my reading

Bandolier vol 10 issue 6 (112)
COPD and inhaler steroids
This means that treating five patients with COPD with inhaled corticosteroids will prevent one exacerbation.
Mortality in six trials averaged 4.1% with placebo, and 3.4% with inhaled corticosteroids (Figure 2). The difference was not statistically significant, with a relative risk of 0.84 (0.6 to 1.2).

bandolier vol 10 issue 6 (112)
People with a BMI of 30 kg/sq metre or more at baseline, both women and men, smokers and non smokers, lost an average of seven years of life (Figure 1). For those with a BMI between 25 and 30 kg/sq metre fewer years were lost, and significant loss of years of life was restricted to female non smokers.

obesity

Bandolier vol10 issue 2
Changing statins in primary care
stopping statin or changing to ineffective dose gave a three fold increase of an eventoccurring
stsins do other things than reducing cholesterol,
when statin changed from simva to atorvastatin lipid control changed for the better and no. of thrombotic evnets after the change was low and no difference from before the change,
(experiment in Otago NZ due to pricing change in statins)

Bandolier vol 10 issue 4
Topical NSAIDS
they work but not known whether they are worth using, and in which patients with chronic conditions they will work best

Volume 327, Number 7407, Issue of 19 Jul 2003

Knee taping reduces symptoms associated with osteoarthritis
Therapeutic tape applied to the knee significantly reduces pain caused by osteoarthritis. In a randomised controlled trial in Australia, Hinman and colleagues (p 135) studied the effects of therapeutic tape, a control tape, and no tape in 87 patients aged 50 years and older with osteoarthritis of the knee. Patients allocated therapeutic tape reported the greatest reduction in pain, and benefits were maintained three weeks after treatment had stopped. The authors suggest that knee tape may reduce pain by realigning the patella and unloading painful soft tissues. They state that knee taping, as an adjunct to exercise and drug treatment for knee osteoarthritis, is a simple and inexpensive self management strategy.

Volume 327, Number 7407, Issue of 19 Jul 2003

Alzheimer's disease may be prevented with NSAIDs
Non-steroidal anti-inflammatory drugs may prevent the development of Alzheimer's disease, though aspirin has only a modest preventive effect.
The risk of developing Alzheimer's disease was reduced by about 30%. The benefit with aspirin was 13%. In addition, long term users of NSAIDs had a greater benefit than intermediate term users. The appropriate dose, duration, and ratios of risk to benefit are still unclear. The authors say that routine use of NSAIDs is not recommended until results from ongoing randomised controlled trials become available.

BMJ 2003;327:89-95 (12 July)
Clinical review
Preventing fractures in elderly people

Box 1: Risk factors (excluding falls) for bone loss, osteoporosis, and fracture in elderly people (adapted from various sources5 16 46 47)

Age over 75 years

Female

Previous fracture after low energy trauma

Radiographic evidence of osteopenia, vertebral deformity, or both

Loss of height, thoracic kyphosis (after radiographic confirmation of vertebral deformities)


Low body weight (body mass index < 19)

Treatment with corticosteroids

Family history of fractures owing to osteoporosis (maternal hip fracture)

Reduced lifetime exposure to oestrogen (primary or secondary amenorrhoea, early natural or surgical menopause (< 45 years))

Disorders associated with osteoporosis (previous low bodyweight; rheumatoid arthritis; malabsorption syndromes, including chronic liver disease and inflammatory bowel disease; primary hyperparathyroidism; long term immobilisation)

Behavioural risk factors
Low calcium intake (< 700 mg/d)
Physical inactivity
Vitamin D deficiency (low exposure to sunlight)
Smoking (current)
Excessive alcohol consumption

Combined calcium and vitamin D is the standard treatment for osteoporosis as well as a preventive measure, particularly in frail elderly people. In elderly institutionalised patients, further hip and nonvertebral fractures were decreased after three years' treatment with 1200 mg calcium and 20 µg (800 IU) vitamin D, with significant benefit at 18 months.17 A community based study found that vitamin D given once every four months decreased the overall risk of fracture by 39%, and in another study 800 IU of vitamin D given to elderly people (mean age 85) over a 12 week period increased muscle strength and decreased the number of falls by almost a half.18 19

good paper on osteopororsis

BMJ 2003;327:70 (12 July
More frequent screening would improve detection of colon cancer
The preliminary report gives the findings on patients who underwent flexible sigmoidoscopy at baseline and at three years (following the trial’s protocol) and were referred to their personal doctors for further evaluation of any abnormalities detected by the screening (JAMA 2003;290:41-8). A polypoid lesion or mass found by the examiner was considered a positive result of screening.

