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Friday, 11 April 2014

Tamiflu and Relenza - confidential trials reveal no significant benefit - Cochrane Research

reposted from: http://www.nhs.uk/news/2014/04April/Pages/questions-over-tamiflu-relenza-effectiveness.aspx
crabsallover highlightskey pointscomments / links.

Links to the science

Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database of Systematic Review. Published online April 10 2014

Further reading

What the Tamiflu saga tells us about drug trials and big pharma. Bed Goldacre, The Guardian, April 10 2014

Sunday, 6 April 2014

Call to make 5 a day fruit and veg into '7 a day'

reposted from: http://www.nhs.uk/news/2014/04April/Pages/Five-a-day-should-be-upped-to-seven-a-day.aspx
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“7 a day fruit and veg 'saves lives’” reports BBC News, while The Daily Telegraph states that “10 portions of fruit and vegetables per day” is best.
The headlines have been prompted by the results of a UK-based study that used information on more than 65,000 randomly selected adults who were participating in the Health Survey for England.
This is an ongoing health survey that looks at health and lifestyle factors such as fruit and vegetable consumption. The researchers followed up participants for an average of 7.7 years after their initial participation.
The researchers found that eating fruit and vegetables was associated with a lower risk of death from any cause, looking especially at deaths as a result of cardiovascular disease and cancer. The higher a person's intake of fruit and vegetables, the greater the protective effects seemed to be.
People who ate seven or more portions a day had a 33% reduced risk of death compared with people who ate less than one portion.
This study provides further evidence of the benefits of eating fruit and vegetables. However, the study does carry limitations, with the most pertinent being that there could have been other factors (confounders) responsible for the associations seen. These could include smoking history, exercise levels and income.
Much of the media’s reporting implies that this study contradicts the official Department of Health advice about eating five portions of fruit and vegetables a day. It should be stressed that the advice in full was to eat at least five portions a day. The “5 a day” target was always meant to be a minimum target to hit, rather than the maximum.

Where did the story come from?

The study was carried out by researchers from University College London. This study was unfunded, but used information for the Health Survey for England, which was funded by the Department of Health and the Health and Social Care Information Centre. In the interests of transparency, it should be made clear that the Behind the Headlines team are employed by the Health and Social Care Information Centre.
The study was published in the peer-reviewed Journal of Epidemiology and Community Health. This article is open-access, meaning that it can be accessed for free from the journal’s website.
The results of this study were reported accurately by the UK media. However, they all reported figures for all causes of mortality, excluding any deaths that occurred in the first year of the study.
This meant that the risk of death they reported (42%) was reduced by a greater extent than when these people were included in the analysis (33%).

What kind of research was this?

This was a cohort study that aimed to assess if fruit and vegetable consumption in a group of people representative of the UK population was linked to:
  • death from any cause
  • death due to cancer
  • death due to cardiovascular disease 
A cohort study is the ideal study design to answer this question. However, this study design is limited by the fact that other confounders could have been responsible for the associations seen.
In the study, people who consumed more fruit and vegetables were generally older, less likely to smoke, more likely to be women, be of a higher social class and have a higher standard of education.
In addition, the proportion of people who were vigorously active increased as more portions of fruit and vegetables were consumed.
Although the researchers tried to adjust for these factors in their analyses, these differences may influence the association seen.

What did the research involve?

The researchers used information on 65,226 adults who were aged 35 years or older, who responded to the Health Survey for England.
Participants were visited by an interviewer who asked about fruit and vegetable consumption on the previous day. They were asked about their consumption of:
  • vegetables
  • fresh, canned and frozen fruit
  • salad
  • pulses
  • dried fruit
  • fruit juices/smoothies
  • dishes made mainly from fruit or vegetables
Responses were coded into portion sizes. A maximum of one portion of pulses, one of fruit juice or a smoothie and one of dried fruit contributed to total daily portions of fruit and vegetables.
The researchers looked at mortality (death) records over 7.7 years (on average), to see if participants had died  and if they had, what they had died of.
The researchers compared the risk of death for people eating less than one portion to people eating more than one portion.
The researchers adjusted their analysis for the following confounders:
  • age
  • sex
  • smoking status
  • social class
  • education
  • body mass index (BMI)
  • level of physical activity
  • alcohol consumption

What were the basic results?

