Written by admin on Friday, April 29th, 2011 in Swine Flu.
BRIDGETOWN, Barbados (CMC) — On the heels of a Swine Flu alert by the Pan America Health Organisation (PAHO), the Trinidad and Tobago-based Caribbean Epidemiology Centre (CAREC) yesterday assured that there was no outbreak of the H1N1 virus commonly known as Swine Flu in the Caribbean.
Written by admin on Thursday, April 28th, 2011 in Swine Flu.
“Heart attacks are far more dangerous in the mornings than at any other time of the day,” reported the Daily Mail. It said that patients who had an attack between 6am and midday suffered a fifth more damage to their heart muscle compared with those who had a heart attack later on.
The story comes from a study of more than 800 heart attack patients, examining the possible association between the time of day that heart attacks happen and the levels of two enzymes in the blood. These enzymes are markers of damage to the heart tissue, and higher levels indicate larger areas of damage.
Patients who had a heart attack between 6am and noon were found to have higher blood levels of these enzymes than those who had heart attacks later in the day, with increases in peak levels of 18.3% and 24.6%. The researchers suggest that these patients had significantly larger heart attacks than those whose heart attacks occurred at other times of the day.
The study was well-conducted and its findings add to what is known about circadian rhythms (the body’s internal 24-hour cycle) and heart risk. The study has several factors that limit its interpretation, however, including the use of a surrogate marker for damage to the heart (enzyme levels), rather than looking at heart damage directly. There may also have been other factors affecting how much damage took place, for example, how quickly people received treatment due to the time of day of their attack.
The study was carried out by researchers from the Hospital Clinico San Carlos and the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), both in Madrid, Spain. There is no report of external funding.
Coverage in the media was generally accurate, although there was little reporting of the study’s limitations. Reports that patients who have heart attacks between 6am and noon suffer one-fifth more damage to their heart muscle comes from an estimate by the researchers, rather than directly from the study results.
The aim of this study was to investigate whether the time of day affected the severity of damage caused by a type of heart attack called ST segment elevation myocardial infarction (STEMI). This was a retrospective cross-sectional analysis of 811 STEMI patients admitted to hospital between 2003 and 2009. This type of heart attack is caused by a prolonged blockage of blood supply to the coronary artery and usually causes large areas of damage to the heart muscle.
The researchers point out that the circadian clock (the body’s internal 24-hour cycle) is known to influence a number of cardiovascular factors, including blood pressure and heart rate, and that heart attacks peak in incidence during the early morning hours. As yet, little research has been carried out in patients to look at whether the degree of damage caused by a heart attack is affected by the time of day it occurs.
Researchers looked at the data on 811 patients who were admitted to hospital between 2003 and 2009 with a STEMI, as defined in current clinical practice guidelines. They obtained information on the time of onset of symptoms from patients’ medical histories, the site of the STEMI (divided into those in the heart’s anterior wall and other locations) and the levels of creatine kinase (CK) and troponin I (TnI), measured on admission and then every four hours. These two enzymes are chemical markers for damage to the heart tissue (infarct) and higher levels of enzymes indicate greater damage.
The researchers divided the 24-hour clock into four equal periods, in phase with circadian rhythms. These were midnight to 6am, 6am to noon (dark-to-light transition), noon to 6pm and 6pm to midnight. The time of day that patients had a heart attack was categorised into one of these four periods. Standard statistical methods were used to assess whether there was a relationship between peak enzyme levels in the blood and the time heart attacks occurred. The results were also adjusted for other factors that could affect the size of someone’s heart attack, such as the presence of diabetes, history of hypertension and the time of year it happened.
The researchers say they found a “circadian variation” in the extent of the damage to heart tissue, as measured by peak levels of the two enzymes, CK and TnI.
In their conclusion, the researchers say that, overall, there is an expected increase of about 20% in the size of infarct in patients with STEMI during the dark-to-light transition period, compared with any other time of day.
The researchers say that the amount of damage caused by heart attacks, as measured by their enzyme levels, was significantly larger in patients who had a heart attack between 6am and noon, than at other times of the day.
They say that, although the reason is not fully understood, it may be due to natural changes in the body during the 24-hour period, so that at certain times there is less “cardioprotection”. For example, circadian variations in heart rate, blood pressure and coronary flow may all be involved.
This study was well-conducted and its findings add to what is known about circadian rhythms and heart risk. As the researchers themselves point out, it also has several limitations.
As experts are reported as saying, whatever time of day a heart attack happens, the more quickly someone is treated, the less damage to the heart they will have. Anyone who experiences heart attack symptoms or observes them in someone else should call 999 immediately.
Morning heart attacks cause more damage. The Independent, April 28 2011
Morning heart attacks ‘are a fifth more severe than later in the day’. Daily Mail, April 28 2011
Heart attacks ‘are worse’ if they happen in the morning. BBC News, April 28 2011
Suárez-Barrientos A, López-Romero P, Vivas D, et al. Circadian variations of infarct size in acute myocardial infarction. Heart 2011, Published Online First April 27
Written by admin on Thursday, April 28th, 2011 in Swine Flu.
“People born in spring are ‘more likely’ to become anorexic,” reported The Independent. The newspaper said the finding comes from the first large-scale study of the link between anorexia and the season of birth.
This study pooled data on birth dates from four UK studies of around 1,300 people with anorexia nervosa and compared these to the distribution of births in the general population. The researchers found that more people who were born between March and June went on to develop anorexia than could be expected when compared to the patterns of birth seen in the general population.
The researchers propose several theories to explain this association, including the mother’s diet during pregnancy, seasonal infections such as flu, and climate, including temperature, rainfall and sunshine levels.
This research highlights increasing interest in how the environment of the developing baby may influence their likelihood of being affected by certain diseases later in life. The effect observed here was small however, and more research and further analysis will be needed to establish just how robust this association is and to investigate the possible causes behind it. The media also includes comments from experts which give these results some context. The experts say that anorexia is a very complex disorder and that several factors contribute to its development.
The study was carried out by researchers from the Wellcome Trust Centre for Human Genetics at the University of Oxford. The work was supported by the Wellcome Trust. The study was published as a short report in the peer-reviewed journal The British Journal of Psychiatry.
Both The Independent and BBC News report the study accurately. The Independent gives several theories explaining the difference in rates of anorexia between people born in different seasons. However, the study was only set up to find associations and it remains unclear why there might be a difference between seasonal rates. The BBC appropriately highlights that other academics have said that the effect was small and the disorder has many causes.
This was a meta-analysis of data from several cohort studies aimed at investigating whether the season in which someone is born affects their risk of developing anorexia nervosa. The researchers combined and compared data from four separate studies. They looked at the distribution of birth days of people who developed anorexia and compared them with those of the general UK population.
The methods that the researchers used are only briefly described in the research paper. The paper does not describe in detail what is already known about this topic, which studies were excluded, or give the separate results of the one Scottish and three English studies that were included in the analysis. As three of these four studies separately showed non-significant results, larger sample sizes will be required in any future research.
To find the articles for their analysis, the researchers searched a scientific literature database called PubMed. They say that they included studies from the UK only, because country-specific factors such as different social and nutritional habits, rates of disease, birth trends and latitude might have confounded the results.
They found four relevant studies for inclusion in their meta-analysis. The largest was published in 2001 and was conducted in Scotland, recruiting 446 people and then following them between 1965 and 1997. This study found that more people who were born between April and June went on to develop anorexia than usual, and that cases peaked in the spring months, while sinking in the autumn months.
