Professor
Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week
of 28th July 2016 (#53)
University
of Notre Dame Australia (Fremantle Campus)
Occasional Editorial Comment
If you open the bog at the bottom of the review, you will find the format is much easier to read.
Must Read or Save Articles
REVIEW ARTICLE
Treatment
of Opioid-Use Disorders
Opioid-use
disorders are common, but most physicians are not trained to recognize and
treat them. This review outlines a general approach to identifying and treating
these disorders.
This is a must save article. I recommend you store this
hyperlink for future use.
This Review Article offers an excellent table (Table 1)
which reviews the diagnostic criteria for an opioid-use disorder based on DSM-5.
The remainder of the article focuses on the specific treatments of these
disorders and the subsequent approaches to rehabilitation and maintenance. The
treatment schedules are very detailed, but the general information needed can
be obtained from reviewing the tables and reading the overview of the problem
which is provided in the first five paragraphs of the article.
Articles Recommended for Medical Students
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL
Case
23-2016 — A 46-Year-Old Man with Somnolence after Orthopedic Surgery
A
46-year-old man had worsening somnolence 1 day after replacement surgery with a
femoral endoprosthetic implant. Fever, tachycardia, hypertension, and tachypnea
developed, and examination revealed somnolence, gaze deviation, rigidity, and
hyperreflexia. A diagnosis was made.
This patient developed deterioration in mental function
14 hours after significant orthopaedic surgery.
The discussion focuses on the effects of medication and the cerebral fat
embolism syndrome. A diagnostic MRI of the head is illustrated.
Perspective
Incorporating
Indications into Medication Ordering — Time to Enter the Age of Reason
Beyond
the five “rights” for safe medication ordering and use — the right patient,
right drug, right dose, right time, and right route — a sixth element must be
correct: the indication. Indications based prescribing can improve medication
use in multiple ways.
Medical students in Australia are routinely taught the
6Rs of prescribing, with the 6th R representing the right indication. In
hospital charts there is a place to document the prescribing indication thought
this appears to be infrequently filled out. There is no place for drug
indication on routine prescriptions but it is a requirement for an Authority Script.
IMAGES IN CLINICAL MEDICINE
Dysphagia
Lusoria
A
46-year-old otherwise healthy man presented with a 1-year history of occasional
dysphagia to solid foods that was not accompanied by weight loss. A
barium-swallow examination revealed posterior oblique indentation of the
proximal esophagus.
This is an extremely unusual cause of dysphagia. However it is another cause for external compression
of the oesophagus for those who like lists of rare disorders.
Recommended
learning:
Review the causes and management of dysphagia. Particularly review the case of dysphagia in
the MED300 weekly clinical cases.
IMAGES IN CLINICAL MEDICINE
Herpes Zoster
Mandibularis
A
70-year-old man presented with a 2-day history of facial edema, rash along the
left lower jaw, and plaque that covered two thirds of the left half of his
tongue. He had had pain, otalgia, and glossodynia 3 days before the outbreak of
the rash.
This is an excellent clinical photograph of a patient
with Herpes zoster involving the
mandibular branch of the trigeminal nerve. Note the typical facial involvement
together with involvement of the anterior 2/3 of the tongue via the lingual
nerve. Vesicles may also have been present on the tympanic membrane which is
innervated by the auriculo-temporal branch of the mandibular nerve.
Recommended
learning:
Review the anatomy of the trigeminal nerve (V), in
particular the motor and sensory innervations and the clinical examination of
the trigeminal nerve.
EDITORIAL
Von
Willebrand Factor — A Rapid Sensor of Paravalvular Regurgitation during TAVR?
ORIGINAL ARTICLE
Von
Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement
In
patients undergoing transcatheter aortic-valve replacement, defects in
high-molecular-weight von Willebrand factor multimers and the closure time with
adenosine diphosphate (a measure of hemostasis) were closely correlated with
postprocedural aortic regurgitation.
Before reading the Editorial
and the study, I strongly recommend watching the accompanying video which
describes the normal biological function of von Willebrand factor (vWF), as
well as the procedure transcatheter aortic-valve replacement (TAVR). I also suggest you review the YouTube presentation.
The premise for this study is that vWF under normal
shear stress circulates as partially unfolded, elongated multimers with exposed
binding sites for platelets and collagen. With active binding, the
zinc-dependent metalloprotease ADAMTS13 cleaves vWF into appropriate sizes to
optimize the clotting process. (In most cases of acquired TTP, an autoantibody
is directed against ADAMTS13).
Under situations of increased shear stress and the
generation of excessive turbulence, such as valvular heart disease (in this
study patients with severe aortic stenosis), hypertrophic obstructive cardiomyopathy
(HOCM), circulatory-assist devices, and extracorporeal membrane oxygenators,
high-molecular weight vWF multimers are cleaved resulting in acquired vWF
deficiency and the potential for bleeding.