During the 7.7 years (on average) follow-up period, 6.7% of participants died (equivalent to 4,399 deaths).
Eating one or more portion of fruit and vegetables was associated with a significantly reduced risk of death from any cause compared to eating less than one portion. The risk of death from any cause decreased as portions of fruit and vegetables increased.
People consuming seven or more portions a day had the lowest risk of death from any cause, with a 33% reduced risk (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.58 to 0.78), compared to those who ate less than one portion a day (a portion was defined as 80g).
Eating three or more portions of fruit and vegetables was associated with a significantly reduced risk of death from cancer and death from cardiovascular disease. Risk of death from cancer was 25% lower in participants eating between five and seven portions, and seven portions or more (HR 0.75, 95% CI 0.62 to 0.91 for 5 to <7 portions; HR 0.75, 95% CI 0.59 to 0.96 for 7 or more portions). Risk of death from cardiovascular disease was lowest in people eating seven or more portions, with a 31% reduced risk (HR 0.69, 95% CI 0.53 to 0.88).
When fruit and vegetable consumption was analysed separately, the risk of death from any cause was lowest in people eating three to less than four portions of fruit per day (HR 0.84, 95% CI 0.76 to 0.93) and three or more portions of vegetables per day (HR 0.68, 95% CI 0.58 to 0.79).
Eating vegetables was associated with greater reductions in risk of death than eating the same number of fruit portions. 
The researchers also looked at the type of fruit and vegetable consumption and found that consumption of vegetables, salad, fresh fruit and dried fruit were associated with decreased risk of death from any cause. However, consumption of frozen or canned fruit was associated with an increased risk of death.

How did the researchers interpret the results?

The researchers conclude that they found “a strong inverse association between fruit and vegetable consumption and all-cause mortality”. They go on to say that “fruit and vegetable consumption was significantly associated with reductions in cancer and [cardiovascular disease] mortality, with increasing benefits being seen with up to more than seven portions of fruit and vegetables daily for the latter [vegetables]. Consuming vegetables appeared to be significantly better than consuming similar quantities of fruit. When different types of fruit and vegetables were examined separately, increased consumption of vegetables, salad, fresh and dried fruit showed significant associations with lower mortality. However, frozen/canned fruit consumption was associated with a higher risk of mortality”.

Conclusion

This UK-based study found that eating fruit and vegetables was associated with a lower risk of death from any cause, and deaths from cardiovascular disease and cancer. The higher the intake of fruit and vegetables, the greater the protective effects seemed to be.
People who ate seven or more portions a day had a 33% reduced risk of death from any cause, a 25% reduced risk of death from cancer and a 31% reduced risk of death from cardiovascular disease, compared with people who ate less than one portion per day.
The researchers found that vegetables may lower risk more so than fruit. Consumption of vegetables, salad, fresh fruit and dried fruit were associated with decreased risk of death from any cause, although consumption of frozen or canned fruit was associated with an increased risk of death.
This study provides further evidence of the benefits of eating fruit and vegetables; however, it is based on only one diet measurement over 24 hours, which may not be representative of a person's usual diet and does not take into account changes in diet over time.
This study is limited by the possibility that other factors (confounders) could have been responsible for the associations seen. In the study, people who consumed more fruit and vegetables were generally older, less likely to smoke, more likely to be women, be of a higher social class and have a higher standard of education.
Despite reporting to the contrary, the results of this study do not go against the current “5 a day” message. This is a minimum recommended level. When it comes to fruit and vegetables, as long as you watch your calorie and sugar intake it is very much the case of “the more the merrier”.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Saturday, 5 April 2014

No proof Earl Grey can fight heart disease

reposted from: http://www.nhs.uk/news/2014/04April/Pages/Earl-Grey-unproven-as-replacement-for-statins.aspx
crabsallover highlightskey pointscomments / links.

