Journals Watch - Birth defects, ACS and C difficile

Missed out on the latest research? Let Dr Raj Thakkar bring you up to date on the latest papers.

20-year survival rate is 97.6 per cent for fetal orofacial anomalies
20-year survival rate is 97.6 per cent for fetal orofacial anomalies

Congenital abnormality survival rates mapped out - Lancet 2010; doi: 10.1016/S0140-6736(09)61922-X
Deciding whether to continue a pregnancy when an unborn child has a congenital defect is incredibly hard. This UK-based survival study may go some way in helping to guide patients with such a dilemma.

Researchers followed more than 10,000 children with a wide range of congenital anomalies to estimate survival rates.

Twenty-year survival was 85.5 per cent for children with one or more anomaly, 89.5 per cent for cardiovascular defects, 79.1 per cent for chromosomal defects, 93.2 per cent for urinary system defects, 83.2 per cent for digestive system disorders, 97.6 per cent for orofacial anomalies and 66.2 per cent for nervous system defects.

While a greater number of parents elected to terminate in 2003 (18.3 per cent) compared with 1985 (12.4 per cent), the data showed that survival rates for some conditions increased during the study period, probably as a result of better neonatal care.The quality of life data may also help us counsel our patients.

Clopidogrel versus ticagrelor in acute coronary syndrome - Lancet 2010; 375: 283-93
Clopidogrel has received bad press recently, particularly when used in patients taking proton pump inhibitors.

Optimal dose and timing of administration in the context of acute coronary syndrome (ACS) is also under debate, and there is concern about the associated risk of bleeding in patients undergoing coronary artery bypass graft procedures.

This randomised, blinded study compared clopidogrel with a more potent P2Y12 inhibitor, ticagrelor, in patients with ST and non-ST elevation ACS with planned early percutaneous intervention.

The primary endpoint was defined as cardiovascular death, MI or stroke. The results showed that ticagrelor produced fewer primary endpoint events than clopidogrel, without an increased risk of bleeding.

The researchers estimate that using ticagrelor instead of clopidogrel for one year in 1,000 patients would lead to 11 fewer deaths, 13 fewer MIs and six fewer cases of stent thrombosis without an increase in the rates of major bleeding.

It would now be interesting to see how these two drugs fair in reducing the risk of cerebrovascular accident in TIA patients.

Monoclonal antibodies against Clostridium difficile - N Engl J Med 2010; 362: 197-205
Clostridium difficile remains a serious threat to life, particularly in vulnerable patients, and despite precautionary measures and antibiotics, incidence of the infection continues to rise.

This double-blind, randomised study assessed the effectiveness of two human monoclonal antibodies against C difficile toxins A and B, given as a single infusion to patients already on metronidazole or vancomycin. The researchers looked at infection recurrence over the next 84 days.

A total of 101 patients received antibodies and 99 received placebo. Recurrence was significantly lower in the treatment group (7 versus 25 per cent). Recurrence in patients with epidemic BI/NAP1/027 strain was still lower (8 per cent versus 32 per cent), although this was not statistically significant (p=0.06). Hospitalisation times did not differ between the two groups.

This study is a major breakthrough in the fight against C difficile, although further research is required.

Effect of dietary salt reduction on future cardiovascular disease - N Engl J Med 2010; doi: 10.1056/NEJMoa0907355
The association between high salt intake and poor health has long been recognised, but this US study has added weight to the notion that dietary salt reduction should be an urgent target for public health.

Researchers used a computer simulation to assess the cardiovascular and economic benefits of reducing dietary salt by 3g (1200mg sodium) per day. They projected that salt reduction could reduce the incidence of CHD, stroke and MI.

The reduction in CHD was particularly noticeable in black patients, although the researchers found all segments of the population would benefit from consuming less salt. The data showed that reducing salt intake could be as beneficial to health as reducing tobacco use, obesity and cholesterol levels.

The authors estimate that a regulatory intervention to limit salt intake could cut healthcare costs in the US by $24 billion per year, and would be more cost-effective than using medications to lower BP.

Pseudomonas aeruginosa infection in patients with cystic fibrosis - Thorax 2009; doi: 10.1136/thx.2009.121657 ce
Pseudomonal colonisation and infection continues to plague patients with cystic fibrosis (CF).

The Early Inhaled Tobramycin for Eradication (ELITE) study assessed the efficacy of inhaled tobramycin in CF patients. In this non-blinded randomised trial, CF patients with Pseudomonas aeruginosa received nebulised tobramycin twice daily for four weeks. Patients were then randomised to either receive four more weeks of tobramycin or to stop treatment.

Median time to recurrence of pseudomonal infection was similar irrespective of whether patients received four or eight weeks of nebulised tobramycin, with more than 90 per cent free from the disease one month after treatment. In both groups the treatment was tolerated.

The data suggests that nebulised tobramycin for 28 days is a safe and effective treatment regime for CF patients with P aeruginosa.

Cigarettes, alcohol and oesophageal cancer - Gut 2010; 59: 39-48
Oesophageal and gastric cancers are devastating diseases long associated with smoking and high alcohol intake.

Researchers from the Netherlands analysed data from a prospective cohort study to determine whether smoking or alcohol are associated with particular cancer subtypes, namely oesophageal squamous cell carcinoma (OSCC), oesophageal adenocarcinoma (OAC), gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA).

The study showed that patients who drank 30mg ethanol on a daily basis were more than four times as likely to develop OSCC than non-drinkers. However, alcohol was not found to be linked with GNCA, OAC or GCA.

Smoking was dose-dependently associated with all cancer subtypes, and when combined with alcohol synergistically raised the risk of OSCC.

The study confirms the need to be vigilant for oesophageal and gastric malignancies in patients who drink or smoke.

  • Dr Thakkar is a GP in Wooburn Green, Buckinghamshire, and a member of our team who regularly review journals

The quick study

  • Congenital abnormalities are associated with a range of 20-year survival rates.
  • Ticagrelor was associated with fewer cardiovascular events than clopidogrel.
  • Clostridium difficile responded to monoclonal antibody treatment.
  • Dietary salt reduction of 3g per day is projected to decrease the incidence of CHD, stroke and MI.
  • Cystic fibrosis patients with P aeruginosa can be treated safely with nebulised tobramycin.
  • Oesophageal cancer risk is raised by consuming cigarettes and alcohol.

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