The other three studies were published between 2002 and 2007 and were all conducted in England, ranging in size from 195 to 393 people. Although these three studies showed a similarly high number of April–June births, the difference between the number of babies who later developed anorexia who were born in the ‘peak’ spring months and the ‘trough’ autumn months was not significant.
The researchers pooled the results using standard and non-standard statistical techniques. They compared the anorexia nervosa birth rates in the first half of the year with the second half. They also compared the rates of anorexia births in spring (March to June) and autumn (September to October) with those of the general population born between 1950 and 1980. The general population rates were obtained from the UK Office for National Statistics and comprised almost 22 million births over a similar period (1950-1980).
The researchers say they found a 15% excess of anorexia births from March to June (odds ratio [OR] 1.15, 95% Confidence Interval [CI] 1.03 to 1.29). This means that, for example, if the background rate of anorexia is 20 per 4,000 births per month then one could expect 23 (15% more) in the months March to June.
In contrast, from September to October there was a 20% deficit from (OR 0.8, 95% CI 0.68 to 0.94).
The distribution of births in the anorexia group was significantly different from that of the general population. Analysis showed that rates of people born with anorexia were higher in the first half of the year compared with the second (OR 1.13, 95% CI 1.01 to 1.26).
The researchers say that their results indicate that environmental risk factors during pregnancy or immediately after birth affect whether someone goes on to develop anorexia in later life. They say that further identification of these risk factors will be “important for disease prevention strategies”.
This research highlights increasing interest in how the environment of the developing baby might influence their likelihood of being affected by certain diseases later in life. The researchers refer to this as the ‘fetal origin of adult disease’ hypothesis. This study appears to support this theory, but further study is needed to confirm this association and investigate the mechanism behind it.
The researchers mention several environmental factors that vary throughout the year that they considered most likely to be linked to the development of anorexia:
The mention of vitamin D levels is also picked up by the newspapers as this has been linked to other psychiatric diseases, including schizophrenia, and neurological conditions, such as multiple sclerosis. However, these researchers appear to suggest that low vitamin D levels may be a result of psychiatric illness rather than a cause.
Overall, this study indicates that the seasons may have a small effect on rates of anorexia in babies born during the spring months. The results do not indicate what the absolute risk of developing the condition might be for a person born in the spring. More research and further analysis of research in other countries will be needed to establish just how robust this association is and to investigate the possible causes behind it.
Anorexia nervosa ‘link to spring birth’. BBC News, April 28 2011
People born in spring are ‘more likely’ to become anorexic. The Independent, April 28 2011
Disanto G, Handel AE, Para AE, et al. Season of birth and anorexia nervosa. The British Journal of Psychiatry 2011, Published ahead of print
Written by admin on Wednesday, April 27th, 2011 in Swine Flu.
The diagnosis and early treatment of ovarian cancer is in the news today, with the publication of new NICE guidance for doctors on recognising ovarian cancer. NICE calls for more initial investigations (such as a blood test) to take place in GP surgeries – this is so that more women are referred to hospital specialists and begin treatment sooner, greatly increasing their chances of survival.
The guidance focusses on areas where there is current uncertainty or wide variation in clinical practice among doctors with regard to the detection of ovarian cancer, particularly in primary care where most women will present. In particular, the guidance gives clear advice on when to carry out a specific blood test when cancer is suspected.
Dr Fergus Macbeth, Director of the Centre for Clinical Practice at NICE said:
“NICE is advising GPs and other primary care professionals to offer women (particularly those over 50) a blood test to measure the level of a protein called CA125 if they present with the following symptoms on a regular basis – bloating, feeling full quickly, lower abdominal pain and needing to urinate urgently or frequently.
“Based on the results of this test, women should then be offered an ultrasound scan of their abdomen and pelvis. If this suggests ovarian cancer, they should then be referred to see hospital specialists within two weeks; this is the existing national target set by the Department of Health.”
The news stories are based on new guidance from the National Institute for Health and Clinical Excellence (NICE). NICE is the independent body that advises health professionals on the prevention and treatment of ill health.
NICE points out that ovarian cancer is the leading cause of death from gynaecological cancer in the UK and its incidence is rising. The outcome for women with this cancer is generally poor, with an overall five-year survival rate of less than 35%. This is because most women are only diagnosed when the disease is advanced, even though many women have symptoms months before, and also because of delays between when they first go to the doctor with symptoms and when referral is made for specialist investigations and treatment.
To increase the survival rates for ovarian cancer, NICE says there is a need for greater awareness of the disease among GPs and for earlier referral and optimum treatment.
“Delayed presentation coupled with lack of awareness around the possible symptoms, unfortunately mean that far too many women are being referred to hospitals for suspected ovarian cancer once their disease is at an advanced stage,” said Mr Charles Redman, a consultant gynaecological oncologist and contributor to the development of the guidelines. He continues, “This is frustrating as the stage of diagnosis is crucial in determining which treatments can then be offered”.
The guidance focuses on areas where NICE says there is either uncertainty or wide variation in clinical practice, regarding the detection, diagnosis and initial management of the disease. The guidance is applicable to women with suspected or confirmed epithelial ovarian cancer (the most common type), as well as women with fallopian tube cancer, borderline ovarian cancer or primary peritoneal carcinoma (a rare cancer of the thin lining covering the organs of the abdomen and pelvis). It does not cover other types of gynaecological cancer or cancer of other abdominal organs.
Specifically, the guidelines advise GPs and other healthcare professionals to offer women (particularly those over 50) a blood test to measure the level of a protein called CA125 if they present with certain symptoms on a regular basis. These symptoms are bloating, feeling full quickly, lower abdominal pain and needing to urinate urgently or frequently. CA125 is often called a ‘tumour maker’; however, testing for CA125 is not a way of detecting any one disease. Levels are known to be raised in women with ovarian cancer, but they can also be raised by other cancers (including other cancers of the gynaecological system, bowel and lung) and other non-cancerous conditions such as endometriosis. However, raised levels in the presence of other symptoms should always raise the suspicion of cancer, until it is ruled out.
Based on the results of these tests NICE advises that women should then be offered an ultrasound scan of their abdomen and pelvis. If this suggests ovarian cancer, they should then be referred to hospital within two weeks, in line with existing targets from the Department of Health.
Below are the “key priorities” which NICE says need to be implemented:
Awareness of symptoms and signs
GPs, says NICE, should offer tests to any woman (especially if they are aged 50 or over) who reports any of the following symptoms, either persistently or frequently (particularly more than 12 times in a month):
GPs should carry out appropriate tests in any woman aged 50 or over who has had symptoms in the last 12 months that may be suggestive of irritable bowel syndrome (IBS), because the onset of IBS is rare in women of this age. Symptoms include changes of bowel habit (for example, constipation or diarrhoea and abdominal pain).
Asking the right questions – first tests
In hospital
Where the results of the blood tests and ultrasound indicate suspected ovarian cancer (calculated using a risk of malignancy index), the woman should be referred to a specialist multidisciplinary team of healthcare professionals who are experienced in treating women with this type of cancer.
The NICE guidance also covers the diagnosis and treatment of ovarian cancer and the support needs of women who have been diagnosed. These further aspects of management of ovarian cancer are not the focus of this Q&A report.
As Dr Craig Dobson, a GP and one of the developers of the guidelines said: "Ovarian cancer is difficult to diagnose from the symptoms alone”. The symptoms of ovarian cancer can often be non-specific and are often confused as those of other conditions, including irritable bowel syndrome. However, experiencing changes in bowel habits (for example, bouts of constipation or diarrhoea) can also be associated with ovarian cancer; as Dr Dobson continues, “It is important for GPs to remember that irritable bowel syndrome rarely presents for the first time in women over fifty. Conversely, most ovarian cancers present in women over the age of fifty. Recurrent or prolonged symptoms require a diagnosis at any age."
