Ketamine breakdown may be depression breakthrough
A specific substance formed from the breakdown of ketamine may be responsible for the rapid and sustained antidepressant effects of the drug, according to research in mice published in Nature. A single administration of this metabolite in mice induced the antidepressant effects of ketamine without its associated side effects. Current pharmacological treatments for severe depression can take weeks to alleviate symptoms, and some patients do not respond to these treatments at all. The drug ketamine has been studied as a promising alternative to existing antidepressants and has shown efficacy in clinical trials, but it has the potential to be abused and can cause feelings of detachment from the environment and self (dissociation), which limits its potential for widespread clinical use. Researchers from the University of Maryland School of Medicine in the US found that a single administration of the ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) in mice had antidepressant effects that were similar to those induced by ketamine and that persisted for at least 3 days. They further showed that (2R,6R)-HNK did not have the side-effects observed following ketamine administration and that, when given the option, mice self-administered ketamine, but not (2R,6R)-HNK. The study also revealed that ketamine’s antidepressant properties in mice were in fact due to the metabolite rather than ketamine itself and that its antidepressant effects were not dependent on the inhibition of a particular receptor in the brain that was previously thought to be involved.

Could doctors be replaced by artificial intelligence?
The role of the doctor as an expensive problem-solver may become redundant in the future, according to health experts commenting in the New Zealand Medical Journal. The authors believe that over the coming years, artificial intelligence (AI) will diagnose most health problems and even decide what treatment the patient should have. The health experts say that humans would continue to be an important part of health care delivery, but in many situations they would only be trained to fill the gaps where artificial intelligence is less capable. “Human doctors make errors simply because they are human, with an estimated 400 000 deaths associated with preventable harm in the US per year,” the authors wrote. “Furthermore, the relentless growth of first world health care demands in an economically-constrained environment necessitates a new solution. Therefore, for a safe, sustainable health care system, we need to look beyond human potential towards innovative solutions such as AI. Initially, this will involve using task-specific AI as adjuncts to improve human performance, with the role of the doctor remaining largely unchanged. However, in the longer term, AI should consistently outperform doctors in most cognitive tasks. Humans will still be an important part of health care delivery, but in many situations less expensive, fit-for-purpose clinicians will assume this role, leaving the majority of doctors without employment in the role that they were trained to undertake.”

Blood pressure, atrial fibrillation and vascular risk
Researchers from the George Institute of Global Health and the University of Sydney, have used data for 4 301 349 patients from the Clinical Practice Research Datalink and found that the association between elevated blood pressure and atrial fibrillation (AF) attenuates with increasing age. The research, published in the International Journal of Epidemiology, found that AF without antithrombotic usage is associated with an increased risk of eight vascular events. A 20mmHg higher than usual systolic blood pressure was associated with a 21% higher risk of AF. However, the strength of the association declined with increasing age. AF without antithrombotic use at baseline was associated with a greater risk of any vascular event than AF with antithrombotic usage (P interaction < 0.0001). AF without baseline antithrombotic usage was associated with an increased risk of ischaemic heart disease (hazard ratio [HR], 2.52; CI 2.23, 2.84), heart failure (HR, 3.80; CI, 3.50–4.12), ischaemic stroke (HR, 2.72; CI, 2.19–3.38), unspecified stroke (HR, 2.59; CI, 2.25–2.99), haemorrhagic stroke, chronic kidney disease, peripheral arterial disease and vascular dementia, but not aortic aneurysm. “AF was further found to be a risk factor for a range of fatal and non-fatal vascular events, suggesting that existing and novel treatments for AF may have greater beneficial effects than currently assumed. Further research should determine whether the described associations are causal,” the researchers concluded.

NEJM reports add to Zika evidence base
A special report and a letter published in the New England Journal of Medicine have added to the evidence base supporting hypotheses about the transmission of, and consequences of, Zika virus for pregnant patients. The letter, written by French researchers, detailed the case of a healthy 24-year-old woman, living in Paris, who developed Zika virus infection despite the facts that “she was not receiving any medication, had not received any blood transfusions, and had never traveled to a region where Zika was epidemic or to tropical or subtropical areas”. Her last trip outside France was to Okinawa, Japan, late in 2015. In mid-February, she had sexual contact with a 46-year-old man who had had Zika virus infection while in Rio de Janeiro in early February. “We cannot rule out the possibility that transmission occurred not through semen but through other biologic fluids, such as pre-ejaculate secretions or saliva exchanged through deep kissing,” the researchers wrote. “But, to our knowledge, no cases of transmission through saliva have been documented.” The special report, by US authors, which “evaluated available data using criteria that have been proposed for the assessment of potential teratogens”, concluded that “a causal relationship exists between prenatal Zika virus infection and microcephaly and other serious brain anomalies”. “Many questions that are critical to our prevention efforts remain, including the spectrum of defects caused by prenatal Zika virus infection, the degree of relative and absolute risks of adverse outcomes among fetuses whose mothers were infected at different times during pregnancy, and factors that might affect a woman’s risk of adverse pregnancy or birth outcomes.”

Spinal decompression plus fusion surgery no better than decompression alone
Swedish research, published in the New England Journal of Medicine, has found that “among patients with lumbar spinal stenosis, with or without degenerative spondylolisthesis, decompression surgery plus fusion surgery did not result in better clinical outcomes at 2 years and 5 years than did decompression surgery alone”. The researchers randomly assigned 247 patients between 50 and 80 years of age who had lumbar spinal stenosis at one or two adjacent vertebral levels to undergo either decompression surgery plus fusion surgery (fusion group) or decompression surgery alone (decompression-alone group). Randomisation was stratified according to the presence of preoperative degenerative spondylolisthesis (in 135 patients) or its absence. Outcomes were assessed with the use of patient-reported outcome measures, a 6-minute walk test, and a health economic evaluation. There was no significant difference between the groups at 2 years in the mean score on the Oswestry Disability Index or in the results of the 6-minute walk test. Results were similar between patients with and those without spondylolisthesis. Among the patients who had 5 years of follow-up and were eligible for inclusion in the 5-year analysis, there were no significant differences between the groups in clinical outcomes at 5 years.

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