What makes aspirin different from other NSAIDs is its ability to thin the blood, and it is used to prevent blood clotting in those at risk of heart disease and stroke. Recently, it has also shown potential to reduce the risk of some cancers.

How does it work?

Aspirin works by inhibiting an enzyme called cyclooxygenase, which generates prostaglandins. These are in turn associated with inflammation, pain and fever.

Through the same enzyme, aspirin also inhibits the production of substances called thromboxanes. These are responsible for the aggregation of platelets in the blood, a process needed to stop bleeding. This is what we mean when we say aspirin “thins the blood.”

The mechanism whereby aspirin might be protective against cancer is not fully understood but certain genetic and other characteristics may identify those who might particularly benefit.

History

In the 16th century BC, Egyptians documented on papyrus that the bark and leaves of willow and related plants had pain-relieving and anti-inflammatory properties. The Greek physician Hippocrates later noted these same properties in the 5th century BC.

Aspirin’s more recent history came from purifying salicylate, the active component in ancient preparations. In 1897, this culminated in the development of acetylsalicylic acid or aspirin.

Today’s interest in aspirin stems largely from the seminal 1971 publication by English pharmacologists John Vane and Priscilla Piper, who discovered its action in inhibiting prostaglandin production. In 1982, Vane shared the Nobel Prize in Physiology or Medicine for his work in this area.

In 1950, an American general practitioner Lawrence Craven noted that patients who had their tonsils removed and chewed Aspergum (a gum containing Aspirin) experienced severe bleeding. He later said daily aspirin appeared to prevent heart attacks in his patients.

Craven’s claims were doubted by fellow doctors because they were not the subject of randomised trials. This was around the time that the importance of blood clots in events such as heart attack was recognised, and methodology that informed the robust design and interpretation of very large clinical trials was developed.

These trials included aspirin among the first therapies tested. A recent overview of such trials showed that aspirin, when compared to inactive placebos, reduced serious vascular events such as heart attack and stroke by about 12% in those who had not previously had such conditions, and by about a fifth in those who had experienced them.

However, the overview also confirmed that benefits came at the cost of severe bleeding (due to aspirin’s ability to prevent clotting) from the stomach and bowel, or resulted in bleeding into the brain.

It is now apparent that factors such as advancing age, smoking and diabetes increase not only the risk of heart attack and stroke, but also major bleeding. This means aspirin can’t be prescribed indiscriminately for everyone.

Aspirin and cancer

In 1988, Melbourne surgeon Gabriel Kune reported that aspirin was associated with lower rates of bowel cancer.

Subsequently, trials supported reduced cancer rate and death in those taking aspirin, not only of the bowel but also of some other organ types. However, cancer was not specified as a major outcome of interest at the beginning of these studies, and because of this, was not examined rigorously.

How is it used?

Australian guidelines for the use of low-dose aspirin to prevent heart events and stroke are clear cut. If aspirin does not cause problems, such as severe bleeding, it should be used life-long in everyone who has experienced heart-related events such as angina, heart attack, coronary bypass surgery and stroke.

In those who haven’t experienced these, decisions on aspirin use must be based on weighing up individual risk of bleeding and these events occurring in the future.

The latest, authoritative recommendations by the U.S. Preventive Services Task Force about prevention of cardiovascular disease and bowel cancer state that for those aged 50 to 69, taking aspirin depends on the estimated risk of events that might be prevented, and also of bleeding and life expectancy.

In those aged less than 50, or 70 years or over, there is insufficient evidence to assess the balance of benefits and harms of initiating aspirin use.

Present Australian guidelines for the prevention of bowel cancer state there is insufficient evidence to recommend aspirin for all people at average risk, and emphasise that diet and lifestyle improvements, as well as screening, are effective in reducing risk.

However, those with a strong family history of bowel cancer should often be referred for specialist assessment and aspirin might be recommended after genetic testing.

The low dose of aspirin typically used is 100mg daily. This is much less than that which might relieve a headache, other pain or fever, and for which paracetamol is generally recommended in the first instance.

Who shouldn’t use it?

Use of aspirin should be discussed with a doctor as it should not be used in those who have had a previous allergic reaction to aspirin or other NSAIDs, are pregnant or breastfeeding, have bleeding or clotting disorders, active stomach bleeding or a history of previous bleeding after treatment with aspirin, gastritis or an active or previous stomach ulcer, a history of gout, or severe kidney or liver failure.

