Lab cuts ‘threat to human health’


Cuts to animal health surveillance mean Britain is at a much greater risk of outbreaks of devastating diseases such as “mad cow disease”, experts say.

The Royal College of Pathologists (RCP) says human health could be at risk.

Edward Peduzie and his father Paul

The RCP is calling for an urgent review of plans to cut the number of animal health surveillance laboratories in England and Wales from 14 to seven.

The Department for Environment, Food and Rural Affairs (Defra) says the cuts are part of an “improved approach”.

Pathologists in these laboratories identified, tracked and helped formulate a response to bovine spongiform encephalopathy (BSE), which first emerged in cattle in 1986.

Variant Creutzfeldt-Jakob disease (vCJD) – the human form of BSE – has killed 174 people, many of them teenagers.

Swine fever
Most recently, the Animal Health and Laboratories Agency (AHVLA) spotted the crossover of tuberculosis (TB) from pet cats to humans.

The agency has also identified outbreaks of other diseases, such as swine fever, Schmallenberg virus and blue tongue.

The RCP warns the proposed cuts will slow down the ability to detect animal infections.

It warns it will lead to an irreversible loss of expertise, and make Britain more vulnerable to BSE-type diseases in the future.

‘Cut costs’
RCP president Dr Archie Prentice said: “The risk is that if we can’t detect an animal infection quickly, it can then spread throughout animal livestock, which is worth £11bn to this country.

“More importantly, the risk is that it can spread to humans before it can be identified in the animal stock.

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When we get five or 10 years down the line and people are dying again, it’s too late to rectify it”

Paul Peduzie
“We are going to be using a system that is not as good as before.

“We are always going to see new organisms that we haven’t seen before and we are always going to see old organisms that we thought had been brought under control, reappearing.

“So if you don’t have this early detection system around, your chance of picking this up is much less.”

He added: “I don’t know anybody who is happy about this.

“We know from what some of the officials at Defra and AHVLA have told us that they wouldn’t do this if they hadn’t been under such pressure to cut costs.”

Juan Lubroth, chief veterinary officer at the Food and Agriculture Organisation of the United Nations, told the BBC the downsizing was “not what the world or the UK needs”.

He said: “This is the wrong direction. By saving millions of pounds, you put at risk billions of pounds.

“With a growing world population and a growing demand for food and agricultural products, the trend for the last 60 years has been more and more of a spillover of animal diseases affecting humans.

“We need these laboratories to be able to respond quickly and prevent pathogens spreading across borders.”

Son died
Paul Peduzie, from Pewsey, Wiltshire, lost his son Edward to vCJD. Edward was 18 when he contracted the disease and 25 when he died in 2009.

He told the BBC the downsizing of the surveillance network would “inevitably mean that more children or adults will end up like my son”.
Edward was 18 when he contracted vCJD
“It makes me feel very sad,” he said. “When we get five or 10 years down the line and people are dying again, it’s too late to rectify it.

“We have the ability to do it now. Don’t throw it away, it’s just not worth it.

“I suppose it may be to some of these people if it’s not your family that suffers.

“But to me, I don’t care whose family it is, from the bottom to the top. Testing is worth it.”

Mr Peduzie said the disease was “horrendous to watch”.

By the end, Edward was unable to talk or move, his lungs had to be constantly drained and he had to be fed intravenously.

“A child is the most precious thing to be taken away,” Mr Peduzie said.

“Too much is talked about the cost of these things. When you actually look at the cost, it’s very small.

“For the life of just one person, it’s money well spent.”

‘Service dismantled’
The changes mean vets will have to have extra training in pathology, and that autopsies may have to be carried out on site on a farm or in a slaughterhouse.

In some cases, farmers themselves will have to find a way to securely transport larger livestock carcasses to a centre further away.

Nick Blaney is a vet who works in and around Stratford on Avon. The local surveillance centre, Luddington, is due to close on Tuesday.

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The new surveillance system puts greater emphasis on gathering and properly assessing surveillance intelligence gathered more widely”

Animal Health and Laboratories Agency
“Pathology is now going to be restricted to carcasses you can pick up and put in the car or send in the post,” he said.

“To see the service dismantled like this, I feel very bitter.”

“We are losing access to a very important function.

“They have a level of equipment and expertise that is second to none in the world.”

“Along with being very important to our clients, this has a national implication.

“We live in a time with increasing concerns about food security.

“Surely this is the very moment when you need to know what’s going on in terms of emerging disease patterns in agriculture.”

‘Recognise threats’
However, according to the AHVLA, this is an improved approach to surveillance.