The findings at three years, although modest, indicate that more frequent screening for colon cancer, by detecting precancerous growths, could have an impact on mortality from this disease," said Dr Robert Schoen, lead author of the study and an associate professor of medicine and epidemiology at the University of Pittsburgh School of Medicine.

Dr Schoen said patients should not necessarily think that a negative result is a permanent clean bill of health. "If you had a colonoscopy last year, I think at five years you might want to check in with your physician and see if there’s anything new that’s been learned [about colon cancer screening]," he said.

BMJ 2003;327:61-62 (12 July)

The metabolic syndrome
The diagnosis of the metabolic syndrome in patients might hold promise for enhanced prevention of diabetes and cardiovascular disease. However, substantial uncertainties remain about the clinical definition of the syndrome and whether risk factor clusters collectively indicate a discrete, unifying disorder. Most importantly, it is unclear whether diagnosing the syndrome will confer benefit beyond risk assessments or treatment strategies associated with diagnosing and treating the syndrome's component traits. The current focus on the metabolic syndrome will possibly prove to be a distracting detour on the route to encouraging more widespread application of evidence based practices to prevent diabetes and cardiovascular disease.

The metabolic syndrome is characterised by the co-occurrence of obesity (especially central obesity), dyslipidaemia (especially high levels of triglycerides and low levels of high density lipoprotein cholesterol), hyperglycaemia, and hypertension. As yet no consensus exists for specific thresholds for establishing the diagnosis of each of these traits as components of the syndrome. Inclusion of insulin resistance or diabetes itself as diagnostic components is also controversial. The individual traits of the syndrome cluster together to a notably greater degree than expected by chance alone, a fact that lends substantial support to the existence of a discrete disorder.3

it is plausible to think that diagnosis of the metabolic syndrome will point us in the right direction for effective prevention of type 2 diabetes and cardiovascular disease, more definitive data on the outcomes and effects of interventions are required before we can confidently head along that route.
The worldwide epidemic of type 2 diabetes is fuelled in large part by a parallel epidemic of obesity and physical inactivity, clearly pointing to prevention of obesity as the most direct route to prevention of the metabolic syndrome and its sequelae. From this perspective, perhaps the best reason to consider a diagnosis of the metabolic syndrome is to identify obese people who are most likely to benefit from aggressive efforts to achieve a healthy weight, physical activity habits, and normal risk factor levels. In the end, even modest changes towards a healthy lifestyle may be the most direct route to treating the metabolic syndrome and preventing its type 2 diabetes and cardiovascular disease outcomes.

diabetes
cardiovascular disease
metabolic syndrome

BMJ 2003;327:9 (5 July)
Finasteride (Proscar), which is manufactured by Merck, reduced the incidence of prostate cancer by nearly 25% in a large, randomised, controlled trial and reduced symptoms of benign prostatic hypertrophy.

But prostate cancers that developed during the course of the trial were more aggressive in the treatment group than in the placebo group, says the study, which is released early online by the New England Journal of Medicine (www.nejm.org) and will be published in the 17 July issue. The study also showed that, in the control group, the number of cancers detected was four times higher than expected.

Although men who took finasteride had fewer prostate cancers, men who did develop prostate cancer while taking finasteride were more likely to have aggressive cancer—defined as a Gleason score of 7 to 10—than the men in the placebo group (P for difference <0.001). However, the Gleason score is based on a pathologist's visual inspection of prostate cancer cells, and finasteride affects the appearance of the cells, perhaps leading to a false estimate of the score. Or the drug might have eliminated less serious cancers, while allowing more serious ones to grow.

Finasteride reduced the risk of prostate cancer in all risk groups. It also reduced urinary tract symptoms of benign prostatic hypertrophy. However, men taking finasteride had more sexual side effects.

BMJ 2003;327:9 (5 July)
Long term use of combined HRT doubles cancer risk
Women over the age of 65 who take combined oestrogen and progestogen hormone replacement therapy (HRT) for five to 15 years or more face a 100% increase in the risk of developing breast cancer, regardless of their pattern of progestogen use, says a new study ( JAMA 2003;289: 3254-63[Abstract/Free Full Text]).

