Quality of life in heart failure not affected by defibrillators

Medical Tribune October 2008 P3

Implantable cardioverter-defibrillators (ICDs) do not decrease quality of life for patients with stable heart failure, a study from Duke University Medical Center, US, has concluded.

The randomized trial involved 2,521 patients – all receiving optimal medical therapy along with either a single-lead ICD, amiodarone or a placebo. Physical functioning did not vary significantly between the groups at baseline, 3, 12 or 30 months, while psychological well-being was significantly improved in the ICD group at 3 and 12 months but not at 30.

Receiving a shock in the month preceding assessment, however, was associated with a reduced quality of life. [N Engl J Med 2008 359(10):999-1008]

Chewing gum speeds recovery from bowel cancer op

Medical Tribune October 2008 P3

Chewing gum could help patients to recover after colectomy, a recent meta-analysis has shown.

The study, including five randomized controlled trials totaling 158 patients, found that gum significantly reduced the time to first flatus and first bowel movement following the operation. Postoperative hospital stay was also reduced, but this result did not reach statistical significance.

The researchers, from Imperial College London, UK, suggest that gum could serve as a form of “sham feeding” which stimulates the production of saliva, gastrointestinal hormones and pancreatic secretions.The potential for substantial cost savings means that larger placebocontrolled trials into the effects of chewing gum are warranted, they conclude. [Arch Surg 2008 143(8):788-93]

Antipsychotic drugs raise risk of stroke

Medical Tribune October 2008 P3

Stroke risk is raised by all antipsychotic drugs and not just atypical types as previously thought, according to UK researchers.

Electronic primary care records were used to identify 6,790 patients with a history of stroke and taking antipsychotic medications. Compared to non-medicated periods, the rate ratio for stroke when taking any antipsychotic drug was 1.73 (95% CI 1.60 – 1.87). For typical antipsychotics alone the ratio was 1.69 (95% CI 1.55 – 1.84), whereas for atypical drugs alone this figure was 2.32 (1.73 – 3.10).

Patients with dementia who took any antipsychotic were at markedly increased risk for stroke (rate ratio 3.50; 95% CI 2.97 – 4.12), and the authors advise that these drugs be avoided where possible in these patients. [BMJ 2008 337:a1227]

Hormone patch improves schizophrenia symptoms

Medical Tribune October 2008 P5
David Brill

Estrogen – often blamed when women behave irrationally or emotionally – could in fact turn out to be an effective treatment for those with mental illness.

Researchers from Australia have shown that estradiol, delivered in the form of skin patches, can alleviate psychotic symptoms in schizophrenic women of childbearing age.

In a randomized trial with 102 participants, those given the patches alongside their regular medications showed significant reductions in both positive and general psychopathological symptoms compared to those on placebo. In many cases the effects were rapid, with hallucinations improving within 2 or 3 days of starting treatment. Improvements in memory and the ability to think clearly about complex issues were also commonly reported following treatment.

Professor Jayashri Kulkarni, who led the study, said that the benefits of hormone therapy might extend to other mental illnesses such as postnatal depression.

She added that further research into the role of estrogen for treating schizophrenia is still needed, but suggested that the hormone could already be used for certain women who have reached a plateau with antipsychotic drugs.

“Even as the data stand there is enough to suggest that for women who have tried standard treatments and haven’t made a brilliant recovery, it is possible and useful for clinicians in everyday practice to think about using a hormonal approach,” said Kulkarni, who is director of the Alfred Psychiatry Research Centre at The Alfred and Monash University in Melbourne. She added, however, that close monitoring for the long-term side effects of estrogen therapy would be needed in such cases.

Participants in the trial were assigned in a double-blind fashion to receive transdermal patches – containing either placebo or 100 μg estradiol – alongside their regular antipsychotics. [Arch Gen Psychiatry 2008 Aug;65(8):955-60]

The trial lasted for 28 days. No notable differences in adverse effects were recorded between the estradiol and placebo groups. Outcomes were assessed using the Positive and Negative Syndrome Scale (PANSS).