It will not just rely on government post-mortems but draw on the expertise of private vets, universities and the livestock industry.

An AHVLA official said: “Far from a loss of expertise, there is a greater emphasis on developing the specific skills of pathology and epidemiology within AHVLA which are so highly valued.

“By introducing more post-mortem providers farmers’ access to pathology will be improved. In areas less accessible to a post-mortem centre a carcass collection and transport system funded by AHVLA will be introduced.

“The recent case of M. bovis in cats was first discovered by a private vet and is an example of how collaborative working is essential for effective surveillance.

“Surveillance for serious diseases such as BSE, foot and mouth and avian influenza is not affected by the changes and AHVLA will continue to investigate all reports of notifiable animal disease.”

Scientists discover eighth colour of the rainbow.


Scientists have identified an invisible eighth colour in the rainbow, a discovery that could have wide-ranging implications on the nature of military camouflage and modern espionage.

 New ‘shade’ was found by firing packets of light through a cloud of supercold sodium atoms and through a string of carbon nanotubes

This light was then funnelled through a series of carbon nanotubes in which the angle of incidence (the measure of how far the light beam deviates from aiming ‘straight on’) was enough to bounce the photos back on themselves, effectively ‘bunching’ the light waves together.

“Really, all it took was a bit of lateral thinking,” said Dr Flora Padyolis, a professor in elementary wave physics at the institution and a lead author on the new study. “If you imagine the spectrum of visible light as analogous to sound waves with each named colour corresponding to a musical note, then what we’ve done is to approach the problem from an entirely new angle, taking what people previously thought was a C natural and listening to it like a B sharp,” she said.

 

The team from West Virginia are quick to point out this new colour “won’t be appearing as a crayon” any time soon, and that the shade is best thought of in similar terms to ‘grue’ and ‘bleen’; the portmanteau words used by linguists to convey the difficulty some languages have differentiating between blue and green.

Online, speculation focused on the supposition this new colour could be the key breakthrough necessary in the invention of a “invisibility cloak”.

While current designs rely on physically bending light around an object or shielding it from a small portion of the spectrum, scientists suggest that simply bathing the target in this previously unseen colour could have dramatic results.

“If we haven’t seen this colour before, how will other people see things we paint it with?” said Dr Padyolis.

The relative simplicity of the new technology could also impact on the consumer market, as researchers claim accessing the colour does not cost “extortionate” amounts. The fashion world is said to be particularly excited.

 

Daylight saving time linked to heart attacks, study shows.


Switching over to daylight saving time, and losing one hour of sleep, raised the risk of having a heart attack the following Monday by 25 percent, compared to other Mondays during the year, according to a new U.S. study released on Saturday.

By contrast, heart attack risk fell 21 percent later in the year, on the Tuesday after the clock was returned to standard time, and people got an extra hour’s sleep.

awake_man_640.jpg

The not-so-subtle impact of moving the clock forward and backward was seen in a comparison of hospital admissions from a database of non-federal Michigan hospitals. It examined admissions before the start of daylight saving time and the Monday immediately after, for four consecutive years.

In general, heart attacks historically occur most often on Monday mornings, maybe due to the stress of starting a new work week and inherent changes in our sleep-wake cycle, said Dr. Amneet Sandhu, a cardiology fellow at the University of Colorado in Denver who led the study.

“With daylight saving time, all of this is compounded by one less hour of sleep,” said Sandhu, who presented his findings at the annual scientific sessions of the American College of Cardiology in Washington.

A link between lack of sleep and heart attacks has been seen in previous studies. But Sandhu said experts still don’t have a clear understanding of why people are so sensitive to sleep-wake cycles.

“Our study suggests that sudden, even small changes in sleep could have detrimental effects,” he said.

Sandhu examined about 42,000 hospital admissions in Michigan, and found that an average of 32 patients had heart attacks on any given Monday. But on the Monday immediately after springing the clock forward, there were an average of eight additional heart attacks, he said.

The overall number of heart attacks for the full week after daylight saving time didn’t change, just the number on that first Monday. The number then dropped off the other days of the week.

People who are already vulnerable to heart disease may be at greater risk right after sudden time changes, said Sandhu, who added that hospital staffing should perhaps be increased on the Monday after clocks are set forward.

“If we can identify days when there may be surges in heart attacks, we can be ready to better care for our patients,” he said.

The clock typically moves ahead in the spring, so that evenings have more daylight and mornings have less, and returns to standard time in the fall. Daylight saving time was widely adopted during World War I to save energy, but some critics have questioned whether it really does so and whether it is still needed.