NICE experts say that the important factor here is the persistence of these symptoms. Age is also a factor to consider, but although most cancers occur in women above the age of 50, the possibility of cancer should not be ruled out in younger woman with unexplained symptoms.
Alongside the abdominal and pelvic symptoms listed above (bloating, pain, feeling full quickly or change in bowel or urinary habit), ovarian cancer can also sometimes cause a change in periods (if the woman is pre-menopausal), or post-menopausal bleeding, or pain during sexual intercourse. Ovarian cancer can also often present with other ‘non-specific’ symptoms common to many cancers, such as feeling very tired, or losing weight for no obvious reason.
The test is a simple blood test, which reportedly costs about £20. It measures blood levels of a key protein called CA125. This can be raised in women with ovarian cancer because CA125 is sometimes produced by ovarian cancer cells. Testing for CA125 has been carried out for many years within the NHS system and is a well-established test used in cases of suspected cancer. The primary purpose of the NICE guidance is to encourage the increased use of the test in primary care and to establish consistency among GPs about when they should be using the test and how they should be responding to the results.
The CA125 test alone cannot diagnose ovarian cancer and having a high level of CA125 does not necessarily mean a woman has ovarian cancer. Some healthy women have naturally high levels and levels can also be raised in women who have other conditions such as endometriosis or fibroids. However, if levels of CA125 are high it can indicate the need for further investigations. Diagnosis of ovarian cancer will most likely be made through the use of ultrasound initially, followed by MRI or CT scans.
As CA125 is non-specific for ovarian cancer, the test can also sometimes “miss” cases of cancer and return lower, less-suspect levels when a woman actually has cancer. This is particularly the case if a woman has early stage disease – women with advanced cancer almost always have high CA125 levels, but not all women with early stage cancer will have raised levels. For this reason, it is vital to take account of the individual’s medical history and presenting symptoms without complete reliance on the blood test, and if symptoms are persistent or unexplained, or there is any doubt at all as to the cause, referral for hospital assessment and urgent ultrasound should always be arranged.
Women who have ovarian cancer have a greater chance of surviving the disease if it is caught earlier. Standard use of blood tests when women first complain of symptoms, by GPs and in other primary care settings, will, NICE says, lead to earlier referrals to cancer specialists and more timely treatment.
The NICE recommendations for use of the blood test by GPs are based on evidence of how the test performs, as well as an evaluation of its cost effectiveness. The CA125 test is, they say, currently the most widely used and reliable tumour marker for ovarian cancer.
The guidelines are important for patients because they set out a recommended standard procedure for investigating possible symptoms of ovarian cancer, which GPs are expected to meet. NICE has also produced information on the new guidelines for patients and carers, in language that is easy to understand.
GPs ’should offer £20 ovarian cancer blood test’. The Daily Telegraph, April 27 2011
Call for action to detect ovarian cancer earlier. BBC News, April 27 2011
Simple blood test could save hundreds from ovarian cancer. The Independent, April 27 2011
A £20 lifesaver: GPs urged to test blood for ovarian cancer to improve survival rates. Daily Mail, April 27 2011
Simple cancer blood test may save hundreds. Daily Express, April 27 2011
The recognition and initial management of ovarian cancer. NICE 2011
Written by admin on Wednesday, April 27th, 2011 in Swine Flu.
“A sprinkling of red chilli peppers on your dinner keeps hunger pangs at bay,” reports the Daily Mail. It said that spicing up a daily diet with chopped chilli peppers could help curb your appetite.
The effects of capsaicin, the chemical that makes peppers and chillies hot, have been studied again in a small trial investigating what effects hot red (cayenne) pepper has on energy expenditure, body temperature and appetite. It used doses that people would normally eat and found that 1g of pepper reduced cravings for salt, sweet and fatty foods and increased energy expenditure. It noted that this effect was greater among the 12 trial participants who did not normally eat spicy peppers compared to the 13 who reported being regular users.
The study was reliably carried out but is very small, with only 25 participants. In particular, the differences between regular and non-users need confirmation in larger studies. Although the news has related this to possible dietary benefits in people trying to lose weight, the participants were all healthy young people of normal weight. This is early preliminary research and further study is needed.
The study was carried out by researchers from Purdue University, in the US. Funding was provided by the National Institutes of Health through a National Research Service Award, and the McCormick Science Institute. The study was published in the peer-reviewed medical journal Physiology and Behavior.
In general, the press accurately represent the reporting of this study. However, as the study was conducted in people of normal healthy weight, that chillies may be of benefit to people trying to lose weight is an assumption that should not be made on the basis of the current study alone.
This was a small, randomised crossover trial, in which the researchers investigated the effect of cayenne red pepper consumption during a meal on skin and body temperature, energy expenditure and appetite levels after the meal. Previous studies have suggested that red peppers (and in particular capsaicin, the chemical that makes peppers and chillies hot) suppress hunger and make the body generate heat. However, these studies have often used more hot pepper or chilli than the average person would choose to eat (for example, 10g/meal, when a person would normally choose to consume about only 1g/meal). This study aimed to test more acceptable cayenne pepper doses consumed during a single meal. In the crossover design, the recruited participants tried, in a random order, three amounts of pepper with their meal: a standard quantity, their chosen quantity or none.
The researchers recruited 35 participants through public advertisements, who were all young (with an average age of 23 years) and had a healthy body weight (BMI 22.6). To be eligible, participants had to be in good health, non-smokers, have a stable weight and have steady dietary and activity habits. Of these 35, the researchers report results for only 25, as three dropped out before the study began, and seven dropped out for various reasons (for example, intolerance to chilli or unwillingness to abstain from caffeine) during the study. The 25 included 13 who reported regularly eating spicy food and 12 who did not.
Participants attended the study centre for six meal visits, one week apart. For three days before each visit the participants were advised to eat either a high-fat diet (before two visits), a high-carbohydrate diet (before two visits) or their normal diet (before two visits). They also had to avoid alcohol, caffeine or strenuous physical activity on these days. On each test day, the participants were asked to arrive an hour before lunchtime, having fasted for 12 hours beforehand. Physiological tests of their resting energy expenditure, body and skin temperature, and appetite were then taken.
The participants’ chosen quantity of cayenne pepper was added to the meal after the two three -day periods in which they had eaten their normal diet (on average 1.8g/meal was chosen by regular spicy food users and 0.3g for non-users). After the two three-day periods in which they had been eating a high fat diet, and the two where they were eating a high carb diet, they were randomly assigned to receive either a standard amount of cayenne pepper (1g per meal) or no cayenne pepper.
The study reports that the doses of pepper were given in either capsule form or “orally” (presumably meaning it was added to the meal in some way). Though it is not clear how the decision to give orally or by capsule was made (e.g. whether it was made randomly on each of the six attendance days or whether participants were assigned to receive the pepper orally on set days and by capsule on others). On the days when no pepper was given, the researchers say that this was by the use of a plain, dummy, capsule.
The participants ate all meals until comfortably full. During a four-and-a-half-hour period after the meals, their energy expenditure, body and skin temperature, and appetite were again assessed at intervals. Appetite had been assessed at 30-minute intervals using a validated appetite questionnaire with responses such as hunger, fullness or desire to eat rated on a visual analogue scale.
Compared with eating no pepper, the standard 1g dose of cayenne pepper significantly increased body temperature by an average of 0.02°C (regardless of the preceding three-day diet). Skin temperature decreased by an average of 0.11°C after the high-fat diet and by 0.23°C after the high-carbohydrate diet. Skin temperature was also lower when the pepper was consumed in capsule rather than oral form, but this had no effect on body temperature. The effects on body temperature did not differ between regular and non-users of spicy food.
