Written by admin on Monday, August 31st, 2009 in Swine Flu.
Colombian President Alvaro Uribe has contracted the H1N1 swine flu virus and is being treated by doctors while continuing to work from his residence, government spokesman Cesar Velasquez said on Sunday.
Written by admin on Friday, August 28th, 2009 in Swine Flu.
The Times and other newspapers have reported on a large international study finding that “weight-loss surgery can eliminate the symptoms of type-2 diabetes in nearly eight out of ten patients”.
The news stories are based on a thorough and well conducted review of the effect of bariatric (weight-loss) surgery on weight and type-2 diabetes. Studies with a total of 4,070 diabetic patients found bariatric surgery to be greatly effective for both reducing weight and improving diabetes, both in the short and long term. There are some limitations to the research, including the fact that it combined studies that had very different methodologies.
The principal point is that the findings must be interpreted in the right context. Bariatric surgery may be expected to lead to some improvement in diabetes because it causes weight loss, but this does not mean that weight-loss surgery is the solution to diabetes. Bariatric surgery is only ever performed as a last resort in morbidly obese people who meet strict criteria, have failed in other attempts at weight loss, have weight-associated comorbid disease and consent to intensive long-term management in a specialist obesity service.
The research was carried out by Dr Henry Buchwald and colleagues from the University of Minnesota and other US institutions. The study was funded by Ethicon Endo-Surgery, Inc., a Johnson & Johnson Company, Ohio, US. The study was published in the (peer-reviewed) medical journal The American Journal of Medicine.
In this systematic review the researchers combined the results of studies in which people had bariatric (weight-loss) surgery, to see the effect it had on weight reduction and type-2 diabetes.
The researchers searched various medical databases for all studies published in English from January 1 1990 to April 30 2006 on banding, gastroplasty, gastric bypass or biliopancreatic diversion/duodenal switch, and that had assessed weight loss and type-2 diabetes outcomes. All study designs were included and their findings combined using a statistical technique called meta-analysis.
The researchers pooled outcomes reflecting improvement in type-2 diabetes within two years of surgery, and longer-term improvement after two years. The studies measured improvement using insulin levels, glycated haemoglobin (HbA1c) tests and fasting glucose levels. The researchers also investigated the effect of type of surgery on diabetes and overall weight reduction.
All studies were assessed for quality. The researchers say that they performed sensitivity analyses based on the quality of the underlying studies, but only appear to report their overall analyses. Data on the studies, patients and treatments were summarised, and outcomes of weight loss and clinical and laboratory manifestations of diabetes were collected. Results were combined for each type of surgery and outcome of interest.
The researchers found 621 studies that met their inclusion criteria. These covered 888 different treatment arms and 135,246 patients. When they looked only at studies that had reported on the resolution of clinical and laboratory manifestations of type-2 diabetes, they found 103 treatment arms involving 3,188 patients. In 19 studies, weight loss and diabetes resolution were reported separately for 4,070 diabetic people. Only 30 studies were randomised controlled trials and of these 10 were rated as class I evidence (a high-quality study).
The average age for people receiving bariatric surgery was 40.2 years. Women made up 80% of the total and the average BMI was 47.9. The review gives extensive results, and weight loss results are reported separately for each type of surgery, but overall weight loss was 38.5kg or 55.9% loss of excess body weight.
There was complete diabetes resolution in 78.1% of patients, and diabetes was improved or resolved in 86.6% of patients. Of the different treatments, biliopancreatic diversion/duodenal switch gave the greatest improvement in weight reduction and diabetes resolution (95.1% resolved). This was followed by gastric bypass (80.3%). Banding procedures gave the lowest improvement (56.7% resolved).
There was a significant postoperative reduction in insulin levels, HbA1c and fasting glucose values. There was little difference between weight loss and diabetes within two years of surgery or longer term after two years.
The reviewers conclude that the clinical and laboratory manifestations of type-2 diabetes are resolved or improved in the vast majority of patients who undergo bariatric surgery. Procedures associated with the greatest loss of excess body weight gave the most pronounced improvement.
This systematic review and meta-analysis pooled the results of all identified studies that examined the effect of bariatric surgery on weight loss and type-2 diabetes. It found surgery to be effective for both, in the short and long term. There are some limitations to the research, which the authors acknowledge, including:
In addition to these, the review pooled studies with very different methodologies. Only a very small proportion of studies were of high quality and although the researchers say they performed sensitivity analyses based on study quality (which suggests they must have pooled only these high-quality studies), they only report these for one outcome. The high-quality studies may give different findings that are more robust.
Given that type-2 diabetes is associated with obesity, high cholesterol and hypertension, it is not surprising that the large reduction in weight and dietary intake associated with bariatric surgery would result in significant improvement in diabetes. However, these findings must be interpreted in the right context. This does not mean that weight-loss surgery is the solution to diabetes. Bariatric surgery is only ever performed as a last resort in morbidly obese people who fulfil the following strict criteria as defined by NICE:
Stomach-stapling surgery can eliminate diabetes symptoms. The Times, August 28 2009
Weight-loss surgery ‘can halt diabetes’. The Metro, August 28 2009
Weight-loss surgery ‘can eradicate diabetes in almost eight out of 10 patients’. The Daily Telegraph, August 28 2009
Buchwald H, Estok R, Fahrbach K, et al. Weight and Type 2 Diabetes after Bariatric Surgery: Systematic Review and Meta-analysis. The American Journal of Medicine 2009; 122: 248-256
Written by admin on Friday, August 28th, 2009 in Swine Flu.