The researchers assessed the effect of combined hormone replacement therapy on the risk of specific types of breast cancer. Among their findings was that the risk of invasive lobular breast cancer increased by 170%. This is the second most common histological type of breast cancer, affecting the lobes in the breast that contain milk producing glands. Lobular cancer accounts for 10% to 15% of cancer cases, and its incidence has increased by 65% in the United States during the last 12 years, which Dr Li says may be partly accounted for by greater use of combined hormone replacement therapy. The risk of ductal breast cancer increased by 50%. This type, involving the ducts that carry milk from the lobules to the nipple, accounts for about 80% of all cases of breast cancer. Women who took the combined therapy had twice the risk of hormone receptor positive breast cancer, which requires oestrogen or progesterone to grow. About two thirds of all breast cancers are either oestrogen receptor positive or progesterone receptor positive.

BMJ 2003;327:5-6 (5 July)

INRs and point of care testing
Despite limitations, overall evidence shows that point of care testing is reliable
Anticoagulant control, however, lacks precision and in most surveys only 50-60% of INR results of patients are in the predetermined therapeutic range.4 This is due, in part at least, to dietary variations, interactions with medications and supplements, and incomplete compliance. In addition there is residual imprecision in the INR, even when experienced laboratories employ automated coagulometers. Finally, in the United Kingdom, most coagulation laboratories take part in the National Quality Assessment Scheme. Samples for INR measurement are distributed regularly in this scheme. On average around 5-10% of laboratories report INR results which are more than 15% outwith the consensus median value in any particular survey (Kitchen S, personal communication, 2003).
Point of care instruments facilitate the management of anticoagulants in primary care, and furthermore they introduce the possibility of patients' self management of oral anticoagulant treatment. The finding of a discrepancy between INRs determined by point of care systems and laboratory measurements is important but not surprising. While it should be the stimulus for better standardisation of point of care testing monitors and improved quality assurance procedures, clinical studies suggest already that point of care testing systems can be effectively introduced into clinical practice. For example, in a trial comparing performance of a point of care system in a number of primary care sites to laboratory results, primary care INR estimations were at least as reliable as laboratory estimations.5 The degree of discrepancy between point of care test results in the study was similar to that found between laboratory INR test results. Another study compared three point of care systems previously validated in laboratory conditions for use in a non-laboratory setting.6 The results showed no significant disagreement between the systems. Again the discrepancies found were comparable to those between laboratory estimations. Such data show that point of care testing systems can be used for warfarin monitoring in primary care.

A difference exists between statistical and clinical significance when considering the INR. Clinical significance is determined by an impact on clinical decision making and for this purpose instruments for point of care testing have been found to be satisfactory.7 However, the size of the discrepancies in measuring INR reported by Poller et al are such that dosing decisions could be affected. Therefore it is reassuring that further evidence is beginning to accumulate to suggest that point of care testing systems can be used to help deliver safe anticoagulant therapy. A difference exists between statistical and clinical significance when considering the INR. Clinical significance is determined by an impact on clinical decision making and for this purpose instruments for point of care testing have been found to be satisfactory.7 However, the size of the discrepancies in measuring INR reported by Poller et al are such that dosing decisions could be affected. Therefore it is reassuring that further evidence is beginning to accumulate to suggest that point of care testing systems can be used to help deliver safe anticoagulant therapy.

Volume 327, Number 7405, Issue of 5 Jul 2003
Effectiveness of nicotine patches is overstated
Former smokers using nicotine patches often return to smoking. In an eight year follow up of people who took part in a randomised trial of the patch, Yudkin and colleagues (p 28) report that nearly half of those who had given up smoking for a year in the original trial had taken it up again, and that relapse rates were similar in nicotine patch and placebo groups. The cost effectiveness of nicotine replacement therapy is therefore overestimated when it is based on relatively short term results. Of all trial entrants, 88% were smoking eight years later, underlining the difficulty that smokers have in giving up.

GP with special interest: apply to local primary care trusts and see if their needs match your hopes and skills. Read more about it on www.gpwsi.org or www.natpact.nhs.uk/special interests

BMJ 2003;326:1418 (28 June)
Mental activity may help prevent dementiaParticipating in mentally challenging leisure activities such as reading and playing board games may help elderly people stay mentally sharp.

Researchers found that people aged 75 years or more who engaged in leisure activities had a lower risk of dementia than other elderly people. It is unclear whether increased participation in leisure activities lowers the risk of dementia or whether participation in such activities declines during the preclinical phase of dementia (New England Journal of Medicine 2003;348:2508-16).