Pepper had a greater effect on the appetite in those who didn’t usually eat spicy food compared to people who regularly ate spicy food. Generally, non-users had less desire to eat salty, fatty or sweet foods after eating 1g pepper than those who ate spicy food regularly. There was no difference in effect on appetite when the dose was delivered orally or via a capsule.
There was an increase in energy expenditure (of about 10kcal) following ingestion of 1g of pepper compared with no pepper. While there was no significant difference in energy expenditure between regular and non-users, (i.e. both user groups increased energy expenditure after eating the pepper), the researchers noted that the greatest effect on energy expenditure occurred when non-users took the pepper in oral form (rather than by capsule), and the lowest effect occurred when regular users consumed it in either capsule or oral forms.
The authors conclude that red pepper has weight management potential. However, they also say that individuals who regularly consume hot red peppers may become desensitised to the effects of red pepper on appetite and energy expenditure.
This study tested the effects of eating hot red pepper at mealtimes on post-meal energy expenditure, body temperature and appetite. It found that, compared with eating no cayenne pepper with the meal, 1g of pepper reduced salt, sweet and fatty food cravings and also increased energy expenditure. The effect was greater in people who did not normally eat spicy peppers compared with those who reported being regular users.
The study is valuable in that it evaluated amounts of hot pepper that are likely to be consumed as part of a normal diet, whereas previous studies have evaluated unusually high amounts of hot pepper. It also investigated the effects of consumption in different subgroups, namely those who were regular and non-users, different pepper doses, people consuming different pre-test diets (high fat, high carbohydrate or normal), and consumption in capsule or oral form. This multiple subgroup testing can be a statistical weakness, as the more comparisons you carry out the more likely you are to find significant differences by chance, but the researchers have made adjustments for this.
In spite of some strengths, this is a small study and can only really be considered to be preliminary research. Only 35 people were enrolled into the trial and of these only 25 completed it.
The main results pertain to the differences between regular non-users and users of spicy foods, but there were only 12 and 13 of these, respectively. Therefore, observed differences between these small groups of people need confirmation in much larger studies to see whether a true difference exists.
In addition, the participants were healthy young people, with a normal BMI. Although the news has said these findings may lead to possible dietary benefits in people trying to lose weight, this has not been tested in this study.
Further randomised trials investigating the effects of supplementary dietary pepper or chilli in people trying to lose weight could be conducted.
A sprinkling of red chilli peppers on your dinner ‘keeps hunger pangs at bay’. Daily Mail, April 27 2011
Red-hot tip to burn fat. Daily Express, April 27 2011
Ludy MJ, Mattes RD. The effects of hedonically acceptable red pepper doses on thermogenesis and appetite. Physiology & Behavior 2011 102; 251-258
Written by admin on Wednesday, April 27th, 2011 in Swine Flu.
BBC News has reported that “diet can ‘reverse kidney failure’ in mice”. It said that a diet high in fat and low in carbohydrate can repair kidney damage in diabetic mice.
The research looked at the effect on kidney function of a “ketogenic diet”, consisting of 87% fat, 5% carbohydrate and 8% protein, compared to a standard carbohydrate-rich diet in mouse models of type 1 and type 2 diabetes.
The diabetic mice, which had abnormal amounts of protein in their urine, indicating poor kidney function, showed improvement in kidney function over eight weeks of being on the ketogenic diet.
This was a small animal study and further research is needed to see what aspect of the diet underlies the effects seen. The implications for humans are limited and, as the researchers point out, it is unfeasible for humans to adopt such a high-fat diet in the long term owing to the health risks of consuming so much fat. Follow-up studies are more likely to look at the proteins involved in fat metabolism and their effect on kidney cells, to try to produce drugs that mimic the effect of the diet. As the BBC points out, the diet “mimics the effect of starvation and should not be used without medical advice”.
The study was carried out by researchers from Mount Sinai School of Medicine, New York. Funding was provided by The Juvenile Diabetes Research Foundation. The study was published in the peer-reviewed medical journal PLoS One.
The research was covered very well by the BBC, which highlighted the preliminary nature of the animal study and that the diet was unlikely to be recommended for people with diabetes.
This animal study investigated the effect of a “ketogenic” diet on mouse models of type 1 or type 2 diabetes, in which the mice had damage to their kidneys. Kidney damage is a common complication of diabetes and is known as diabetic nephropathy. The high levels of blood sugar associated with diabetes gradually cause damage to the tiny blood vessels and microstructures of the kidney, affecting their ability to filter correctly. Leakage of blood proteins (albumin) into the urine is the key sign of diabetic nephropathy.
A ketogenic diet is high in fat, low in carbohydrate and contains an average amount of protein. It mimics starvation and encourages the body to burn fats rather than carbohydrates. Burning fats replaces glucose as the energy source.
In both type 1 and type 2 diabetes, the body is less able to regulate blood glucose levels. Insulin is the hormone that regulates blood sugar levels. Type 1 diabetes results from the body’s failure to produce insulin. Type 2 results from insulin resistance, or a lack of sensitivity of the body’s cells to the actions of insulin.
The researchers used two mouse models of diabetes: a type of mouse called the Akita mouse, which produces less insulin (mimicking type 1 diabetes), and db/db mice, which are less responsive to insulin (mimicking type 2 diabetes). The researchers set up two experiments, one comparing 28 Akita and 28 normal mice, and the other comparing 20 db/db and 20 normal mice.
The mice were all 10 weeks old at the start of the study. The researchers collected urine samples when the mice were 20 weeks of age. At that time in the Akita versus control study, half of the mice from each group were placed on a ketogenic diet (5% carbohydrate, 8% protein, 87% fat). The other half of the animals were kept on a standard high-carbohydrate control diet (64% carbohydrate, 23% protein, 11% fat).
In the db/db versus control study, the ketogenic diet was started in half the mice from each group when the mice were 12 weeks old. The mice were kept on the ketogenic diets for eight weeks and urine samples were collected. The researchers measured levels of albumin in the mouse urine samples to assess how well their kidneys were functioning.
The Akita mice had a shorter life expectancy than the normal mice. The researchers expected that the Akita mice would not survive on the standard diet for eight weeks. They found that after 2 weeks on the standard diet (when the mice were 22 weeks old) two of the Akita mice had died. The researchers therefore decided to cull all of the Akita mice and also the normal mice that had received the standard diet so that they could compare the gene activity of Akita versus the control mice on the standard diet when they were the same age. The Akita and normal mice that were given the ketogenic diet all survived for the full eight weeks of the study, therefore the researchers compared the gene activity of the akita mice verses the control mice on the ketogenic diet when they were 28 weeks old. In the db/db versus normal mice study all of the mice that had received either the standard or the ketogenic mice were followed for the full eight weeks.
The Akita mice developed high blood sugar at four weeks of age and by the time they were 20 weeks their urine samples showed that they had developed kidney damage. Within one week of switching to the ketogenic diet when they were 20 weeks old, their blood sugar levels were in the normal range. Although the researchers sacrificed all of the non-diabetic mice and Akita mice who had received the control diet 2 weeks after they started the diet, they continued to monitor the non-diabetic mice versus the Akita mice on the ketogenic diet. They found, based on urine measurements, that the kidney damage seen in the Akita mice was reversed within two months on the ketogenic diet.