A cup of Earl Grey 'as good as statins' at fighting heart disease,” reports The Daily Telegraph, entirely without proof.

The science behind this headline did not show Earl Grey was as good as statins (a class of drugs used to lower high cholesterol) in people.

The study was early stage research on a small group of rats in a laboratory. None of the research involved humans, tea, or any assessment of heart disease.

The research involved an extract called HGMF, taken from the bergamot fruit; a citrus fruit used to flavour teas such as Earl Grey.

Rats with high cholesterol levels were fed a high cholesterol diet for three weeks and given either the bergamot extract (HMGF) or the commonly used statinsimvastatin.

The researchers found that HMGF had cholesterol-lowering effects similar to that of simvastatin. Though importantly, as the research was in rats, it is not possible to say that HGMF would work the same way in humans, unless directly tested.

Furthermore, this study tested a pure extract rather than tea containing the extract, the effects of which may be different. For instance it is unclear how much Earl Grey you would need to be exposed to a comparable level of HGMF; it may take gallons of the stuff.

This study is absolutely not a reason to stop taking prescribed statins to replace them by drinking Earl Grey tea as this could be dangerous.

Where did the story come from?

The study was carried out by researchers from the University of Calabria (Italy) and was funded by the Italian National Project.

The study was published in the peer-reviewed Journal of Functional Foods.

The Daily Telegraph and the Mail Online reporting was potentially misleading and arguably irresponsible.

While the main body of the article was factually accurate, the headlines (one of which was on the front page of the Telegraph) implied that drinking Earl Grey tea had been proven to be as effective as statins.

Statins are known to be effective and have a large weight of evidence from human research proving this. By contrast, the effects of Earl Grey tea, as far as we are aware, have barely been researched, so they are not on an equal playing field. So suggestions that Earl Grey is “just as effective” are unfounded.

This could have encouraged people who had been prescribed statins, some of which are at high risk of experiencing a cardiovascular disease such as a heart attack or stroke, to stop taking their medication.

What kind of research was this?

This was an animal study looking at the effect of bergamot extract on the cholesterol profile of rats with high cholesterol and comparing it with a commonly used statin called simvastatin.

Statins are a class of related drugs currently used to lower cholesterol levels in people at risk of cardiovascular disease, the main cause of death in many westernised countries. The drugs lower cholesterol levels by acting on an enzyme called 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) in the body.

The researchers were looking to see if other compounds might work in a similar way to statins and affect the same enzyme. They decided to investigate bergamot (Citrus bergamia Risso), a citrus fruit widespread in the Mediterranean area.

The fruit has anecdotal cholesterol-lowering properties and the study authors said it was only toxic at very high levels, implying it might be relatively safe. The researchers state bergamot essence is used in teas, jams and sherbet, but there was no special mention of Earl Grey in the underlying research. It appears the media has made a link with this specific tea as it apparently contains high levels of the extract and is well known to a UK readership.

What did the research involve?

The study used 48 rats with high cholesterol to compare the cholesterol-lowering effects of bergamot extract 3-hydroxy-3-methyl-glutaryl flavanones (HMGF) with the commonly-used statin, simvastatin. The rats’ diets were carefully controlled so all that differed was their cholesterol treatment – bergamot or statin.

Body weight, blood cholesterol levels, cellular protein levels, liver enzyme activity and genetic regulatory mechanisms were all monitored and recoded for evidence of cholesterol-lowering properties in the different treatment groups.

Contrary to the headlines, the experiments involved a dry extract from bergamot fruit peel. Unfortunately for the rats they did not get to sample any tea, Earl Grey or otherwise. 

The important measures were total cholesterol, another type of blood fat (triglycerides), and specific subtypes of cholesterol called very low density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). HDLs are the so called “good” cholesterol, whereas LDLs are the “bad” cholesterol. This is a simplistic account of their roles within the body, but is sometimes useful.

