HDR PLANNING & HOT TOPICS

HDR PLANNING & HOT TOPICS Nov 3rd 2010

This Afternoon • HDR Planning 14.00 – 15.15 • Tea break 15.15 • Hot topics 15.30 – 17.00

Planning

Hot Topics • Pub quiz style • Split into 3 groups • Question and answers • Discussion • Top team each round will win a prize

Aims • To consider the latest studies and how they influence our prescribing in relation to: - Aspirin - Glucosamine • To review the latest research into the use of PSA in screening for prostate cancer

1) Aspirin • Who do you think needs to be prescribed aspirin? (as currently under debate....ignore diabetic patients, focus on those with cardiovascular risk)

Aspirin – the study • Lancet 2009: 373: 1849 • Antithrombotic Trialists Collaboration (ATTC) meta analysis looked as use of aspirin in primary and secondary prevention. • A large study • All compared aspirin to placebo • The outcomes were CV events and the rate of harm

Primary prevention • Aspirin DOES NOT reduce the CV MORTALITY • Aspirin DOES reduce CV EVENTS – but the risk reduction v small (NNT 1666) • HARMS for every 3333 treated over 12m there would be one additional GI/extra cranial bleed (NNH 3333) • DTB agree, current practice is recommended that: • Aspirin shouldn’t be started for primary prevention • In those already taking it – explain current evidence to patient.

Secondary Prevention • Aspirin prevents 1 CV event per year for every 66 people treated (NNT 66) • Aspirin prevents 1 vascular death for every 344 people treated • There was insufficient data to report on GI/extra-cranial bleeds or haemorrhagic CVAs • DTB • Secondary prevention 75mg aspirin/day • (no evidence of improved protection with increase dose – but increased dose does increase GI haemorrhage risks)

Aspirin – Questions and Answers • Who do you think needs to be prescribed aspirin? • Not for primary prevention • Secondary prevention require 75mg OD • Secondary prevention would include those with TIA/stroke, previous MI, angina.

2) Glucosamine • Who should be prescribed glucosamine? • What advice should you give a patient when commencing treatment? • In which patients is the use of glucosamine contraindicated?

Glucosamine • Glucosamine is only indicated in patients with knee OA (DTB 2008; 46:81-4) • NICE does not support the use of glucosamine in OA (NICE, 2008)

Derbyshire Medicines Management May 2010 Advice • A trial of glucosamine sulphate 1500mg once daily is recommended as a treatment option in patients suffering from osteoarthritis of the knee, after trying, or in conjunction with paracetamol. • Use may mean that potentially toxic NSAIDs or coxibs need not be used. • It may take several weeks for the full effect to be seen. • If prescribed generically – the community pharmacy chooses the brand to supply. Expensive brands cost up to £90 for a thirty day supply • Medicines Management recommends that glucosamine sulphate is prescribed as the brand Valupak. Thirty days supply of the 1500mg strength costs only £2.83.

What should we tell patients? • None of the clinical trails have shown glucosamine is particularly effective • It may reduced pain in some people • It probably won’t improve function • It’s unclear whether it has any long term effects (slowing disease progression) • Glucosamine in safe in most people – but there are CIs • Glucosamine may take several weeks to work – trial for 3 months, if pain is no better, consider stopping

Glucosamine - Questions and Answers • Who should be prescribed glucosamine? • Only those with knee OA • What advice should you give a patient when commencing treatment? • May improve pain, probably won’t improve function, long term effects unclear, if no improvement at 3 months – consider stopping • In which patients is the use of glucosamine contraindicated? • Pregnant, breast feeding, allergic to shellfish and those on warfarin

PSA Testing Questions 1) What percentage of men with a normal PSA have clinically significant prostatic cancer? 2) What percentage of men with raised PSA will not have prostate cancer? 3) List 3 advantages and 3 disadvantages of the PSA test

PSA • PSA is a glycoprotein produced by the prostate • The amount produced can increase due to malignant and benign processes

PSA • PSA has long been used in general practice. • There is currently lots of debate over whom should have a PSA test, there is no agreed criteria for testing. • But, questions to consider; • Could the PSA be a useful screening tool? • Would screening reduce mortality?

BMJ 2009;339:b3537 • Looked specifically at how well PSA performs as a screening test depending on cut off values chosen. • The authors concluded that additional biomarkers would be needed before population screening should be introduced.

Systemic review of PSA screening – BMJ 2010; 34:c4543 • Systemic review of PSA screening – BMJ 2010; 34:c4543 • Pooled results from 6 major PSA screening studies (inc. PLCO and ERSPC) • Meta-analysis of 387,286 men showed: • Screening increased your risk of being given a diagnosis of prostate cancer • Screening had no impact on death from prostate cancer or overall mortality

PLCO Screening Trial (NEJM 2009; 360: 1310-0) • 76,000 men (aged 55-74) were randomised to usual care or annual screening for prostate cancer • 40-52% of the men in the control group had screening each year • Screening picked up more cancers than usual care • Mortality from prostate cancer was not reduced in those who had been screened • Screening did not appear to pick up earlier tumours (similar rates of all stages in control and screening group)

ERSPC (NEJM 2009; 360:1320-8) • RCT 180,000 men aged 50-74 in 7 European countries. • Randomised to “no screening” or to “PSA once every 4 years” • Twice as many cancers were diagnosed in the screening group compared to the control group • Those who had undergone screening were 20% less likely to die of prostate cancer • Benefit of screening only seen in those aged 55 or more, not in those 50-54 • There was a significant rate of over diagnosis (detecting tumours that would never become clinically significant)

ERSPC (continued) • 1410 men would need to be screened to prevent one death from prostate cancer • 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer.

Comparing ERSPC and PCLO • Different cut-off values for action (3ng/ml v 4ng/ml) • Study population selection • Improved prostate cancer treatment over the course of the PCLO trial • Follow up of PCLO may not have been long enough.

What do these trials mean to our practice? • National Screening Committee have recommended that a prostate cancer screening programme should not be introduced in the UK • Men who ask for a PSA should continue to be offered the full range of information to allow them to make an informed decision

PSA Summary • PSA test has significant failings • Screening MIGHT save lives, but we don’t know whether it actually does any good...which is a far more important question. • Treating men with clinically unimportant cancers exposed them to harm with no benefits • PSA should not be done routinely without discussing risks and benefits with the patient • A single PSA <1ng/ml in a man’s 60s largely rules out the risk of clinically significant prostate cancer.

PSA Answers (1) 1) What percentage of men with a normal PSA have clinically significant prostatic cancer? • 20% 2) What percentage of men with raised PSA will not have prostate cancer? • 66%

PSA Answers (2) 3) List 3 advantages and 3 disadvantages of the PSA test • Advantages • Reassurance if result is normal • May indicate cancer before symptoms present • May find cancer at an early stage • If treated may avoid worse outcomes, e.g. death • Even if aggressive/advance cancer, treatment may prolong survival • Disadvantages • False negatives • May have unnecessary tests and anxiety • Cannot differentiate slowly growing ‘v’ aggressive cancers • May cause unnecessary anxiety if it’s a slow, clinically insignificant ca • 48 men will undergo treatment to save one life

The End • Questions?

HDR PLANNING & HOT TOPICS