In the db/db type 2 diabetes mouse model, the mice developed high blood sugar by 12 weeks of age. At this time, half of the db/db mice and the non-diabetic mice were placed on the ketogenic diet. The ketogenic diet reduced blood sugar levels by around 50%, but they were still outside normal levels. Within eight weeks of being on the diet, the abnormalities in the urine samples indicating kidney damage were almost completely corrected. The db/db mice, compared with the non-diabetic mice, gained weight while on the ketogenic diet.
When the researchers examined the activity of genes in the kidney, they found there were nine genes that were more active in the Akita mice and db/db mice compared with the non-diabetic mice. However, the increased activity of these genes completely reversed in the Akita mice and largely or completely reversed in the db/db mice given the ketogenic diet.
In the laboratory, the researchers then examined the structure of the kidneys themselves in the db/db mice. They found that the abnormal structure indicating kidney damage was less common in the db/db mice on the ketogenic diet compared with mice on the standard diet, but their kidneys still showed damage compared with non-diabetic mice.
The researchers say that previous studies of models of type 1 diabetes have found that good glucose control could prevent, but not reverse, kidney damage. This present study showed that the ketogenic diet could actually reverse the damage.
The researchers say that their research proves that manipulating a diet can prevent some of the damage caused by diabetes. However, they say that the “ketogenic diet is probably too extreme for chronic use in adult patients” and may produce side effects. They say that if they can refine what aspects of the diet caused the effects then this may lead to the development of drugs that act in a more targeted way.
This preliminary animal research shows that a high-fat, low-carbohydrate diet was associated with some benefit in mouse models of type 1 and type 2 diabetes, in terms of reducing the kidney damage usually seen in these animals.
Though this animal model is meant to be representative of the kidney damage that can occur in people with diabetes, it is not clear whether a similar effect would be seen in humans. This research is unlikely to lead to a similar diet-based therapy for people with diabetes, as the side effects of eating such a high-fat diet are likely to outweigh any benefits. It is more likely that this study may form the basis for further studies looking at the proteins involved in fat metabolism and how they can affect kidney function and damage.
The researchers demonstrated that kidney function was restored over time by measuring albumin in the urine before and after the diet. However, as they only looked at the structure of the kidney at the end of the study it is not clear whether damage to the structure of the kidney was reversed by the diet, or whether the diet had prevented subsequent damage. To see if damage to the kidney structure was reversed the researchers would need to compare the structure of the kidney in age-matched mice before and after the diet. This small study would need further follow-up in animals to see the precise effect of this diet on the kidneys.
This study has no current implications for the prevention or treatment of diabetic nephropathy in humans.
Diet ‘can reverse kidney failure’ in mice with diabetes. BBC News, April 26 2011
Poplawski MM, Mastaitis JW, Isoda F, Grosjean F, Zheng F, et al. (2011) Reversal of Diabetic Nephropathy by a Ketogenic Diet. PLoS ONE 6 (4)
Written by admin on Wednesday, April 27th, 2011 in Swine Flu.
“Aspirin and other popular painkillers could prevent Prozac from working properly,” the Daily Mail reported. This news story was based on research that was predominantly in mice, examining the effects of combining anti-inflammatory painkillers such as ibuprofen and aspirin with a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), to which Prozac belongs.
The study found that SSRIs work by increasing the levels of a depression “biomarker” called p11. The anti-inflammatory drugs prevent SSRIs from increasing the levels of this protein. They also blocked the mouse behavioural response to SSRIs, but had no effect on other types of antidepressant.
The researchers followed up their study by looking at medical records of people who had been in a clinical trial and who were receiving the SSRI, citalopram. They found that people who had taken anti-inflammatories were less likely to have improvements in their depression at 12 weeks. However, the human follow-up study can only show an association, and cannot tell us whether the anti-inflammatory drugs caused the SSRIs to be less effective.
This was well-conducted basic research but, at the moment, there is insufficient evidence of its application to humans. The observations from analysing human data suggest that further follow-up examining how anti-inflammatory painkillers alter the effectiveness of SSRI antidepressants is warranted.
The study was carried out by researchers from Rockefeller University New York. Funding was provided by the Skirball Foundation and grants from the United States Army Medical Research Acquisition Activity (USAMRAA) and the National Institutes of Health, Mental Health and Aging. The study was published in the peer-reviewed medical journal Proceedings of the National Academy of Sciences.
The Daily Mail highlighted that this research was in mice with follow-up work using human medical records. There are a couple of points that may lead to misinterpretation. The newspaper said that “many complain that the ‘happy pills’ do nothing to lift their depression and now scientists have worked out why”. However, this study does not resolve the issue of why some people do not respond to antidepressants and there are likely to be many reasons underlying this. The report also said that antidepressants were successful in just 40% of people taking aspirin-like medications, while the research paper put this figure at 45%.
This animal study used mice to investigate the effects of antidepressants when combined with anti-inflammatory medications (painkillers). The researchers followed up their findings by looking at data from a study that followed a cohort of people taking antidepressants to see whether those who took anti-inflammatory medications alongside their antidepressants had different outcomes to those who did not.
The researchers said that chemicals called cytokines, involved in the body’s immune response, may play a role in depression. This theory follows the observation that many patients undergoing certain cytokine treatments develop depressive symptoms, and some cytokines can regulate brain chemicals such as serotonin, which is linked to depression.
The researchers were interested in a protein called p11, which is a biochemical marker of depression. They said that mice that have been genetically modified so that they don’t produce this protein show some symptoms of depression. However, mice that have been genetically modified to produce more p11 show anti-depressant responses in mouse behavioural tests. They said that in tests in rodents, three types of antidepressant treatment (selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs] and electroconvulsive therapy [ECT]) have been shown to cause an increase in p11 levels in the rodent brain. The researchers wanted to see what effect anti-inflammatory drugs would have on the p11 protein.
The researchers treated the mice with the SSRI citalopram (brand name Cipramil) either by itself or alongside the anti-inflammatory drug ibuprofen. They then measured the levels of certain cytokines and p11 in the front area of the mouse brain.
They used genetically modified mice that did not produce the cytokine IFN? or the cytokine TNF? to see if either of these were necessary for citalopram to increase p11. They also looked at the effect of these cytokines on the level of p11 in normal, non-genetically modified mice by injecting the mice with these cytokines.
The researchers then looked at the effect of three anti-inflammatory drugs (ibuprofen, naproxen or aspirin) and a different class of painkiller (paracetamol) on mouse behaviour after the mice had received one of a variety of antidepressants.
The mice received either:
The researchers then analysed data from a trial of antidepressants in humans. The trial, called the “sequenced treatment alternatives to relieve depression (STAR*D)”, looked at data from 1,546 participants taking the antidepressant citalopram. The study also collected records of their symptoms at week 12 and whether they had taken an anti-inflammatory medication during the 12-week period.
In the mouse research, giving the mice either aspirin or ibuprofen with the antidepressants citalopram or Prozac blocked the increase of p11 normally seen with these antidepressants. However, aspirin or ibuprofen did not block the increase of p11 caused by a tricyclic antidepressant (desipramine).
The researchers found that two cytokines, IFN? and TNF?, were regulated by both the antidepressant citalopram and by ibuprofen. They showed that in mice that did not produce either IFN? or TNF?, citalopram no longer increased p11 levels. Injecting mice with either of these cytokines raised p11.
In the mouse behavioural tests, all types of antidepressant caused the mice to be less hesitant (an antidepressant response). However, giving ibuprofen alongside either of the SSRIs (citalopram or Prozac) reduced their antidepressant effects on the behavioural tests. Ibuprofen had less effect on the behavioural response to tricyclic antidepressants and it had no effect on the response to other types of antidepressants.
All three of the anti-inflammatory painkillers and paracetamol reduced the antidepressant effects of citalopram in mice.
