Professor Brian Andrews NEJM Recommendations
for Medical Students and Tutors
Week of 14th April 2016 (#38)
University of Notre Dame Australia (Fremantle
Campus)
Occasional Editorial Comment
None
Must Read Articles
CLINICAL PRACTICE
Diabetic
Sensory and Motor Neuropathy
Painful
peripheral neuropathy is common among patients with diabetes mellitus.
Management includes lifestyle interventions and pharmacologic therapy to
control cardiovascular risk factors and medications to control pain.
This is a superb, easily read clinical review on diabetic
neuropathy which should be read by all medical students, particularly MED300
and MED400 students. The hyperlink should
be saved for future reference. It provides the answers to all of the questions
you did not know you needed to ask in order to understand this area.
Diabetic neuropathy represents a common clinical problem which is
well outlined in the review. Key clinical points are tabulated. Evidence based
diagnosis and evaluation, clinical management and pharmacotherapy are also well
described. There is a detailed table (Table 2) of drugs, their classes, adverse
events, and the number of patients needed to treat (NNT) to produce 50%
improvement in a single patient. The review discusses the symptoms and signs
associated with large and small nerve fibre damage (Table 1).
A pearl I gleaned from Goodman and Gilman’s Textbook of
Pharmacology many years ago was the use of oral 4% pilocarpine eye drops (2
drops in water bid) to counteract the anticholinergic side effects,
particularly due to the tricyclic antidepressants which have one of the best
NNPs in treating diabetic neuropathy.
Recommended
learning: Review the common causes of peripheral neuropathy, focusing on
diabetic neuropathies.
Must Save Articles
The above review article on diabetic neuropathy
Articles Recommended for Medical Students
IMAGES IN CLINICAL MEDICINE
“Frog
Sign” in Atrioventricular Nodal Reentrant Tachycardia
There is an interesting video of fast regular jugular venous cannon
A waves which disappear with abrogation of the tachyarrhythmia by carotid sinus
massage. There is an accompanying ECG of the arrhythmia and a good description
of the mechanism. The term “frog sign” is not generally used. Just use the common physiologically descriptive
term “cannon A waves.”
Recommended
learning: Review the physiology of the jugular venous pulse wave and the
conditions that can be diagnosed using this valuable clinical sign.
EDITORIAL
Fusion
for Lumbar Spinal Stenosis — Safeguard or Superfluous Surgical Implant?
The two articles (http://www.nejm.org/doi/full/10.1056/NEJMoa1513721, http://www.nejm.org/doi/full/10.1056/NEJMoa1508788) in
this issue of the Journal are well
summarised together with the current literature in the accompanying Editorial.
In essence, the studies indicate that for patients with symptomatic
lumbar spinal stenosis with or without degenerative spondylolisthesis, the
addition of spinal fusion to decompressive surgery (laminectomy and/or foraminotomy)
did not improve clinical outcomes significantly.
In the Swedish study of 247
randomized patients, spinal fusion did not improve clinical outcomes at 2 and 5
years (see inclusion and exclusion criteria in Table 1). Both groups had a similar frequency of repeat
lumbar spine surgery (21% versus 22%). Spondylolisthesis
is defined as greater than 3 mm slippage.
In the US study involving 66
patients randomized at multiple centres, addition of spinal fusion showed only a
minimal improvement in outcomes. There were more repeat operations in the
decompression alone group (34% versus 14%, but with a barely significant p
value of 0.05). Spondylolisthesis
defined as grade 1 with slippage between 3–14 mm, although patients with >3
mm instability at the listhesis were excluded.
Although there were some differences in the outcome measures, the
overall data failed to show an outcome advantage with the addition of spinal
fusion surgery over decompression surgery alone. With the addition of fusion
surgery, there was more blood loss at surgery and longer hospital stays.
Recommended
learning: The indications for referring a patient with low back pain to a
surgeon and the expected results of the surgery.
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL
Case
11-2016 — A 12-Year-Old Boy with Malaise, Fevers, Abdominal Pain, and Pallor
A
12-year-old boy presented with a 1-month history of fever and abdominal pain.