"Teetotallers suffer higher levels of depression than drinkers”, reported The Daily Telegraph. It said scientists have found that people who abstain are also more likely to lack social skills, have higher levels of anxiety and even have more mental health issues than “those considered heavy drinkers”.
The results from this large population study of 38,390 people in Norway show an increased risk of anxiety and depression for abstainers, and also for those who drink heavily. However, it cannot explain why abstainers and low-level alcohol consumers may have a higher risk of common mental disorders. Although the study cannot prove causation, it has some strengths, including taking into account many social and health factors that could have confounded this association. Importantly, a person may be drinking low or high levels of alcohol as a result of their anxiety or depression, rather than the other way round. This study does not prove that low alcohol consumption causes depression and does not endorse a lifestyle of heavy drinking as being better for mental health than abstinence.
The research was carried out by Jens Christoffer Skogen and colleagues from universities, hospitals and other institutions in Norway. The first author received support from members of the Network of Psychiatric Epidemiology (NEPE), and Sverre Nesvåg at Alcohol and Drug Research Western Norway. Another author was supported by the Biomedical Research Centre for Mental Health at the Institute of Psychiatry, Kings College London and the South London and Maudsley NHS Foundation Trust. The study was published in the peer-reviewed medical journal Addiction.
This cross-sectional study examined the association between levels of anxiety and depression and alcohol consumption. It tested the theory of a “U-shaped relationship” between drinking and mental health disorders, where abstainers and heavy drinkers have an increased risk of anxiety and depression compared to moderate drinkers.
Researchers used data from both the first and second Nord-Trøndelag Health Studies (HUNT). HUNT-1, conducted between 1984 and 1986, established a database of health-related information for all people aged 20 or over living in the Nord-Trøndelag County. In 1995-97 the same population was assessed in HUNT-2. In total, 93,000 individuals were eligible to participate in the HUNT studies, and 67% of the men and 76% of the women taking part in HUNT-1 also took part in HUNT-2.
In these analyses, the researchers included all participants of HUNT-2 who gave information about alcohol consumption, mental health and potential confounders. The analyses included 38,390 people, which is 41% of the total eligible population.
Alcohol consumption was measured by a questionnaire that assessed alcohol consumption over a two-week period. Alcohol consumption was assessed by alcohol units, one unit being equivalent to a 35cl bottle of beer (4.5%), a 12cl glass of wine (12%) or a 4cl shot of spirits (45%).
Abstainers were identified by being asked the question, “Are you an abstainer?”, and as people who reported no alcohol consumption during the two-week period. Those who said they were an abstainer but reported drinking alcohol were classified according to their reported consumption (there were 41 people with such an inconsistent response) and those who did not report drinking any alcohol but said they were not an abstainer were classified as “non-consumers”. Alcohol drinkers were categorised into gender-specific percentiles of consumption.
Anxiety and depression were measured using a validated rating scale (timing of assessment not reported). Potential confounding factors that can influence both alcohol consumption and risk of mental health problems were accounted for in analyses. These included gender, age and social class.
In a subsample of 20,337 people, heavy drinking was also assessed for the previous 11 years in those who were current abstainers. This was to examine the risk of mental health problems being related to a previous heavy drinking habit (termed “sick-quitting”).
In the total sample of 38,390 people there were 4,446 (11.6%) self-reported alcohol abstainers and 8,570 (22.3%) who did not regularly drink alcohol, but did not consider themselves abstainers (non-consumers). Alcohol abstainers were more commonly female, older and had more chronic illness than non-consumers and moderate consumers.
When sick-quitting was assessed, current abstainers were found to have mostly been non-consumers (58.1%) or abstainers (30.9%), but rarely high consumers (1.5%) in the previous 11 years.
The researchers found the expected U-shaped association between alcohol consumption and the risk of anxiety and depression. Compared to moderate drinkers, abstainers of alcohol had increased risk of anxiety (OR 1.34, 95% CI 1.19 to 1.52 [adjusted for age and gender]) and of depression (OR 1.52, 95% CI 1.30 to 1.77).
Adjusting for socioeconomic status, social network, other illness, sick-quitting, age (depression only) and gender (anxiety only) slightly lessened the strength of this association, but it remained significant. The risk for abstainers was slightly greater than for those who reported no usual alcohol consumption in a two-week period, but did not label themselves as abstainers.
The researchers conclude that the risk of anxiety and depression is increased in people who drink low levels of alcohol compared to those who drink moderately. In particular, risk increased for individuals who label themselves as abstainers.
This large cross sectional study of a Norwegian population demonstrated an association between depression and anxiety, and both abstaining from alcohol and heavy drinking. Efforts were made to take into account many social and health factors that might confound this association, and also the possibility that current anxiety or depression in an abstainer may reflect a previous heavy drinking problem.