The mechanisms for the estrogen effect are unclear, but the researchers suggest that the hormone could rapidly enhance blood flow to the brain and improve cerebral glucose metabolism. Alternatively the effect may be mediated through modulation of the dopamine or serotonin neurotransmitter systems, or through the remodeling of neural pathways, they wrote.

“The other thing that was really interesting was that we didn’t have much problem recruiting for the study,” Kulkarni added.

“Many women patients have intuitively noted a change in their body menstrual cycle and associated that with changes in their mental state, so when we offered something
that seemed to fit with that sort of intuition it was really taken up very well by the patients,” she said.

Second-ever face transplant hailed as a success

Medical Tribune October 2008 P9
David Brill

Two years after the world’s second face transplant, the operation seems to have been a success.

Despite some complications, including three episodes of acute rejection, the patient is now healthy, able to eat, drink and talk as normal and has accepted his new face, the Chinese surgical team reported in The Lancet. [2008 Aug 23;372:631-8]

The tissue graft survived well, regaining normal skin temperature, texture and color, and did not become infected at any point.

Professor Shuzhong Guo and colleagues from the Fourth Military Medical University in Xi’an, Shaanxi Province, China, performed the procedure in April 2006. The recipient is a 30-year-old man from Yunnan Province whose face was badly disfigured by a bear in October 2004.

The graft, which was taken from a 25-year old male who had died in a road traffic accident, comprised the top lip, the whole nose, the intact parotid gland, zygomatic bone, the front wall of the maxillary sinus, and a section of the infraorbital wall.

The patient experienced an acute rejection episode three months after surgery and again at five and 17 months. These episodes involved reddening of the skin, swelling and inflammation, but were all successfully controlled with various regimens of tacrolimus, methylprednisolone and prednisone.

Hyperglycemia developed after three days but was controlled with insulin therapy. Renal, hepatic and gastrointestinal function were not adversely affected by the procedure.

“This case suggests that facial transplantation might be an option for restoring a severely disfigured face, and could enable patients to readily reintegrate themselves back into society,” the doctors wrote in the study.

The first-ever partial facial transplant was performed in November 2005 by a team of surgeons led by Professor Bernard Devauchelle from the Centre Hospitalier Universitaire Amiens, France. The recipient was a 38-year-old woman whose face had been bitten by her dog. [Lancet
2006;368:203-9]

The Chinese case differed in that the graft included bone as well as skin, and was taken following cardiac death rather than brain death.

A third transplant was carried out in January 2007 by another French team, which reported their 1-year follow-up in the same journal issue as the Chinese case. [Lancet 2008 Aug 23;372:639-45] The recipient was a 29-year-old man who had a massive plexiform neurofibroma affecting the middle and lower part of his face. He experienced two rejection episodes but has otherwise made a good functional and psychological recovery, the doctors reported, lending further support to the viability of the procedure.

‘Hollywood heart attacks’ put real lives at risk

Medical Tribune October 2008 P10
David Brill

Television portrayals of heart attacks are causing people to overlook real-life symptoms, a UK charity warned recently.

A survey, commissioned as part of a national campaign by the British Heart Foundation (BHF), found that four out of 10 people based their knowledge of heart attack symptoms on movies and television. However, these typically overdramatic scenes often fail to reflect the reality of the situation, the charity said.

“The classic ‘Hollywood heart attack’ – clutching the chest and falling down in pain – is generally the image that’s conjured up when people think about heart attacks but there’s a full range of symptoms that can be much more subtle,” said Mr. David Barker, head of communications at the BHF.

He added that heart attack victims often delay calling an ambulance because they don’t recognize the seriousness of their symptoms and simply wait to see if they will pass.

Just 18 percent of the 2,014 respondents in the UK survey were familiar with the signs of a heart attack and only 6 percent had discussed the matter with their GP.

The BHF campaign has been emphasizing that heart attacks vary from person to person and encouraging the public to seek prompt medical attention should they experience any symptoms. Besides classical chest pain, these include aching in the arms and jaw, sweatiness, shortness of breath and nausea, which can sometimes be dismissed as indigestion.