Researchers cited limitations to the study, noting it was restricted to one state and heart attacks that required artery-opening procedures, such as stents. The study therefore excluded patients who died prior to hospital admission or intervention.

Diet soda consumption associated to heart disease.


Americans have developed a taste for diet soda, which can provide them with an extra kick without the extra calories but, according to new research, if they consume more than two drinks a day it could put them at higher risk of heart disease.

AFP Photo / Joe Raedle

The American College of Cardiology announced in a new study that, while drinking diet soda alone may not necessarily hurt an individual’s health, someone who shops for Diet Pepsi instead of the original may be doing so to make up for other unhealthy habits.

Scientists found that women who drank two or more diet beverages each day were 30 percent more likely to experience a heart attack or similarly dangerous cardiovascular “event,” and 50 percent more likely to die. Dr. Ankur Vyas, a cardiovascular disease specialist at the University of Iowa Hospitals and Clinic, told CNBC the team examined 60,000 middle-aged women over 10 years.

Our study suggests an association between higher diet drink consumption and mortality,” Vyas said Saturday when the results were unveiled. “It’s not an extreme risk.”

To begin the study, the subjects answered a questionnaire regarding which foods and drinks they consumed, with a special emphasis on diet soda and diet fruit flavored drinks.

Nine years later, 8.5 percent of the respondents who drank at least two diet drinks each day had some sort of heart disease, just more than the 6.8 percent who drank less than four drinks per week. Of the women who drank two or less diet drinks a month, 7.2 percent had some kind of heart disease.

Vyas, who has made headlines for the latest in a line of studies purportedly exposing the risk of diet drinks, admitted the results are not as clear as one may expect.

We found an association, so we can’t say that diet drinks cause these problems,” he told CNBC.

Those who drank the most diet drinks, though, were determined to be more likely to have high blood pressure, to be overweight, to smoke, and be at risk of a number of potentially fatal maladies.

Dr. Vyas’ study comes two months after soda drinkers were shaken by a much more serious finding: the chemical used to give a number of popular soft drinks their brownish color may contain an additive that causes cancer.

Dr. Urvashi Rangan, executive director of Consumer Reports’ Food Safety & Sustainability Center, issued a statement in January asserting that the magazine tested dozens of cans and bottles of 4-methylimidazole (4-MeI). California had previously added 4-MeI to the state list of potentially toxic chemicals under Proposition 65 after previous studies found that long-term exposure to the chemical contributed to lung cancer in mice. Proposition 65 requires products containing potentially harmful chemicals to place warning labels on the container.

Of the 81 cans and bottles of soda tested, 29 samples exceeded the 29-microgram amount of 4-MeI allowed under the law. Pepsi One, for example, turned out to contain between 39.5 and 195.3 micrograms, while Malta Goya exceeded even that with 307.5 to 352.5 micrograms in each container. None of the containers were labeled, according to Consumer Reports.

There’s no reason why consumers should be exposed to an avoidable and unnecessary risk that can stem from coloring food brown,” Rangan said.

Consumer Reports had encouraged the US Food and Drug Administration to examine whether the soda companies were adhering to both California and federal regulations, although observers cautioned customers to use common sense.

It’s possible to get more than 29 micrograms of 4-MeI in one can of some of the drinks we tested,” Dr. Rangan went on. “And even if your choice of soft drink contains half that amount, many people have more than one can per day.”

Other recent reports have suggested that, among other things, diet soda can lead to weight gain, strokes, and kidney failure, among other issues. Dr. Rasa at Rush University Medical Center in Chicago, Illinois told Fox 32 News that “there is nothing good for the body.” One patient told reporters Rasa has said more than once that drinking two or more bottles of diet soda can do serious harm to vital organs.

I had drunk a lot of soda, at least 64 ounces a day and thinking I was losing weight, etcetera by doing it,” the patient said. “And my doctor advised me that the chemicals were really bad.”

Anti-anxiety drugs, sleeping pills linked to risk of death .


Anti-anxiety drugs and sleeping pills have been linked to an increased risk of death, according to new research from the University of Warwick.

The large study, published in BMJ, shows that several anxiolytic (anti-anxiety) drugs or hypnotic drugs (sleeping pills) are associated with a doubling in the risk of mortality. Although these findings are based on routine data and need to be interpreted cautiously, the researchers recommended that a greater understanding of their impact is essential.

Professor Scott Weich, Professor of Psychiatry at the University of Warwick, explained “The key message here is that we really do have to use these drugs more carefully. This builds on a growing body of evidence suggesting that their side effects are significant and dangerous. We have to do everything possible to minimise over reliance on anxiolytics and sleeping pills.”

