Professor Brian Andrews NEJM Recommendations for Medical Students and
Tutors
Week of the 31st December 2015 (#23)
University of Notre Dame Australia
(Fremantle Campus)
Occasional Editorial Comments
None
MUST READ SECTION
None
Articles Recommended for Medical Students
EDITORIAL
Simple, Effective, but Out of Reach? Public
Health Implications of HCV Drugs
The data is now in: hepatitis C is a curable viral infection
but the cost is prohibitive for most individuals, both in the US and Australia.
The cost has major public health implications.
There are three
articles in this issue of the Journal (and an earlier article in the Journal in
2014 using sofosbuvir and ribavirin) indicating that a twelve week course of
sofosbuvir (a NS5B inhibitor) and velpatasvir (a NL5A inhibitor) combined in a
single tablet daily dose is effective at eliminating the virus (all genotypes
1-6, including the resistance genotype 3) in up to 98% of patients and that the
addition of ribavirin to this regimen only increased adverse effects without
adding any therapeutic benefits. The main adverse effects of this combination
were headaches, fatigue, nausea and insomnia.
The cost in the US for
a twelve week course is between US $83,000 and $153, 000!!! Double that for a
24 week course or if the course needs to be repeated. This studies only
describe cure (absence of viral RNA) at 12 weeks and we await the long term
results, though word on the street is that the cure may well be sustained in
most patients after one course.
Recommended learning:
Hepatitis C,
epidemiology, virology, pathology and sequelae, modes of transmission and
treatment.
Review the hepatitis C
non-structural proteins NS5B and NS5A and their roles in viral replication:
these are the targets of the two drugs sofosbuvir and velpatasvir respectively
which you will all be using in the future to treat hepatitis C.
Perspective
Value-Based Cancer Care
Perspective
Measuring the Value of Prescription Drugs
It is only appropriate
that these two Perspectives follow
the articles on the cost of curing hepatitis C.
The first relates to
the cost of newer drugs to treat cancer and the second to evaluating the value
of prescription drugs generally but focusing on costs, namely how are the
benefits and the cost of the drug reconciled?
With respect to newer
cancer drugs, virtually none offer a cure, with some only improving the
disease-free survival but not overall survival. In the US, usual costs for new
drugs can range from $10,000 to $30,000 per month, with some newer check-point
inhibitor combinations costing up to $100,000 per month. Granted this is
usually not long term therapy like biologics used in rheumatoid arthritis, but
the cost is still impossible for most of us to seriously appreciate, until we
or one of our patients require the treatment.
Several major
organizations in the US (documented in the Perspectives)
have attempted to define various arbitrary criteria by which each therapy can
be evaluated and a scaled therapeutic value determined.
Memorial Sloan Kettering Hospital in New York has developed a web site (www.DrugAbacus.org) whereby the physician and the patient can determine an
appropriate cost for the drug based on the analysis of various parameters which
can provide + or – financial determinants.
The Institute of Medicine has defined six
value criteria:
The first three are
generally measured in clinical trials:
1.
Safety
(toxicity)
2.
Effectiveness
(clinical benefit)
3.
Efficiency
(cost)
while the second three
are infrequently reported:
4.
Timeliness
5.
Equity,
and
6.
Patient-centeredness
The second Perspective expands on the first but
considers cancer and non-cancer drugs, including the drugs for hepatitis C
cure.
Suffice it to say, an
attempt at the National level in the US is being made to develop
semi-quantitative, partly evidence based assessment parameters to reconcile
spirally cost increases with “total benefit.”
Important Articles Related to Mechanisms of Disease and
Translational Research
Check out the
neuroscience in the Narcolepsy review
Other areas which should be of interest to medical students
Perspective
Report from Paris
This is an
interesting, easy read from personal perspectives on how French physicians
dealt with the terrorist shootings in Paris in November 2015 and the public
health implications.
REVIEW
ARTICLE
Narcolepsy
http://www.nejm.org/doi/full/10.1056/NEJMra1500587
This an excellent review
on a subject that I believed, before I read the article, was rare and probably
had very little to add to my knowledge.
Suffice it to say I became
fascinated by an area about which I knew virtually nothing.
The review provides an
excellent neuroscientific update on sleep, particularly the role of orexin A
and B in sleep, REM, narcolepsy and cataplexy. Of note, narcolepsy has the highest association
between HLA and disease at 98% (HLA-DQB1 06:02)
(This is very closely followed by birdshot chorioretinopathy associated with
HLA-A29 in 80 - 97.5% and our ophthalmology colleagues may have difficulty
relinquishing this record). There follows a discussion about the gene
implications, infection and the immune response leading to an autoimmune loss
of lateral hypothalamic cells which produce orexin. There is a discussion of
drug therapy used to treat narcolepsy and will provide MED400 students a chance
to review a range of psychoactive medications again.
EDITORIAL
Choosing Benefits while Balancing Risks (of Home Birthing)
http://www.nejm.org/doi/full/10.1056/NEJMe1511068
This is an Editorial
describing the pros and cons of home birthing which accompanies i) a study from
Portland, Oregon indicating that the perinatal mortality from in-hospital
births was 1.8 versus 3.9 in out-of-hospital births per 1000 deliveries and ii)
a point-counterpoint clinical scenario based discussion in which the patient described
may do well with a home delivery.
The following points
can be made:
i)
Perinatal
mortality, while low in both groups, is clearly increased in home births and
highest in nulliparous patients (in the UK where 8% of women elect to deliver
at home, where home delivery is more streamlined than in Australia and the US,
50% of women ended up delivering in hospital)
ii)
A major argument for home deliveries revolves
around the higher CS rate in in-hospital deliveries. In the US, and also
Australia, the rate of C sections in in-hospital deliveries is higher with the
US in-hospital CS delivery rate around 25%
compared with 5% of planned home deliveries.
iii)
Epidural
anaesthesia is not available in home deliveries while it is in most hospitals,
urban and rural in Australia. It’s like the old days when you had major dental
work done without local anaesthesia: who wants this?
iv)
There is a
higher frequency of PTSD in women who deliver at home due to the traumatic
experience in some patients (source Lincoln Brett)
v)
Hospitals are becoming more “consumer
friendly”, even water deliveries, and increased instruction and initiation of
breast feeding. Surely the CS rate can be lowered, though clearly the patient
can indicate to the obstetrician that they do not want a CS unless really necessary.Editorial comment: It would be
interesting to determine if there is any correlation between women who elect
for home delivery and those who elect not to immunize their children!
vi)
There is
no doubt that women who elect to have a home delivery are taking a risk with
the child’s future and they have to decide if they will live with the permanent
consequences if the delivery goes bad, even though the risk is small.
Ethical
question: If a pregnant women is
strongly advised to have a hospital delivery due to concerns about risks to the
baby but elects to have a home delivery and the child suffers from permanent
long term damage, should Society (or insurance) be responsible for the
long-term cost?
