)

p

30-day death from any cause or non-CABG major bleedinga

0.60 (0.43–0.82)

0.001

30-day death from any cause, reinfarction, or non-CABG major bleeding

0.72 (0.54–0.96)

0.02

Non-CABG major bleeding

0.43 (0.28–0.66)

<0.001

Major bleeding (TIMI definition)

0.62 (0.32–1.20)

0.15

Severe or life-threatening bleeding (GUSTO definition)

0.61 (0.22–1.68)

0.33

Definite stent thrombosisb

2.89 (1.14–7.29)

0.02

a. Primary end point 
b. Academic Research Consortium criteria

No significant differences were seen at 30 days for the composite of death, reinfarction, ischemia-driven revascularization, or stroke, or for any stroke or ischemic stroke. A committee blinded to treatment assignment adjudicated bleeding episodes and clinical events.

As discussant, Stone pointed out that PCI via the radial artery, rather than the femoral artery, was done in only 6% of cases in HORIZONS AMI but in 47% of EUROMAX patients. Some predicted that the greater proportion of radial procedures would lead to a much lower major bleeding rate and make it hard for bivalirudin to show an effect. A EUROMAX subgroup analysis found, however, that the benefits of bivalirudin over the heparin-based strategy were consistent for different kinds of patients, including whether their PCI was by the radial or femoral routes.

“Therefore, bivalirudin is beneficial regardless of the access site, and this is because most bleeding in the STEMI and ACS setting is not access-site related,” he said. It’s the non–access-site bleeds to pose the greater threat to later outcomes. So, he said, “the advantages of bivalirudin are present in patients undergoing radial as well as femoral intervention, and radialists should pay attention to this.”

Stone said EUROMAX raises the question of whether using cangrelor (the Medicines Company) as part of the accompanying antiplatelet therapy might help prevent stent thrombosis with bivalirudin, and that’s being addressed in HORIZONS-AMI-2, which is starting soon.

Too Much Information? Geneticist Mark Robson Discusses Accidental Genetic Findings.


Genetic testing of tumors is becoming increasingly common in cancer care. The molecular alterations found in a tumor can provide critical information for making an accurate diagnosis and determining the best treatment.

Although current clinical testing usually focuses on a panel of specific mutations, cancer centers are developing programs to analyze entire cancer genomes routinely — an approach made possible by cheaper sequencing costs — in order to individualize care. This process raises a thorny issue: What happens when a genome analysis of a person’s tumor reveals that he or she is at risk for developing a different type of cancer or other disease?

Recently, Memorial Sloan-Kettering Clinical Genetics Service Chief Kenneth Offit, Clinical Genetics Service Clinic Director Mark E. Robson, and researcher Yvonne Bombardpublished a viewpoint in the Journal of the American Medical Association regarding this question of incidental genetic findings, which cancer researchers have dubbed the “incidentalome.”

We asked Dr. Robson to discuss some of the issues surrounding accidental genetic findings and what Memorial Sloan-Kettering is doing to address them.

What is an example of a genetic variation that might be discovered by accident while sequencing the genome of a patient’s tumor?

For instance, you could be sequencing a lung cancer tumor in search of an EGFR mutation to target with an anticancer drug, and find a mutation in BRCA1, which is associated with increased risk for breast and ovarian cancer. Since most of a tumor’s DNA sequence is identical to the sequence of a normal cell from that same patient, this additional variation is probably inherited — and is what is called a germline mutation.

In that situation, are you obligated to inform the patient? It’s a very complex question. There are many variables to consider, such as individual preference, whether anything can be done to control risk, and whether other people — such as close relatives — may be affected.

Has this actually become a problem for doctors and researchers, or is it still a hypothetical situation for now?

Right now, most clinical testing of tumors is for a relatively limited number of specific mutations, not the full genome. But soon we’re going to be testing for a much broader panel of genes, increasing the chances of incidental findings.

On the research side, it’s quickly becoming an issue. Many tumor samples that have been stored in tissue banks for years or decades are now being fully sequenced. If incidental discoveries are made during that process, is there an obligation to try to find those patients and inform them? This has not been established, and there are obvious practical barriers. We need to lay the intellectual groundwork now for how we’re going to respond to these questions.