“That’s not to say that they cannot be effective. But particularly due to their addictive potential we need to make sure that we help patients to spend as little time on them as possible and that we consider other options, such as cognitive behavioural therapy, to help them to overcome anxiety or sleep problems.”

The study accounted, where possible, for other factors such as age, smoking and alcohol use, other prescriptions and socioeconomic status. Crucially, the team controlled for contributing risk factors such as sleep disorders, anxiety disorders and other psychiatric illness in all participants.

34,727 people were tracked for seven and a half years on average from the time that they first received prescriptions for either an anxiolytic or hypnotic drug.

Benzodiazepines were the most commonly prescribed drug class, including diazepam and temazepam. The study also examined the effects of two other groups of drugs; the so-called ‘Z-drugs’ and all other anxiolytic and hypnotic drugs. Many patients received more than one drug over the course of the study, and 5% received prescriptions for drugs from all three groups.

Journal Reference:

  1. S. Weich, H. L. Pearce, P. Croft, S. Singh, I. Crome, J. Bashford, M. Frisher.Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort studyBMJ, 2014; 348 (mar19 5): g1996 DOI:10.1136/bmj.g1996

Self-healing engineered muscle grown in the laboratory.


Biomedical engineers have grown living skeletal muscle that looks a lot like the real thing. It contracts powerfully and rapidly, integrates into mice quickly, and for the first time, demonstrates the ability to heal itself both inside the laboratory and inside an animal.

The study conducted at Duke University tested the bioengineered muscle by literally watching it through a window on the back of living mouse. The novel technique allowed for real-time monitoring of the muscle’s integration and maturation inside a living, walking animal.

Both the lab-grown muscle and experimental techniques are important steps toward growing viable muscle for studying diseases and treating injuries, said Nenad Bursac, associate professor of biomedical engineering at Duke.

The results appear the week of March 25 in the Proceedings of the National Academy of Sciences Early Edition.

“The muscle we have made represents an important advance for the field,” Bursac said. “It’s the first time engineered muscle has been created that contracts as strongly as native neonatal skeletal muscle.”

Through years of perfecting their techniques, a team led by Bursac and graduate student Mark Juhas discovered that preparing better muscle requires two things — well-developed contractile muscle fibers and a pool of muscle stem cells, known as satellite cells.

Every muscle has satellite cells on reserve, ready to activate upon injury and begin the regeneration process. The key to the team’s success was successfully creating the microenvironments — called niches — where these stem cells await their call to duty.

“Simply implanting satellite cells or less-developed muscle doesn’t work as well,” said Juhas. “The well-developed muscle we made provides niches for satellite cells to live in, and, when needed, to restore the robust musculature and its function.”

To put their muscle to the test, the engineers ran it through a gauntlet of trials in the laboratory. By stimulating it with electric pulses, they measured its contractile strength, showing that it was more than 10 times stronger than any previous engineered muscles. They damaged it with a toxin found in snake venom to prove that the satellite cells could activate, multiply and successfully heal the injured muscle fibers.

Then they moved it out of a dish and into a mouse.

With the help of Greg Palmer, an assistant professor of radiation oncology in the Duke University School of Medicine, the team inserted their lab-grown muscle into a small chamber placed on the backs of live mice. The chamber was then covered by a glass panel. Every two days for two weeks, Juhas imaged the implanted muscles through the window to check on their progress.

By genetically modifying the muscle fibers to produce fluorescent flashes during calcium spikes — which cause muscle to contract — the researchers could watch the flashes become brighter as the muscle grew stronger.

“We could see and measure in real time how blood vessels grew into the implanted muscle fibers, maturing toward equaling the strength of its native counterpart,” said Juhas.

The engineers are now beginning work to see if their biomimetic muscle can be used to repair actual muscle injuries and disease.

“Can it vascularize, innervate and repair the damaged muscle’s function?” asked Bursac. “That is what we will be working on for the next several years.”

 

Journal Reference:

  1. Mark Juhas, George C. Engelmayr, Jr., Andrew N. Fontanella, Gregory M. Palmer, and Nenad Bursac. Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivoPNAS, March 2014 DOI:10.1073/pnas.1402723111

New Drugs at FDA: CDER’s New Molecular Entities and New Therapeutic Biological Products of 2014.


Innovation drives progress. When it comes to innovation in the development of new drugs and therapeutic biological products, FDA’s Center for Drug Evaluation and Research (CDER) supports the pharmaceutical industry at every step of the process. With its understanding of the science used to create new products, testing and manufacturing procedures, and the diseases and conditions that new products are designed to treat, FDA provides scientific and regulatory advice needed to bring new therapies to market. The availability of new drugs and biological products often means new treatment options for patients and advances in health care for the American public. For this reason, CDER supports innovation and plays a key role in helping to advance new drug development.