Dr. Aaron Wong, a senior consultant at the National Heart Centre (NHC), Singapore, called on the Singapore Heart Foundation to launch a similar public awareness campaign.

Although good progress has been made at streamlining processes within Singapore’s hospitals, there are often still significant delays in getting patients there in the first place, he said.

“The sooner we open up the [occluded] artery the less likely it is that the patient is going to die. Every 10 minutes of time saved can reduce the mortality by about 1 percent, so if you come in within an hour of a heart attack the chances of surviving are much, much higher than for those who wait for 6 or 7 hours,” he said.

Wong also urged patients to travel to hospital by ambulance so that treatment can be given en route. Some patients in the past have been diagnosed with myocardial infarction at their GP’s clinic and then dispatched to hospital in a taxi, he said.

The BHF campaign, which was endorsed by several high-profile UK figures, included a compelling 2-minute advertisement shown on national television which depicted a heart attack from the perspective of the viewer. Barker estimates that 6.5 million people – over a quarter of the total audience share – tuned in for the event.

The UK ambulance service also backed the initiative, with a spokesman saying: “We’d rather attend a false alarm than arrive too late.”

Wong estimates that the NHC sees around 600 to 800 cases of ST-segment elevation myocardial infarction per year, but said that many do not present within 12 hours of their attack and are not eligible for primary percutaneous coronary intervention (PCI).

Those who do arrive in time can now expect to receive PCI within 70 or 80 minutes, he said, acknowledging the success of initiatives to reduce door-to-balloon time. The NHC is now planning the next phase, whereby electrocardiography will be performed in the field and transmitted to the hospital in advance of the patient’s arrival, he added.

Stress is a killer, if you’re a man

Medical Tribune October 2008 SFXIII
David Brill


Men with stressful jobs
may be justified in delegating
work to their
female colleagues and hitting the
gym, in light of a new study which
suggests that stress increases
the risk of death for men but not
women.
Danish researchers found that
after 22 years of follow-up, men
who reported high stress levels
were at elevated risk for all-cause
mortality compared to those who
were less stressed (adjusted hazard
ratio [HR] 1.32; 95% CI 1.15 –
1.52).
For highly-stressed women,
however, no significant increase
was evident.
The study was based on registry
data from 12,128 people
who reported their stress levels
between 1981 and 1983 as part of
the Copenhagen City Heart Study.
[Am J Epidemiol 2008;168:481-91]
The researchers measured stress
at baseline using two simple
questions about intensity and frequency
of stress, generating an
overall score between 0 and 6. However
they carried out no further
assessment in the years between
the start and end of the study.
Dr. Chua Hong Choon, chief of
general psychiatry at the Institute
of Mental Health in Singapore,
said that while men and women
do tend to handle stress differently
he was not convinced by the
mortality link demonstrated in the
study.
“They measured whether patients
were stressed or not and
then they looked to see whether
they died years and years later.
The relationship is very weak actually,”
he said.
“They only did one assessment
of stress but we all know that stress
is not a static thing, it’s a dynamic
thing. You could be stressed today
but tomorrow something could
happen and you feel on top of the
world.”
Men in the study were almost
six times as likely to commit suicide
if they were stressed, and
nearly twice as likely to die from
respiratory disease (adjusted HRs
5.91 and 1.79, respectively). The
link between stress and death
varied by age, with men under
55 having the greatest risk of allcause
mortality.
“Handling stress is an important
part of managing our health
and GPs should be aware of this
association and discuss stress
management strategies with their
patients,” Chua said.
He underlined the need for
doctors to talk to patients and help
them learn to handle their stress in
a positive way, rather than simply
prescribing sleeping pills or other
medications to numb the feelings.
Effective stress management
for men typically involves physical
activity such as going to the gym,
he said, whereas women may prefer
to relax in the bath or at a spa.
An unexpected finding of the
study was that women were apparently
less likely to die of cancer
if they were stressed (adjusted
HR 0.73, 95% CI 0.57 – 0.93). The
authors suggest that exposure to
stress may inhibit estrogen synthesis,
thereby reducing the incidence
of hormone-dependent
cancers. Chua added, however,
that this was probably an erroneous
finding.