What steps have been taken at Memorial Sloan-Kettering to address the issue?

This summer, our Institutional Review Board (IRB), which oversees all of our patient-related research, updated part of our patient consent policy. When patients agree to have a tissue sample taken, they are asked whether they are open to being re-contacted if an investigator finds something that might affect their health.

Under the new procedure, if a researcher finds something that might be important to communicate to the patient, the specific question will be put before the IRB and carefully considered. If there is agreement the information should be conveyed, and the patient has indicated that he or she wants to be re-contacted, we’ll reach out to that person. We think this protects the people participating in our studies without restricting important research.

With all the genetic research taking place at Memorial Sloan-Kettering, is the IRB facing a deluge of these cases?

So far, no. The way the analyses are being conducted is that the computer looks for mutations in specific spots and subtracts all other information about the inherited genetic sequence before the investigator sees it. In other words, if you have genetic variants present in the tumor that are also in the normal cells, they are being filtered out by the software. The investigator ends up seeing variants that are only in the tumor.

As we pointed out in the JAMA paper, this is one way of limiting potential incidentalome issues.

But some researchers don’t have the germline DNA sequence available for comparison purposes, so while sequencing the tumor they see potentially relevant variations. For example, they could be sequencing a prostate cancer genome and see a mutation in theBRCA1 gene, which increases risk of other cancers.

The question becomes, under what circumstances do you tell the patient, and what about the patient’s siblings or children who may carry the mutation as well? In addition, sometimes multiple variants associated with disease risk may be found — and how do we provide counseling for all of them at once?

Have you gotten a sense from patients about what their preference usually is regarding being informed of these incidental genetic discoveries?

Commonly, people say, “I want to know everything,” but the devil’s in the details when you start considering the risk for diseases that can’t be prevented or treated. We are setting up focus groups of patients and unaffected people to try to understand how people think when they are confronted with these situations and how they prioritize different types of genetic information. We also have an active IRB protocol in which we are giving people who had their sequence determined as part of research studies the opportunity to learn their results.

Right now, it’s not clear what the dividing lines are. We want to reach a point where mutations are sorted into different categories, where certain incidental findings are nearly always appropriate to communicate to patients, others almost never so, and some require more context to determine.

We’re moving from the traditional model of asking patients if they would like to hear the results of a specific test before that test is performed, to this brave new world where we’re trying to help people make decisions about genetic information revealed by accident that is not possible to fully anticipate. It’s a very complicated issue, but it also offers a tremendous opportunity to benefit patients.

If you are interested in participating in the focus group, call 646-888-4867. Everyone is welcome, including patients, relatives, Memorial Sloan-Kettering employees, and the general public. No sequencing is provided.

Source: MSKCC

 

 

 

Rituximab outperformed steroids in Graves’ ophthalmopathy.


Despite data presented earlier at the American Thyroid Association Annual Meeting showing that rituximab was not effective in treating Graves’ ophthalmopathy, another presenter here said that the drug does improve disease state when compared with methylprednisolone.

“Response to rituximab was as high as 93%, compared to 69% observed after IV steroid,”Mario Salvi, MD, from the University of Milan in Italy, said. “Preliminary evidence of NOSPECS class 2 signs shows improvement after rituximab.”

Similar to the study presented earlier at the meeting, Salvi said the primary endpoint was a change of two or more points in the clinical activity score (CAS) at 24 weeks. Secondary endpoint was a reduction of disease severity by at least two NOSPECS classes.

Inclusion criteria included euthyroid for at least 6 to 8 weeks and affected by active Graves’ ophthalmopathy. Any previous steroid treatments had to be stopped at least 3 months before study inclusion.

Patients were randomly assigned to IV methylprednisolone (n=16; mean age, 50.4 years) or rituximab (Rituxan, Genentech; n=16; mean age, 51.9 years). In both groups, six patients had received previous steroid treatment. Originally, Salvi said, patients in the rituximab group were receiving 1,000 mg in two doses, but after two adverse reactions, they lowered the dosage to 500 mg. There was no difference between these two treatment dosages at 24 weeks.