Each year, CDER approves a wide range of new drugs and biological products. Some of these products are innovative new products that never before have been used in clinical practice. Others are the same as, or related to, previously approved products, and they will compete with those products in the marketplace.

Certain drugs are classified as new molecular entities (“NMEs”) for purposes of FDA review. Many of these products contain active moieties that have not been approved by FDA previously, either as a single ingredient drug or as part of a combination product; these products frequently provide important new therapies for patients. Some drugs are characterized as NMEs for administrative purposes, but nonetheless contain active moieties that are closely related to active moieties in products that have previously been approved by FDA. For example, CDER classifies biological products submitted in an application under section 351(a) of the Public Health Service Act as NMEs for purposes of FDA review, regardless of whether the Agency previously has approved a related active moiety in a different product. FDA’s classification of a drug as an “NME” for review purposes is distinct from FDA’s determination of whether a drug product is a “new chemical entity” or “NCE” within the meaning of the Federal Food, Drug, and Cosmetic Act.

Link to the 2013 Novel New Drugs Summary (PDF - 3MB)

 

The list below includes the NMEs approved by CDER in calendar year 2014.

(The Drug Name link provides full product details, i.e., prescribing information, approval history, and reviews.)

 

No.

Drug Name

Active Ingredient

Date

What it’s used for

8. Otezla apremilast 3/21/2014 To treat adults with active psoriatic arthritis (PsA)
Press Release
7. Impavido miltefosine 3/19/2014 To treat a tropical disease called leishmaniasis
Press Release
6. Neuraceq florbetaben F 18 injection 3/19/2014
For Positron EmissionTomography (PET) imaging of the brain
5. Myalept metreleptin for injection 2/24/2014 To treat the complications of leptin deficiency
Press Release
4. Northera droxidopa 2/18/2014 To treat neurogenic orthostatic hypotension (NOH)
Press Release
3. Vimizim elosulfase alfa 2/14/2014 Treatment for Mucopolysaccharidosis Type IVA (Morquio A syndrome).
Press Release
2. Hetlioz tasimelteon 1/31/2014 To treat non-24- hour sleep-wake disorder (“non-24”) in totally blind individuals. Non-24 is a chronic circadian rhythm (body clock) disorder in the blind that causes problems with the timing of sleep.

Press Release

1. Farxiga dapaglifozin 1/8/2014 To improve glycemic control, along with diet and exercise, in adults with type 2 diabetes.
Press Release

 

Aspirin in Patients Undergoing Noncardiac Surgery.


There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not.

Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.

The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata.

 

DISCUSSION

In this trial, the use of low-dose perioperative aspirin, as compared with placebo, did not reduce the rate of a composite of death or nonfatal myocardial infarction (the primary outcome) or the rates of the two secondary composite outcomes. The use of perioperative aspirin increased the risk of major bleeding (hazard ratio, 1.23; 95% CI, 1.01 to 1.49). The results with respect to the primary and secondary outcomes were consistent in the initiation stratum and the continuation stratum.

In a meta-analysis of data from trials involving more than 110,000 patients who were not undergoing surgery, the use of aspirin, for primary and for secondary prevention, reduced the relative risk of myocardial infarction by 20% and 25%, respectively.9 In contrast, the Pulmonary Embolism Prevention (PEP) trial included 13,356 patients undergoing surgery for a hip fracture.13 Patients received 160 mg of aspirin or placebo before surgery and daily for 35 days. Aspirin was associated with an increased risk of myocardial infarction (hazard ratio, 1.33; 95% CI, 1.00 to 1.78), although the number of myocardial infarctions (184) was much lower than that in our study (624; hazard ratio with aspirin, 0.98; 95% CI, 0.84 to 1.15).

Consistent with our findings, the PEP trial and other perioperative trials have shown that aspirin significantly increases the risk of bleeding requiring a transfusion.13,14 In previous surgical trials with hundreds of venous thromboembolism events, the use of aspirin decreased the risk of deep-vein thrombosis and pulmonary embolism by one third.13,14 In our study, relatively few patients had deep-vein thrombosis (60 patients) or pulmonary embolism (64 patients), and more patients in our study than in the PEP trial received concomitant anticoagulant prophylaxis (65.0% vs. 44.4%).