Staring disaster in the face

Medical Tribune October 2008 P11
David Brill SFXV

Dr. Arif Tyebally is a veteran of disaster relief missions in South East Asia. He spoke to Medical Tribune’s David Brill about dealing with tsunamis, earthquakes and cyclones.

December 26 2004 was a day that
changed the lives of countless people.
As a 9.3-Richter earthquake
shook the ocean floor off the coast of Sumatra,
the tsunami that resulted at the surface
killed more than 200,000 and left some half a
million homeless.
Dr. Arif Tyebally witnessed the devastation
first hand. Arriving in Aceh, Indonesia,
as part of the emergency relief effort, he saw
homes destroyed, families separated and
people living through hardships he had never
imagined possible.
“To this day I can’t think of anything that
could be worse than the tsunami,” he says.
“It was unbelievable. Thousands of homes
just flattened. Nothing can recreate it, and
nobody can describe how bad it really was.
I don’t think anyone could be prepared for
what we saw.”
On a regular day, Tyebally, 33, is a pediatrician
at KK Women’s and Children’s Hospital
in Singapore. He decided to volunteer
for the mission to Aceh when he saw the extent
of the destruction on television. While
millions donated their money, he felt that offering
his medical expertise was a better way
to help.
On arrival in Aceh, the Singapore team
lived in a camp for internally displaced
people, where they set up and ran a general
clinic. Being part of the second wave of relief
teams, there were few acute injuries from the
tsunami itself, and they treated mainly postdisaster
complications such as gastroenteritis
and respiratory and skin infections. With
local pediatric facilities severely stretched –
one local hospital with facilities having been
completely destroyed and another badly
flooded – Tyebally helped to run a makeshift
pediatric department in a nearby military
hospital.
In spite of the devastation all around
them, the residents of the camp showed a resilience
which inspired Tyebally.
“People would go back to where their
homes used to be to search amongst the
rubble, and if they could find something like
a sewing machine they’d take that back and
start to work from the camp. And the children
still went to school, even if they’d lost
their parents. I’m sure they must have been
going through really hard times, but it was
good to see that despite the situation that
they were in they were all trying to get back
to their daily lives,” he says.
Tyebally spent 10 operational days in
Aceh, treating some 70 patients each day. For
many, however, the tsunami had left wounds
that he was powerless to heal. He recalls the
thousands of photos of missing children that
lined the walls, and the haunting memory of
one lady who spent weeks going from hospital
to hospital looking for her child, long
after the waters had subsided.
“You can’t really help someone like that,”
he says. “You just have to talk to them. They
probably know that there isn’t much hope,
but for a mother any hope is still hope. It’s
very sad to see things like that happening.”
With some of these memories still troubling
him to this day, you could have forgiven
Tyebally for shying away the next time a
natural disaster struck in Asia. Yet in October
2005 he found himself among the first official
medical teams to arrive in Muzaffarabad,
Pakistan, following a 7.6-Richter earthquake
which left some 80,000 people dead.
The Singapore team set up a hospital –
again within a tented camp – comprising an
emergency room, wards and an operating
theater. Unlike in Aceh, however, the team
was treating mostly acute cases such as fractures
and open wounds. Some patients, he
says, had walked for 5 days with fractured
hips in order to receive treatment.
The conditions encountered in Pakistan
were also a challenge for the relief teams.
Aftershocks from the earthquake were common,
while sleeping in tents in an inaccessible
mountainous region with winter approaching
ensured that living conditions
were far from luxury.
For Tyebally, who speaks Bahasa Indonesia,
the language barrier in Pakistan was another
new problem which he had not faced
in Aceh. He soon realized the need to work
closely alongside local volunteers, many of
whom had given up paid jobs to come and
help out at the disaster zone. He was touched
by how helpful the people were – both in assisting
with the logistics of the team’s medical
operations and acting as interpreters for
the patients and local medical staff.
With two disaster relief missions under
his belt, Tyebally was elevated to Singapore’s
team leader when Cyclone Nargis struck
Myanmar at the beginning of May this year.
With much of the world denied access to the
country, Tyebally and his team found themselves
operating for the first time without the
coordination and resources of the UN.
Undeterred, the 23-man team managed
to treat nearly 5,000 patients in just 2 weeks,
operating from their base in Twan Te – a
town around an hour’s drive southwest of
Yangon. They worked out of a local hospital
but also set up mobile clinics and travelled
by boat to deliver aid to the region’s more
remote corners.
Two weeks had passed between the advent
of the cyclone and the arrival of international
aid, and the team mostly encountered
a similar post-disaster caseload to that seen
in Aceh. There were also many patients with
untreated chronic diseases such as hypertension
and diabetes who took the opportunity
to seek medical attention from the doctors.
Myanmar also presented Tyebally with
one case that he will never forget – a young
girl with ascariasis, a parasitic infection in
which worms mature in the intestine and
migrate up the respiratory tract.
“The family didn’t seem very upset
or perturbed by it. In fact she came in for
something else and oh, by the way, there are
worms coming out of her mouth,” he says.
Everywhere Tyebally has been he has
been struck by the gratitude that the people
have shown him. Sometimes he wishes he
could do more, he says, but adds that even
when nothing can be done the patients are
often glad of the sense of closure that comes
from knowing their fate.
He shrugs off the notion that his work is
heroic, describing it simply as a form of charity
work like any other.
“It takes so little for us to give to make a
big difference to the lives of the people. Not
many people want to go on such missions
because there are dangers, but I think that
the benefits – the sense of satisfaction and
the fact that you can help people – outweigh
these.”
His experiences, he adds, have helped
him not just in a professional context but also
to grow and develop as a person.
“You gain as much from the patients as
they gain from you. You see how resilient
they are in the face of suffering, and how
they can turn their lives around and get back
to their normal routines despite all that has
happened. It really makes you appreciate
what you have.”
Tyebally, it seems, is just one of those
whose lives were forever changed by that
fateful day in 2004. And next time disaster
strikes, he says, he’ll be ready to go where
the people need him.