In the human part of the study the researchers found that, of 1,546 participants, 810 were in remission from their depression by 12 weeks. Of these, 182 had taken an anti-inflammatory during the 12 weeks while the other 628 had not. There were 227 participants that were treatment resistant (not in remission) and had taken an anti-inflammatory at least once during the 12 weeks of treatment. The remaining 509 participants who were treatment resistant had not taken any anti-inflammatory drugs during this period.
This meant that of those participants who took an anti-inflammatory, 45% were in remission and 55% were treatment resistant at 12 weeks. Of those participants who did not take an anti-inflammatory 55% were in remission and 45% were treatment resistant. The difference between the remission rates was statistically significant (p=0.0002).
The researchers also looked at people taking painkillers other than anti-inflammatories (such as paracetamol). People taking other painkillers were also less likely to achieve remission (37% in remission) compared with those not taking painkillers (54% in remission, p=0.0002).
The researchers said that their research shows that anti-inflammatory drugs inhibit the SSRI antidepressant induced increases in p11 and antidepressant-like behaviours in rodents.
They say this association is confirmed “in a dataset from a large-scale real-world human study (STAR*D) underscoring the clinical significance of these results”. They say that they are currently trying to understand the mechanisms by which anti-inflammatories and other painkillers have this effect on the SSRI class of antidepressants, but they suggest that doctors should “consider these findings when designing treatment strategies for their patients that include SSRIs”.
This predominantly animal research found that non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen reduce the increase in p11 (a marker for depression) when mice are treated with SSRIs, which are a commonly used class of antidepressant. Furthermore, anti-inflammatories and other painkillers have been shown to reduce antidepressant behaviour in mice.
The researchers followed up this study by looking at patient data. However, although they found some associations between use of anti-inflammatories and other classes of painkiller and a reduced remission rate in patients taking a particular SSRI drug (citalopram), they point out that they cannot say whether the painkillers caused this effect.
They go on to say that to evaluate fully the effects of anti-inflammatories and other painkillers on SSRI antidepressant response in humans would require a prospective double-blind randomised clinical study. This would also allow standardised treatments to be assessed. This is important as the people in the clinical trial from which the data were analysed may have been on different antidepressant treatment regimens and different quantities of painkiller medication or other medications.
The researchers say that they are currently looking at the biological mechanisms underlying the observed effect.
This was well-conducted basic research, and the observations from analysing human data suggest that further follow-up is strongly warranted to investigate the effect of painkillers on the effectiveness of SSRI antidepressants.
How painkillers like aspirin and ibuprofen may stop happy pills working. Daily Mail, April 26 2011
Warner-Schmidt JL, Vanover KE, Chen EY, et al. Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. Proceedings of the National Academy of the United States of America 2011. Published online before print April 25
Written by admin on Wednesday, April 27th, 2011 in Swine Flu.
“Babies who persistently cry and those who have difficulties with sleeping or feeding are more likely to develop behavioural problems in later life,” reported The Independent.
The story is based on an analysis of 22 studies looking at the possible association between difficulties such as excessive crying, problems feeding and sleeping problems in infants in the first year of life (known as regulatory problems) and the later development of childhood behavioural disorders such as ADHD and aggression. Researchers found that babies who experienced these problems were more likely to have behavioural difficulties later than those who did not. The most likely behavioural disorders for older children were “externalising” problems such as aggressive behaviour or temper tantrums.
This study collectively involved 16,848 children, of whom 1,935 had regulatory problems. The analysis is appropriate but limited by the nature of the studies included. The difficulty of defining “regulatory problems” in infants, and the problem of relying on information from parents were among the studies’ limitations. Importantly, the worst outcomes were in babies from “multi-problem families” who had poor parent-child interaction, social difficulties, depression and stress in the mother and a “negative” family environment. This indicated that these problems in both infancy and later childhood may be markers for psycho-social problems rather than directly associated with each other.
The study was carried out by researchers from the University of Basel, Switzerland, the University of Warwick and the University of Bochum, Germany. The study was published in the peer-reviewed medical journal Archives of Disease in Childhood. Funding came from several sources including the Swiss National Science Foundation and F Hoffmann-La-Roche, a pharmaceutical company.
Generally, the study was reported accurately in the media. Although the Daily Mail reported that the findings suggest that crying babies were 40% more likely to grow up to display unruly behaviour, the 41% statistic reported by this study cannot be interpreted in this way as it represents the average change in scores across all studies using several different measures all standardised so that the study results can be pooled together. The Daily Mail did also report comments from one author who pointed out that the problems in babies that led to later issues were abnormally severe.
This was a meta-analysis of 22 previous studies that investigated infant regulatory problems (excessive crying, sleeping difficulties and/or feeding problems in the first year of life) and their later behaviour in childhood. The results of these studies were combined and statistical tests used to look for possible associations between the two.
The researchers point out that these problems are common, with about 20% of infants affected. Although many of these difficulties are transient, persistent difficulties may predict behavioural problems later in life. The aim of this study was to test the nature and strength of any associations.
The researchers carried out a meta-analysis of 22 prospective cohort studies from 1987 to 2006 that statistically tested the association between infant regulatory problems and later childhood behavioural problems. They carried out a computer-based search of the literature on this topic, which produced an initial pool of 72 studies. To be included, studies had to meet certain inclusion criteria. Only prospective studies including at least one follow-up assessment were eligible. They had to focus on crying, sleeping and/or feeding problems in the first year of life, either occurring in isolation or in combination. They also had to include a measure of four behavioural difficulties: internalising problems (such as depression and anxiety), externalising problems (such as aggressive behaviour), ADHD symptoms (such as inattention) and general behaviour problems.
The researchers say identifying regulatory problems was a “major challenge” since consistent diagnostic criteria were lacking. For this study, excessive crying was defined as intense, unsoothable crying bouts for no apparent reason in the first three months of life. “Persistent regulatory problems” were defined as excessive crying beyond the third month of life, and sleeping and feeding problems that occurred at initial assessment and at follow-up.
The studies used a combination of parent interviews (60%), questionnaires (41%), infant diaries (32%) and observations to assess regulatory problems. Most informants were parents of the children included.
The researchers used statistical methods to assess the relationship between regulatory problems in infancy and later behavioural problems. To do this, they used a “standardised weighted mean effect size”, a statistical measure that is useful when different studies use diverse instruments with different scales to assess behavioural problems.
The researchers identified 22 eligible studies with 16,848 children, of whom 1,935 had regulatory problems.
Of the 22 studies, 10 examined the effects of excessive crying, four sleeping problems, three feeding problems and five multiple regulatory problems.
The researchers say their analysis suggests that children with previous regulatory problems have more behavioural problems later in childhood than controls, with children from “multi-problem” families having the worst outcomes. They say their findings highlight the need for better understanding of the development of child mental disorders and for early intervention, particularly in families with other problems.
This meta-analysis had a number of limitations which the authors acknowledge:
It is difficult to make any robust conclusions from these findings, but interpreting them to mean that infants with these problems are automatically at greater risk of behavioural problems later is probably unwise.
Importantly, babies with regulatory problems who went on to develop behavioural disorders often came from “multi-problem families” with poor parent-child interaction, social difficulties, depression and stress in the mother and a “negative” family environment. The researchers acknowledge that it was difficult to adjust for these factors in the analysis, and it is possible that the “regulatory problems” and later behavioural difficulties are both markers for psycho-social problems.