Before the experiment all rats were stabilised on regular rodent food before being randomly divided into four groups of 12 animals each:
  • control group: received a regular diet for three weeks
  • high cholesterol control group: received a high cholesterol diet for three weeks (regular diet +2% cholesterol +0.2% cholic acid; a bile acid that has a role in fat absorption and moderating cholesterol levels)
  • high cholesterol group treated with statin: received the high cholesterol diet for three weeks (regular diet +2% cholesterol +0.2% cholic acid); from the 2nd to the 3rd week each rat was given simvastatin (20 mg/kg bodyweight/day) 
  • high cholesterol group treated with bergamot extract HMGF: received the high cholesterol diet (regular diet +2% cholesterol +0.2% cholic acid) for three weeks; from the 2nd to the 3rd week each rat was given HMGF (60 mg/kg bodyweight/day
The main analysis compared the cholesterol lowering effects of simvastatin with the bergamot extract HMGF.

What were the basic results?

Both the bergamot extract and simvastatin reduced total cholesterol (in blood and in the liver), triglyceride levels, and VLDL and LDL levels – the bad cholesterol. However, an increase in HDL content – the good cholesterol – was observed exclusively in the HMGF-treated rats.
Both bergamot extract and simvastatin regulated enzymes were involved in cholesterol metabolism in a similar way at a protein and gene regulation level. This implied the changes observed were not coming from some other secondary effects of the extract and were direct result of changes to how cholesterol was metabolised in the rats’ livers.
The study investigated the safety of the extract to some degree. It found the extract had a low toxicity to cells in the body, and did not cause DNA damage at doses lower than 90 micrograms per millilitre.

How did the researchers interpret the results?

The researchers stated that their study “demonstrated that the three statin-like flavanones, extracted from bergamot peel and contained in HMGF, exert a similar behaviour [in] respect to commercial simvastatin on a model of hypercholesterolaemic rats [rats with high cholesterol levels]” and that “the daily supplementation of HMGF in the diet could be very effective for the treatment of hypercholesterolaemia”.

Conclusion

This animal experiment indicated that the bergamot extract HMGF may have cholesterol-lowering effects similar to that of the commonly used statin, simvastatin, when given to mice with high cholesterol levels that were fed high cholesterol diets for three weeks.
The main limitation of the study was that none of the research involved humans. Therefore, it is not possible to say the bergamot extract would work the same way in humans, unless directly tested. Furthermore, this rat study tested a pure extract rather than tea containing the extract, the effects of which may be different. For instance, taking milk in tea could potentially affect how the extract is metabolised in the body compared to a pure extract.

The headlines indicated Earl Grey tea could help fight heart disease, but based on the underlying research study only, there is little evidence for that. Also the study made no assessment of the long-term health benefits of the reductions in cholesterol in the rats. For example, the effects may have been temporary.

There needs to be more robust research in humans to find out if bergamot extract holds any real promise in lowering cholesterol levels and so fighting cardiovascular diseases such as heart disease and strokes in the future.

We would not want anyone to think this research is a reason to stop taking statins and replace them with drinking tea containing bergamot extract; this could potentially be dangerous. If you have any concerns about your cholesterol levels, or any cholesterol-lowering treatments that you are currently prescribed, consult your doctor.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Tuesday, 1 April 2014

JBS3 Report

reposted from: http://www.jbs3risk.com/pages/report.htm
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Recommendations from each section

General Recommendations
  • Use JBS3 risk calculator to estimate both 10-year risk and lifetime risk of CVD in all individuals except for those with existing CVD or certain high risk diseases i.e. diabetes age >40 years, patients with chronic kidney disease (CKD) stages 3-5, or familial hypercholesterolaemia (FH).
  • Total cholesterol and HDL-cholesterol from a non-fasting blood sample should be used for lipid profile estimate of CVD risk in the JBS3 calculator
  • Non-HDL-cholesterol, measured from a non-fasting blood sample as total cholesterol minus HDL-cholesterol, should be used in preference to LDL-cholesterol as the treatment goal for lipid-lowering therapy.
  • Intensive risk factor modification with diet, lifestyle intervention and pharmacological therapy in patients with existing CVD, without the need for estimation of CVD risk.
  • Intensive risk factor modification with diet, lifestyle intervention and pharmacological therapy, in individuals at particularly high risk of developing CVD: i.e. diabetics age >40 years, patients with CKD stages 3–5, or FH without the need for estimation of CVD risk.
  • Diet, lifestyle intervention and pharmacological therapy in people at high short-term risk. Thresholds for treatment with statins based on 10-year CVD risk will be informed by NICE guidelines.
  • Diet, lifestyle intervention and for some people, pharmacological therapy, in those with increased modifiable lifetime risk as informed by JBS3 calculator metrics.