But not all activities seem to be equally effective in reducing the risk of dementia. People who reported often playing board games, reading, playing a musical instrument or doing crossword puzzles were less likely to develop dementia than people who said they engaged in those activities only rarely. However, writing and taking part in group discussions seemed to offer no protection against memory-robbing conditions such as Alzheimer’s disease.

Researchers have shown that people who develop dementia tend to halt their activities as a result. Consequently experts have debated whether people who do less mental exercise and later develop dementia are inclined to abandon their activities because they had an early, undetected form of the disease. To address this concern the researchers excluded people who developed dementia in the first seven years of the study, as they might have had an early form of the disease when the study began.

In an accompanying editorial Dr Joseph Coyle, of Harvard Medical School in Boston, agreed that promoting leisure activities among elderly people couldn’t do any harm and might help. While researchers continue to investigate the relative contributions of genes and the environment to dementia, "seniors should be encouraged to read, play board games, and go ballroom dancing, because these activities, at the very least, enhance their quality of life, and they just might do more than that," he writes.

BMJ 2003;326:1411-1412 (28 June)
Persistent atrial fibrillation: rate control or rhythm control
Rate control is not inferior to rhythm control
In conclusion, although these five randomised trials have compared heterogeneous groups of patients, several consistent messages have emerged for patients for whom cardiologists felt that randomisation to rate or rhythm control was an acceptable strategy. Firstly, with current anti-arrhythmics a rhythm control approach does not lead to an improvement in symptom control or quality of life or a reduction in clinical events in the short to medium term. In fact, in the longer term, mortality may increase. Secondly, maintenance of sinus rhythm remains poor, even with an aggressive strategy combining electrical cardioversion and current anti-arrhythmics. Hence we would advocate long term therapeutic anticoagulation for most patients treated with rhythm control, even if sinus rhythm is achieved in the short term. Thirdly, adverse side effects remain a problem.

The present data are thus consistent and strong enough to promote a rate control approach as the initial strategy for the vast majority of patients with persistent atrial fibrillation. For the minority who remain highly symptomatic aggressive rhythm control with consideration of invasive treatments such as pulmonary vein ablation or improved rate control with atrioventricular nodal ablation with back up ventricular pacing should be considered.

Volume 326, Number 7404, Issue of 28 Jun 2003

Paperless records are better than traditional system
Electronic medical records are more complete and understandable than paper records. In a cross sectional study of 529 records in 25 general practices, Hippisley-Cox and colleagues (p 1439) found that 89% of paperless records and 70% of paper records were medically understandable. Almost 90% of paperless records had at least one diagnosis, compared with 32% of paper based records. Drug dose reporting was far better in the electronic records than in the paper records (87% versus 33%). However, from interviews the authors found that the method of reporting did not affect the doctors' recall of patients or consultations.

Volume 326, Number 7404, Issue of 28 Jun 2003
Measure cholesterol in everyone over 50
Current UK guidelines on who should have a cholesterol measurement fail to identify 20% of people who may benefit from treatment to reduce their risk of heart disease or stroke. Wilson and colleagues (p 1436) compared four different methods of selecting people for cholesterol measurement: the national service framework criteria, Sheffield tables, age threshold of 50 years, and fixed cholesterol values. They found that targeting everyone over 50 for cholesterol measurement and coronary risk assessment is a simple and efficient way of identifying people in the general population at increased risk of heart disease.
cardiovascular disease

Volume 326, Number 7404, Issue of 28 Jun 2003

Pill could reduce cardiovascular disease considerably
Taking a single combination pill daily could reduce the incidence of cardiovascular disease by over 80%. In the first of three articles in this issue, Wald and colleagues (p 1419) present the concept of combining six active components in one pill (the Polypill) taken every day from age 55, or sooner if people have a diagnosis of cardiovascular disease or diabetes. They argue that the combination of a statin, a thiazide, a blocker, an angiotensin converting enzyme inhibitor, folic acid, and aspirin simultaneously reduces four key cardiovascular risk factors: low density lipoprotein cholesterol, blood pressure, serum homocysteine, and platelet function. The authors' systematic review and meta-analysis of over 200 studies (p 1423) shows that the use of statins can lower low density lipoprotein cholesterol by 1.8 mmol/l, which could decrease the risk of ischaemic heart disease by 60% and stroke by 17%. Their examination of 354 randomised controlled trials (p 1427) found that giving drugs at half the standard dose can significantly lower blood pressure with minimal adverse effects, which in turn reduces the risk of stroke by 63% and ischaemic heart disease by 46%. In an accompanying editorial, Rodgers (p 1407) says that the Polypill may have enormous potential for preventing cardiovascular disease, including in developing countries.