Aspirin should be taken with water, with or without food. Taking an enteric-coated tablet, which is designed to prevent the aspirin from being released in the stomach, decreases the chance of an upset stomach.

How much does it cost?

Aspirin is relatively cheap and the cost can range from A$0.95 for a 24-pack of 300mg tablets to A$2.99 for 100 tablets of 100mg.

Other points of interest

The ongoing ASPirin in Reducing Events in the Elderly (ASPREE) study, conceived and initiated in Australia, has completed recruitment and is following up more than 16,700 healthy Australians aged 70 years and over, and almost 2,500 people in the United States. It involves more than 2,000 Australian general practitioners as co-investigators.

The primary question investigated is whether aspirin improves healthy active life years (time lived free of dementia or physical disability), outcomes fundamentally important to the elderly. This encapsulates the net effect of benefits and risks of aspirin.

The trial will also provide unique data concerning whether aspirin prevents cancer in the elderly. It is anticipated that ASPREE’s findings will be reported in 2018.

Surgeons often decide to perform procedures because that’s what’s usually done, it’s what they’re taught, it sounds logical or it fits with observations from their own practice.

If the surgeon’s decision is in line with evidence from scientific studies, there’s little problem. But if the two conflict, either the surgeon’s opinion or the evidence is wrong.

The best way to test whether surgery works (particularly when the outcome is subjective, such as with pain) is to compare it with a sham or placebo procedure. The idea is to keep the patients and those who measure the effectiveness “blinded” to which treatment is given.

A review of studies comparing surgery to sham or placebo surgery showed surgery was no better than placebo in just over half of the studies. And in studies where surgery was better than placebo, the difference was generally small.

As an example, two studies compared placebo surgery to keyhole surgery (arthroscopy) of the knee in patients with degenerative conditions (arthritis, meniscus tears and catching and clicking). Both studies showed no important difference in surgery outcomes between the two groups.

What about other options?

We don’t always need to compare surgery with a sham. Sometimes comparing surgery with non-surgical treatment (like physiotherapy or medications) is more appropriate.

One study looked at all orthopaedic surgical procedures performed on more than 9,000 patients in three hospitals over three years. Only half the procedures were compared with non-operative treatment. And of that half, about half were no better than not operating.

So there are two problems in surgery: an evidence gap (in which there’s a lack of high quality evidence) and an evidence-practice gap (where there’s high quality evidence that a procedure doesn’t work, yet is still performed).

Part of the problem is that operations are often introduced before there’s good quality evidence of their effectiveness in the real world. The studies comparing them to non-operative treatment or placebo often come much later – if at all.

When should surgery be funded?

Doctors should not perform surgical procedures and taxpayers should not have to cover their cost until there’s high quality evidence they work. It should be unethical for surgeons to introduce a new technique without studying whether or not it works.

Unfortunately, the opposite is true: ethical approval is not required before surgeons can start performing new procedures, but it is required to study the effectiveness of that procedure.

Often, procedures surgeons consider effective are later shown not to be.

In the US in the 1980s, a new procedure for the lung disease emphysema touted removing some lung tissue. Animal studies and (non-comparative) human studies were encouraging. So the procedure became common.

Some surgeons called for a trial comparing the procedure to non-operative treatment. But proponents of the procedure said this would deprive many people of the procedure’s benefits, the effectiveness of which was obvious.

Medicare in the US decided only to fund the surgery if patients took part in a trial comparing it to non-surgical treatment. The trial was done and the surgery was found wanting, with no overall benefit over non-operative treatment. The trial cost the government some money, but much less than paying for the procedure for decades until someone else studied it.

This type of solution should be considered in Australia: new procedures should only be funded by the public if they are performed as part of a trial to adequately test their effectiveness.

Once evidence is available, the key is using it to make good decisions about the effectiveness of a particular procedure for an individual patient. So how should surgeons do that? The answer lies in measuring the right outcomes to begin with and then making shared decisions.

How do we know if surgery works?

Billions are spent worldwide on surgical procedures that may not be effective. But how should we define effectiveness?

There is a growing acceptance that doctors should partner with patients to identify outcomes important to them. These might include avoiding complications and an unexpectedly long stay in hospital. But they should also consider longer-term quality of life, disability and survival.