Crying babies ‘more likely to grow into problem children’. Daily Mail, April 21 2011
Cry-baby ‘link to behavioural problems’. BBC News, April 21 2011
Excessive crying in babies linked to later problems. The Independent, April 21 2011
Hemmi MH, Wolke D, Schneider S. Associations between problems with crying, sleeping and/or feeding in infancy and long-term behavioural outcomes in childhood: a meta-analysis. Archives of Disease in Childhood 2011. Online First April 20
Written by admin on Wednesday, April 27th, 2011 in Swine Flu.
“TB screening misses 70% of latent cases,” reported The Guardian. The newspaper says that experts have called for a change to tuberculosis (TB) screening policy. They suggest that a relatively new blood test should now be used to screen arrivals to the UK from the Indian subcontinent for hidden TB as well as arrivals from other high-risk areas of the world. This, they say, would mean treatment could be given to prevent most cases of the latent or hidden form of the disease from developing into full infectious TB.
This is a well designed study, and goes towards answering a clear and important question for policy decision makers. It is accompanied by an analysis of the overall cost of a change to policy and, importantly, the cost of averting an additional case of TB in people from different countries, allowing the researchers to suggest the best approach to screening those who come to the UK from these areas of the world.
Several papers have focused on the fact that the previous technique for screening for active TB, using X-ray alone, missed 70% of latent TB. This new strategy identified 92% of latent cases, therefore “missing” only 8%. UK guidance currently specifies the groups of people who are offered screening for active TB and includes those arriving in the UK from countries known to have high rates of TB. By specifying countries for screening for latent TB as well as active cases, and using this new test, it is likely that more people can be treated and cured of this increasingly common illness.
Recent NICE guidance, updated earlier this year, has a section on new entrant screening and advises a co-ordinated programme linked to local services that is designed to detect latent TB and start treatment where needed. A positive IGRA test is one of the suggested tests, along with a positive tuberculin skin test in people under 35 years. This study was unpublished at the time and NICE asked for this sort of cost-effectiveness study to target the treatment of latent TB better. There is a small difference between the guidance and the conclusions of this study, relating to the countries that are recommended for this sort of screening for latent TB. Details of this are given below.
The study was carried out by researchers from Imperial College London and other TB services around the UK. The research was funded by the Medical Research Council. The study was published in the peer-reviewed medical journal The Lancet Infectious Diseases.
The news coverage is generally accurate. The newspapers do all emphasise the poor accuracy of chest X-rays when used as a screening test for TB, though the study did not look at this. They all then go on to describe the new study and its main findings, along with the researchers’ call for a change to screening policy. Quotes from a range of commentators are also included, including a comment from the Department of Health that the research backs up the latest guidance from the National Institute for Health and Clinical Excellence (NICE) on TB, issued in March 2011.
This was a cohort study accompanied by a cost effectiveness analysis. Between 2008 and 2010 the researchers analysed data collected from 1,229 immigrants to the UK, from immigration centres in Westminster, Leeds and Blackburn. All three centres were using a relatively new blood test called the interferon-gamma release-assay (IGRA) specifically to test for TB. Only people aged 35 or younger who had been screened for latent or hidden TB infection using this test were included in the analysis. In a decision analysis model, the results for people from different countries of origin were modelled separately so that the researchers could test the strategy for different levels of underlying TB.
The research was carefully conducted and has provided a clear answer to the question of how accurate the test is when used in a population similar to those in these centres. It has also provided an estimate of cost effectiveness and the cost per case of avoided TB, the results of which look favourable and will help to inform immigrant screening policy. There are some practical limitations to how the study was conducted in terms of selection of patients and the assumptions the researchers had to make in the decision model. There are also different IGRA tests available, so this one may not necessarily be the best one. Despite these points, the testing strategy looks promising.
The researchers explain that cases of diagnosed TB have risen in the UK from 6,167 to 9,040 in the 10 years to 2009, and this is mainly due to rising numbers of cases in foreign-born immigrants. They say that national guidance for immigrant screening is hampered by a lack of data. They wanted to address this shortfall by finding out the number of cases of latent infection in immigrants to the UK and by examining the prevalence (rate of latent cases found per 100,000 population) so that they could define the groups that should be screened. They also wanted to model the cost-effectiveness of different strategies so that they could estimate the number of additional cases of full TB that could potentially be avoided with each strategy and at what cost to the tax payer.
TB is a bacterial infection caught by breathing in the bacteria that cause it. These bacteria are spread through sneezing or coughing by someone who has TB. There are two main types of TB, active and latent. In active TB, some people become ill a few weeks or months after breathing in the bacteria and can spread the disease. However, in most people, the body’s immune system kills the bacteria and the person does not get ill. In other people, the bacteria are not killed but stay in the body at a low level, and the person does not get ill and is not infectious. This is called latent TB. The bacteria can start to multiply again months or years later (for example, if the person’s immune system is weakened by another disease such as HIV) and active TB can develop.
In this study, the participants were all foreign-born new entrants who had come to the UK within the past five years and were aged 35 years or younger. They were screened between January 2008 and July 2010 in Westminster, Leeds and Blackburn following referral by “port-of-entry” screening systems, health protection units or after registration with primary-care services. These centres serve a total of 1.6 million people, of which 6.5% are born abroad.
All participants were screened first with a symptom questionnaire followed by four blood tests, including the one-step IGRA test of interest. Immigrants who were symptomatic or who had a positive IGRA result were referred for chest radiography and further clinical assessment to see if they had active tuberculosis. Those with latent infection were offered treatment with either three months of two drugs or six months of one drug, in accordance with their wishes and standard UK guidance.
The researchers also asked about age and sex, BCG vaccination status (ascertained through documentary evidence, reliable history of vaccination or a characteristic scar) and country of origin.
The researchers used standard techniques for their cost effectiveness analysis. They costed the benefit of using this test from a UK National Health Service perspective, modelling the use of IGRA testing for 20 years. Two main questions were asked:
Of 1,229 immigrants, 245 (20%) tested positive in the IGRA tests, 982 (80%) tested negative and two people (0.2%) had indeterminate results.
They say that positive results were independently linked to the TB incidence in immigrants’ countries of origin. This means that test results were more likely to be positive in countries with higher rates of TB after taking into account other factors that were also linked to an increase in rates (male sex and age).
They say that the current national policy for detecting active TB used a chest X-ray in people from countries where more than 40 per 100,000 population per year develop TB. If this was used to screen for latent TB, it would fail to detect 71% of individuals with latent infection.
From the modelling analysis, they found that the most cost-effective strategy would be to screen people for latent TB from countries with a TB incidence of more than 250 cases per 100,000 per year. Using the IGRA test would result in an additional cost of £17,956 for each case of tuberculosis prevented compared with the next most effective strategy.
The next most cost effective strategy would be also to screen immigrants from the Indian subcontinent, where there are more than 150 TB cases per 100,000 people per year. It was estimated that this would identify 92% of infected immigrants and prevent an additional 29 cases of TB over 20 years compared with no screening.
The researchers say that implementation of screening for latent infection would be cost effective. They recommend the level of incidence (150 cases per 100,000 per year) that identifies most immigrants with latent tuberculosis, and which is likely to prevent substantial numbers of future cases of active TB.
Until recently, it has been unclear who best to screen for latent TB. This research supports recent decisions made by NICE regarding how to screen and adds to the evidence on who, from a cost-effectiveness perspective, it might be best to target. This was clearly an area that needed research, as the screening for active TB using a chest X-ray was not effective at identifying latent TB. There are several points the researchers make about their research:
Overall, this is a useful study which is likely to be discussed by those deciding on immigration screening policies. The one-step IGRA blood test may prove to be the preferred option, however it is too soon to say this is the best approach. It is not the only test and further work is needed to compare different screening protocols (such as tuberculin skin test with IGRA compared with skin test alone or IGRA alone). There are also different types of IGRA test, some of which may have different costs.
