Calories burnt depend on time of day

US researchers have discovered that the number of calories people burn while at rest changes with the time of day. When at rest, people burn 10% more calories in the late afternoon and early evening than in the early morning hours. The findings reinforce the important role of the circadian clock in governing metabolism. They also help to explain why irregularities in eating and sleeping schedules due to shift work or other factors may make people more likely to gain weight. To determine changes over the course of the day in metabolism apart from the effects of activity, sleep–wake cycle and diet, the researchers studied 13 people in a special laboratory for 37 days, without any clues about what time it was outside. There were no clocks, windows, phones or internet. Seven participants underwent a recurrent circadian disruption protocol whereby their sleep–wake cycles or “days” were extended to 28 hours (the equivalent of traveling westward across four time zones each day for 3 weeks) with 11.67 hours in bed and 16.33 hours of wake time; six control participants maintained a normal 24-hour day with 8–10 hours in bed. All participants had a protocol that kept caloric intake, time in bed sleep opportunity, and exercise levels consistent over the duration of the study. The data showed that resting energy expenditure is lowest at the circadian phase the researchers designated as ~ 0°, corresponding to the dip in core body temperature in the late biological night. Energy expenditure was highest at circadian phase ~ 180°, about 12 hours later, in the biological afternoon into evening. The researchers found that participants’ respiratory quotient, which reflects macronutrient utilisation, varies by circadian phase too. This measure was lowest in the evening and highest in the biological morning. The researchers will next look at how appetite and the body’s response to food vary with the time of day. They are also exploring how the timing, duration and regularity of sleep influences those responses. Their study was published in Current Biology.

Artificial intelligence: servant or director of medical care?

An editorial in the BMJ has asked whether machines using artificial intelligence (AI) could ever make doctors obsolete. Dr Jörg Goldhahn, from the Institute for Translational Medicine in Switzerland, argued that, given the speed at which machines can learn, reason and self-correct, they could not be matched by humans. “The notion that today’s physicians could approximate this knowledge by keeping abreast of current medical research while maintaining close contact with their patients is an illusion, not least because of the sheer volume of data,” Dr Goldhahn wrote. Machine learning is also not subject to the same level of potential bias seen in human learning that reflects cultural influences and links with particular institutions, for example, he said. In addition, “trust is important [to patients] … but machines and systems can be more trustworthy [than humans] if they can be regarded as unbiased and without conflicts of interest”. The opposing view was presented by Vanessa Rampton, from the McGill Institute for Health and Social Policy in Canada, and Professor Giatgen Spinas, at University Hospital in Switzerland, who maintained that machines will never replace doctors entirely. “It can be crucial for patients to feel that they have been heard by someone who understands the seriousness of the problem and whom they can trust,” Rampton and Spinas argued. “Computers aren’t able to care for patients in the sense of showing devotion or concern for the other as a person, because they are not people and do not care about anything. Sophisticated robots might show empathy as a matter of form, just as humans might behave nicely in social situations yet remain emotionally disengaged because they are only performing a social role … A machine will never be able to show us true comfort. Ultimately, no one wants to be told he or she is dying by an entity that can have no understanding of what that means. We see AI as the servant rather than the director of our medical care,” they concluded.

Smoking, diabetes, high blood pressure increase women’s risk of heart attack

Australian researchers from the George Institute for Global Health have found that smoking, diabetes and high blood pressure increase the risk of a heart attack more in women than in men. The study, published in the BMJ, of 472 000 participants aged 40–69 years, found that smoking, diabetes, high blood pressure and having a body mass index (BMI) of 25 or over puts both men and women at increased risk of having a heart attack. However, while male current smokers have over twice the risk of a heart attack than men who have never smoked, female smokers were found to have over three times the risk of women who have never smoked, giving them a so-called excess risk. An excess risk was also found among women with high blood pressure, and type 1 and type 2 diabetes, but not with a high BMI. The excess risk of heart attack among people smoking 20 or more cigarettes per day when compared with people of the same sex who have never smoked was twice as big in women as in men. High blood pressure was associated with a more than 80% higher relative risk in women than in men, while type 1 diabetes was associated with an almost three times higher relative risk, and type 2 diabetes a 47% higher relative risk in women than in men. Researchers also looked at the risk of heart attack associated with ageing. While the increase in risk posed by factors such as smoking and high blood pressure lessened in both sexes as they grew older, the additional excess risk experienced by women was found to persist with ageing.

Drug could target leading cause of stroke in young people

A study led by researchers at the Centenary Institute in Sydney has identified a drug currently used to treat patients with cancer as a potential treatment option for a leading cause of stroke in young people. Cerebral cavernous malformations (CCM) occur when abnormal and dilated thin-walled blood vessels form clusters in the brain, altering blood flow. The condition affects as many as one in 200 people, and can cause bleeding, epilepsy and stroke. Most patients with CCM have no known genetic abnormality and only learn of their condition when they have a magnetic resonance imaging scan on their brain for an unrelated condition (eg, a blow to the head). Other patients only discover their condition after experiencing a symptom, such as a seizure or a stroke. Currently, the only treatment for CCM is surgery, which is not always possible, highlighting the urgent need for non-invasive, pharmacological treatment options. In a study published in Science Advances, researchers have identified a suitable candidate. Ponatinib is a drug that has been approved by the US Food and Drug Administration and is currently used to treat patients with cancer. Through using mice models, the researchers have discovered the drug also inhibits the signalling pathway of the enzyme MEKK3 — a process that is one of the causes of CCM. “Our next goal is to synthesise derivatives of ponatinib for specific use in CCM to maximise its efficacy, and to minimise any side effects,” the researchers said.

What’s new online at the MJA

12 November Perspective: Medicinal cannabis for chemotherapy-induced nausea and vomiting: prescribing with limited evidence
Mersiades et al; doi: 10.5694/mja17.01099
Although medicinal cannabis can now be prescribed for CINV, high quality clinical trial evidence is required to determine its efficacy and safety … FREE ACCESS for 1 week

12 November Podcast with Dr Antony Mersiades, medical oncologist and Clinical Trials Fellow at the National Health and Medical Research Council Clinical Trials Centre at the University of Sydney, talking about cannabis for chemotherapy-induced nausea and vomiting … FREE ACCESS permanently

12 November Editorial: Deprescribing proton pump inhibitors: why, when and how
Bytzer; doi: 10.5694/mja18.00674
The focus should primarily be on avoiding unnecessary long term prescribing of PPIs … FREE ACCESS for 1 week

12 November Podcast with Professor Peter Bytzer, Deputy Head of the Faculty of Medical and Health Sciences at the University of Copenhagen in Denmark, talking about deprescribing PPIs … FREE ACCESS permanently

12 November Research Letter: Gluten in “gluten-free” manufactured foods in Australia: a cross-sectional study
Halmos et al; doi: 10.5694/mja18.00457
More frequent gluten testing would reduce the risk for people with coeliac disease … FREE ACCESS permanently



The TGA should re-investigate the evidence for carbon dioxide laser therapy for vulvovaginal atrophy
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