This is important when a good operation might be a bad choice. Some medical conditions herald a terminal decline in health, for which living longer is not as good as living well. A good operation may also be a bad choice in cases where attempts at prolonging life are futile.

Sharing decisions

Shared decision-making takes into account beliefs, preferences and views of the patient as an expert in what is right for them, supported by clinicians who are the experts in effective therapeutic options.

Patients should have the opportunity to ask further questions when deciding whether to go ahead with surgery to see if surgery is consistent with their values and lifestyle goals. For the critically ill, frail or confused, this discussion should often include the person’s spouse, family or next of kin.

The right decisions in surgery are patient-centred, based on good evidence, clearly communicated and made in a supportive environment. Everyone – doctors, other health professionals, the patient, sometimes their family, and the public – have a right and a responsibility to be included.

It’s a sobering fact that one in two Australian men and one in three Australian women will be diagnosed with some form of cancer by the age of 85. It’s even more alarming when you consider these statistics do not include the most common skin cancers (basal cell carcinoma and squamous cell carcinoma of the skin). It is estimated hundreds of thousands of Australians are treated for these each year.

The number of new cases of cancer diagnosed has increased dramatically in the last three decades. In Australia, 47,445 new cases of cancer were diagnosed in 1982 and 122,093 in 2012. This has led some to think the risks of acquiring cancer are on the increase in modern society.

Of course, increased population accounts for much of the increase in these figures. But the other major factor is modern medicine increasing our lifespan. As we survive diseases and live longer, more of us are succumbing to cancer.

The risk of cancer increases as we age

A closer look at the cancer figures in relation to age at diagnosis shows a clear and dramatic increase in cancer as we age. For children and adults up to their forties, the incidence of cancer is quite low, but then increases quite dramatically as we get older.

The incidence of cancer is around ten times higher in people 60 years and older, than in those under 60.

Cancer: a disease of our genes

So, why is it we’re more likely to get cancer as we get older? Cancer is a disease caused by errors in our genes – the DNA code in our cells that provides the blueprints for all cell functions. These errors arise for a number of reasons.

Chemical carcinogens and radiation are two factors many immediately think of, and can be major players in some cancers. Chemical carcinogens in cigarette smoke contributing to lung cancer and UV radiation contributing to melanoma are two obvious examples.

We can also inherit some genetic errors. For example, defective BRCA genes are passed down in some families and contribute to a number of cancers, including those of the breast and ovary. Some viruses can also contribute to cancer, such as the human papillomavirus (HPV) with cervical cancer.

Another main reason for genetic errors arising, however, comes from normal biology. The body is made up of many trillions of individual cells, and in most cases these individual cells have a defined lifespan.

As these cells die they’re replaced by new cells that arise from the division of another cell into two; a process that requires replication of all of the cell’s DNA.

Despite this DNA replication being highly controlled and very accurate, the sheer number of times it is performed in the lifespan of a person (estimated to be 10,000 trillion times!) means the introduction of a significant number of errors into the DNA of some of our cells from this fundamental process is inevitable.

Many gene errors are needed for cancer to develop

So we all have “errors” in our genes. The vast majority of these errors have no effect, or simply add to our individual uniqueness. For example, some “errors” in the MC1R gene have fortuitously given us individuals with red hair.

But some specific errors in certain genes can be “cancer-promoting” by causing the cells to become overactive and not restrained by the usual mechanisms the body cleverly employs to keep every cell in check.

Human cells are incredibly well controlled, with many safety mechanisms. This means single “cancer-promoting” errors in the DNA code of a cell do not cause cancer. Instead, many different “cancer-promoting” errors are required in genes that control specific types of cell processes, like cell division, programmed cell death and cell movement.

Studies have shown the number of different “cancer-promoting” genetic errors required in a single cell is at least six. For the development of most cancers it is likely many more are needed. Only when all of these errors are present in the same cell can that cell have a chance to progress to producing a cancer.

To accumulate the “right” set of errors to drive transformation of a normal cell into cancer normally takes a long time. Thus, the longer we live, the more time there is for errors in our genes to accumulate.