Tests on immigrants ‘miss most TB’. The Independent, April 21 2011
TB screening misses 70% of latent cases. The Guardian, April 21 2011
TB screening ‘missing most cases’. BBC News, April 21 2011
Pareek M, Watson JP, Ormerod LP, et al. Screening of immigrants in the UK for imported latent tuberculosis: a multicentre cohort study and cost-effectiveness analysis. The Lancet Infectious Diseases, Early Online Publication, April 21 2011
Written by admin on Wednesday, April 27th, 2011 in Swine Flu.
“A breath test that can detect cancer with an ‘electronic nose’ has been developed by scientists,” reported the Daily Express. The newspaper said the device detects microscopic chemical changes that are emitted in the breath of people with head and neck tumours.
The news report is based on a small study that looked at breath samples from 62 people using the Na-Nose, 16 of whom had head and neck cancer, 20 had lung cancer and 26 were healthy. The test was able to distinguish between these individuals by looking at the presence and levels of certain chemicals in their breath samples. Only two healthy individuals were falsely suggested to have head and neck cancer.
This small study had promising results, but the findings will need to be confirmed in much larger samples, representative of the different types and stages of head and neck cancer. If the results are favourable, then the Na-Nose would need to be trialled against existing standards of care to assess its potential benefits and risks.
A non-invasive breath test for various cancers is an appealing option, particularly for those cancers that are difficult to detect in other ways. Undoubtedly, this is an area that will receive much more research in the future. As the Daily Express reports, it would probably be many more years before a breath test could be available in a clinical environment.
The study was carried out by researchers from Technion – The Israel Institute of Technology – and Rambam Health Care Campus in Israel. Funding was provided by the European Commission. The study was published in the peer-reviewed British Journal of Cancer.
The BBC and the Daily Express both cover this study well, indicating that the study is preliminary, and that it could take years to see whether the test could be used in a clinical setting.
This was a cross-sectional study, looking at the ability of a breath test to distinguish between people with head and neck cancer (HNC), healthy individuals and those with lung cancer. The breath test in question uses a device called the Nanoscale Artificial Nose (or Na-Nose). The Na-Nose uses gold nanoparticle gas sensors that can detect and separate different odours, even at very low concentrations. The device has already been tested for its ability to detect other cancers (breast, lung, colon and prostate cancer).
Head and neck cancer can affect various tissues in the head and neck, including bone, soft tissues, salivary glands, skin and mucous membranes. The researchers report that HNC is the eighth most common malignancy worldwide, that it is often diagnosed late as it lacks specific symptoms and that there are no screening methods available. They say that less than half of individuals achieve an overall cure from HNC, and that lifelong follow-up is needed, as patients often develop a second primary cancer (a new cancer), most commonly HNC or lung cancer.
This sort of study is usually used in the earlier stages of assessing the performance of a new diagnostic or screening test. Tests that show promise in these early stages need then to be tested in larger samples that are more representative of the population in which the test might be used. Finally, if the test performs well enough it might go on to be tested in randomised controlled trials. These trials usually compare the test with standard current practice, to assess whether it offers any benefits (such as reducing the number of deaths) and what the associated harms might be (for example, false negatives, psychological distress and unnecessary investigations due to false positives). If the test was to be used in screening the entire population, or a subgroup of the population, then the cost of providing the test would need to be weighed up against the potential benefits and harms.
The researchers collected breath samples from 40 healthy individuals, 22 people with head and neck cancer (HNC) and 25 people with lung cancer (who were matched for age and gender to those with HNC). These breath samples were then tested using the Na-Nose device, to see whether it could detect differences between the three groups.
The participants were all adults (age 24-78 years), some were smokers and some non-smokers. Participants with HNC had been diagnosed using standard methods, including biopsies. Among the participants with HNC, four had earlier stage cancers (stages I and II), and 18 had later stage cancers (stages III and IV). Participants with lung cancer all had stage III or IV cancers. The average age of the healthy controls was younger than that of the participants with cancer (45 years versus 60 years for HNC participants, and 66 years for lung cancer participants). There was a greater proportion of women in the healthy sample (57% female, while less than 15% of the cancer groups were female). The researchers report that the Na-Nose test has been designed not to be sensitive to differences in age, gender and smoking habits.
The researchers collected breath samples under the same conditions for all participants. The inhaled air was filtered to remove any particles or volatile organic chemicals using a mouthpiece. The exhaled samples were collected in a way that allowed collection of air that had been in the balloon-like structures in the lungs called the alveoli, where gases diffuse into and out of the blood. The breath samples from the HNC patients were collected before they received any treatment.
Sixty-two breath samples were tested using the Na-Nose (16 HNC, 20 lung cancer, 26 healthy). The test used five sensors to detect five different volatile organic chemicals. Statistical methods were used to group (or “cluster”) the breath samples based on the similarity of the chemical profiles seen.
To support and validate the findings of the Na-Nose analysis, the chemical composition of 40 of the breath samples was also assessed using standard techniques called gas chromatography and mass spectrometry.
The researchers found that the Na-Nose device could distinguish between breath samples from the three different groups of individuals: those with head and neck cancer, those with lung cancer and healthy individuals.
The Na-Nose correctly identified 24 out of 26 healthy individuals (two were falsely identified as having HNC). All 16 people with HNC were correctly identified, as were all 20 individuals with lung cancer.
Gas chromatography and mass spectrometry showed that there were differences in the chemical composition of breath samples from these three groups. The researchers identified groups of six or seven volatile organic compounds that could be used to distinguish between the three groups.
The researchers concluded that their findings “could lead to the development of a cost-effective, fast, and reliable” breath-based test for identifying individuals with head and neck cancer. They say that the Na-Nose test has potential for use as a screening tool.
This study tested whether the Na-Nose device could distinguish between individuals with head and neck cancer, healthy individuals and those with lung cancer. Although the results from this study appear promising, they are very preliminary. Only 16 patients with head and neck cancer were tested, and much larger samples would be needed to confirm the results. Ideally, such a study would include a broader spread of individuals who are representative of the different stages and types of head and neck cancer.
One limitation of the study is that it is not clear whether the people carrying out the analyses knew which individuals had which diagnosis, which could lead to bias. The authors themselves acknowledge that a larger, blinded trial is needed.
If the test continues to show promise in larger studies, it might go on to be tested in randomised controlled trials, to assess whether it offers any benefits (such as reducing the number of deaths from head and neck cancer) and what the associated harms might be (for example false negatives, psychological distress and unnecessary investigations due to false positives). The tool is most likely to be considered as a screening device for head and neck cancer, which is not currently screened for.
Head and neck cancers are currently diagnosed using methods such as endoscopy and biopsy when suspicion is raised due to symptoms of cancer (which will be variable depending on the type of cancer). However, symptoms of some cancers may be non-specific or only reveal themselves when the cancer is already advanced. If the new breath test were approved for screening, one of the most important considerations would be who to screen. If the test was to be used in screening the entire population, or a subgroup of the population, then the cost would also need to be weighed up against the potential benefits and harms.
A non-invasive breath test for various cancers is an appealing option, particularly if it is difficult to detect the cancer in other ways. Undoubtedly, this is an area that will receive much more research in the future. As the Daily Express reports, it would probably be many more years before a breath test could be available in a clinical environment.
Cancer breath test ’step closer’. BBC News, April 20 2011
Electronic ‘nose’ can sniff out cancer with a simple breath test. Daily Express, April 20 2011
Hakim M, Billan S, Tisch U, et al. Diagnosis of head-and-neck cancer from exhaled breath. British Journal of Cancer 2011