At 12 weeks, the difference between the two groups was not significant, but at 24 weeks, 93% of patients in the rituximab group improved, as compared with 69% of the steroid group (P<.02).

“Rituximab was more effective than IV methyprednisolone in inactivating Graves’ orbitopathy, as assessed at 24 weeks,” Salvi said. “Graves’ orbitopathy remained invariably inactive after rituximab during follow-up.”

The researchers are confident in the response seen from methylprednisolone as it is as high as seen in recently published studies, Salvi said.

These results were preliminary and final analysis is expected shortly, he added.

PERSPECTIVE

 

Kenneth D. Burman

·         Both of the studies and each of the investigators did an excellent job in performing their studies. These studies are complex as it is difficult to recruit patients and to monitor them closely.

My initial impression is that the studies were designed differently. The Mayo Clinic study had rituximab as the active agent vs. placebo as the control, whereas the Italian study had rituximab as the active agent vs. intravenous steroids as an active control.

The doses of rituximab were also different. Salvi reduced the dose of rituximab mid-study and the lower dose was 500 mg/day vs. a total of 2,000 mg/day earlier in the study; the Mayo Clinic study used 2,000 mg. Salvi, et al suggested the lower dose was equally efficacious, but this needs to be explored further.

The major controversy relates to the patient population studied and whether the patients had received previous therapy, how recently this therapy had been given, the extent of therapy and the duration of disease. Stan, et al noted that about two-thirds of their patients did not receive treatment prior to the rituximab treatment, while Salvi, et al noted that six patients in each arm of their study had steroid treatment, but not within 3 months of the study.

Salvi, et al did indicate that their patients had progressive disease, which can defined by various scales. The CAS score, which was the sole measure in Salvi’s study, takes into account a multitude of factors. Stan, et al asserted that 24 of his 25 patients were classified as progressive as well. If the disease is progressive and treated early, the effect of immunomudulatory treatment is expected to be more efficacious. It is difficult to know with certainty if both studies analyzed patients at similar time points in the progression of ophthalmopathy.

Rituximab is not approved by the FDA for the treatment of Graves’ ophthalmopathy, The question now arises whether rituximab is effective in the treatment of progressive Graves’ ophthalmopathy given the apparent different results in these two clinical trials. Perhaps, the most appropriate advice is to refer these patients to large, tertiary medical centers that have extensive experience in treating patients with progressive Graves’ ophthalmopathy. Given that most physicians treating Graves’ ophthalmopathy are not experienced with using rituximab, and also give these conflicting results, it seems most prudent to not advise individual physicians to consider using rituximab therapy in this context outside of a tertiary medical center or a clinical trial.

o    Kenneth D. Burman, MD

o    Chief of the Endocrine Section at Washington Hospital Center 
Professor of Medicine 
Georgetown University

 Soure: Endocrine Today

Scientists Officially Link Processed Foods To Autoimmune Disease.


The modern diet of processed foods, takeaways and microwave meals could be to blame for a sharp increase in autoimmune diseases such as multiple sclerosis, including alopecia, asthma and eczema.

A team of scientists from Yale University in the U.S and the University of Erlangen-Nuremberg, in Germany, say junk food diets could be partly to blame.

‘This study is the first to indicate that excess refined and processed salt may be one of the environmental factors driving the increased incidence of autoimmune diseases,’ they said.

Junk foods at fast food restaurants as well as processed foods at grocery retailers represent the largest sources of sodium intake from refined salts.

The Canadian Medical Association Journal sent out an international team of researchers to compare the salt content of 2,124 items from fast food establishments such as Burger King, Domino’s Pizza, Kentucky Fried Chicken, McDonald’s, Pizza Hut and Subway. They found that the average salt content varied between companies and between the same products sold in different countries.

U.S. fast foods are often more than twice as salt-laden as those of other countries. While government-led public health campaigns and legislation efforts have reduced refined salt levels in many countries, the U.S. government has been reluctant to press the issue. That’s left fast-food companies free to go salt crazy, says Norm Campbell, M.D., one of the study authors and a blood-pressure specialist at the University of Calgary.

