Pregnant women should avoid NSAIDs, says RCOG
Women who know they are pregnant should avoid using non-steroidal anti-inflammatory
drugs (NSAIDs), the Royal College of Obstetricians and Gynaecologists
(RCOG) has advised.
The advice was given in response to a new study which has shown that the
use of NSAIDs during pregnancy is associated with an increased risk of
miscarriage. The study did not show an increased risk of congenital abnormality,
low birth weight or preterm birth associated with NSAID use.
Dr Gunnar Nielsen (Odder hospital, Denmark) and colleagues compared the
use of NSAIDs in 4,268 women who had had miscarriages, with NSAID use
in 29,750 women who had had live births. They also examined the medical
records of 1,462 pregnant women who had received prescriptions for NSAIDs
during the period from 30 days before conception to birth. The odds ratio
for miscarriage, compared with pregnancies ending in birth, was 6.99 (95
per cent confidence interval, 2.75 to 17.74) for women collecting prescriptions
for NSAIDs during the week before miscarriage. This fell to 2.69 (1.81
to 4.00) in women who had collected their prescriptions between seven
and nine weeks before miscarriage. The incidence of congenital abnormalities
in babies born to women who had collected prescriptions for NSAIDs early
in their pregnancy was slightly higher than in women who had not received
NSAIDs (4.2 per cent versus 3.3 per cent) but the difference was not significant.
The researchers note that their findings should be treated with caution
because their data do not indicate whether a woman might have received
a prescription for a NSAID because of pain that might have been a precursor
of miscarriage. The study is published in the British Medical Journal
(2001;322:266). In their statement issued on February 2, the RCOG said:
"It is important to note that the authors of the paper emphasise that
they have not shown that these drugs cause miscarriage, only that they
are associated with miscarriage. . . . However, it would be better if,
for the moment, women who knew they were pregnant avoided these drugs,
particularly as there are effective alternatives, such as paracetamol."
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Risedronate reduces risk of hip fracture, say researchers
The bisphosphonate risedronate (Actonel) reduces the risk of hip fracture
in elderly women with osteoporosis but not in those with risk factors
other than low bone mineral density, according to the results of a new
study.
In a randomised, controlled trial involving 9,331 elderly women, subjects
were enrolled into one of two groups and then randomised to receive either
risedronate (2.5mg or 5mg) or placebo daily for three years. The first
group included 5,445 women aged between 70 and 79 years who had osteoporosis
and low bone mineral density. The second group included 3,886 women aged
80 or above, who had been enrolled mainly because they had risk factors
other than low mineral bone density.
Dr Michael McClung (Oregon Osteoporosis centre, Portland, United States)
and colleagues found that the incidence of hip fractures in women with
established osteoporosis who received risedronate was 1.9 per cent, compared
with 3.2 per cent among those taking placebo. The effects of the 2.5mg
and 5mg doses of risedronate were similar, say the researchers.
Among the women with mainly non-skeletal risk factors, the incidence of
hip fracture in those who received risedronate was 4.2 per cent compared
with 5.1 per cent among the placebo group. Information on bone mineral
density was not available for most of the women in this group but of the
941 women who were known to have low bone mineral density, the incidence
of hip fracture was 7.2 per cent in women who received risedronate compared
with 9.7 per cent among those who received placebo.
The researchers say that measuring bone mineral density is important for
identifying women for whom drug therapy to prevent hip fracture is appropriate.
Women with the most advanced disease (ie, those with low mineral density
at the femoral neck and a history of vertebral fractures) may benefit
most from treatment with risedronate, they conclude (New England Journal
of Medicine 2001;344:333).
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Review indicates aspirin prevents pre-eclampsia
Low-dose aspirin reduces the risk of pre-eclampsia in pregnancy, a review
has shown. However, the benefit is moderate so individual assessment is
needed to identify which women are likely to benefit from treatment.
A systematic review of 39 trials (30,563 women) comparing antiplatelet
drugs with placebo was conducted by researchers from Oxford and Australia.
Most studies compared aspirin alone with placebo (28,802 women). The use
of antiplatelet drugs was associated with a 15 per cent reduction in the
risk of pre-eclampsia. This result was consistent across all the trials,
regardless of risk status, dose of aspirin or gestation at trial entry.
Use of antiplatelet drugs was also associated with an 8 per cent reduction
in risk of pre-term birth and a 14 per cent reduction in risk of foetal
or neonatal death.
