Lancet

‘Sugar gel’ helps premature babies

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A dose of sugar given as a gel rubbed into the inside of the cheek is a cheap and effective way to protect premature babies against brain damage, say experts.

Dangerously low blood sugar affects about one in 10 babies born too early. Untreated, it can cause permanent harm.

Researchers from New Zealand tested the gel therapy in 242 babies under their care and, based on the results, say it should now be a first-line treatment.

Their work is published in The Lancet.

Sugar dose

Dextrose gel treatment costs just over £1 per baby and is simpler to administer than glucose via a drip, say Prof Jane Harding and her team at the University of Auckland.

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This is a cost effective treatment and could reduce admissions to intensive care services which are already working at high capacity levels”

Andy ColeBliss

Current treatment typically involves extra feeding and repeated blood tests to measure blood sugar levels.

But many babies are admitted to intensive care and given intravenous glucose because their blood sugar remains low – a condition doctors call hypoglycaemia.

The study assessed whether treatment with dextrose gel was more effective than feeding alone at reversing hypoglycaemia.

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Neil Marlow, from the Institute for Women’s Health at University College London, said that although dextrose gel had fallen into disuse, these findings suggested it should be resurrected as a treatment.

We now had high-quality evidence that it was of value, he said.

Andy Cole, chief executive of premature baby charity Bliss, said: “This is a very interesting piece of new research and we always welcome anything that has the potential to improve outcomes for babies born premature or sick.

“This is a cost-effective treatment and could reduce admissions to intensive care services, which are already working at high capacity levels.

“While the early results of this research show benefits to babies born with low blood sugars, it is clear there is more research to be done to implement this treatment.”

Source: BBC

Hip replacement death rate halved

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Death rates following hip replacement surgery fell by half in England and Wales between 2003 and 2011, a study in The Lancet has found.

Although death within 90 days of surgery is rare, mortality decreased from 0.56% to 0.29% in an analysis of more than 400,000 patients.

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The researchers said that fitter patients and better physiotherapy could be behind the decrease.

They added that simple treatment options would reduce the risk further.

Researchers from the universities of Bristol, Oxford, East Anglia and Exeter used data from the UK’s joint-replacement database, the National Joint Registry, to look at death rates following this type of surgery.

In their study they found that 1,743 patients died within 90 days of surgery during the eight years.

In 2004, 24,723 patients had hip replacement surgery and 139 of those died within 90 days.

While in 2011, there were 60,727 hip replacement operations carried out and 164 patient deaths.

Quick fix

The reason for the fall in death rates could be down to a number of factors.

The researchers identified the use of a spinal anaesthetic as likely to lead to fewer complications. Specific treatments to stop blood clots after surgery were also linked to a lower risk of death.

We need to concentrate efforts on reducing the risk of death in high risk groups such as those with severe liver disease.”

Prof Ashley BlomUniversity of Bristol

But people are also living longer and patients are recovering more quickly after surgery as a result of better post-operative care. For example, patients are encouraged to get up and start walking around the day after surgery.

The study said: “More recent generations of old people… are generally fitter and less frail than old people at the start of the study.

“Likewise, other aspects of surgery and anaesthesia have improved sufficiently to account for the change in mortality rates.”

The research team noticed that people with certain medical conditions were at a much higher risk of dying following surgery – particularly those with severe liver disease, those who had had a heart attack and those with diabetes and renal disease.

Those patients who died were most likely to be elderly men, they said.

‘Surprising’

But there were also some unexpected findings. Overweight people (with a body mass index of 25-30) appeared to have a lower risk of death after hip surgery than those patients with a “normal” BMI of 20-25.

Ashley Blom, professor of orthopaedic surgery at the University of Bristol, said: “The finding that overweight people have a lower risk of death is surprising, but has been confirmed by other recent studies, and challenges some of our preconceptions.

“We need to concentrate efforts on reducing the risk of death in high risk groups such as those with severe liver disease.”