At present there is not much we can do to prevent ageing. But we can reduce risks from external factors, such as avoiding chemical carcinogens like those in cigarette smoke, reducing exposure to UV radiation from the sun and, where appropriate, participating in vaccination programs for HPV

The world’s population, and Australia’s, is ageing. The number of adults aged 65 and over is increasing, as is the proportion of the population they represent. However, there are a number of myths associated with what happens to our brain and bodies as we age.

1. Dementia is an inevitable part of ageing

Dementia prevalence increases with age. That is, your chance of having a diagnosis of dementia is greater the older you are. But if you are lucky enough to reach old age, you won’t necessarily have dementia. Dementia is a clinical diagnosis that is characterised by impairments in cognition (the way we think) and functional abilities (that enable us to live independently).

The major type of dementia is Alzheimer’s disease, although there are many other types, such as vascular dementia (related to vascular changes in the brain such as stroke), frontotemporal dementia (brain atrophy most pronounced in temporal and frontal cortical regions of the brain), Lewy body dementia (related to a particular protein deposit called a Lewy body) and mixed – where different types occur at the same time.

However, less than 2% of adults 65-69 years of age have a dementia diagnosis, and this rises to over 30% for those 90 years and over. The flip side of this is that nearly 70% of those aged 90 years and over don’t have dementia. In Australia in 2014, the median age at death was 79 years for males and 85 years for females; so, most of us won’t die with a dementia diagnosis.

2. Cognition declines from the 20s

Cognition refers to the way we think, but there are lots of types of thinking skills. For example, the speed at which we can respond (processing speed), our ability to remember objects (general memory), and our knowledge of words and their meaning (vocabulary knowledge). These cognitive domains show different patterns of change across adulthood.

Processing speed and general memory do appear to decline from the 20s, which means we are slower at responding to relevant cues and a bit more forgetful as we age. But this is not the case for vocabulary knowledge. On average, we will reach our peak word knowledge in our 60s, and our performance will not markedly decline after that. In fact, multiple studies show the older your age, the better your performance on the New York Times crossword.

3. I can’t change my risk of dementia

It has been estimated that up to 30% of worldwide dementia cases are preventable through lifestyle choices. Evidence shows mid-life heart factors, especially diabetes, high blood pressure, obesity and physical inactivity, increase the risk of developing dementia in late-life, as does having depression, smoking and having low educational attainment.

So, one way to decrease your risk of dementia is to reduce your heart risk factors – for example, exercise more and reduce your weight if you are obese. Engaging with cognitively stimulating activities such as formal (such as university) and informal (such as short-courses) education, and social meetings, has been shown to reduce the risk of dementia.

This evidence ties in nicely with recent studies from Europe and the US, which have demonstrated an individual’s risk of dementia has actually decreased over the past two decades. Why? Well, it is appears that older adults are now more physically and cognitively healthy than their predecessors.

4. I’ll get dementia if my parents did

Late-life dementia, which is diagnosed when you are 65 years and over, is only influenced slightly by the genetics your parents passed onto you. Nine genes have been identified that either increase or decrease your risk for dementia. There is one that carries some influence: apolipoprotein E. If you have one combination (E4E4 alleles), you are at 15 times more likely to get dementia as someone with the more typical combination (E3E3). However, all other identified genes have only a small effect, with each putting you at a 20% increased or decreased risk of developing the disease.

To put these genetic risks in perspective, they are smaller than each of the lifestyle factors mentioned above. That is, dementia is more likely to be caused by obesity (60% more likely) or being inactive (80% more likely). These comparisons are not perfect, as it may be that genes related to dementia also relate to these lifestyle factors, but it does show how powerful lifestyle factors are.

5. My weight will stay the same

Simple physics energy laws tell us that if the calories we are eating match the energy we are burning, our weight will essentially be stable. Most people believe in this simple and truthful nutritional dogma, but fail to take into account the significant effects of ageing on energy metabolism.

As we age, our body composition changes. In particular, we tend to have a reciprocal change in fat (increase) and muscle (decrease), and these changes appear to be different in men and women. Men appear to have a steeper decline in muscle tissue, which accounts for a decline in the total energy expenditure of about 3% per decade.

In women, the rate is slightly slower compared to men (about 2% per decade). This simply means if you continue to eat and exercise at the same level as you age, you will likely gain weight, and this will mostly consist of body fat.

Ageing is not a passive biological process. We need to better understand our body and its changes if we want to maintain health and prevent the onset of diseases such as dementia.