Experts divided on prostate screening for obese men

Medical Tribune October 2008 SFXVII
David Brill

A new study from the US has prompted
debate among urologists about how
best to screen obese men for prostate cancer.
The research in BJU International concluded
that prostate-specific antigen (PSA)
screening is less effective at detecting cancers
in the obese, who typically experience
more aggressive disease than men of normal
weight.
Lead author Professor Stephen Freedland,
from the Duke University Medical
Center, US, said that obese men have lower
PSA levels and the screening threshold
should therefore be lowered accordingly.
However one of Singapore’s leading
urologists disagreed with the conclusions of
the study and said that he would not adjust
screening practices for obese patients.
Freedland et al. conducted a retrospective
analysis of two different patient databases,
identifying a total of 3,389 cases of
prostate cancer treated by radical prostatectomy
(RP) between 1988 and 2007. [BJU Int
2008 Aug 7; Epub ahead of print]
They found that high BMI was linked to
poor outcomes after RP in patients whose
prostate cancer was detected by PSA screening
but not among those whose cancer was
detected by digital rectal exam.
Worse outcomes were only evident,
however, among PSA-detected cancers that
were treated since 2000. Obesity was not
significantly associated with cancer recurrence
for those treated before 2000.
“I’m personally using a lower PSA
threshold for obese men,” said Freedland.
“Whatever you would use, it should probably
be somewhere between 10 to 20 percent
lower for obese men, depending on the
degree of obesity.”
Associate Professor Kesavan Esuvaranathan,
a senior consultant at National University
Hospital in Singapore, said however
that the data from the study do not provide
a statistically sound method for determining
the PSA cut-offs for obese men.
“I will continue to use 4 ng/ml as a
standard cut-off and a sharp increase in
PSA velocity for patients who are already
on follow-up, as triggers for a prostate biopsy.
In patients with PSA in the 4 to 10 ng/
ml range, I would also use free and/or total
PSA as a guide in management,” he said.
Esuvaranathan, who is president of the
Singapore Urological Association, said that
there may be many different causes for the
poor outcomes seen among obese men with
prostate cancer.
“It is not quite true that the year 2000
is an adequate cut-off point ... PSA testing
has been in use in the US from the early 90s
and I’d like to see the data that shows that
the intensity of screening increased at this
somewhat arbitrary time point,” he added.
Freedland said that the lower PSA values
seen in obese men could result from
their increased blood volume, which could
dilute the blood and give lower PSA measurements.
The same adjustment principle
could apply when screening for any tumorderived
cancer marker, he added.
A second paper by Freedland and colleagues
linked obesity to increased positive
surgical margins following RP, suggesting
that this surgery is more difficult in obese
patients. [BJU Int 2008 Aug 6; Epub ahead
of print]