Three months earlier, he had traveled to the Dominican Republic. Laboratory
evaluation revealed anemia and an elevated C-reactive protein level. Diagnostic
tests were performed.
This is an interesting case of a boy presenting with abdominal pain
who was found to have iron deficiency anaemia. The case is discussed from the
perspectives of both an ED physician and of a paediatrician.
When you come across a new drug, in this case chemotherapeutic
agents, I recommend that you store the drug information in Wikipanion. This
data base will allow you to search for the drug and store the information
(class, basic biology, MOA, drug interactions, and hyperlinks) in folders
designated for specific drug classes.
Recommended
learning: For MED400, broad immunopathological classification of lymphomas,
including Hodgkin’s lymphoma, as well as the clinical presentations of
Hodgkin’s lymphoma.
INTERACTIVE MEDICAL CASE
Eye of
the Beholder
This
interactive feature presents the case of a 47-year-old man with swelling around
his left eye and a sensation of tightness in his throat. Test your diagnostic
and therapeutic skills at NEJM.org.
This interactive case involves a patient presenting with
periorbital swelling, pharyngeal-upper oesophageal dysphagia, and hoarseness.
This facilitates clinical reasoning and the development of a differential
diagnosis.
Important Articles Related to Mechanisms of Disease and
Translational Research
CLINICAL IMPLICATIONS OF BASIC RESEARCH
Obesity
— On or Off?
A recent
genetic study of body-mass index, adiposity, and gene expression in mice
provides evidence of an epigenetic mechanism of susceptibility to obesity.
Obesity is the major disease epidemic in developed countries.
Several weeks ago, a basic science article was reviewed which showed that mice
exposed to sustained cold developed inducible beige fat cells which readily
metabolised fatty acids. These mice experienced not only weight loss but also a
reduction in insulin resistance. This property could be transferred to mice
exposed to normal temperatures by transferring to them the intestinal
microbiome from the cold exposed mice.
Today a further mouse study is reviewed (Dalgaard et al, Cell 2016)
in which a mutation in the Trim28 transcription factor leads to obesity
associated with a doubling in the number of adipocytes in the mouse. A
functional Trim28 gene down-regulates a cluster of genes (IGN1 cluster) which
normally function as an “on” switch for obesity in the mouse. Mutations in Trim
28 in mice (or reduced functional levels of Trim28 found in human adipose
tissue) lead to up-regulation of IGN1 and weight gain.
These studies refocus on a possible hereditable component of obesity,
in particular epigenetic environmental factors such as the ambient
temperature. In this series of
experiments (see review for details), no differences in DNA methylation were
observed.
A common response among students is, “so what.” If obesity can be managed by education, self-control,
elimination of processed foods, reduced portion size and fat intake, exercise,
and if necessary judicious use of bariatric surgery. Why is this study
important? There is some validity to that reaction, however, if specific gene
clusters involved in overeating and/or fat metabolism can be identified and
modified by epigenetic factors e.g. cold exposure, drugs, this will be a
massive windfall for pharmaceutical companies and will provide a more
scientific physiological-genetic basis for weight loss.
Other Articles which should interest medical students
Perspective
The
Virtues and Vices of Single-Payer Health Care
Democratic
presidential candidate Bernie Sanders has made Medicare for All a centerpiece
of his platform, reopening an old debate. What are the virtues and vices of
single-payer reform? Is it a realistic option for the United States or a
political impossibility?
This Perspective provides
a historical perspective for evolution of the Health Care System in the US, in
particular the political machinations and the role of special interest groups
in determining policy. It also discusses the current election cycle and how election
promises might realistically play out with health care policy.
Perspective
What Do
I Need to Learn Today? — The Evolution of CME
As the
U.S. continuing medical education system evolves, it will help if physicians
are more self-aware, educators create more powerful learning environments,
regulators promote innovation, and health care systems recognize the strategic
value of education in driving change.
