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[Comment] Pragmatic trials in critically ill children are CATCHing on

The many barriers impeding performance of clinical trials in critically ill children1 have resulted in a paucity of evidence guiding bedside practice.2 Children admitted to a paediatric intensive care unit are heterogeneous. Not only does age vary (ie, from newborn babies to adolescents), but also the broad causes of illness include congenital disorders, recovery from surgery, neurological emergencies, overwhelming infections, and traumatic injuries. Traditional explanatory trials are designed to test causal research hypotheses by assessing a tightly controlled intervention in a selected subgroup of patients.

[Comment] Antibiotic stewardship: prescribing social norms

With a burgeoning world population, expansions in medical intervention, and intensified agriculture, the need for antibiotic stewardship is increasingly clear.1 Declining efficacy of antimicrobial prophylaxis for surgery or chemotherapy,2 and emergence of pan-resistant pathogens,1 warn of a post-antibiotic era. In the evolutionary arms race of antimicrobial resistance, rejuvenating the neglected pipeline for new agents provides only a partial solution.3 The key challenge worldwide is translating awareness of resistance into effective stewardship.

[Correspondence] The GAS trial – Authors’ reply

Beverley Orser and colleagues correctly point out the limitations of our study,1 which were also highlighted in our discussion and the accompanying Comment.2 We agree that a more extensive follow-up of the children aged 5 years is essential, that indeed is our primary outcome. We also agree with Markus Weiss and colleagues that there are many other factors besides possible anaesthetic neurotoxic effects that might influence the short-term and long-term outcome of anaesthesia and surgery in infants.

A new way to breathe easier

A minimally invasive surgical procedure to prevent airways constricting could substantial improve control of asthma and reduce reliance on medication to manage the condition.

An Australian trial of 17 patients has found that bronchial thermoplasty, which involves using the heated tip of a catheter inserted into the airway to burn away excess smooth muscle, has found the procedure to be safe while delivering significant benefits in controlling asthma.

The procedure has been likened to the use of laser surgery to improve eyesight, and Director of Thoracic Medicine at Peninsula Health, Associate Professor David Langton, who was lead researcher of the trial, said the technique could be a game changer.

“We’re at the tip of a new paradigm for how we treat asthma,” A/Professor Langton. “The results of these trials could have a global impact and completely revolutionise our approach.”

Around 2.3 million Australians have asthma, and up to 10 per cent have difficulty managing the condition using standard treatments such as inhalers.

The trial involved patients with both moderate and severe forms of the condition, and found response to bronchial thermoplasty was greatest among those suffering asthma the worst. Encouragingly, the benefits have been sustained.

A/Professor Langton has called for the widespread adoption of the procedure.

“This is a safe, effective, affordable procedure that has the potential to transform the lives of people struggling to control their asthma, offering the hope of less medication and an improved quality of life,” he said. “The sooner we can make it available to those that need it, the better.”

The research was presented to the Thoracic Society of Australia and New Zealand’s Annual Scientific Meeting.

Adrian Rollins

News briefs

Gender differences in pre-hospital care

A Swedish study published in BMC Emergency Medicine has found that female trauma patients were less likely to be given the highest pre-hospital priority, the highest pre-hospital competence level, and direct transport to the designated trauma centre compared with male trauma patients. A retrospective observational study based on local trauma registries and hospital and ambulance records in Stockholm County, Sweden, was conducted. A total of 383 trauma patients (279 males and 104 females) over 15 years of age with an Injury Severity Score (ISS) of more than 15 transported to emergency care hospitals in the Stockholm area were included. Male patients had a 2.75 higher odds ratio (95 % CI, 1.2–6.2) for receiving the highest pre-hospital priority compared with females on controlling for injury mechanism and vital signs on scene. “We found differences in trauma mechanism between genders, namely, that the second most common trauma mechanism for females was a low-energy fall (26.9 %) … Perhaps this might be one of the reasons why females, despite severe injury, are not recognised at scene as potential severe trauma patients since the trauma mechanism is considered to be of low energy. Recognising gender differences with educational efforts and in pre-hospital trauma management protocols may expedite the trauma care of female patients.”

Bad hair day in space for some astronauts

Research published in PLOS One has found that spaceflight alters human hair follicle gene expression, leading to a possible “inhibition of hair growth in space”, particularly among male astronauts. “We found that FGF18 expression in the hair follicle changed during spaceflight. Hair follicle growth during anagen is strongly suppressed by the local delivery of FGF18 protein. Epithelial FGF18 signaling and reduction of expression in the milieu of hair stem cells are crucial for the maintenance of resting and growth phases,” the authors wrote. They also found that “FGF18 expression is known to decrease in growing hair follicles; the increase in FGF18 expression in several astronauts during flight potentially reflects a temporary arrest in the hair growth cycle; FGF18 expression appears to be very sensitive to whether an astronaut is in space or earth-bound; FGF18 easily recovered to baseline levels after returning to Earth”. Gender also has its effect, they found. “Although there are many differences such as hormone levels or functions between males and females, female astronauts appear to have a better response against the features of the space environment, as one example, FGF18 expression in females was more stable in space than in males.”