2. Lifestyle Recommendations

Smoking
  • Professional support on how to stop smoking should be given, at every available opportunity, with provision of self-help material and referral to more intensive support, e.g. stop smoking services.
  • The JBS3 risk calculator emphasises the benefits for early smoking cessation and the diminishing but still substantial returns for quitting at an older age.
  • Patients should be offered behavioural counselling, group therapy, pharmacotherapy or a combination of treatments that have been proven to be effective.
  • Nicotine replacement therapy (NRT), varenicline or bupropion should be offered to people who are planning to stop smoking as part of an abstinent-contingent treatment in which the smoker makes a commitment to stop smoking on or before a particular date (target stop date).
  • People who have heart or respiratory diseases, and those who live with them, should be made aware of the risks of both active and passive smoking (second-hand smoke).
  • For specific recommendations on quitting smoking in pregnancy and following childbirth, see NICE public health guidance 26.
  • The importance of stopping smoking during pregnancy should be emphasized and guidance from the National Institute for Health and Clinical Excellence (NICE) followed.[1]
Diet
Professional support to consume a diet associated with the lowest cardiovascular risk should be provided based on the following principles:
  • Intake of saturated fat to <10% of total fat intake (preferably in lean meat and low-fat dairy products)
  • Replace saturated fat with poly-unsaturated fat where possible
  • Consume five portions per day of fruit and vegetables
  • Consume at least two servings of fish (preferably oily) per week
  • Consider regular consumption of whole grains and nuts
  • Keep salt consumption <6 g per day
  • Limit alcohol intake to <21 units per week for men and <14 units per week for women
  • Avoid/reduce consumption of:
    • Processed meats or commercially produced foods which tend to be high in salt and trans fatty acids
    • Refined carbohydrates, such as white bread, processed cereals
    • Sugar-sweetened beverages
    • Calorie-rich, but nutritionally poor snacks, such as sweets, cakes and crisps
  • Children and young people should be supported to consume a diet based on the same principles.
Physical activity and exercise
  • An increase in overall levels of sustained physical activity and avoidance of prolonged sedentary behaviour are important for reduction of CVD risk.
  • Emphasise walking, cycling and other aerobic physical daily activities, at moderate intensity, as part of an active lifestyle, for at least 150 minutes per week in bouts of ≥ten minutes, or 75 minutes per week of vigorous physical activity, or a combination of the two.
  • Muscle-strengthening activities performed on at least two occasions per week
Exercise training
General population and those at low to moderate risk of CVD:
  • Exercise training, incorporating a warm up and cool down period, should be performed at moderate to high intensity two to three times per week for 30 to 40 minutes each time.
  • The mode of exercise should be aerobic and, where possible, continuous allowing for a steady progression in effort, e.g. walking programmes, cycling, jogging, swimming.
  • The time spent exercise training contributes to meeting the 150 minutes per week physical activity recommendation (as above).
Patients with established CVD and those considered at higher risk of CVD:
  • A more structured approach is needed in managing patients and in all cases, assessment and specific goal setting, with risk stratification, delivered by professionals skilled in health-related exercise is preferable.
  • Exercise on referral and community-based exercise initiatives are recommended for patients at risk of CVD.
  • Cardiac rehabilitation programmes are recommended for patients with established CVD and in those following a CVD event.