Volume 326, Number 7403, Issue of 21 Jun 2003


Fluticasone propionate reduces risk of relapse in atopic dermatitis
Fluticasone propionate cream or ointment, applied twice weekly as part of an emollient maintenance treatment, reduces the risk of relapse in patients with atopic dermatitis. Results from Berth-Jones and colleagues' randomised, double blind, placebo controlled, parallel group trial (p 1367) show that after initial stabilisation treatment, the risk of flares was significantly lower in the group applying fluticasone propionate twice weekly than in the placebo group. Median time to relapse was six weeks for emollient alone and more than 16 weeks for additional fluticasone propionate.

BMJ 2003;326:1286 (14 June)

Working night shifts can be hazardous to health. Women who work rotating night shifts face an increased risk of developing colorectal cancer, a new prospective observational study has found (Journal of the National Cancer Institute 2003;5:825-8).

Researchers led by Dr Eva Schernhammer of Harvard Medical School in Boston, Massachusetts, and from the Ludwig Boltzmann Institute of Applied Cancer Research in Vienna, Austria, uncovered this link by following 78 586 women nurses who were enrolled in a longitudinal epidemiological study known as the nurses health study.

The researchers found that women who worked 15 or more years of rotating night shifts faced a 35% increased risk of developing malignant tumours of their large intestine and rectum compared with those who never worked such shifts (relative risk 1.35, 95% confidence interval 1.03 to 1.770).

Although it is unclear exactly why working night shifts may increase tumour risk, the researchers speculate that it may be related to a disruption in circadian rhythms, which are mediated by the pineal gland.

The pineal gland, located in the posterior mid-brain, secretes melatonin, a hormone involved in the sleep-wake cycle and believed to possess antineoplastic effects. Blood levels of melatonin follow a daily cycle, with peak levels normally occurring between 1 am and 2 am.

The synthesis and release of melatonin is regulated by light exposure—it is stimulated by darkness and inhibited by exposure to light. People exposed to light at night, such as nurse night shift workers, therefore have suppressed melatonin levels. Melatonin levels in turn are thought to help regulate the secretion of oestrogens.

Commenting on this hypothesis, Dr Schernhammer said: "There is good evidence from experimental animal and in vitro studies that melatonin protects against cancer. For instance, removal of the pineal gland boosts tumour growth in animal models and melatonin doses reduce tumours in them."

Previous research has also linked sleep deprivation to the development of breast cancer in women (Journal of the National Cancer Institute 2001;93:1557-62, 1563-9). though this finding needs to be confirmed through further work. Only 5819 of the 78 586 respondents worked 15 years or more of rotating night shifts.

Unanswered questions are whether stable night shift workers would also face the same increased risk and whether other factors, such as levels of the stress hormone cortisol, and oestrogen levels are influencing the results. Also unknown is whether administration of exogenous melatonin would reduce the risk.

BMJ 2003;326:1232 (7 June)
Postmenopausal women who take combined oestrogen and progestogen hormone replacement therapy (HRT) face twice the risk of developing dementia than women who do not, a new study says (JAMA 2203;289:2651-62).

The finding deals a fresh blow to the practice of routine hormonal supplementation in postmenopausal women and contradicts previous observational and epidemiological studies that indicated that oestrogen replacement therapy could protect against Alzheimer’s disease and vascular dementias (JAMA 2002;288:2123-9, 2170-1).

It is unclear why HRT should increase the risk of dementia, but researchers speculate that it may be due to an increase in lacunar strokes. Another study in the same issue of JAMA (289:2673-84) analysed the effect of combination HRT on the risk of stroke and found that women who took HRT had a 31% (2% to 68%) higher risk of ischaemic and haemorrhagic stroke. A study evaluating the effect of oestrogen supplementation alone is ongoing.

BMJ 2003;326 (7 June)

Quantitative ultrasound scanning increases detection of osteoporosis Quantitative ultrasound scanning is better than asking about risk factors for osteoporosis to select women for subsequent bone densitometry. Hodson and Marsh (p 1250) added quantitative ultrasound scanning to assessment of risk factors in 200 women aged 60-69 attending a nurse led primary care clinic. Ultrasound scanning performed better than risk factor inquiry for predicting osteoporosis. A combination of the two methods identified 90% of the women with osteoporosis and increased prediction for those without osteoporosis.
BMJ 2003;326 (7 June)