FDA clears experimental Zika blood test for use

The US Food and Drug Administration (FDA) has announced that it will allow the use of an experimental test to screen blood donations for contamination with the Zika virus, the New York Times reports. Puerto Rico, who had halted local blood donations and had imported almost 6000 units of blood from the US, will therefore be able to resume local collection. Zika poses a special challenge to blood banks, the report said, because roughly 80% of people who are infected do not have symptoms. “A handful of cases of Zika infection via blood transfusion have been reported in Brazil. During the 2013 French Polynesian outbreak, researchers found roughly 3% of asymptomatic blood donors actually tested positive for Zika infection, which they deemed unexpectedly high. It is not yet known how commonly recipients of Zika-contaminated blood end up infected, or how they fare.”

ASR hip replacement case settles for $250 million

Hundreds of Australians implanted with a defective hip device will be eligible for a share of $250 million in compensation following the conditional settlement of a long-running class action, the ABC reports. A worldwide recall of DePuy ASR devices in 2010 involved around 100 000 patients worldwide and 5500 in Australia, with approximately 1700 of those patients eligible for a share in the settlement. The settlement was negotiated after 17 weeks in court, but has yet to be approved by the Federal Court. A lawyer speaking on behalf of those bringing the class action said hundreds of Australian patients had yet to have revision surgery and they were welcome to join the class action which will remain open for a period. “There was no admission of liability by the makers of the ASR DePuy hip replacements as a part of the settlement.”

[Editorial] Fixing emergency general surgery in England

In 2012, mortality rates for emergency laparotomies were reported to vary from 3·6% to 41·7% across 35 hospitals in England. Such shocking variation between health providers is one of the key problems facing emergency general surgery in England and little seems to have improved since 2012. A Nuffield Trust report commissioned by the Royal College of Surgeons aims to define these problems and outline potential solutions. With the challenges posed by the UK’s ageing population, declining numbers of doctors in training, and hospitals struggling to fill 24/7 staffing rotas, such solutions are needed now more than ever.

The world is turning to flab

Rich countries are facing an epidemic of severe obesity and around one in five worldwide will be obese by the middle of next decade unless there is a major slowdown in the rate at which people are putting on weight, according to a major international study involving data from 19 million adults across 186 countries.

Already, more than 2 per cent of men and 5 per cent of women are severely obese, and researchers have warned that the prevalence is set to increase and current treatments like statins and anti-hypertensive drugs will not be able to fully address the resulting health hazards, leaving bariatric surgery as the last line of defence.

In a result which underlines the extent of the obesity challenge, research by the NCD Risk Factor Collaboration* has found that that between 1975 and 2014, the prevalence of obesity among men more than trebled from 3.2 per cent to 10.8 per cent, while among women it surged from 6.4 to 14.9 per cent.

The study’s authors warned that on current trends, 18 per cent of men and 21 per cent of women will be obese by 2025, meaning there was “virtually zero” chance of reaching the global target of halting the prevalence of obesity at its 2010 level.

Instead, in the next nine years severe obesity will supplant underweight as a bigger public health problem, especially for women.

“The world has transitioned from an era when underweight prevalence was more than double that of obesity, to one in which more people are obese than underweight,” the study, published in The Lancet, said.

But although the world is getting fatter, it is also getting healthier, confounding concerns about the detrimental health effects of being overweight.

Writing in the same edition of The Lancet , British epidemiologist Professor George Davey Smith said that the increased in global body mass index (BMI) identified in the study had coincided with a remorseless rise in average life expectancy from 59 to 71 years.

Professor Davey Smith said this was a paradox, given the “common sense view that large increases in obesity should translate into adverse trends in health”.

Generally, a BMI greater than 25 kilograms per square metre is considered to be overweight, while that above 30 is obese and above 35, severely obese.

As the BMI increases above the “healthy” range, it is associated with a number of health consequences including increased blood pressure, higher blood cholesterol and diabetes.

The fact that increased BMI has not so far been associated with decrease longevity has led Professor Davey Smith to speculate that in wealthier countries access to cholesterol lowering drugs and other medications have dampened the adverse health effects, sustaining improvements in life expectancy despite increasing weight.