3. Childhood and Adult Obesity Recommendations

  • Multidisciplinary approaches to obesity management in children and young people are required with a 'lifetime risk' message. These include interventions during the early post-partum period as well as regular monitoring of childhood weight and family counselling.
  • With appropriate training all health care professions should be able to Ask and Assess adiposity and Advise appropriate adult patients on evidence based ways to target weight change.

4. Lipid Recommendations

  • Non-fasting blood samples should be taken to measure total cholesterol (TC) and HDL-cholesterol. The JBS3 risk calculator enables entry of these two measures and it is expected that non-HDL-c (TC minus HDL-c = non-HDL-c) will gradually replace LDL-c in clinical practice as well as in clinical trials.
  • All high risk people should receive professional lifestyle support to reduce total and LDL-c, raise HDL-c, and lower triglycerides to reduce their CVD risk.
  • Cholesterol-lowering drug therapy is recommended in:
    • Patients with established CVD
    • Individuals at particularly high risk of CVD: diabetes age > 40 years, patients with CKD stages 3-5, or FH
    • Individuals with high 10-year CVD risk (threshold to be defined by NICE guidance)
    • Individuals with high lifetime CVD risk estimated from heart age and other JBS3 calculator metrics, in whom lifestyle changes alone are considered insufficient by the physician and person concerned
  • Statins are recommended as they are highly effective at reducing CVD events with evidence of benefit to LDL-c levels <2 mmol/L which justifies intensive non-HDL-c lowering.
  • Statins are safe with trial evidence showing no effects on non-cardiovascular mortality or cancer. There is a small increase in risk of developing diabetes but the benefits of cholesterol lowering greatly exceed any risk associated with diabetes. If statin intolerance develops a stepwise strategy involving switching agents and re-dosing is recommended.
  • Despite low HDL-c levels contributing to CVD risk, drug therapy to raise HDL has not been shown to reduce CVD risk and is not currently indicated.

5. Blood Pressure Recommendations

  • Hypertension should be suspected when office BP is persistently elevated, i.e. ≥140/90mmHg.
  • Ambulatory BP monitoring (ABPM) is recommended to confirm the diagnosis of hypertension (Daytime mean ABPM 135/85mmHg).
  • All high risk people should receive professional lifestyle support to reduce their blood pressure which may avoid the need for, or complement the use of, drug therapy for hypertension and reduce CVD risk.
  • People with an office BP >160/100 mmHg, an 24-hour day time ABPM average or home APBM average of >150/95 mmHg (stage 2 hypertension) should be offered pharmacological therapy to reduce BP.
  • People with an office BP >140/90 mmHg, but <160/100 mmHg, a 24-hour daytime ABPM average or home APBM average of >135/85 mmHg (stage 1 hypertension) and established CVD, hypertensive target organ damage, diabetes, CKD, or a high lifetime risk assessed by JBS3 calculator, should be offered pharmacological therapy to reduce BP.
  • People with stage 1 hypertension without established CVD, hypertensive target organ damage, diabetes, CKD, or a significant increase in lifetime risk assessed by JBS3 calculator, should receive advice on lifestyle interventions and be scheduled for annual BP and lifetime risk assessment to inform future need for therapy.
  • Pharmacological treatment for patients with hypertension should follow the current NICE guidance (CG127) treatment algorithm:
    • Patients <55 years of age should be offered an ACE inhibitor or ARB as preferred initial therapy
    • Patients aged ≥55 years should be offered a Calcium Channel Blocker (CCB) as preferred initial therapy
  • Combinations of drug treatment are usually required to optimise BP control for the majority of patients.
  • Thiazide-like diuretics are an alternative to CCB and are preferred for patients intolerant of CCBs, or with heart failure or at high risk of heart failure.
  • Beta-blockers are not preferred unless there are specific indications for use, i.e. in patients with symptomatic angina or chronic heart failure.
  • For pregnant women or women planning pregnancy, when BP treatment is being considered, the recommendations of the NICE guideline CG107 Hypertension in pregnancy should be followed.


Monday, 31 March 2014