But he said that the “dramatic” overall fall in death rates was “extremely good news”.

“It is also very exciting that we can further reduce the risk of post-operative death by adopting relatively simple measures,” Prof Blom said.

A spokesperson from Arthritis Research UK, welcomed the findings.

“This is great news for people in the UK who have osteoarthritis and require hip replacement surgery.

“Although not everyone who has arthritis will need hip replacement surgery, for many people, it’s their only hope to reduce the pain, disability and stiffness associated with the disease.

“There are however always risks associated in having major surgery such as hip replacement surgery, so we advise people to discuss these risks with their surgeon before they decide to have a hip replacement.”

Source: BBC

 

Skin drug may treat type 1 diabetes

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A drug that was used to treat a skin disorder has shown signs of being able to treat aspects of type 1 diabetes.

A small trial on US patients suggests that alefacept helps the body produce its own insulin, which is key for people with type 1 diabetes.

Type 1 diabetes affects around 400,000 people in the UK.

Researchers said the drug could be better than other treatments because it protects the immune system – but more research was needed.

The findings are published in The Lancet Diabetes & Endocrinology.

Alefacept (sold as Amevive) was used to treat the skin disorder psoriasis in the US before it was withdrawn by its manufacturer in 2011. The drug was never approved for the European drug market.

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Type 1 diabetes will one day be cured. It’s a matter of time, money and excellent research”

Karen Addington Chief executive of JDRF

Psoriasis, like type 1 diabetes, is an autoimmune disorder that occurs when the immune system attacks healthy skin cells.

In clinical trials of the drug on psoriasis, the drug was found to attack specific types of T-cells that were also involved in attacking insulin-producing cells in type 1 diabetes.

So researchers, led by a team at Indiana University, Indianapolis, decided to investigate if it could have any effect on newly diagnosed type 1 patients.

Preserve insulin

In the trial, which is continuing, 33 patients received weekly injections of alefacept for 12 weeks, followed by a break of 12 weeks, and then another 12 weekly doses.

Another 16 participants were given placebo injections following the same schedule.

The researchers found no difference in how well the pancreas produced insulin two hours after eating food, but they did find “significant differences” between the two groups four hours after eating.

At this point, the group who received the drug showed they were able to preserve insulin while the placebo group‘s insulin levels decreased.

What is type 1 diabetes?

Type 1 diabetes is an autoimmune condition, where the immune system attacks the cells of the pancreas that produce insulin.

This results in insulin deficiency and the body being unable to regulate blood sugar.

Scientists suspect the condition often follows a trigger such as a viral infection.

After 12 months, the same group showed no significant increase in insulin use, yet those in the placebo group did.

The first group also had fewer episodes of hypoglycaemia, low blood glucose levels. which are common in people with type 1 diabetes.

‘Small successes’

Lead researcher Prof Mark Rigby, of Indiana University, said the first 12 months of the trial were encouraging.

“Although the primary endpoint was not met, several key secondary endpoints were significantly different between treatment groups, suggesting that alefacept might preserve pancreas cell function during the first 12 months after diagnosis.”

He said the initial findings meant that in the future the drug “could be used to stabilise type 1 diabetes and prevent its progression” – but it was unlikely to be a cure.

He added that the trial would continue and further measurements would be taken after 18 months and 24 months.

Writing about the study in The Lancet, Dr Kevan Herold, of Yale University, said: “It is important to underscore these small successes since, as in other fields such as oncology and infectious diseases, the small achievements acquire greater significance when they are combined.”

Karen Addington, chief executive of JDRF, the type 1 diabetes charity that helped fund the study, said the outcome was promising.

“The results of this study appear worthy of further exploration. Small steps forward such as this take us closer to a world without type 1 diabetes.

“It is a challenging and complex condition. But type 1 diabetes will one day be cured. It’s a matter of time, money and excellent research.”

Does Air Pollution Increase the Risk for Acute Heart Failure?