The authors comment that the cause of pre-eclampsia remains unknown but
is associated with a deficiency in production of a vasodilator, prostacyclin,
and over-production of a vasoconstrictor, thromboxane, which stimulates
platelet aggregation. The hypothesis that antiplatelet drugs might prevent
or delay pre-eclampsia had been widely tested, but large trials and meta-analyses
had failed to confirm any benefit. However, this study found a moderate
effect. The authors comment that the moderate effect would mean that a
relatively large number of women would need to be treated to prevent the
death of one baby. They add that starting treatment before 12 weeks or
using higher doses of aspirin cannot be recommended until more information
is known about safety (British Medical Journal 2001;322:329).
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Promising results for inhaled insulin
The development of inhaled insulin took a step forward this week as
trial results suggested that it could offer a well-tolerated alternative
to insulin injections.
Dr Jay Skyler (University of Miami, United States) and colleagues, from
the inhaled insulin study group, compared the efficacy of inhaled insulin
with that of subcutaneous insulin injections in a 12-week trial. Thirty-five
patients with type I diabetes were assigned inhaled insulin three times
daily before meals, with a long-acting insulin injection given at bedtime.
A control group of 37 patients with type I diabetes were assigned insulin
injections two or three times daily, according to their normal regimen.
The researchers found no differences between the groups in terms of changes
in glycosylated haemoglobin concentrations over the study period. There
were no significant differences in blood glucose profiles, or in the occurrence
and severity of hypoglycaemia. Inhaled insulin was well tolerated, they
say. Pulmonary function was stable over the study period and did not differ
between the treatment groups, and there were no serious adverse reactions.
Patients were more satisfied with inhaled insulin than with subcutaneous
insulin injections. Specifically, inhaled insulin was rated higher with
regard to ease of administration, comfort, convenience, time with dosing,
flexibility of eating schedule and ease of taking insulin many times a
day.
The authors conclude: "This proof-of-concept study showed that inhaled
insulin could replace preprandial subcutaneous insulin injections in patients
with type I diabetes, and that equivalent glycaemic control could be sustained
for three months." (Lancet 2001;357:331.)
In an accompanying leading article, Professor Edwin Gale (diabetic medicine
division of medicine, University of Bristol) cautions that the research
is at an early stage (ibid, p324). He points out that the sample size
was small and that it is too early to conclude that inhaled insulin is
as good as conventional injections. In addition, he says that inhalation
is not an efficient way of delivering insulin.
In the trial, the inhaled insulin was delivered using a dry-powder formulation
using an aerosol delivery device. The insulin was packaged in individual
blisters which contained either 1mg or 3mg of human insulin, delivering
the equivalent of 3 or 9 units, respectively, to the systemic circulation.
Dr Skyler and colleagues report that patients in the trial required an
average of 12.2mg of insulin a day. Assuming inhaled insulin has 10 per
cent bioavailability, this is equivalent to about 37 units of subcutaneous
insulin per day, they say. The patients had previously used a mean of
18 units subcutaneously per day. Professor Gale points out that 12.2mg
insulin is equivalent to 350 units and concludes: "Inhalation is
thus likely to be a costly and clumsy alternative to the needle."
A spokeswoman for Diabetes UK welcomed the study but added that it would
be several years before there was a clear indication of whether it was
a breakthrough. She added that there were a number of companies involved
in producing insulin inhaler devices.
In a second trial, the inhaled insulin study group found that inhaled
insulin was well tolerated in patients with type 2 diabetes. The 12-week
open-label study, which involved 26 patients, found that inhaled insulin
improved glycaemic control from baseline (stabilised on insulin) and demonstrated
no adverse pulmonary effects (Annals of Internal Medicine 2001;134:203).
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No link between vaccination and multiple sclerosis,
studies show
Vaccination does not seem to trigger the onset of multiple sclerosis
or relapses of existing disease, according to two studies published in
the Journal of the American Medical Association (2001;344:319 and
327).
In the first study, researchers from the Vaccines in Multiple Sclerosis
study group say that there has been some concern about a possible link
between vaccination and relapses of multiple sclerosis.
Consequently, they assessed 643 patients with multiple sclerosis who had
suffered a recent relapse and compared exposure to vaccination immediately
before the relapse with that in control periods that were not followed
by a relapse.
When all reported vaccinations were considered, the relative risk of relapse
was 0.76 (95 per cent confidence interval, 0.44 to 1.31).
The authors comment: "This study suggests that commonly administered
vaccines (specifically, against tetanus, hepatitis B and influenza) do
not increase the risk of relapse in patients with multiple sclerosis."
In the second study, researchers from the Harvard school of public health,
Boston, United States, looked for a link between immunisation against
hepatitis B and the onset of multiple sclerosis. They checked the vaccination
records of 192 women who had just been diagnosed as having the disease
and 534 healthy controls, and compared those who had been immunised against
hepatitis B with those who had not.
