Change in how paramedics use oxygen could reduce deaths

Thursday, 24 October 2013

Islamabad, Oct 25 (Newswire): A change to the way paramedics use oxygen when treating patients with chronic lung disease could cut the death rate in these cases by up to 78%, according to a new study published on the British Medical Journal website.

Researchers based in Australia found the risk of death in patients with chronic obstructive pulmonary disease (COPD) was significantly reduced by using titrated (controlled) oxygen therapy instead of the current common approach of high concentration oxygen.

High concentration oxygen is used routinely by many paramedics in emergency situations for patients with acute breathlessness caused by episodes of COPD, a condition that affects over 200 million people across the world.

However, giving high concentration oxygen to patients with severe lung disease can lead to a build up of carbon dioxide in the blood, which can induce respiratory failure.

Hospital audits have also shown an association between using high concentration oxygen and adverse outcomes such as an increase in mortality, length of hospital stay, need for ventilation and admission to high dependency units.

For these reasons, the British Thoracic Society together with 21 other UK Colleges and Societies produced a guideline in 2008 which recommended that oxygen therapy for patients with COPD should be titrated to achieve a blood oxygen saturation of 88-92% compared with a target saturation range of 94-98% for most other medical emergencies. This guidance was implemented by the UK ambulance service in 2009.

Researchers from Tasmania carried out a study involving 405 patients aged 35 and over who were treated by 62 paramedics from the Tasmanian Ambulance Service and transported to a local hospital.

The participants were split into two groups -- one group (226) was treated with the standard high concentration oxygen approach and the other (179) with titrated oxygen therapy -- and data collected over a 13-month period between 2006 and 2007.

A confirmed COPD subgroup was identified retrospectively as those patients with a definite diagnosis of COPD during the study and this included 214 patients, 117 of whom were treated using high concentration oxygen and 97 with titrated oxygen with a target range of 88-92%.

Results showed significant differences in outcomes, depending on which approach was used.

Overall mortality was 9% (21 deaths) in the high concentration oxygen group and 4% (7 deaths) in the titrated oxygen group. This difference was more pronounced in the confirmed COPD subgroup for which there was a 9% (11 deaths) mortality rate in the high concentration group compared with a 2% mortality rate (2 deaths) in the titrated group.

Overall, titrated oxygen therapy reduced the risk of death from respiratory failure by 58% for all patients and 78% for confirmed COPD patients compared to high concentration oxygen therapy.

Patients who received high concentration oxygen were also significantly more likely to develop respiratory acidosis (a condition in which decreased respiration causes increased blood carbon dioxide and decreased pH) or hypercapnia, when there is too much carbon dioxide in the blood.

The researchers conclude: "Our findings provide the first high quality evidence from a randomised controlled trial for the development of universal guidelines and support the British Thoracic Society's recent guidelines on acute oxygen treatment, which recommend that oxygen should be administered only at concentrations sufficient to maintain adequate oxygen saturations."

In an accompanying editorial, senior doctors Ronan O'Driscoll and Richard Beasley warn that routine use of high concentration oxygen may also be harmful in several other medical emergencies, including heart attack and stroke."

They conclude: "After more than 200 years of haphazard use, it should be recognised that oxygen should be prescribed for defined indications in which its benefits outweigh its risks and that the patient's response must be monitored."

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Dad's weight and diet linked to offspring's risk of diabetes

Islamabad, Oct 25 (Newswire): Medical researchers have for the first time shown a link between a father's weight and diet at the time of conception and an increased risk of diabetes in his offspring.

The finding, reported in the journal Nature, is the first in any species to show that paternal exposure to a high-fat diet initiates progression to metabolic disease in the next generation.

"We've known for a while that overweight mums are more likely to have chubby babies, and that a woman's weight before and during pregnancy can play a role in future disease in her children, partly due to the critical role the intrauterine environment plays in development," said study leader Professor Margaret Morris, from UNSW's School of Medical Sciences.

"But until now, the impact of the father's environment -- in terms of his diet -- on his offspring had not been investigated." The work formed the basis of the PhD study of Dr Sheau-Fang Ng, who showed that paternal environmental factors such as diet and weight are important contributors to disease in the next generation.

In the Nature study, male rats were fed a high fat diet to induce obesity and glucose intolerance and then mated with normal weight females. The resulting female offspring exhibited impaired glucose tolerance and insulin secretion as young adults.

"This is the first report of non-genetic, intergenerational transmission of metabolic consequences of a high fat diet from father to offspring," Professor Morris said.

"A family history of diabetes is one of the strongest risk factors for the disease; however until now, the extent of any influence of non-genetic paternal factors has been unclear."

Professor Morris said the research showed that overweight fathers can play a role in "programming" epigenetic changes in their offspring, possibly through effects on their sperm caused by their consumption of high-fat food. Epigenetics is a process whereby changes in gene expression -- and hence function -- can occur even when there are no alterations in the DNA sequence.

Professor Morris said the study expands our understanding of the role environmental factors might play on a child's physiology and metabolism.