Taking some nutrient supplements together with antidepressants can enhance the medication’s effects, our research has found.

Published this week in the American Journal of Psychiatry, our review of the evidence found that omega-3 fish oil, methylfolate, vitamin D and amino acid compound S-adenosine methionine (known as SAMe) supplements increased the effects of antidepressant medication for those with clinical depression.

We reviewed 40 clinical trials that explored the effects of using nutrient supplements together with antidepressants as therapy for clinical depression.

The strongest finding in our meta-analysis – a combination of outcome data from several studies into one analysis – was that taking omega 3 fish oil supplements high in the fatty acid EPA, in combination with antidepressants, was significantly more effective than a dummy pill.

Many studies have shown omega-3 supplements are good for general brain health and improving mood. But this is the first analysis of studies that looks at using the supplements in combination with antidepressant medication for clinical depression.

Our findings mean we have an evidence-based, safe approach that could be considered a mainstream treatment for depression. But we advise anyone considering changing or initiating treatment to consult their doctor.

Nutrients and mental health

Dietary nutrients, such as vitamins B, C and D, omega-3 fatty acids and minerals such as zinc and magnesium, are critical for brain health. We also know that when given as supplements, they may be beneficial to mental health.

Doctors recommend some of these supplements in cases where a blood test has confirmed nutrient deficiencies. But doctors are often hesitant to advise using supplements as part of mental health therapy. This is partly because it’s unknown whether prescribing nutrients with antidepressants is more effective for depression, and whether there are safety concerns about this approach.

To answer these questions, our research team from the University of Melbourne and Harvard Medical School examined worldwide trials from the 1960s to today. The studies had aimed to see if certain nutrients were effective in improving a person’s depression when taken together with different types of antidepressants, such as the popular selective serotonin re-uptake inhibitors (SSRIs).

Overall, we found more patients in the studies showed an improvement in mood when prescribed omega-3 fish oil, methylfolate, vitamin D and SAMe supplements in combination with antidepressant medication, compared to those who took medication only.

The evidence revealed mixed results for zinc, vitamin C and tryptophan (an amino acid molecule that is a precursor to some neurotransmitters such as serotonin). Folic acid didn’t work particularly well, nor did the compound inositol (a small molecule structurally similar to glucose).

How nutrients could complement medications

We are increasingly understanding how some nutrients may improve depression.

Omega-3 and SAMe, for instance, can alter mood-regulating neurotransmitter levels in the brain in a similar way to certain antidepressant medications.

Other nutrients, when taken together with antidepressants, could potentially give depression sufferers the extra boost they need as they may work on an additional range of brain chemical pathways. Omega-3 and zinc, for instance, may act by reducing inflammation, which has been implicated in depression.

Nearly 2 million Australians take antidepressants. But research shows many with depression still experience some symptoms despite several months of treatment with antidepressant medication.

The mental health of people who have an inadequate response to antidepressants can potentially be improved by supplementing their use with nutrients. Clinicians and the public can consider therapeutic doses of particular nutrients as a potential low-cost approach to reducing depression in these instances.

Our evidence review found no major safety concerns in combining many of the nutrient supplements studied with medications, but it is important to stress that supplements can differ in quality. We advise people to always speak with their medical professional before changing or initiating any treatment.

It is also important for those suffering from depression to see medications and supplements as one potentially important element in an integrative approach. This should include psychological care and consideration of lifestyle factors, such as a good wholefood diet, exercise and sufficient sleep.

We are recruiting for an NHMRC-funded clinical trial in Melbourne and Brisbane to see if using these nutrients in combination will enhance the effects of antidepressant medication even more.

The United States Food and Drug Administration (FDA) approved the drug flibanserin (sold under the brand name Addyi) for the treatment of women with hypo-active sexual desire disorder (HSDD) in August 2015.

Australia hasn’t followed suit, though flibanserin is available through internet pharmacies. However, its limited effectiveness and serious side-effects should cause potential users to rethink purchasing flibanserin online.

What does it ‘treat’?

Hypo-active sexual desire disorder HSDD was listed in the DSM-4, the previous edition of the Diagnostic and Statistical Manual of Mental Disorders. The disorder relates to persistently deficient (or absent) sexual fantasies and desire for sexual activity, which causes marked distress and relationship problems.