The age-adjusted relative risk of developing multiple sclerosis for vaccinated
women was 0.9 (0.5 to 1.6) and that for women vaccinated in the two years
before diagnosis was 0.7 (0.3 to 1.7). "We found no evidence of an
increased risk of multiple sclerosis among women who had been vaccinated
against hepatitis B," the authors say. They add that concern about
possible increases in the risk of developing the disease does not justify
changes in vaccination policy that could compromise or delay the control
of infection.
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Formoterol found to be superior to terbutaline when
used "as required"
A trial comparing the long-acting b-agonist, formoterol, with terbutaline
has found that formoterol provides better asthma control when used "as
required" than the shorter-acting drug.
Asthma guidelines recommend that long-acting b-agonists should be given
regularly and not on an "as required" basis. However, Professor
Anne Tattersfield (respiratory medicine unit, City hospital, Nottingham)
and colleagues comment that formoterol has a quick onset of action and
should be effective for rescue purposes. The researchers conducted a three-month
study in 362 patients to assess the safety and efficacy of inhaled formoterol
and terbutaline used "as required". Patients in the double-blind
trial were randomly assigned formoterol 4.5µg or terbutaline 0.5mg,
by turbohaler, to be used only when required.
Patients in the formoterol group had a longer time to their first exacerbation
of asthma (the primary endpoint) than patients assigned terbutaline. The
relative risk of having a first exacerbation in the formoterol group compared
with the terbutaline group was 0.55.
In addition, the researchers report that lung function improved to a greater
extent in the formoterol group and these patients took fewer inhalations
of rescue medication. Both treatments were well tolerated, they say. The
number and pattern of adverse events were similar in both groups, and
the mean changes in serum potassium concentration and other laboratory
values were small and similar between the groups.
The researchers comment that there is limited information on the dose
equivalence of the two drugs. They suggest that at the doses used, formoterol
was probably given at a lower equivalent dose than terbutaline but that
it has a longer duration of action.
They add that formoterol might also have advantages over terbutaline in
terms of relative safety, particularly in patients needing high doses
of medication or with cardiac abnormalities because of the reduction in
exacerbations, the need for less b-agonist and, where higher doses are
needed, less systemic activity (Lancet 2001;357:257).
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Another role for statins?
New research suggests that statins may prevent type 2 diabetes. Dr Allan
Gaw (director, clinical trials unit, Glasgow Royal infirmary) and colleagues
analysed data from the West of Scotland Coronary Prevention Study (WOSCOPS).
They found that patients taking pravastatin had a 30 per cent reduced
risk of developing type 2 diabetes.
The analysis showed that 139 out of 5,974 men aged between 45 and 69 years
developed diabetes during the three to six year follow-up. Of the 139
that developed diabetes, 59 per cent were in the placebo group and 41
per cent in the pravastatin group. At the start of the trial, all the
men had fasting blood glucose levels of 7.0mmol/L or below (Circulation
2001;103:357).
Previous studies have shown that statin treatment is beneficial in diabetic
patients but this is the first study to show a preventive effect. The
mechanism by which pravastatin reduces the risk of diabetes is not known,
nor is it known whether this will be prove to be a class effect or a property
of pravastatin only, says Bristol Myers Squibb (manufacturer of pravastatin
[Lipostat]).
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Mirena — a cost-effective alternative to hysterectomy?
The levonorgestrel-releasing intra– uterine system, Mirena, is a cost-effective
alternative to hysterectomy for treating menorrhagia, research has shown.
A Finnish study has shown that health-related quality of life improved
significantly with both treatments but that the intrauterine system (IUS)
was more cost-effective.
The researchers report that women aged between 35 and 49 years with menorrhagia
(mean menstrual blood loss, 129ml) were randomised to two treatment groups.
In the first treatment group, 117 women had an IUS inserted. Mean menstrual
blood loss measured in 25 of the women after a year was 13ml. The remaining
women had amenorrhoea or negligible bleeding, apart from one woman who
still had menorrhagia. However, a third of women had the device removed;
the most common reason for this was intermenstrual bleeding. Twenty per
cent of these women had subsequently undergone a hysterectomy. In the
second treatment group, 107 women underwent a hysterectomy.
After 12 months, measures of health- related quality of life showed a
significant improvement in both groups. The only difference between the
groups was that pain scores were better in the hysterectomy group. Cost-effectiveness
was assessed as direct cost per woman and in terms of productivity loss.
The decision to treat menorrhagia with hysterectomy rather than with an
IUS was about three times more expensive at 12 months after treatment.
The researchers comment that, while the IUS is economical in the short
term, it may result in further costs in the longer term. However, their
overall conclusion is that after one year, cost-effectiveness favours
the IUS (Lancet 2001;357:273).
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