However, cross-sectional studies such as this cannot prove causation. People may drink low or high levels of alcohol because of their anxiety or depression, so the results do not necessarily mean that alcohol consumption was the cause of the mental disorder. In addition, people are likely to report their alcohol consumption differently and there is possibly some bias in the way people with anxiety or depression report their alcohol use.
As such, the results provide little information on why abstainers and low-level alcohol consumers may have a higher risk of some mental health problems. As the authors say, it is not possible to speculate from this study about the relationship between alcohol consumption and other mental or general health conditions, as only depression and anxiety were assessed.
News reports that non-drinkers have even more mental health issues than heavy drinkers are an inaccurate reflection of this study’s findings. Those who drank heavily also had increased risk of anxiety and depression. Aside from mental health, the health risks associated with heavy drinking are also well established. The study findings do not endorse a lifestyle of heavy drinking as being better for mental health than abstinence.
Teetotallers suffer higher levels of depression than drinkers. The Daily Telegraph, August 28 200
Non-drinkers more prone to depression, says study. The Guardian, August 28 2009
Christoffer Skogen J, Harvey SB, Henderson M, et al. Anxiety and depression among abstainers and low-level alcohol consumers. The Nord-Trøndelag Health Study. Addiction 2009; 104: 1519 – 1529
Written by admin on Wednesday, August 26th, 2009 in Swine Flu.
A study suggests that “women with ovarian cancer are dying because GPs are failing to detect the early signs of the disease”, The Times warned. It said that a study suggests family doctors may be overlooking a main symptom – a distended abdomen – because it is not included in the guidance for urgent investigation.
This well designed study identified symptoms that women with ovarian cancer commonly report to their GPs in the year before diagnosis. It identified seven key symptoms; mainly abdominal distension, abdominal pain and urinary frequency.
Despite what was reported in the newspapers, the study does not indicate that symptoms of ovarian cancer are being missed by GPs as the patient data it used was limited and did not include the patient’s history or outcome of consultation. However, the study is very valuable in drawing attention to the need for all doctors to have a high index of suspicion for ovarian cancer when any woman presents with abdominal distension, and to carefully evaluate urinary or gynaecological symptoms or general symptoms such as loss of appetite that may otherwise be assumed to be from another cause.
This research was carried out by Dr William Hamilton and colleagues from the National Institute for Health Research (NIHR) School for Primary Care Research at the University of Bristol. The study was funded by the Department of Health’s NIHR School for Primary Care Research funding scheme and published in the peer-reviewed British Medical Journal.
The aim of this case control study was to identify and quantify the symptoms that women with ovarian cancer report to their GP in the year before they are diagnosed.
Using the records of 39 general practices in Devon and Exeter, the researchers searched for all women aged 40 or over who were diagnosed with ovarian cancer between 2000 and 2007. A total 97,500 women in this age group were found, of whom 255 had been diagnosed with ovarian cancer or suspected ovarian cancer. After excluding 43 women for a number of reasons, such as other malignancies, benign disease, diagnosis before 2000 and those who had moved out of the area, 212 cases were available for analysis.
Diagnosis of ovarian cancer was taken as histological confirmation (available for 80%) or specialist diagnosis. At the time of the study, 113 of the diagnosed women (53%) had already died. Each case was matched to five age-matched controls without ovarian cancer (1,060 following exclusions; average age 67).
The medical records for each case and control were collected and made anonymous. Three researchers who were unaware which patients had been diagnosed with cancer (blinded) coded all symptoms recorded in consultations in the year prior to the date of diagnosis.
Only symptoms present in more than 5% of cases and controls were included in the analyses. A positive predictive value (PPV) was calculated for each symptom (or combination of symptoms). Positive predictive value is the probability that someone who has the symptom (or combination of symptoms) actually has ovarian cancer.
Seven symptoms were more common in women diagnosed with ovarian cancer:
In the year before diagnosis, 85% of cases and 15% of controls reported to their GP with at least one of the symptoms. When the analysis was confined to symptoms reported more than six months before date of diagnosis abdominal distension, abdominal pain and urinary frequency were still associated with ovarian cancer (meaning that the other symptoms were more commonly reported nearer to the time of diagnosis).
On examination of the patient, signs associated with a diagnosis of ovarian cancer were an abdominal mass, or a mass palpable vaginally or rectally, and abdominal tenderness. Women diagnosed with ovarian cancer had visited their GP on more occasions in the past year compared to controls (average 10 occasions versus six).
The researchers conclude that women with ovarian cancer usually have symptoms and have reported them to primary care, sometimes several months prior to diagnosis. They say that this study provides “an evidence base for selection of patients for investigation, both for clinicians and for developers of guidelines”.
This well designed study investigated the symptoms that women with ovarian cancer presented to their GP with in the year before diagnosis. It identified seven key symptoms reported more frequently in women later diagnosed with ovarian cancer. Principally, these were abdominal distension, abdominal pain and urinary frequency. When considering this, a couple of points should be kept in mind:
This important study draws attention to the need for healthcare practitioners to consider ovarian cancer in women presenting with the symptoms highlighted by this study. Further analysis is needed to investigate symptom combinations, the influence of age and the thresholds for referral.