This review focuses on the role of CME in the US (CPD in Australia)
in the accreditation of clinicians for licensure and for regulatory and specialty
board requirements. It addresses the issue of regulatory authorities
recognising the value of education in driving clinical practice and quality
improvement as well as the promotion of life-long learning.
Perspective
The
Public and the Gene-Editing Revolution
Polls
conducted over recent decades give a sense of what the U.S. public thinks about
gene therapy and gene editing in adults, children, and human embryos or
germline cells, as well as of whether and for what reasons Americans would
consider undergoing genetic testing.
This Perspective reviews
the results of polls taken of the US public regarding the recent advances in
gene-editing and their application. The results of polls on public attitudes
about genetic testing are represented in Table 1. In general, “the public favors gene therapy
for clinical use in patients with serious diseases. The majority do not support
gene editing in human embryos or germline cells, but the level of opposition
varies depending on its goals,” specifically if used for eliminating disease
(more in favour) or altering phenotype or personality (strongly opposed).
IMAGES IN CLINICAL MEDICINE
Metronidazole-Associated
Encephalopathy
A
58-year-old man with cryptogenic cirrhosis was admitted to the ICU with
confusion after a fall. He had been taking metronidazole for C.
difficile infection. MRI of the brain showed a fluid-attenuated inversion
recovery (FLAIR) signal in the dentate nuclei of the cerebellum.
As the cause of the confusion in this patient is unclear and is associated
with an abnormality in the dentate nucleus of the cerebellum, the best course
of action is to admit you do not know the cause and to consult the literature.
This rare side effect of metronidazole can be similarly stored in your brain
stem.
Recommended
learning: Review the pharmacology of metronidazole, its clinical indications
and its common side effects.
SPECIAL REPORT
A
Proactive Response to Prescription Opioid Abuse
The FDA
has committed to working with other agencies, health care providers, industry,
and patients and families to deal proactively with the opioid abuse crisis,
while safeguarding appropriate access to vitally important pain medications for
the patients who need them.
This is a further publication on the concern US regulatory bodies
(FDA, CDC, and the National Academy of Medicine) have on prescribing and
overuse of narcotics for chronic pain and the use of these prescribed drugs by
other parties. This is a difficult balancing act between patients in pain not being
compromised by lack of availability of pain relief versus the inappropriate use
of opiates leading to misuse, addiction, and drug overdose.
Table 1 reviews the
issues and the FDA responses. The availability of naloxone in conjunction with
opioids has been a major advance. Further, OTC naloxone and IM auto-injectors
and intranasal naloxone for opioid overdose should be considered. As mentioned
in earlier blogs, this problem is not unique to the US.
ORIGINAL ARTICLE
Effect
of Avoidance on Peanut Allergy after Early Peanut Consumption
A
previous trial showed that early consumption of peanuts resulted in fewer cases
of allergy than did avoidance. In a follow-up study, all participants avoided
peanuts from 5 to 6 years of age; those who had eaten peanuts in early life
retained the ability to do so.
An earlier study on the same cohort over 60 months compared the introduction
of peanuts to the diet during the first 11 months of life versus avoidance of
peanuts in the diet for 60 months after birth. Children who consumed peanuts
over 60 months had an 81% reduction in peanut allergy at 5 years of age over
those who had not been given peanuts.
The current study involves the same two groups who were followed
for a further 12 months in which peanuts were withheld in the earlier peanut
consumption group and with maintained avoidance in the other. The results are
best appreciated in Figure 3. In essence, those who consumed peanuts for the
first 60 months had fewer manifestations of peanut allergies (positive peanut
wheal, peanut specific IgE and arah2 specific IgE) at 72 months (4.8% versus
18.6%) and higher levels of peanut-specific IgG4 and higher levels of peanut-specific
IgG4:IgE ratios. Overall, there was no increase in the prevalence at 72 months
of peanut allergy in the group administered peanuts for the first 60 months and
then stopped for the subsequent 12 months.
How long this state will last is unknown, though long term follow-up is
undoubtedly planned.