Many low-fat foods rely on salt–and lots of it–for their flavor. One packet of KFC’s Marzetti Light Italian Dressing might only have 15 calories and 0.5 grams fat, but it also has 510 mg sodium–about 1.5 times as much as one Original Recipe chicken drumstick. (Feel like you’re having too much of a good thing? You probably are.

Bread is the No. 1 source of refined salt consumption in the American diet, according to the Centers for Disease Control and Prevention. Just one 6-inch Roasted Garlic loaf from Subway–just the bread, no meat, no cheeses, no nothing–has 1,260 mg sodium, about as much as 14 strips of bacon.

How Refined Salt Causes Autoimmune Disease

The team from Yale University studied the role of T helper cells in the body. These activate and ‘help’ other cells to fight dangerous pathogens such as bacteria or viruses and battle infections.

Previous research suggests that a subset of these cells – known as Th17 cells – also play an important role in the development of autoimmune diseases.

In the latest study, scientists discovered that exposing these cells in a lab to a table salt solution made them act more ‘aggressively.’

They found that mice fed a diet high in refined salts saw a dramatic increase in the number of Th17 cells in their nervous systems that promoted inflammation.

They were also more likely to develop a severe form of a disease associated with multiple sclerosis in humans.

The scientists then conducted a closer examination of these effects at a molecular level.

Laboratory tests revealed that salt exposure increased the levels of cytokines released by Th17 cells 10 times more than usual. Cytokines are proteins used to pass messages between cells.

Study co-author Ralf Linker, from the University of Erlangen-Nuremberg, said: ‘These findings are an important contribution to the understanding of multiple sclerosis and may offer new targets for a better treatment of the disease, for which at present there is no cure.’

It develops when the immune system mistakes the myelin that surrounds the nerve fibres in the brain and spinal cord for a foreign body.

It strips the myelin off the nerves fibres, which disrupts messages passed between the brain and body causing problems with speech, vision and balance.

Another of the study’s authors, Professor David Hafler, from Yale University, said that nature had clearly not intended for the immune system to attack its host body, so he expected that an external factor was playing a part.

He said: ‘These are not diseases of bad genes alone or diseases caused by the environment, but diseases of a bad interaction between genes and the environment.

‘Humans were genetically selected for conditions in sub-Saharan Africa, where there was no salt. It’s one of the reasons that having a particular gene may make African Americans much more sensitive to salt.
‘Today, Western diets all have high salt content and that has led to increase in hypertension and perhaps autoimmune disease as well.’

The team next plan to study the role that Th17 cells play in autoimmune conditions that affect the skin.
‘It would be interesting to find out if patients with psoriasis can alleviate their symptoms by reducing their salt intake,’ they said.

‘However, the development of autoimmune diseases is a very complex process which depends on many genetic and environmental factors.’

Stick to Good Salts

Refined, processed and bleached salts are the problem. Salt is critical to our health and is the most readily available nonmetallic mineral in the world. Our bodies are not designed to processed refined sodium chloride since it has no nutritional value. However, when a salt is filled with dozens of minerals such as in rose-coloured crystals of Himalayan rock salt or the grey texture of Celtic salt, our bodies benefit tremendously for their incorporation into our diet.

“These mineral salts are identical to the elements of which our bodies have been built and were originally found in the primal ocean from where life originated,” argues Dr Barbara Hendel, researcher and co-author of Water & Salt, The Essence of Life. “We have salty tears and salty perspiration. The chemical and mineral composition of our blood and body fluids are similar to sea water. From the beginning of life, as unborn babies, we are encased in a sack of salty fluid.”

“In water, salt dissolves into mineral ions,” explains Dr Hendel. “These conduct electrical nerve impulses that drive muscle movement and thought processes. Just the simple act of drinking a glass of water requires millions of instructions that come from mineral ions. They’re also needed to balance PH levels in the body.”
Mineral salts, she says, are healthy because they give your body the variety of mineral ions needed to balance its functions, remain healthy and heal. These healing properties have long been recognised in central Europe. At Wieliczka in Poland, a hospital has been carved in a salt mountain. Asthmatics and patients with lung disease and allergies find that breathing air in the saline underground chambers helps improve symptoms in 90 per cent of cases.

Dr Hendel believes too few minerals, rather than too much salt, may be to blame for health problems. It’s a view that is echoed by other academics such as David McCarron, of Oregon Health Sciences University in the US.