Women with ovarian cancer ‘dying because GPs fail to spot signs’. The Times, August 26 2009
Most ovarian cancer victims face delays in diagnosis that can kill. Daily Mail, August 26 2009
Ovarian cancer ‘is being missed’. BBC News, August 26 2009
Hamilton W, Peters TJ, Bankhead C, Sharp D. Risk of ovarian cancer in women with symptoms in primary care: population based case-control study. BMJ 2009; 339: b2998
Written by admin on Tuesday, August 25th, 2009 in Swine Flu.
“Millions of lives could be saved by a groundbreaking discovery that has found a way to stop tumours growing and spreading”, according to the front page of the Daily Express. The newspaper says that scientists have found out how breast cancer cells “turn off” microRNA molecules, allowing cancer to spread, and are working on a drug based on their findings.
The complex research behind this story has shed more light on the processes behind how the hormone oestrogen affects breast cancer cells. This research did not aim to develop a new treatment for breast cancer, and did not specifically look at tumour growth or spreading, but may add to our understanding about the biology of cancer and help to identify new ways of treating it. More research will be needed to investigate further the role of microRNAs in breast cancer, and to determine whether new treatments targeting or imitating these molecules are likely to be useful. It is too early in this process to know whether talk of a “cure” based on these findings is realistic.
This research was conducted by Dr Leandro Castellano and colleagues from Imperial College London and the Howard Hughes Medical Institute in the US. The study was funded by the Breast Cancer Campaign charitable fund and published in the peer-reviewed medical journal Proceedings of the National Academy of Sciences of the USA.
This was a laboratory study using genetic techniques to look at how the hormone oestrogen affects breast cancer cells.
Within the body’s cells oestrogen molecules bind to proteins called oestrogen receptors, to form a ‘complex’ that can bind to DNA and affect which genes are switched on. The researchers thought that oestrogen might also affect the production of small pieces of genetic material called microRNAs. MicroRNAs are short strands of ribonucleic acid (RNA) similar in structure to DNA that are involved in regulating how genes work. Unlike the ‘messenger’ form of RNA they do not contain instructions for producing proteins themselves.
In order to look at whether oestrogen affected the production of microRNA the researchers treated breast cancer cells with oestrogen and looked at how this affected the levels of a range of different microRNA molecules. These results were compared to those from breast cancer cells that had been genetically engineered to prevent oestrogen having an effect. They then carried out further experiments to confirm whether the microRNAs identified were being regulated by oestrogen in the breast cancer cells.
The researchers then compared the levels of the microRNAs in samples of breast cancer tissue both with and without high levels of the oestrogen receptor protein (called oestrogen receptor positive and negative respectively). They also looked at whether these microRNAs would be able to regulate the production of oestrogen receptors and of proteins that work with the oestrogen receptor.
The researchers identified a range of microRNA strands that were affected by oestrogen. These microRNAs came from three different microRNA “clusters” – groups of microRNAs made together in one long strand, which undergoes processing within the cell, firstly to produce individual precursor microRNAs and then later to produce mature microRNAs.
The researchers mainly focused on one cluster (called mir-17-92) that is produced from instructions found on the long arm of chromosome 13. Previous research had suggested that this area of chromosome 13 was involved in breast cancer, and that the mir-17-92 microRNA cluster has been implicated in lung cancer and lymphoma blood cancer.
The researchers confirmed that production of the mir-17-92 cluster of microRNAs was being switched on by oestrogen. They also showed that production of the mir-17-92 cluster was higher in breast cancer tissue that had higher levels of oestrogen receptor proteins. One of the precursor microRNAs made from this cluster (called pre-miR-18a) was produced in larger amounts in oestrogen-receptor-positive breast cancer tissue than in oestrogen-receptor negative breast cancer tissue, but levels of the mature microRNA (called miR-18a) did not differ.
The microRNAs produced from the mir-17-92 and other two clusters identified were shown to “turn down” the production of the oestrogen receptor and related proteins.
The researchers suggest that the mir-17–92 cluster acts as a tumour suppressor in breast cancer. They say that this is the first time that research has identified a role for microRNAs in the process by which oestrogen receptors regulate their own production within breast cancer cells in response to oestrogen.
This complex research has shed more light on the effect that oestrogen can have on breast cancer cells. Although this research itself did not aim to develop a new treatment for breast cancer, work that improves our understanding of the biology of cancer can help to identify new ways of treating it.
More research will be needed to investigate further the role of microRNAs in breast cancer in order to determine whether treatments that target or imitate these molecules are likely to be useful. This research is welcome as the initial step towards understanding this relatively unexplored aspect of breast cancer: however, despite what some news coverage may suggest, the work does not yet demonstrate a cure for this, or any other type of cancer.
Breast cancer breakthrough. Daily Express, August 24 2009
Scientists ‘close to breast cancer cure’ after British researchers find a way to stop tumours growing. Daily Mail, August 25 2009
Scientists two years from developing ‘potential cure’ for breast cancer. The Daily Telegraph, August 25 2009
Castellano L, Giamas G, Jacob J et al. The estrogen receptor-?-induced microRNA signature regulates itself and its transcriptional response. PNAS, Published online before print August 24 2009
Written by admin on Tuesday, August 25th, 2009 in Swine Flu.