The hypothesis generated for this study involves TAVR
for treating severe aortic stenosis. If the valve is placed successfully, only minimal
to mild paravalvular aortic regurgitation (AR) should result. Moderate to severe paravalvular AR is
described in 12% of patients with the first generation of the valve and in 4%
with the second generation.
With severe aortic stenosis (Figure 2 in study), the
high MW vWF multimers represent approximately 61% of vWF present in pooled
normal human plasma and with subsequent correction of the AR, the percentage
increases to 100% within five minutes. A similar parallel improvement in
clotting test (CT-ADP (closure-time with ADP) is seen with correction of the
paravalvular AR.
The mortality rate at one year in those undergoing TAVR
is twice as high in those patients with residual moderate to serve resultant
paravalvular AR (Figure 4).
Important Articles Related to Mechanisms of Disease and
Translational Research
None
Other Articles which should interest medical students
ORIGINAL ARTICLE
Liraglutide
and Cardiovascular Outcomes in Type 2 Diabetes
Patients
with type 2 diabetes and high cardiovascular risk were assigned to receive
either the glucagon-like peptide 1 analogue liraglutide or placebo. The rate of
first occurrence of cardiovascular death, nonfatal MI, or nonfatal stroke was
lower with liraglutide.
ORIGINAL ARTICLE
Empagliflozin
and Progression of Kidney Disease in Type 2 Diabetes
Among
patients with type 2 diabetes at high cardiovascular risk, the rates of
progression of kidney disease and clinically relevant renal events were lower
among patients receiving empagliflozin, a sodium–glucose cotransporter 2
inhibitor, than among those receiving placebo.
EDITORIAL
Cardiac
and Renovascular Complications in Type 2 Diabetes — Is There Hope?
These two articles describe placebo-controlled, double
blind trials involving patients with type 2 diabetes mellitus who were at high
risk for cardiovascular events. In general, the first study used liraglutide, a
glucagon-like peptide 1 agonist, to determine the effects of the drug on limiting
macrovascular complications of diabetes.
The second article focussed on the prevention of microvascular
complications of diabetes in the kidney using empagliflozin, a sodium-glucose
cotransporter 2 (SGLT2) inhibitor. Both drugs improved diabetic control over placebo.
In the first
study, liraglutide was added to standard diabetic therapy (4688 patients
received liraglutide and 4672 placebo) and patients were followed for a median
time of 176 weeks after randomization. Moreover in this group, there was a
significant reduction in death from cardiovascular causes (p=0.007) and death
due to any cause (p=0.02) (Figure 1). There were no differences in nonfatal
myocardial infarction and strokes or hospitalization for heart failure. When
the primary composite outcome was subsequently reanalysed as an expanded
composite outcome (Table 1), where coronary revascularisation and
hospitalization for either unstable angina or heart failure were added to death
from cardiovascular causes, or nonfatal MI or stroke, the p value fell from
0.01 to 0.005.
In the other study using empagliflozin, a total of 7018
patients were randomized to receive empagliflozin (4685 patients) or placebo
(2333 patients) and further broken down into those with baseline creatinine
clearances less than (25.5%) or greater (74.5%) than 60 ml/minute, with a
minimum of 30 ml/minute. Two doses of empagliflozin studied. Overall,
empagliflozin was superior to placebo in slowing the progression of kidney
disease (Figure 1) and in significantly improving seven renal outcome measures
(Figure 2). Empagliflozin resulted in a fall in eGFR with both doses over the
first four weeks of the 192 week study and then rose, such that by 80 weeks,
eGFR was higher than placebo over the remainder of the study.
Both of these studies were reviewed in the accompanying
Editorial. All patients studied had extensive
cardiovascular disease, although in the liraglutide study eligible patients
less than 60 years of age had to have a coexisting cardiovascular condition and
if 60 or older, one cardiovascular risk factor would suffice (? effect of age).
Both studies were large, expensive, and
multicentre and employed patient populations which were similar, though not
identical. As summarized in the Editorial,
it appears that both therapies add to the management of type 2 diabetic
patients with a high risk for cardiovascular events with more studies and drugs
to come. The problem I have with all of these studies is how to reconcile the
differences in study design, the varying inclusion and exclusion criteria and
the number of similar drugs coming on the market. I wonder where SGLT1
inhibitors, that reduce glucose absorption from the intestine, will fit into
the treatment of type 2 diabetes mellitus.
Recommend
learning:
Review the mechanisms of action and the underlying
physiology of the groups of non-insulin therapies used to treat diabetes
mellitus:
1. Sulfonlyureas
3. Thiazolidinediones
4. DPP-4
inhibitors
5. Glucagon-like
peptide-1 analogues
6. Sodium-glucose
cotransporter 2 inhibitors (SGLT2 inhibitors) (http://www.nejm.org/doi/full/10.1056/NEJMcibr1506573)
7. Acarbose
By the end of MED200, you should have a working
knowledge of the medication groups used to treat diabetes mellitus, not just
metformin and the sulfonylureas.
