Estrogen and exacerbations in cystic fibrosis
N Engl J Med 2012 DOI: 10.1056/NEJMoa1106126
It is not unusual to find patients with cystic fibrosis (CF) developing chronic pseudomonal infection. Women with CF tend to fare worse and this is thought to be secondary to the higher rate of mucoid conversion of Pseudomonas aeruginosa. Greater mucopolysaccharide production results in a high risk of exacerbations and poorer lung function.
This study looked at the influence of estrogens on P aeruginosa taken from women with and without CF. Several key findings were discovered.
Prolonged estrogen exposure increased the mucoid morphology of pseudomonas and short-term estrogen exposure caused increased bacterial hydrogen peroxide levels, which the researchers suggested could damage DNA.
There was a correlation between estradiol levels and infective exacerbations of CF; exacerbations were more prevalent in the follicular phase of the menstrual cycle. The oral contraceptive pill was associated with a reduction in exacerbations.
Hopefully, we will soon receive guidance on this. Meanwhile, should all female patients with CF be offered the oral contraceptive pill?
Lowering LDL cholesterol in low-risk patients
Lancet 2012 doi:10.1016/S0140-6736(12)60367-5
We are taught that high-risk patients benefit from statins and it is recommended that those with a 10-year QRISK in excess of 20% should be offered cholesterol-lowering agents. What about patients with a low risk of cardiovascular disease?
This meta-analaysis involving a large number of patients concluded that statins did reduce the risk of major adverse cardiovascular events irrespective of disease risk.
Furthermore, the magnitude of risk reduction was equal in high- and low-risk patients. This also translated to a reduction in coronary revascularisation procedures and all-cause mortality. In patients with a five-year risk of cardiovascular events of less than 10%, 11 per 1,000 events were prevented for every 1.0mmol/L reduction in LDL.
We need to consider these data against current guidelines and whether we should prescribe these drugs more readily.
Dementia follow-up care by memory clinics or GPs
BMJ 2012; 344: e3086
These authors set out to establish whether memory clinics are more or less effective than GP care for dementia patients after diagnosis.
This RCT in the Netherlands compared nine memory clinics with 159 GPs. Quality of life ratings, including those from carers, were used as the main outcome measure.
The researchers found there was no significant difference between the two care environments. Clearly, further considerations need to be taken into account, such as GP training; but this study makes a strong argument to manage post-diagnosis care of dementia in primary care, assuming GPs are given appropriate resources.
Azithromycin and the risk of cardiovascular death
N Engl J Med 2012; 366: 1881-90
This study aimed to assess the possible effect of antibiotics in increasing risk of cardiac death. The researchers looked at almost 350,000 prescriptions of azithromycin and compared them to more than a million controls, who took no antibiotics, or took other routine antibiotics such as amoxicillin.
Those patients who took azithromycin had a statistically significant 2.88 times increased risk of cardiovascular death in the first five days of treatment compared with controls who took no antibiotics. Amoxicillin conferred no added risk.
To put this into perspective, there were 47 excess deaths with azithromycin compared with amoxicillin for every million courses taken.
Unsurprisingly, those with a higher underlying risk of cardiovascular disease were at the greatest risk.
Colorectal cancer incidence and flexible sigmoidoscopy
N Engl J Med 2012 10.1056/NEJMoa1114635
England's national screening programme for colorectal cancer uses faecal occult blood. But should we adopt screening with flexible sigmoidoscopy instead?
Almost 155,000 people aged 55-74 years were studied. Each patient in the intervention arm had an initial screen with flexible sigmoidoscopy and just over half of these had a further screen after three to five years.
The incidence of colorectal cancer in the screening group was 11.9 cases per 10,000 people per year, whereas 15.2 cases per 10,000 people per year were diagnosed in the control group. This equates to a 21% risk reduction of having cancer with screening. Mortality was lower in the intervention arm.
Lifestyle interventions during pregnancy
BMJ 2012; 344: e2088
This systematic review and meta-analysis looked at the effect of lifestyle advice during pregnancy on birthweight and obstetric complications.
More than 7,000 women were analysed, focusing on diet and physical activity interventions. The interventions resulted in a mean 1.42kg reduction in weight gain during pregnancy, compared with controls.
Physical exercise translated to a small reduction in birthweight of 60g (mean). There was also a statistically significant reduction in the risk of pre-eclampsia (OR 0.74) and shoulder dystocia (OR 0.39).
Dietary advice resulted in an average 3.84kg reduction in pregnancy weight gain and a greater reduction in adverse outcomes than physical activity interventions.
- Dr Thakkar is a GP in Wooburn Green, Buckinghamshire, and a member of our team who regularly review the journals.
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