Dr. David Sencer and others about the Swine Flu vaccine of 1976. Note the admitted lack of safety and informed consent to the public, even as TV ads frightened American citizens into getting a shot. Think anything has changed?
Written by admin on Tuesday, August 25th, 2009 in Swine Flu.
Children are more likely to develop diabetes in winter, newspapers have reported. The Times said that a large international study of 31,000 children from 53 countries suggests there is a correlation between the seasons and type 1 diabetes. It said the trend was more prevalent in boys and older children (5-14 year olds) of both sexes.
The news stories are based on a large, well-conducted time series study that demonstrates a seasonal variation in the diagnoses of type 1 diabetes across the world. The researchers conclude that the seasonality “is a real phenomenon”, but that more data are needed on populations living in the southern hemisphere, such as southern Africa, Australia and South America “to complete the picture”. There are no explanations that account for the differences seen between girls and boys and the differences in the age groups.
The study has highlighted an issue that needs more research. At present, the implications of these findings for individuals are unknown as these rates were calculated for clinics and countries. More research into how seasonality influences the onset of diabetes at an individual level is needed. It is also important to acknowledge the possibility that the study was biased by differences between the diabetes centres in different countries.
The research was carried out by Dr Moltchanova and colleagues from the National Institute for Health and Welfare, Helsinki, Finland. The research was funded by the EU GEOBENE Project and by the Academy of Finland and published in the peer-reviewed medical journal Diabetic Medicine.
The aim of this study was to determine whether there is a worldwide seasonal pattern in the clinical onset of type 1 diabetes. It is a time series study (a type of ecological study), for which the researchers used statistics from the World Health Organization (WHO) on the incidence (number of new cases) of type 1 diabetes in 0 to 14 year olds during the period 1990 to 1999. This information was collected as part of the WHO DiaMond (Diabetes Mondiale) study: a 10-year project involving 105 treatment centres across 53 countries.
Each country submitted annual data on gender, ethnicity, date of birth and treatment, using standardised forms. The rate of new cases occurring in each geographical area was calculated as the number of new cases of type 1 diabetes divided by the total number of resident children under 15 years of age. Out of 40.5million ‘at risk’ children under the age of 15 years, a total of 31,091 cases of type 1 diabetes were diagnosed in this period.
In their analyses, the researchers divided the children into three age groups: 0-4, 5-9 and 10-14 years. Statistical techniques were used to determine whether there were variations in the monthly totals of diabetes diagnosed and whether these trends corresponded with the seasons in both the northern and southern hemispheres. Essentially, the researchers were analysing the annual trends in incidence, comparing the actual incidence per month with that expected if there were a completely uniform monthly distribution (calculated by dividing the total annual incidence by 12 months).
There was seasonal variation in the numbers of new cases of type 1 diabetes in 42 of the 53 centres. Of these, 28 had the highest number of new cases in the winter months (October to January), while 33 had their lowest in the summer months (June to August). Two of the four southern hemisphere countries demonstrated a different pattern (a peak during July to September and a trough in January to March).
Distance from the equator had an effect, with countries further away from the equator (with a high or low latitude) more likely to show a seasonality effect. Longitude did not make a difference. Boys had a more pronounced pattern of seasonality than girls, and seasonality was also more evident in older children (5-14 year olds) than younger children (0-4).
The link between number of new cases and the seasons seemed to depend on the total number of cases diagnosed in a centre, with the centres that diagnosed more cases having a stronger association.
The study confirms the findings of other smaller studies, that there is a global pattern of seasonality with type 1 diabetes. Cases tend to peak in the winter months and trough in the summer months in both the southern and the northern hemispheres.
The results from this large, well-conducted study confirm what has been seen in previous small studies. However, any interpretation of these findings should take into account several shortcomings that the researchers themselves raise:
Although the study was well conducted and efforts were made to standardise the data from the different centres, it is possible that there were differences in diagnostic practice or reporting between the centres that may have biased the results. As an ecological design, the study looked at the effect of seasons on the incidence of diabetes in a population group, such as a clinic or country. This means that there are no definite implications for individuals. The study’s value is in generating theories of how diabetes may be caused and in pointing future investigation in a particular direction, rather than showing that season is a definite factor.
Overall, the researchers conclude that the seasonality of type 1 diabetes “is a real phenomenon”, but that more data are needed on populations living below the 30th parallel (for example southern Africa, Australia and South America) “to complete the picture”.
Diabetes ‘most likely to occur among children in winter’. The Times, August
24 2009
Children ‘more likely to develop diabetes in winter than in summer’. The Daily Telegraph, August 24 2009
Risk of diabetes ‘rises in winter’. The Metro, August 24 2009
Moltchanova EV, Schreier N, Lammi N and Karvonen M. Seasonal variation of diagnosis of Type 1 diabetes mellitus in children worldwide. Diabetic Medicine 2009; 26: 673-678
Written by admin on Tuesday, August 25th, 2009 in Swine Flu.