But he warned this effect would only be limited – many people would not be able to afford such treatments, and pharmacological interventions can only alleviate some of the health problems associated with being obese, meaning many health effects are likely to emerge in greater number later on as the incidence of obesity increases.

One of the most important aspects of the NCD Risk Factor Collaboration report is the insight it provides into differences in the nature and prevalence of weight problems between countries and regions.

For instance, it shows that the biggest increase in men’s BMI has occurred in high-income English-speaking countries, while for women the largest gain has been in central Latin America.

At the extreme, the greatest prevalence of overweight and obesity was in American Samoa, where the age standardised mean BMI for was 32.2, and for women, 34.8. Other areas where the mean BMI for both men and women exceeded 30 included Polynesia, Micronesia, the Caribbean, and several countries in the Middle East and north Africa, including Kuwait and Egypt.

The researchers found that male and female BMIs were correlated across countries, though women on average had a higher BMI than men in 141 countries.

But, in a sign that the rate of weight gain in a country may slow after a certain point, the researchers found that from 2000 BMI increased more slowly than the preceding 25 years in Oceania and most high income countries.

Alternatively, it sped up in countries where it had been lower. After 2000, the rate of BMI increase steepened in central and eastern Europe, east and southeast Asia, and most countries in Latin America and Caribbean.

The results suggest that public health campaigns and other polices aimed at curbing weight gain and encouraging healthier diets and more physical exercise are so far having little effect, spurring policymakers to consider different measures.

Though not canvassed in the study, one idea gaining support intnationally is for governments to impose a tax on sugary foods.

The United Kingdom will levy a tax on sugary drinks from next year, similar to one already in place in Mexico, and the World Health Organisdaiton has backed the policy as a way to curb the rapid increase in cases of diabetes in the world.

While overweight and obesity has become a major public health problem, particularly in wealthier countries, inadequate nourishment remains a health scourge in much of the world.

The NCD Risk Factor Collaboration report shows that millions continue to suffer serious health problems from being underweight, and warned that “the global focus on the obesity epidemic has largely overshadowed the persistence of underweight in some countries”.

As in other respects, global inequality in terms of weight have increased in the past 40 years, and while much of the world is getting fatter, in many areas under-nutrition remains prevalent.

The study found that more than 20 per cent of men in India, Bangladesh, Timor Leste, Afghanistan, Eritrea, and Ethiopia are underweight, as are a quarter or more of women in Bangladesh and India.

* The study drew on 1698 population-based data sources involving body mass index measurements taken from 9.9 million men and 9.3 million women in 186 countries between 1975 and 2014.

Adrian Rollins

 

[Comment] A new standard for malignant pleural mesothelioma

Mesothelioma is an asbestos-related malignancy that begins in the pleural lining of the lung, pericardium, peritoneum, or testes. Early-stage pleural mesothelioma can be resected, but almost always recurs. Many patients are diagnosed at an advanced stage of disease, at which point surgery has no role. Since 2003, the standard treatment for unresectable disease has been combination chemotherapy with cisplatin and pemetrexed.1 Despite many attempts, until now, no regimen has further improved survival.

A real knees up

Patients suffering osteoarthritis and other debilitating knee complaints have reported major improvements in pain and mobility following injections with their own stem cells.

In a development that could transform the lives of thousands and reduce the need for costly joint replacement surgery, scientists at the Melbourne Stem Cell Centre have reported “excellent” results in a trial of the use of stem cells to manage osteoarthritis and isolated cartilage lesions.

Interim results of the trial show there was a statistically significant improvement in pain and function after one month, and after nine months more than 65 per cent of patients aged 41 to 60 years experienced at least a 50 per cent reduction in pain.

The researchers, led by the Centre’s Chief Clinical Investigator, Dr Julien Freitag, were particularly excited by the progress of a 26-year-old patient with osteo chondritis dessicans.

The patient, who had undergone seven major knee operations in 12 years, joined the trial in June last year and MRI scans since then show that his cartilage has begun to regrow and pre-existing damage to the knee is starting to reverse.

While the privately-funded trial is yet to be completed, Dr Freitag said the interim results were “extremely encouraging”, and confirmed that the promise of regenerative therapies such as the use of stem cells was now “closer to reality”.

He said MRI analysis showed consistent stabilisation and a halt to the progress of arthritis in test subjects, and regrowth of cartilage in some.

Importantly, the improvements have been sustained beyond 12 months.

The technique involves using liposuction to obtain a sample of the patient’s stem cells, which are isolated and expanded before being injected back into them.

The results have been so promising that patients in the trial’s control group have been invited to undergo the treatment after 12 months of data collection.

See also: Push for crack on unproven stem cell therapies

Adrian Rollins