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Certain types of air pollution have a significant temporal association with heart failure–related hospitalization and mortality.
Air pollution has been associated with increased risk for myocardial infarction To assess its potential association with risk for acute heart failure (HF), researchers systematically reviewed the literature and ultimately identified 35 relevant studies in 12 countries, published from 1995 to 2010. All 35 studies tracked levels of specific air pollutants (both gases and particulate matter) and rates of HF-related hospitalization and mortality. A random-effects model was used to estimate the overall risk from each pollutant.

The risk for HF-related hospitalization or death was temporally and significantly associated with exposure to carbon monoxide (3.5% greater risk per 1 part per million), sulphur dioxide (2.4% greater risk per 10 parts per billion), and nitrogen dioxide (1.7% greater risk per 10 parts per billion) — but not ozone. Increases in concentrations of particulate matter were also significantly associated with the risk for HF-related hospitalization or death (from 1.6% to 2.1% greater risk per 10 μg/m3, depending on the size of the particulate), predominantly on the day of exposure. A mean reduction of 3.9 μg/m3 in particulates that have a diameter <2.5 μm (PM2.5) was estimated to prevent nearly 8000 HF-related hospitalizations and save roughly $US300 million per year.

COMMENT

These data show that air pollution has a strong temporal association with heart failure–related hospitalization and death. Thirty-four of the 35 analyzed studies were conducted in developed countries, where even small improvements in air quality are likely to have major effects on population health and healthcare costs. We still need more studies from developing nations, where (as the authors note) cities often have PM2.5 levels up to 10-fold higher than U.S. National Ambient Air Quality Standards allow. Air quality must remain a key target for global health policy and research.

Source: NEJM

 

 

 

Probiotics Do Not Reduce Diarrhea Risk in Large Trial.

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Probiotic supplements did not prevent antibiotic-associated diarrhea (AAD) or Clostridium difficile diarrhea (CDD) in a large randomized, double-blind, placebo-controlled trial.

Stephen J. Allen, MD, from Swansea University, United Kingdom, and colleagues reported the results in an article published onlineAugust 8 in the Lancet.

The researchers recruited patients 65 years or older to the Probiotic lactobacilli and bifidobacteria in antibiotic-associated diarrhoea andClostridium difficile diarrhoea in the elderly (PLACIDE) trial if they were exposed to 1 or more oral or parenteral antibiotics in the preceding 7 days or were about to begin antibiotic therapy. Participants were enrolled from 5 hospitals between December 1, 2008, and February 28, 2012, and were excluded if there were existing diarrhea or CDD in the previous 3 months, significant immune system compromise, any illness requiring intensive care, prosthetic heart valve, or underlying gastrointestinal disease. The primary study outcomes were the occurrence of AAD within 8 weeks of recruitment and CDD within 12 weeks of recruitment.

Overall, 1493 patients were randomly assigned to the microbial preparation group and 1488 to the placebo group. Of those, the researchers included 1470 and 1471, respectively, in the primary-endpoint analyses. Antibiotic exposure was similar between the 2 groups. The probiotic preparation consisted of a capsule containing 2 strains of Lactobacillus acidophilus and 2 strains of bifidobacterium.

The researchers found no difference between the groups in the incidence of ADD (including CDD). In the probiotics group,159 (10.8%) patients developed ADD compared with 153 (10.4%) patients in the placebo group (relative risk [RR], 1.04; 95% confidence interval [CI], 0.84 – 1.28; P = 0.71).

The study authors also found that CDD was an uncommon cause of ADD, occurring in only 12 (0.8%) participants in the microbial preparation group and 17 (1.2%) participants in the placebo group (RR, 0.71; 95% CI, 0.34-1.47; P = 0.35).

“Our trial suggests that properties common to many so-called probiotic bacteria, such as the production of lactic acid, are not effective against AAD in older inpatients,” write Dr. Allen and colleagues.