Scientists may have developed “a more sensitive test for the asbestos-related cancer mesothelioma”, according to BBC News. This devastating cancer is usually diagnosed by looking for cancerous cells in the fluid surrounding the lungs (cytology), but this method is not a very sensitive test and does not distinguish well between mesothelioma and other cancers.
In a well conducted diagnostic study, researchers in Oxford assessed the accuracy of combining cytology with their new test, which measures the amount of the protein mesothelin in fluid around the lungs. They demonstrated that this is a valuable addition to the usual cytology tests given to people presenting with possible mesothelioma. Importantly, the researchers suggest that this test should be used alongside cytology, although it also performed well alone. This potential new method has the benefit of being performed on the same fluid samples currently used in diagnosis by cytology, meaning it might easily be added to current testing programmes.
This research was conducted by Dr Helen Davies and colleagues from the Oxford Centre for Respiratory Medicine and other institutions in the UK. The research was funded by several organisations including the British Lung Foundation, the Department of Health Clinical Lecturer Award and the Medical Research Council. It was published in the American Journal of Respiratory and Critical Care Medicine, a peer-reviewed medical journal.
This was a diagnostic study looking at the accuracy of a new form of test to detect the cancer mesothelioma by examining the presence of proteins in lung fluid. This method was compared against the gold standard test for the cancer, which relies on cytology of the fluid (looking for cancerous cells). Mesothelioma is a form of cancer related to asbestos exposure.
People with mesothelioma often present with pleural effusion (excess fluid in their lungs), which can affect breathing. However, not everyone who presents with effusion will have mesothelioma, and some will have other forms of cancer or benign pleuritis (non-cancerous lung disease). Cytology of pleural effusions is good at identifying cancers, but it is not very specific to mesothelioma.
Mesothelin is a protein produced by cancerous mesothelioma cells and released into the fluid around the lungs. Measuring the level of mesothelin in the blood is already used to monitor, and sometimes to diagnose, this cancer, but several other studies have suggested that measuring mesothelin directly from the pleural fluid may be a better method. The researchers here set out to describe the accuracy and use of such a test.
In total, the researchers used 429 samples of pleural fluid collected from 209 patients at the Oxford Pleural Unit. In their first experiment they collected pleural fluid samples from 167 patients presenting with symptoms of pleural effusion who were being investigated for possible malignancy. Analysis was possible in 166 of these samples.
Based on cytology, tissue samples or clinical diagnosis samples were classified as being malignant or benign. The type of cancer was also identified. The researchers compared the levels of mesothelin in the pleural fluid of those with mesothelioma, those with metastatic cancers in the lung and those with benign disease. They used statistical methods common in diagnostic testing to determine how accurate a test this was and the optimal concentration for detecting mesothelioma.
They also compared the value of the mesothelin test with that of using pleural fluid cytology alone, to see which was the best test. In other experiments, they assessed the effect of pleurodesis (sticking the pleural membranes together to prevent further liquid building up) on levels of mesothelin in lung fluid. They also measured levels of mesothelin over time in 33 patients with malignancy, seven of whom had mesothelioma, to see how they changed. Some patients were inoculated with bacteria in their lungs to assess the effect of infection on mesothelin levels.
The study has many results and a selection is presented here. Combined diagnostic methods showed 24 of the 166 patients had mesothelioma, 67 had a non-mesothelioma cancer and 75 had benign pleural effusion. The researchers found that the mesothelin levels were 6.6 times higher in patients with mesothelioma compared to those with metastatic cancers, and 10.9 times higher than those with benign disease. Only two people with benign disease had elevated mesothelin.
The researchers calculated various measures of effectiveness for the mesothelin lung fluid test as a method of distinguishing mesothelioma from all other causes of pleural effusion. These measures were:
Of the 13 false positives, 12 of them were other lung cancers (adenocarcinoma).
Compared to pleural fluid cytology on its own, using mesothelin levels was a better test with greater sensitivity (71% versus 35%). When the tests were used together, mesothelin levels improved the diagnosis of mesothelioma by cytology. a concentration greater than 20nM correctly identified the eight mesothelioma cases out of the 47 that cytology identified as malignant.
In the 105 patients with negative cytology results, mesothelin levels increased confidence that underlying mesothelioma was correctly excluded: negative cytology and negative mesothelin had a specificity of 97% and a negative predictive value of 94%.
Pleurodesis led to a statistically significant reduction in the levels of mesothelin in pleural fluid at 24 and 48 hours, but had no effect on the levels of mesothelin in the blood. The presence of bacteria had no notable effect on mesothelin levels.
The researchers conclude that detection of mesothelin levels in pleural fluid contributes valuable information to the use of pleural fluid cytology alone, especially when the cytology results are inconclusive or suspicious. They say that, as many patients with mesothelioma fall into the ‘suspicious’ category following standard diagnostic tests, adding another assessment of mesothelin to the examination process may benefit up to 3,000 patients in Western Europe every year. As current investigations usually involve sampling of the pleural fluid, mesothelin analysis can easily be included within existing programmes.
This well-conducted study demonstrates that diagnostic accuracy for mesothelioma is improved by combining a test assessing the levels of mesothelin in the pleural fluid with diagnosis through cytology (looking for cancerous cells).
