Journals Watch - Smoking during pregnancy and Crohn's disease

Not had time to read the latest journals? Dr Tillmann Jacobi brings you up to date with the latest research.

A study found that smoking during pregnancy led to significantly lower HDL cholesterol in children (Photograph: SPL)
A study found that smoking during pregnancy led to significantly lower HDL cholesterol in children (Photograph: SPL)

Long-term lipid risk for children of women who smoke during pregnancy
Eur Heart J 2011; doi: 10.1093/eurheartj/ehr174

The immediate negative effects of smoking during pregnancy are fairly well known but the long-term effects on babies remain unclear. This community-based longitudinal study investigated more than 600 newborns of women who had smoked during pregnancy and followed them up eight years later to measure lipoproteins, BP and arterial wall thickness.

At follow-up, 405 of the children were apparently healthy but showed disturbing differences compared with children of non-smoking mothers. These children had significantly lower protective HDL-cholesterol (1.32 versus1.50 mmol/L) but higher triglycerides (1.36 versus1.20 mmol/L) than their peers.

This remained true even after adjusting the results for a number of external factors, such as physical activity, breast feeding and postnatal cigarette exposure. BP and arterial wall thickness showed no significant difference. This study quite powerfully displays an unapparent but probably significant long-term implication of smoking during pregnancy.    

Changes in diet and lifestyle and long-term weight gain
N Engl J Med 2011; 364: 25, 2392-404

This prospective cohort study of 120,877 healthy and normal-weight men and women examined the link between lifestyle factors and long-term weight changes. The participants were assessed at four-year intervals between 1986 and 2006 with multivariable adjustments made for age, BMI and lifestyle factors.

Within each four-year period participants gained on average 3.35 lb (5th to 95th percentile, -4.1 to 12.4), mainly due to increased intake of potato chips, potatoes, sugar-sweetened beverages and red or processed meats. Weight loss was associated with the increased intake of vegetables, whole grains, fruits, nuts and yogurt. Lifestyle factors included physical activity, alcohol intake, smoking, sleep and television watching.

Healthcare professionals could probably achieve more by advising on some relevant specific dietary and other lifestyle behaviours to prevent or reduce obesity in patients rather than using the ‘eat less and exercise more’ generalisation.

Risk of serious adverse cardiovascular events associated with varenicline
CMAJ 2011; doi: 10.1503/cmaj.110218

The smoking cessation drug varenicline has been marketed extensively so that significant numbers of informed patients feel encouraged to specifically request it. This study analysed data from 14 double-blind RCTs involving more than 8,000 participants. Varenicline was associated with a significantly increased risk of serious adverse cardiovascular events compared with placebo (1.06 per cent in the treatment group versus 0.82 per cent in the placebo group).

This concern is additional to the well-documented and not uncommon observations of potentially severe negative effects of varenicline on mental health. Put into perspective of the efficiency of the drug (a meagre quit rate of 14 per cent at 24 weeks) and the treatment cost (typically £1 per tablet) this article questions the claimed ‘superiority’ of the drug over nicotine replacement therapy or ‘cold turkey’ cessation.

Which dose of aspirin in diabetics to reduce cardiovascular and overall mortality?
J Gen Intern Med 2011; doi: 10.1007/s11606-011-1757-y 
This meta-analysis is a useful contribution to the ongoing debate regarding the most appropriate (and safest) dose of aspirin in patients with high cardiovascular risk.

Pharmacologic evidence suggests that adequate antiplatelet activity in patients with diabetes requires more than 100mg aspirin daily but clinical practice and many trials typically use smaller doses. The analysis included 21 studies with more than 17,500 patients with diabetes in total. All-cause mortality was the primary outcome of interest. Thirteen studies used ≤100mg of aspirin, four studies used 101-325mg and eight studies used 325mg or more of aspirin.

The analysis confirmed that aspirin used for secondary prevention was generally associated with a significantly lower risk of overall mortality. However, there was no indication that the outcomes improved with doses above 100mg of aspirin a day.

Topical tacrolimus for vitiligo
J Dermatol 2011; 38: 536-40

Vitiligo can be a distressing condition and difficult to manage. Current conventional active treatments include topical corticosteroids and phototherapy, although many cases are quite unresponsive to these. Topical tacrolimus has been suggested in previous studies without much further published investigation.

This cohort study of 42 patients (22 adults and 20 children) with any type of vitiligo showed an encouraging response rate of 76 per cent to a twice-daily treatment of 0.1% tacrolimus ointment for six months. Vitiligo acrofacialis responded less favourably than other forms of vitiligo.

Children had a nine times higher chance of a good response than adults, and tacrolimus treatment within five years of onset of symptoms seemed to be a favourable factor. The authors cautiously propose tacrolimus mainly for the known difficult types of vitiligo rather than as a general first-line treatment option for all types.

Thalidomide for refractory Crohn's disease
J Pediatr Gastroenterol Nutr 2011; doi: 10.1097/MPG.0b013e318228349e

This study on the use of thalidomide in a small cohort of children with severe refractory Crohn's disease had some encouraging outcomes. The study included 12 patients who had not responded to conventional immunosuppression therapy with azathioprine, 6-mercaptopurine, methotrexate and anti-TNF biologic agents, such as infliximab. About half of them also had complications, such as strictures or fistulae.

The trialled rescue therapy with thalidomide showed significant improvements in all measured outcomes. This included laboratory evaluations and the Harvey-Bradshaw Index for Crohn’s disease activity, as well as observations of occurences of surgical interventions or hospitalisations (reduced from 6.3 to 1.3) and change in prednisone dose (reduced from a mean of 13.9mg/day to 2.3mg/day).

Moreover, five fistulas closed completely and one partially. The most common temporary side-effect (peripheral neuropathy) in 42 per cent of patients resolved within three months after stopping the treatment. Thalidomide, in contrast to its negative reputation in the past, could potentially be an effective rescue therapy for children with severe Crohn’s disease.

Sequential therapy for better Helicobacter pylori eradication
Helicobacter 2011; 16: 229-33
Traditional triple-therapy for Helicobacter pylori eradication is showing declining success rates globally as well as in the UK. Some previous international studies recommended sequential therapy as an alternative and documented improved success rates.

This Israeli cohort study evaluated a trial of the sequential treatment approach on more than 120 patients who had a positive rapid urease test and positive urea breath test for H pylori. The patients received omeprazole 20mg twice daily and amoxicillin 1g twice daily for five days followed by omeprazole 20mg twice daily, clarithromycin 500mg twice daily and tinidazole 500mg twice daily for another five days.

The result at retesting at least one month after completing the treatment was an impressive eradication rate of more than 90 per cent. Although resistance of H pylori to certain treatment regimens can differ between localities it is good to consider and search for new options to improve outcomes.

    • Dr Tillmann Jacobi is a GP in York and a member of our team who regularly review the journals

    Reflect on this article and add notes to your CPD Organiser on MIMS Learning

      CPD IMPACT: EARN MORE CREDITS

        These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

        • Identify pregnant women who continue to smoke and consider additional appointments and support to encourge smoking cessation. The suggestions of the above study could be useful discussion points in consultations and to share with midwives.
        • Conduct a search for patients in the practice population who are taking doses of aspirin higher than 75mg and check the reasons, rationale and safety.
        • Consider an audit on H pylori detections in the practice to analyse the outcomes of failed treatments. Consider a discussion with your local microbiology department regarding updates on recommended therapies.

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