"It adds another level to our understanding of the causes of the growing epidemics in obesity and diabetes," she said. "While here we studied female offspring, we need to examine whether the effect is also found in males."

The work was carried out in collaboration with scientists in the UNSW Schools of Medical Sciences and Biotechnology and Biomolecular Sciences, the Garvan Institute, and the University of Adelaide.

Professor Morris will present the findings at the Australia and New Zealand Obesity Society meeting in Sydney.

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Major component in turmeric enhance effect of chemotherapy drug in head and neck cancer

Islamabad, Oct 25 (Newswire): Curcumin, the major component in the spice turmeric, when combined with the drug cisplatin enhances the chemotherapy's suppression of head and neck cancer cell growth, researchers with UCLA's Jonsson Cancer Center have found.

A naturally occurring spice widely used in South Asian and Middle Eastern cooking, Turmeric has long been known to have medicinal properties, attributed to its anti-inflammatory effects.

Previous studies have shown it can suppress the growth of certain cancers, said Dr. Marilene Wang, a professor of head and neck surgery, lead author of the study and a Jonsson Cancer Center researcher.

"Head and neck cancers, particularly cases diagnosed in a later stage, are terrible cancers that often require very radical surgeries and chemotherapy and radiation," Wang said.

"They often don't present until late, and the structures in the head and neck are so vital that our treatments often cause disfigurement and severe loss of function. So using non-toxic curcumin as a treatment was a very appealing idea."

The study, done in cells in Petri dishes and then in mouse models, appears in the October issue of the journal Molecular Cancer Therapeutics.

In India, women for years have been using turmeric for medicinal purposes, as an anti-aging agent rubbed into their ski, to treat cramps during menstruation, as a poultice on the skin to promote wound healing and as an additive in cosmetics, said scientist Eri Srivatsan, an adjunct professor of surgery and a Jonsson Cancer Center researcher who, along with Wang, has been studying curcumin and its anti-cancer properties for six years.

A 2005 study by Wang and Srivatsan first showed that curcumin suppressed the growth of head and neck cancer cells, first in cells and then in mouse models. In the animal studies, the curcumin was applied directly onto the tumors in paste form because it did not dissolve in saline, which would have allowed it to be injected.

In need of a better way to deliver the curcumin, the team collaborated with Dr. Kapil Mehta of M.D. Anderson Cancer Center and found that encapsulating the tumor in a liposome, an artificially prepared vehicle that enclosed the spice component within its membrane, made the treatment injectable.

The curcumin was injected into the tail vein of a mouse, where it circulated into the blood stream, slowing down and eventually stopping the cancer growth, a study in 2008 found.

"This was a very positive finding, developing an efficient way to deliver the treatment," Wang said. "Our study also showed that the curcumin was very well tolerated."

In this study, the team wanted to combine the curcumin with the chemotherapeutic drug cisplatin, which is very toxic at the doses needed to fight head and neck cancers, damaging kidneys, the ears and the bone marrow.

They hoped that if they added curcumin to the mix, they might be able to lower the cisplatin dose and cause less organ damage. Their finding, that the curcumin made the cisplatin work better, was very promising, Wang said.

"We knew that both the curcumin and the cisplatin, when given alone, had an effect against head and neck cancers," Wang said. "This finding that curcumin enhances cisplatin means that, in the future, we may be able to give this chemotherapy in lower doses."

The study noted that "the mechanisms of the two agents through different growth signaling pathways suggest potential for the clinical use of sub-therapeutic doses of cisplatin in combination with curcumin, which will allow effective suppression of tumor growth while minimizing the toxic side effects."

The study found that curcumin suppressed head and neck cancer growth by regulating cell cycling, Srivatsan said. It binds to an enzyme and prevents the enzyme IKK, an inhibitor of kappa B kinase, from activating a transcription factor called nuclear factor kappa B (NF?B), which promotes cancer growth. Cisplatin's suppressive action involves a different pathway through the tumor suppressor proteins p16 and p53, both proteins that again inhibit the activity of cancer growth promoter NF?B.

"We needed to know the mechanism to help us translate this from the lab into the clinic," Wang said. "That information will help us make better decisions on how to design therapies."

The next step in the clinical setting is to give patients oral curcumin prior to surgery and, after surgery, study the excised tumors to determine curcumin's effect on tumor markers, specifically whether there is reduced expression of markers such as growth promoting NF?B.

They also will be monitoring to determine if the curcumin results in any side effects. After that, the team would give curcumin to patients also getting chemotherapy and radiation to see if the tumor suppression found in the cells lines and mouse models can be replicated in humans.

Although turmeric is used in cooking, the amount of curcumin needed to produce a clinical response is much larger, about 500 milligrams. Expecting a positive effect through eating foods spiced with turmeric is not realistic, the researchers said.

Curcumin also has a suppressive effect on other cancers, Wang said, including breast, colon and pancreatic cancers. However, the mechanism of suppression in those cancers has not yet been uncovered. It also may be effective against Alzheimer's and aging, Wang said.

The study was funded by the VA Greater Los Angeles Surgical Education Research Center, UCLA Academic Senate, the National Institutes of Health and the Veterans Administration.

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