For a diagnosis, HSDD could not be due to the physiological effects of a substance or a general medical condition. Estimates of the prevalence of sexual desire problems vary widely depending on the criteria used – from 3% to 31% in one study. Others suggest up to 43% of women may experience low sexual desire.

However, there is fierce debate about the definition of disorders of sexual desire, with HSDD described as a “highly controversial diagnostic construct”.

The newer DSM-5, published in May 2013, combined features of HSDD and another condition known as female sexual arousal disorder, to form a new condition, female sexual interest/arousal disorder (FSIAD). This has stricter diagnostic criteria and as yet unknown prevalence.

Originally trialled as an antidepressant, flibanserin found new life as a treatment for low sexual desire in women.

After being rejected for approval by the FDA in 2010, developers Boehringer Ingelheim transferred the rights to Sprout Pharmaceuticals, which finally and controversially secured FDA approval in August 2015.

How it works

Flibanserin modulates neurotransmitters in the brain, increasing levels of dopamine and norepinephrine and decreasing serotonin.

As dopamine and norepinephrine promote sexual arousal, and serotonin reduces sexual arousal, flibanserin may increase libido by improving the balance between these neurotransmitter systems.

Problems and controversies

The US FDA approval process was mired in controversy, particularly in relation to the active role of Sprout Pharmaceuticals in lobbying. It funded a high-profile public advocacy campaign called Even the Score, which misleadingly claimed the drug was initially rejected because of FDA sexism.

Despite counter campaigns by scientists and doctors, the FDA scientific advisory committee voted 18 to six in favour of approving the drug, with the condition that risk-management options were put in place.

The committee members were concerned the drug had significant risks from side-effects, particularly if used off label or taken in combination with alcohol, and few benefits. The committee’s recommendation that the drug be approved therefore attracted widespread criticism that it allowed politics to trump clinical science.

Within hours of the FDA approval, Sprout Pharmaceuticals was acquired by Valeant for $US1 billion. Valeant set the price of Addyi at $US800 per month, leading to accusations of price gouging.

Sales flagged as insurers refused to cover the drug. With its stock value plummeting, Valeant reportedly dismissed the drug’s entire sales team and said it planned to reintroduce the drug at a later date. The company may be waiting until the 18-month restriction on direct-to-consumer marketing is over.

Safety and efficacy

A recent review of studies – including five published and three unpublished randomised clinical trials involving 5,914 women – concluded the overall quality of the evidence for both efficacy and safety outcomes was very low.

The published studies reported more favourable outcomes than unpublished studies. The authors’ attempts to gain further information from study leaders and sponsors were not successful.

Side-effects include dizziness (11.4% of users), drowsiness (11.2%), nausea (10.4%), fatigue (9.2%), insomnia (4.9%) and dry mouth (2.4%). The most serious problems – low blood pressure and a resulting loss of consciousness – are amplified by concurrent alcohol use.

Other serious adverse events were uncommon but flibanserin can’t be viewed as safe without further studies including a broader range of diverse women.

The FDA approved flibanserin on condition it carry a black-box warning not to drink alcohol while taking the medication.

The manufacturer is also required to undertake three additional studies to examine the side-effects among women using alcohol with the drug. Strangely, the evidence about alcohol interactions with flibanserin presented to the FDA included data on 25 healthy volunteers, of whom only two were women.

Side-effects are lessened if taken at night, but it has been reported about one out of every eight women will discontinue flibanserin because of adverse effects.

A rigorous meta-analysis showed that, on average, flibanserin led to one-half an additional sexually satisfying event per month. This is a less optimistic finding than the (still underwhelming) one extra sexually satisfying event per month frequently quoted by reports.

Availability and cost

Flibanserin is approved for prescription only in the US; it is not available in Australia. US doctors must be certified before prescribing it, and dispensing pharmacists must also complete training.

In the first month it was available, Addyi (the brand name of flibanserin) was prescribed just 227 times, compared with more than half a million for Viagra in its first month. Doctors had prescribed the drug fewer than 4,000 times as of February this year.

In the US, a one-month supply of flibanserin (one 100mg tablet per day, taken at bed time) costs between $US200 to $US830, depending on insurance coverage and means of acquisition. That’s a lot of money for an extra sexually satisfying experience every two months.