Although the authors note that this “is the largest trial so far for this problem,” they acknowledge study weaknesses such as low ethnic diversity and lack of participation by eligible patients resulting from an unwillingness to take an additional preparation.

“Our findings do not provide statistical evidence to support recommendations for the routine use of microbial preparations for the prevention of AAD and CDD,” conclude the study authors.

In an accompanying editorial, Nick Daneman, MD, FRCPC, from the University of Toronto, Ontario, Canada, points out that recent meta-analyses have shown large positive effects with the use of probiotic supplements. He also notes that statistical variations such as a low event rate in the current study and overlapping confidence intervals between this study and the meta-analysis may account for the differing results.

However, the size of the current study “dwarfs” previous studies, most of which, he says, were small single institution efforts. “PLACIDE is a large and rigorous negative study, and we must judge whether it can tip the balance of probiotic evidence,” he writes.

“At the very least, the low absolute risk reductions in PLACIDE question the cost-effectiveness of probiotics,” writes Dr. Daneman. In addition, “lactobacilli and bifidobacteria are only two types of non­pathogenic bacteria, and we must consider whether they can really tip the balance of a diverse gut ecosystem,” he concludes.

Funding for this study was provided by the Health Technology Assessment program of the National Institute for Health Research, with additional funding provided by the County Durham and Tees Valley, National Institute for Health Research Comprehensive Local Research Network. Dr. Allen has done research in probiotics supported by Cultech, UK; has been an invited guest at the Yakult Probiotic Symposium; and has received research funding from Yakult, UK. The other authors and the editorialist have disclosed no relevant financial relationships.

Source: Lancet.

 

 

 

Source: Medscape.com

 

Glucocorticoid-induced osteoporosis: mechanisms, management, and future perspectives.

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Glucocorticoids are widely used for their unsurpassed anti-inflammatory and immunomodulatory effects. However, the therapeutic use of glucocorticoids is almost always limited by substantial adverse outcomes such as osteoporosis, diabetes, and obesity. These unwanted outcomes are a major dilemma for clinicians because improvements in the primary disorder seem to be achievable only by accepting substantial adverse effects that are often difficult to prevent or treat. To understand the pathogenesis of glucocorticoid-induced osteoporosis, it is necessary to consider that the actions of glucocorticoids on bone and mineral metabolism are strongly dose and time dependent. At physiological concentrations, endogenous glucocorticoids are key regulators of mesenchymal cell differentiation and bone development, with additional regulatory roles in renal and intestinal calcium handling. However, at supraphysiological concentrations, glucocorticoids affect the same systems in different and often unfavourable ways. For many years, these anabolic and catabolic actions of glucocorticoids on bone were deemed paradoxical. In this Review, we highlight recent advances in our understanding of the mechanisms underlying the physiology and pathophysiology of glucocorticoid action on the skeleton and discuss present and future management strategies for glucocorticoid-induced osteoporosis.

Source: Lancet

 

 

 

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE).

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Background

Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations.

Methods

This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses.

Findings

The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03—1·45] per 10 μg/m3). For PM2·5 the HR was 1·18 (0·96—1·46) per 5 μg/m3. The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10—2·08) and 1·55 (1·05—2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99—1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95—1·07] per 20 μg/m3) or traffic intensity on the nearest street (HR 1·00 [0·97—1·04] per 5000 vehicles per day).

Interpretation

Particulate matter air pollution contributes to lung cancer incidence in Europe.

Source: Lancet

 

Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study.

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Summary

Background

A new betacoronavirus—Middle East respiratory syndrome coronavirus (MERS-CoV)—has been identified in patients with severe acute respiratory infection. Although related viruses infect bats, molecular clock analyses have been unable to identify direct ancestors of MERS-CoV. Anecdotal exposure histories suggest that patients had been in contact with dromedary camels or goats. We investigated possible animal reservoirs of MERS-CoV by assessing specific serum antibodies in livestock.

Methods

We took sera from animals in the Middle East (Oman) and from elsewhere (Spain, Netherlands, Chile). Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. Results were confirmed by virus neutralisation tests for MERS-CoV and bovine coronavirus.