Observational data suggest that the discontinuation of aspirin before surgery results in an increased thrombotic risk.19,23 In our study, among the 4382 patients in the continuation stratum, we found no increase in thrombotic events owing to preoperative withholding of aspirin.

In the nonoperative setting, aspirin prevents myocardial infarction in patients with or at risk for atherosclerotic disease. However, in our study, aspirin did not prevent perioperative myocardial infarction. We offer three potential explanations for this finding. First, previous studies and our post hoc multivariable analysis showed that major bleeding was associated with perioperative myocardial infarction.3,24 The absolute increase in bleeding risk with aspirin is greater in the perioperative setting than the nonoperative setting. It is possible that aspirin prevented some perioperative myocardial infarctions through thrombus inhibition and caused some myocardial infarctions through bleeding and subsequent mismatch between the supply of and demand for myocardial oxygen, thus resulting in the overall neutral effect in our study. Second, the lower boundary of the hazard ratio for myocardial infarction was 0.84, and we cannot exclude the possibility of a missed moderate effect that would be consistent with results of other aspirin trials.9 Third, coronary-artery thrombus may not be the dominant mechanism of perioperative myocardial infarction.5,6

The results with respect to the primary and secondary outcomes were similar across the two aspirin strata. There were significant between-group differences in one tertiary outcome (acute kidney injury with receipt of dialysis) and two safety outcomes (major bleeding and stroke) in one aspirin stratum but not the other (Table S4 in the Supplementary Appendix). The interaction P value for the aspirin stratum was not significant for two of these outcomes (i.e., acute kidney injury with receipt of dialysis and major bleeding), suggesting that there is no significant difference in effect across the aspirin strata for these two outcomes and that the results in the overall population provide the most reliable effect estimates.

Our data suggest that among patients on a long-term aspirin regimen, stopping aspirin 3 or more days before surgery may decrease the risk of major bleeding. Because we did not randomly assign patients according to the timing of aspirin cessation before surgery, we cannot determine the most effective timing to minimize bleeding risk. Studies have suggested that hemostasis is unimpaired if at least 20% of the platelets have normal COX-1 activity25,26 and 12% of circulating platelets are replaced every 24 hours.27,28 Therefore, stopping aspirin 72 or more hours before surgery may be adequate to minimize the risk of perioperative bleeding.

We observed one significant interaction: aspirin appeared to reduce the incidence of stroke in the initiation stratum but not in the continuation stratum (P=0.01 for interaction). Several considerations suggest that this is a spurious subgroup effect.29 First, there were only 15 strokes in the initiation stratum, so the power to detect a change is small. Second, the effect of aspirin on reducing the risk of stroke in the initiation stratum was large (hazard ratio, 0.25), an effect that was inconsistent with the effect in the nonoperative setting on the basis of analyses of more than 1000 strokes and the perioperative data from the PEP trial with 103 strokes (hazard ratio for aspirin, 1.10; 95% CI, 0.75 to 1.62).9,13 Third, since this analysis was 1 of 19 tertiary or safety subgroup analyses that we performed, the results may be a chance finding. Finally, our hypothesized direction was opposite to that observed (i.e., we expected more benefit in the continuation stratum because of an aspirin-withdrawal effect). Therefore, the best estimate of the effect of aspirin on stroke is probably reflected in the overall population (hazard ratio, 0.84; 95% CI, 0.43 to 1.64).

If clinicians plan to use an anticoagulant agent for perioperative prevention of venous thromboembolism, our results suggest that starting or continuing aspirin throughout the perioperative period will provide no additional benefit but will increase the risk of major bleeding. However, our findings do not resolve the issue of the relative merits of aspirin versus other anticoagulant agents for perioperative thromboprophylaxis.30 Although the POISE-2 trial is a large study by perioperative standards, the lower boundary (0.86) and upper boundary (1.15) of the hazard ratio for the primary outcome show that we have not excluded the possibility of appreciable benefit or harm.

It should be noted that we excluded patients who received a bare-metal coronary stent less than 6 weeks before surgery or a drug-eluting coronary stent less than 1 year before surgery. Observational data have suggested that perioperative aspirin prevents myocardial infarction and stent thrombosis in these two groups of patients.31

For patients on a long-term aspirin regimen, the most effective time to restart aspirin would be 8 to 10 days after surgery, when the bleeding risk has diminished considerably. If physicians consider starting aspirin after surgery to treat a thrombotic event (e.g., stroke or myocardial infarction), they can expect an absolute increase of 1.0 to 1.3 percentage points in the risk of life-threatening or major bleeding if aspirin is administered within the first 2 days after surgery. Physicians and their patients will have to weigh this risk against the high risk of death from the thrombotic event and the potential benefits of aspirin.3,12,16

In conclusion, the administration of aspirin before noncardiac surgery and throughout the early postsurgical period had no significant effect on the rate of death or nonfatal myocardial infarction but increased the risk of major bleeding. These findings apply both to patients who were not already receiving aspirin and to those who were on a long-term aspirin regimen.

Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding.

6 Ways to Relax During Stressful Times.


“If you ask what is the single most important key to longevity, I would have to say it is avoiding worry, stress and tension. And if you didn’t ask me, I’d still have to say it.” ~ George Burns

Modern life creates a heavy load of stress for many people. After a long day of commuting, work and family obligations, it can be difficult to unwind and relax. The following activities can help anyone quickly find some zen.

1. Deep Breathing

Stopping activity to focus on breathing is one of the quickest ways to calm down and relieve stress. Proper deep breathing is done by sitting up straight, with a hand placed on the stomach. The person should breathe in through the nose and exhale slowly through the mouth. This method works best when wearing comfortable clothes.

2. Meditation

Meditation is a form of inner focus that reduces anxiety. It starts with deep breathing and reciting a mantra, such as “I’m feeling peaceful.” The person should let distracting sounds and thoughts pass by. This relaxation technique can be done at home or office and will increase productivity while fighting off stress.

3. Connecting

Reaching out to talk to a friend or family member, whether in person or by phone, can alleviate stress levels and be a tool for problem resolution. People who have an extended social circle tend to be happier and feel more balanced in their lives and are less prone to depression and anxiety.

4. Laughing

While it is common knowledge that laughing can make a person feel better, it also has beneficial effects on the body by lowering the stress hormone cortisol while releasing endorphins, which act as pain relievers as well as mood boosters. Laughing also helps people to connect to one another and form new bonds.

5. Listening to Music

Listening to soothing sounds or music, along with singing, are great ways to relax. Some may prefer to create a playlist of natural sounds, such as the tide, chirping birds or wind chimes, while others may enjoy more upbeat sounds.

6. Decompressing

 

Take some time for you each day. Decompressing can be as simple as throwing on your favorite shorts, t-shirts and hoodies and relaxing at home. Try placing a heat wrap around the shoulders and neck for 15 minutes or using a foam roller to ease away the tension of a difficult day. Receiving a message from a loved one can aid in relaxation and reconnection and bring a feeling of peace.

The business of daily life can leave little time for a person to tend to their own needs. Using the six tips above can be helpful in carving out some space to breathe, focus, relax and have a more positive outlook.

How do you deal with stress? What are the things that help you relax when you’re confronted with stressful people and situations? You can share your comment by joining the conversation below :)

What to Do When Your Life Is Going Nowhere Fast.


“The bad news is time flies. The good news is you’re the pilot.” ~Michael Altshuler

When I was in college I was looking for a job that was less demanding compare to my current one. I wanted a job that didn’t require me to work holidays and weekends. I need time to rest and do my homework since I had a full course load.

Then I found it and was hired for a job that met my specifications exactly. Although it required a few more hours of work a week it was fine because it was less stressful.

I actually liked the job. No more sitting in my car in the parking lot before my shift, reflecting on how much I didn’t want to go in and talking myself out of driving away. I finally had a job that I didn’t dread going to, at the time.

While it met all my desires when I first started, sometime after I graduated my infatuation with it faded.

It was a great job for what I needed it for then. But after certain factors in that equation no longer existed, it sucked.

It was wonderful as a part time job while I was in school. It was a breeze for me. I was even able to do some of my homework at work. I decided to go full time since my schooling was complete.

Some years after I realized I was stuck. My professional plans had changed in my mind but not in reality.

See, I never planned on staying at that job for too long. It was just something that worked perfectly for the situation I was in. But I wasn’t in that situation anymore, but I was still working there.

Even though I was stuck, generally it didn’t seem like a bad thing. My bills were paid, I was saving money and my job wasn’t running me ragged. That’s probably why I didn’t notice it sooner.

One day at work I was sitting in my cube when I experienced a random moment of consciousness. In that moment I became extremely aware of where I was compared to where I wanted to be or even where I thought I’d be by then. That’s when it really hit me, I wasn’t going anywhere.

I just sat there thinking “How did I get here?” “How did this become my only prospect for a career?” But I knew how I got there, and even if I didn’t, it really didn’t matter. I needed to focus on getting out.

After 7 years in the same position the only thing I had to celebrate was 3 weeks of vacation a year and a kitchen pan set I got for my fifth anniversary. It really was the only perk, the only thing I was happy about.