Targeting doctors reduces falls among the elderly

Medical Tribune October 2008 P11
David Brill

Fall-related injuries among
the elderly can be reduced
through a scheme to educate
doctors, researchers from the
Yale School of Medicine, US, have
shown.
The study found that injury
rates among over-70s were reduced
by 9 percent in a region where a
clinician-targeted strategy was implemented,
as compared to an area
with no such intervention.
Fall-related use of medical
services also decreased by 11 percent
– equivalent to some 1,800
fewer hospital visits and savings
of around US$21 million in healthcare
costs.
The project, run by the Connecticut
Collaboration for Fall
Prevention (CCFP), promoted evidence
from previous clinical trials
and encouraged clinicians to incorporate
the findings into practice.
[N Engl J Med 2008;359:252-6]
Specific recommendations included
managing patients’ visual
problems, reducing their medications
and working on balance,
gait and strength training. The
information was disseminated
through various methods, including
recruiting opinion leaders
to influence colleagues, and
performing outreach visits and
demonstrations at the participating
facilities.
Dr. Noor Hafizah Ismail, a
Singapore-based falls prevention
expert, said that the CCFP strategy
would be considered should
an intervention to reduce falls in
the community be undertaken in
future, but added that the data
would need to be carefully assessed
first.
“The results do suggest there is
some benefit in introducing practice
changes in primary healthcare
givers, but it is hard to prove that
there is cause and effect as there
was no direct follow-up of patients
who had the intervention,” she
said, noting that patient outcomes
in the study were assessed indirectly
using a statewide hospital
database.
The Falls and Balance Clinic
at Tan Tock Seng Hospital, where
Ismail is a senior consultant, currently
adopts an approach similar
to recommendations in the American
Geriatric Society guidelines,
she said.
The CCFP intervention was
introduced (in a nonrandomized
fashion) to a single region of Connecticut
between 2001 and 2004.
Clinicians from a range of disciplines
– including primary care,
emergency departments, outpatient
rehabilitation and home care
– were invited to participate.
The rate of serious fall-related
injuries in the intervention region
dropped from 31.9 per 1,000 person-
years prior to the intervention
(1999 to 2001) to 28.6 afterwards
(2004 to 2006). In a region where
the strategy was not implemented,
the comparable injury rates were
31.2 and 31.4.
Fall-related use of medical services
in the intervention region increased
from 70.7 to 74.2 per 1,000
person-years over this period,
whereas in the usual-care region
the rate rose much more sharply,
from 68.1 to 83.3.
The effects of the CCFP strategy
on both injury rates and medical
service usage persisted for a
further year after conclusion of the
evaluation period.
Fall-related injuries are a common
cause of morbidity among the
elderly and are estimated to account
for some 10 percent of emergency
department visits in those
over 65.
“Doctors need to be vigilant in
identifying patients at risk of falls,”
said Ismail, adding that “the strongest
predictor of future falls is a
previous fall history.”