He says salt has always been part of the human diet, but what has changed is the mineral content of our food. Instead of eating food high in minerals, such as nuts, fruit and vegetables, people are filling themselves up with “mineral empty” processed food and fizzy drinks.

Source: preventdisease.com

         

Effects of Sulfonylureas on Tumor Growth.


Type 2 diabetes mellitus patients are at higher cancer risk, probably because of hyperinsulinemia and insulin growth factor 1 pathway activation. The effects of antidiabetic drugs on cancer risk have been described and discussed in several studies suggesting opposite effects of the biguanide metformin and sulfonylureas on cancer incidence and mortality. The anticancer mechanisms of metformin have been clarified, and some clinical studies, particularly in breast cancer patients, have been published or are currently ongoing; however, data about the effects of sulfonylureas on cancer growth are less consistent. The aims of this work are to review preclinical evidence of second-generation sulfonylureas effects on tumor growth, to clarify the potential mechanisms of action, and to identify possible metabolic targets for patient selection. Most evidence is on the adenosine triphosphate-sensitive potassium channels inhibitor glibenclamide, which interacts with reactive oxygen species production thus inducing cancer cell death. Among diarylsulfonylureas, next-generation DW2282 derivatives are particularly promising because of the proapoptotic activity in multidrug-resistant cells.

 

Source: The Oncologist.

 

Alopecia With Endocrine Therapies in Patients With Cancer.


Abstract

Background. Whereas the frequency of alopecia to cytotoxic chemotherapies has been well described, the incidence of alopecia during endocrine therapies (i.e., anti-estrogens, aromatase inhibitors) has not been investigated. Endocrine agents are widely used in the treatment and prevention of many solid tumors, principally those of the breast and prostate. Adherence to these therapies is suboptimal, in part because of toxicities. We performed a systematic analysis of the literature to ascertain the incidence and risk for alopecia in patients receiving endocrine therapies.

Methods. An independent search of citations was conducted using the PubMed database for all literature as of February 2013. Phase II–III studies using the terms “tamoxifen,” “toremifene,” “raloxifene,” “anastrozole,” “letrozole,” “exemestane,” “fulvestrant,” “leuprolide,” “flutamide,” “bicalutamide,” “nilutamide,” “fluoxymesterone,” “estradiol,” “octreotide,” “megestrol,” “medroxyprogesterone acetate,” “enzalutamide,” and “abiraterone” were searched.

Results. Data from 19,430 patients in 35 clinical trials were available for analysis. Of these, 13,415 patients had received endocrine treatments and 6,015 patients served as controls. The incidence of all-grade alopecia ranged from 0% to 25%, with an overall incidence of 4.4% (95% confidence interval: 3.3%–5.9%). The highest incidence of all-grade alopecia was observed in patients treated with tamoxifen in a phase II trial (25.4%); similarly, the overall incidence of grade 2 alopecia by meta-analysis was highest with tamoxifen (6.4%). The overall relative risk of alopecia in comparison with placebo was 12.88 (p < .001), with selective estrogen receptor modulators having the highest risk.

Conclusion. Alopecia is a common yet underreported adverse event of endocrine-based cancer therapies. Their long-term use heightens the importance of this condition on patients’ quality of life. These findings are critical for pretherapy counseling, the identification of risk factors, and the development of interventions that could enhance adherence and mitigate this psychosocially difficult event.

 

Source: The Oncologist.

 

 

Aiming for a Better Understanding and Management of Cancer-Related Fatigue.


Cancer-related fatigue (CRF) is a serious symptom of patients with cancer and deteriorates their daily quality of life. Whereas fatigue is a common problem in the general population, with a prevalence of about 30%, up to 99% of patients with cancer have fatigue of more intense severity. CRF is directly related to the biology of cancer, but it can also be caused by anticancer treatment. We reviewed current evidence about the potential pathophysiological mechanisms causing CRF. Clinical methods to determine the presence and severity of CRF and potential treatment options to reduce CRF will be discussed. After reading this review, the reader will have knowledge of the current understanding of CRF and will be able to give evidence-based advice to patients with CRF.

 

Source: The Oncologist.