If that was my only goal I achieved it, but it wasn’t. Instead I had wasted most of those years playing it safe.

After a while I was comfortable where I was. Even though it was a dead end job I couldn’t motivate myself to do something about it. When I thought about getting another job I focused on the annoying parts of the process.

It seemed like all was lost. But as stagnant as I felt, I still had two choices, surrender like most of my colleagues have and accept this as my fate or take action against it.

Somewhere after graduation I veered off course, I forgot that this was a transition job in my life. Adjusting to adulthood and all its daily responsibilities made me neglect the bigger picture.

I didn’t want to wake up one day and realize that I was depressed and unhappy. That most of my life had passed by and I had done nothing with it. That my dream of having a career I’d enjoy was still just a dream. So I chose action.

Here are 7 steps you can take to have your life move in a better and more meaningful direction:

1. Personal Time

You need time to yourself to sort out your thoughts. This is a good time to reflect on what is bothering you, what you want and figure out solutions to resolving your issues.

To be most effective this cannot be done during the commercial break of your favorite drama. Try to be one with your thoughts with as little distractions as possible.

I know you’re busy but you need to do this. You are just as important as your other tasks. So the same way you found a way to add them to your schedule, pencil yourself in.

2. Be Accountable

This was kind of big for me. I often didn’t share my goals or plans with others because I didn’t want people to remind me of my lack of progress. Just someone asking me how it was going with it would remind me that nothing was going on. It was kind of embarrassing.

I wasn’t embarrassed because I said I was going to do it and didn’t, I mean plans change. I felt that way because it made me realize how separated from myself I was. I was always the person who got things done. I loved that person but I didn’t feel like her anymore.

Not holding yourself accountable is one of the quickest ways to become stagnant. Remain connected with your goals and review your progress.

3. Construct a Time Frame

Now that you’re going to hold yourself to it, give yourself a deadline.

If you just say you’re going to complete a goal you have all the time in the world. You can put it off forever.

For each action you need to establish a time frame. Designate when to start it and when you should complete it. This will also help when you’re creating an action plan. I’ll know exactly when to do each step.

It also helps reduce procrastination and maintain momentum.

4. Let Go of Fear

When you’re comfortably unhappy you reject change because you’re terrified of it. You’re used to things the way they are, even though you don’t like it. Fear is just another factor for stagnation.

Part of the reason I stayed at my job is because I was afraid of the level of success I desired. I know it sounds weird but I wanted to do something that wasn’t familiar to me. I mean I’ve been successful in the past but this was different. This was something that would impact my life for decades.

You just need to get over your fear of change and any fears related to your goals.

You know how I got over my fears? I just asked myself, what’s scarier, doing something you’ve never done or you`re afraid to do, or being in the exact same place you are today, 20 years from now? I think you know the answer to that one.

5. Change Your Mind

Your biggest obstacle is in your head.

Once you’ve combat your fears, attack that little voice in your head that says you can’t do it.

While you were addressing your fears you may have had to change your perspective on a few things. You’ll need to continue to do that to succeed.

There are different ways to look at things, the positive and the negative. You need to stay positive in order to keep going. This is what keeps you motivated. If you think you can’t you won’t even bother trying.

When I did this, things got easier. It’s like I was open to all these new things.

6. Find a Mentor

Achievement of a goal and motivation can seem attainable when you realize that other people have been in your shoes.

The chance of you finding someone who was in the exact same situation and trying to achieve the same is unlikely. But you can find other commonalities in someone else’s story of triumph.

It was very helpful to me to know that other people overcame similar professional struggles to do what they love. Some even rose from worse circumstances, like being laid off.

If they can do it, so can you.

Go For It

Turn your dream into an action plan. Break it down into smaller steps that lead straight to the objective.

Continue to enforce the time line and hold yourself accountable. While keeping an eye on your progress, make any changes you deem necessary to make a difference.

Like with me, when I first sent out my resume I wasn’t getting any calls to set up an interview or even a screening. After a short while I decided to revamp my resume.

Seeing as I already had one created it seemed like a tedious task but it got easier as I broke it down. I first learned about new resume formats, wording that was more descriptive and then what should be included and removed. After those tweaks the phone started to ring.

Your life will be so much more satisfying when you get things moving. As you’re continuing with your action plan things will progress and you won’t feel like you’re going nowhere. You’ll be moving closer to your goals and farther away from stagnation.

Progress will heighten your sense of accomplishment and propel your confidence. And when you’re feeling good, life is good.

Have you ever felt stuck? What did you do to get back on track? You can share your comment by joining the conversation below.

:)