This study was conducted in people with a high background risk of having mesothelioma. In fact, the participants’ chance of having mesothelioma before entering the study was 24/167 or 14%. This means that the findings need to be confirmed in other populations, preferably people at different levels of risks of the disease to ensure that the predictive values obtained in this study can be more widely replicated.
It is important to consider what resources are required when discussing the introduction of any new diagnostic test. With mesothelin detection, pleural fluid is already being collected for analysis, so this would not involve any further sampling or invasive procedures for patients. However, consideration must be given to the laboratory and reporting facilities that would be required.
Overall, the test improves the accuracy of methods for diagnosing mesothelioma, a cancer which, unfortunately, offers a very poor rate of long-term survival. This improvement is greatest when the method is combined with cytology, offering a high specificity that means that a positive result effectively confirms the diagnosis.
The researchers, importantly, are therefore advocating that this test be used in addition to the usual explorations, and not as a replacement for them, and they say that it will be particularly useful in those patients who have ‘suspicious’ pleural effusions diagnosed by cytology.
‘Better’ test for asbestos cancer. BBC news, August 24 2009
Davies HE, Sadler RS, Bielsa S et al. Clinical Impact and Reliability of Pleural Fluid Mesothelin in Undiagnosed Pleural Effusions. Am J Respir Crit Care Med, Vol 180. pp. 437-444, (2009)
Written by admin on Monday, August 24th, 2009 in Swine Flu.
Children are more likely to develop diabetes in winter, newspapers have reported. The Times said that a large international study of 31,000 children from 53 countries suggests there is a correlation between the seasons and type 1 diabetes. It said the trend was more prevalent in boys and older children (5-14 year olds) of both sexes.
The news stories are based on a large, well-conducted time series study that demonstrates a seasonal variation in the diagnoses of type 1 diabetes across the world. The researchers conclude that the seasonality “is a real phenomenon”, but that more data are needed on populations living in the southern hemisphere, such as southern Africa, Australia and South America “to complete the picture”. There are no explanations that account for the differences seen between girls and boys and the differences in the age groups.
The study has highlighted an issue that needs more study. At present, the implications of these findings for individuals are unknown as these rates were calculated for clinics and countries. More research into how seasonality influences the onset of diabetes at an individual level is needed. It is also important to acknowledge the possibility that the study was biased by differences between the diabetes centres in different countries.
The research was carried out by Dr Moltchanova and colleagues from the National Institute for Health and Welfare, Helsinki, Finland. The research was funded by the EU GEOBENE Project and by the Academy of Finland and published in the peer-reviewed medical journal Diabetic Medicine.
The aim of this study was to determine whether there is a worldwide seasonal pattern in the clinical onset of type 1 diabetes. It is a time series study (a type of ecological study), for which the researchers used statistics from the World Health Organization (WHO) on the incidence (number of new cases) of type 1 diabetes in 0 to 14 year olds during the period 1990 to 1999. This information was collected as part of the WHO DiaMond (Diabetes Mondiale) study: a 10-year project involving 105 treatment centres across 53 countries.
Each country submitted annual data on gender, ethnicity, date of birth and treatment, using standardised forms. The rate of new cases occurring in each geographical area was calculated as the number of new cases of type 1 diabetes divided by the total number of resident children under 15 years of age. Out of 40.5million ‘at risk’ children under the age of 15 years, a total of 31,091 cases of type 1 diabetes were diagnosed in this period.
In their analyses, the researchers divided the children into three age groups: 0-4, 5-9 and 10-14 years. Statistical techniques were used to determine whether there were variations in the monthly totals of diabetes diagnosed and whether these trends corresponded with the seasons in both the northern and southern hemispheres. Essentially, the researchers were analysing the annual trends in incidence, comparing the actual incidence per month with that expected if there were a completely uniform monthly distribution (calculated by dividing the total annual incidence by 12 months).
There was seasonal variation in the numbers of new cases of type 1 diabetes in 42 of the 53 centres. Of these, 28 had the highest number of new cases in the winter months (October to January), while 33 had their lowest in the summer months (June to August). Two of the four southern hemisphere countries demonstrated a different pattern (a peak during July to September and a trough in January to March).
Distance from the equator had an effect, with countries further away from the equator (with a high or low latitude) more likely to show a seasonality effect. Longitude did not make a difference. Boys had a more pronounced pattern of seasonality than girls, and seasonality was also more evident in older children (5-14 year olds) than younger children (0-4).
The link between number of new cases and the seasons seemed to depend on the total number of cases diagnosed in a centre, with the centres that diagnosed more cases having a stronger association.
The study confirms the findings of other smaller studies, that there is a global pattern of seasonality with type 1 diabetes. Cases tend to peak in the winter months and trough in the summer months in both the southern and the northern hemispheres.
The results from this large, well conducted study confirm what has been seen in previous small studies. However, any interpretation of these findings should take into account several shortcomings that the researchers themselves raise:
Although the study was well conducted and efforts were made to standardise the data from the different centres, it is possible that there were differences in diagnostic practice or reporting between the centres that may have biased the results. As an ecological design, the study looked at the effect of seasons on the incidence of diabetes in a population group, such as a clinic or country. This means that there are no definite implications for individuals. The study’s value is in generating theories of how diabetes may be caused and in pointing future investigation in a particular direction, rather than showing that season is a definite factor.