Findings

50 of 50 (100%) sera from Omani camels and 15 of 105 (14%) from Spanish camels had protein-specific antibodies against MERS-CoV spike. Sera from European sheep, goats, cattle, and other camelids had no such antibodies. MERS-CoV neutralising antibody titres varied between 1/320 and 1/2560 for the Omani camel sera and between 1/20 and 1/320 for the Spanish camel sera. There was no evidence for cross-neutralisation by bovine coronavirus antibodies.

Interpretation

MERS-CoV or a related virus has infected camel populations. Both titres and seroprevalences in sera from different locations in Oman suggest widespread infection.

Source: Lancet

 

 

Mers coronavirus: Dromedary camels could be source.

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Dromedary camels could be responsible for passing to humans the deadly Mers coronavirus that emerged last year, research suggests.

Tests have shown the Mers (Middle East Respiratory Syndrome) virus, or one that is very closely related, has been circulating in the animals, offering a potential route for the spread.

The study is published in the journal Lancet Infectious Diseases.

But the scientists say more research is needed to confirm the findings.

The Mers coronavirus first emerged in the Middle East last year. So far, there have been 94 confirmed cases and 46 deaths.

While there has been evidence of the virus spreading between humans, most case are thought to have been caused by contact with an animal. But until now, scientists have struggled to work out which one.

‘Smoking gun’

To investigate, an international team looked at blood samples taken from livestock animals, including camels, sheep, goats and cows, from a number of different countries.

They tested them for antibodies – the proteins produced to fight infections – which can remain in the blood long after a virus has gone.

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The definitive proof would be to isolate the virus from an infected animal ”

Professor Paul KellamWellcome Trust Sanger Institute

Professor Marion Koopmans, from the National Institute of Public Health and the Environment and Erasmus University in The Netherlands, said: “We did find antibodies that we think are specific for the Mers coronavirus or a virus that looks very similar to the Mers coronavirus in dromedary camels.”

The team found low levels of antibodies in 15 out of 105 camels from the Canary Islands and high levels in each of the 50 camels tested in Oman, suggesting the virus was circulating more recently.

“Antibodies point to exposure at some time in the life of those animals,” Prof Koopmans explained.

No human cases of the Mers virus have been reported in Oman or the Canary Islands, and the researchers say they now need to test more widely to see if the infection is present elsewhere.

This would include taking samples from camels in Saudi Arabia, the country where the virus is the most prevalent.

‘Priority search’

Prof Koopmans said: “It is a smoking gun, but it is not definitive proof.”

Commenting on the research, Professor Paul Kellam from the Wellcome Trust Sanger Institute in Cambridge and University College London, said the research was helping to narrow down the hunt for the source of the virus.

But he told BBC News: “The definitive proof would be to isolate the virus from an infected animal or to be able to sequence and characterise the genome from an infected animal.”

Health officials say confirming where the virus comes from is important, but then understanding how humans get infected is a priority.

Gregory Hartl, from the World Health Organization, said: “Only if we know what actions and interactions by humans lead to infection, can we work to prevent these infections.”

Data suggests that it is not yet infectious enough to pose a global threat and is still at a stage were its spread could be halted.

Source: BBC

Probiotics Fail to Reduce Antibiotic-Related Diarrhea.

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High-dose probiotics do not prevent diarrhea in older hospitalized patients, according to a large study in the Lancet.

Nearly 3000 inpatients aged 65 and older who were on antibiotic therapy were randomized to 21 days of a placebo capsule or a capsule containing lactobacilli and bifidobacteria, taken once daily. After 8 weeks, the incidence of antibiotic-associated diarrhea or Clostridium difficile diarrhea did not differ significantly between the groups.

The authors conclude: “Our findings do not provide statistical evidence to support recommendations for the routine use of microbial preparations for the prevention” of diarrhea.

Source: Lancet