Overall, the researchers conclude that the seasonality of type 1 diabetes “is a real phenomenon”, but that more data are needed on populations living below the 30th parallel (for example southern Africa, Australia and South America) “to complete the picture”.
Diabetes ‘most likely to occur among children in winter’. The Times, August
24 2009
Children ‘more likely to develop diabetes in winter than in summer’. The Daily Telegraph, August 24 2009
Risk of diabetes ‘rises in winter’. The Metro, August 24 2009
Moltchanova EV, Schreier N, Lammi N and Karvonen M. Seasonal variation of diagnosis of Type 1 diabetes mellitus in children worldwide. Diabetic Medicine 2009; 26: 673-678
Written by admin on Friday, August 21st, 2009 in Swine Flu.
A report on suspected adverse drug reactions to Tamiflu and Relenza has been published by the Medicines and Healthcare products Regulatory Agency (MHRA). This is the first weekly report, and is based on information gathered between April 1 and August 13 2009.
The MHRA has stressed that the report involves only suspected reactions to the antivirals, and the actual causes could be due to other illnesses or could be purely coincidental rather than being caused by the drugs themselves. It also says the list cannot be used to determine how often these side effects occur or be used to make direct comparisons between the safety of Tamiflu and Relenza. Known side effects of Tamiflu and Relenza are available in the product information (see http://emc.medicines.org.uk/) or at www.mhra.gov.uk/swineflu.
The information is submitted by healthcare professionals and members of the public via a special website for reporting adverse drug reactions (ADRs) and the Yellow Card Scheme. It also includes reports submitted by the manufacturers of the drugs.
There have been a total of 533 reports (together reporting 895 suspected adverse reactions) in association with Tamiflu. The most common fall within recognised side effects of Tamiflu and include mild allergic reactions, gastrointestinal problems, and headache and dizziness. The MHRA reports that these can also be caused by flu-like illness. No new safety issues have been identified.
Possible drug interaction between Tamiflu and warfarin
There have been several reports suggesting a possible interaction between Tamiflu and warfarin leading to a prolonged blood clotting time. Available evidence is currently insufficient to establish whether such cases are a true drug interaction between the two or whether blood-clotting control in these patients may have been affected by underlying infection and associated illness.
Therefore, at present there is no change to the product information for Tamiflu and patients should continue to take Tamiflu and warfarin as advised by their healthcare provider. All reports of a possible interaction with warfarin remain under close review by the MHRA.
Suspected adverse drug reactions with a fatal outcome
There have been two reports of patients dying following treatment with Tamiflu: one case of unexplained death and one case of acute hepatic failure. Both cases have been fully evaluated and in neither case is there evidence to confirm that Tamiflu was the direct cause of death, which was possibly due to underlying infection and illness.
Neuropsychiatric adverse events
Neuropsychiatric adverse effects, including convulsions and delirium (with symptoms such as confusion, abnormal behaviour, hallucinations, agitation, anxiety and nightmares) are listed as possible side effects in the Tamiflu product information.
However, flu itself can be associated with a variety of neurologic and behavioural symptoms, sometimes without obvious signs of a severe infection. Some studies have found that these types of events are no more frequent in flu patients on Tamiflu compared with those who have not taken the drug. It therefore remains unclear whether these neuropsychiatric events may be a true side effect of Tamiflu or whether they are due to underlying infection (or a combination of both).
Reported cases will remain under close review by MHRA, but those reported so far do not raise any new safety concerns. Nonetheless, patients should remain vigilant to the possibility of such events and discuss any serious concerns with their healthcare provider.
Serious skin reactions
Some patients treated with Tamiflu have reported serious skin disorders such as Toxic Epidermal Necrolysis (TEN), Stevens-Johnson Syndrome (SJS) and erythema multiforme (blistering conditions of the skin). They are listed as possible side effects of Tamiflu in the product information.
However, such conditions may also be caused by various infections including influenza. It is therefore unclear whether cases of severe skin disorders in influenza patients are due to Tamiflu or to the underlying infection and illness. The MHRA will continue to keep such reports under close review.
A total of 12 reports (including 19 suspected adverse reactions) have been reported in association with Relenza. Most resemble known side effects of Relenza such as allergic reactions and bronchospasm. Most other reported events such as diarrhoea, nausea, vomiting, fatigue, headache and dizziness can also be caused by flu-like illness. No new safety issues have been identified.
Relenza in pregnancy
There has been one reported case of miscarriage in early pregnancy. Cases of miscarriage are not uncommon in early pregnancy and some may inevitably occur by coincidence following Relenza therapy without the drug playing any role in the event. There is no evidence to indicate that Relenza carries any risks in pregnancy, to either the foetus or expecting mother.
This is supported by a recent review of available evidence by European regulatory authorities. Indeed, this review led to a recommendation that, due to the potentially serious risks of H1N1 swine influenza in pregnancy, the benefits of using Relenza (and Tamiflu) in treating influenza in pregnant or breastfeeding women outweigh any known risks.