Professor
Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week
of 16th February 2017 (#82)
University
of Notre Dame Australia (Fremantle Campus)
Occasional Editorial Comment
None
Must Read Articles
ORIGINAL ARTICLE
Bariatric
Surgery versus Intensive Medical Therapy for Diabetes — 5-Year Outcomes
Five-year
data showed that among patients with type 2 diabetes and a BMI of 27 to 43,
bariatric surgery plus intensive medical therapy was more effective than
intensive medical therapy alone in decreasing or resolving hyperglycemia, even
among those with a BMI of less than 35.
This is an important study that compares the results of
intensive medical therapy (IMT) alone versus IMT plus bariatric surgery. In the study, an equal number of patients had
a sleeve gastrectomy or gastric bypass/Roux-en-Y. In Australia, most surgeries
are now sleeve gastrectomies, or the correction of complications from earlier
gastric banding.
Overall the results at five years demonstrate that IMT
+ surgery is clearly superior to IMT in all parameters (see Table 1, Figure 1).
It should be noted that the study was conducted at three pre-eminent institutions
(Harvard, the Cleveland Clinic, and Baylor) where “optimal’ IMT is the type of
medical therapy one could only strive to attain in most sites in the US or
Australia where diabetes is managed. In other words, optimal IMT is very
difficult to achieve in other sites, probably making the results seen with
bariatric surgery more significant. In
the 87 patients who had bariatric surgery it was remarkable that only one
patient during the study had significant complications requiring revision
surgery. Adverse events are documented
in Table 2. The long-term data on renal and ophthalmological complications is awaited.
Articles Recommended for Medical Students
Perspective
Addressing
the Fentanyl Threat to Public Health
Governments
can address widespread fentanyl-related deaths by pursuing a harm-reduction
approach involving increased transparency for users and public health and
public safety organizations, harm-reduction policing, expanded naloxone use,
and targeted treatment.
This Perspective outlines the public health and medical
complications following the introduction of fentanyl as an additive to heroine
or non-prescribed morphine. Fentanyl, a potent synthetic opioid, is relatively
easy and cheap to produce. Fentanyl has
been involved in 41% of deaths from morphine overdose in the US from 2012
through 2014. In these situations,
naloxone needs to be administered earlier and at escalated doses in patients
where both fentanyl and morphine are combined, rather than with morphine alone.
This will become an increasing problem in Australia as fentanyl is added to
street morphine or heroine.
SPECIAL ARTICLE
Opioid-Prescribing
Patterns of Emergency Physicians and Risk of Long-Term Use
In
this analysis involving Medicare patients seen in emergency departments, rates
of opioid prescribing varied widely among emergency physicians. Patients seen
by physicians who prescribed opioids more frequently were more likely to use
opioids on a long-term basis.
This is a study which attempts to quantify the risks of
long-term use of opioids (180 days or more) in patients presenting to the ED in
pain and who receive opioids for relief of the pain. Patients, who have not received opioids
within previous six months and who received treatment within the same hospital
from high-intensity opioid prescribers were more likely to be taking opioids at
six months than if they had initially visited a low-intensity opioid prescriber.
This is a complex, well controlled and difficult study to undertake and must be
read carefully. Rates of opioid
prescribing appear to vary by a factor of three within the same hospital. The
population studied is an older Medicare population in the US, thus rates of
long-term opioid use following a single ED visit for pain may differ from a
younger population who do not have the comorbid diseases seen in the older
population (Table 1).
IMAGES IN CLINICAL MEDICINE
Gas
in the Left Atrium and Ventricle
A
60-year-old man with clinically significant coexisting cardiac conditions
presented with chest pain. Shortly after his initial admission, he suddenly
collapsed. Scans showed air in his left ventricle.
The moral of the story is to pick a cardiologist who
does the most procedures with the lowest frequency of adverse events.
Important Articles Related to Mechanisms of Disease and
Translational Research
None
Other Articles which should interest medical students
ORIGINAL ARTICLE
Survival
and Neurodevelopmental Outcomes among Periviable Infants
This study assessed survival and neurodevelopmental outcomes among infants born at 22 to 24 weeks of gestation, as measured at 18 to 22 months of corrected age, and showed that the rate of survival without neurodevelopmental impairment increased between 2000 and 2011.
EDITORIAL
Neonatal
Intensive Care — The Only Constant Is Change
This is a study that addresses mortality and
neurodevelopmental outcomes at 18 – 22 months (corrected age) in infants born
between 22 - 24 weeks of gestation in three time periods (2000-2003, period 1; 2004
– 2007, period 2; and 2008 – 2011, period 3). It was conducted at 11 centres in
the US and was NIH funded.
In infants born at 22 weeks in whom no active treatment
was provided (76 -79% over the three periods), there was no change in the death
rates (95-98%) or in the number of surviving infants with or without
neurocognitive defects (NCDs) over the three periods (Table 2).
In infants born at 23 weeks, in whom active treatment
was provided in 70 – 73%, the death rate did not change significantly (76% in
period 3 and 80% in periods 1 and 2), although the number of infants surviving
without NCDs increased from 7% in period 1 to 13% in period 3 (p = 0.005).
However, in infants born at 24 weeks in whom active
treatment was provided (94 – 96%), the death rate fell from 51% to 44% (p
<0.001) and the number of infants surviving without NCDs rose from 28 to 32%
(p = 0.007) without any significant change in the percentage of infants born
with NCDs over the three time periods. Thus, the improvement in mortality was
not associated with an increased percentage of infants born with NCDs.
The study is analysed in the accompanying Editorial.
Advances have occurred with improvements in perinatal and neonatal care. The
limitations of the study are discussed, as are comparative studies in other
countries together with the philosophy of care provided at these gestational
ages.
ORIGINAL ARTICLE
Baricitinib
versus Placebo or Adalimumab in Rheumatoid Arthritis
In
a phase 3 randomized trial of 1307 patients with rheumatoid arthritis receiving
background methotrexate, the oral JAK1 and JAK2 inhibitor baricitinib showed
superior efficacy to placebo and to the anti–tumor necrosis factor α monoclonal
antibody adalimumab.
Since the introduction
of the biological agent etanercept (Enbrel) by Wyeth, rheumatologists have learned
how to use methotrexate successfully in rheumatoid arthritis. Prior to this study, rheumatologists were
afraid to use the current therapeutic doses of methotrexate, unlike our
oncology colleagues, because of fears of producing bone marrow failure or cirrhosis. The Wyeth funded study compared Enbrel directly
with methotrexate, using an initial mean methotrexate dose of 17.5
mg/week. Rheumatologists were stunned by
the effectiveness of methotrexate, as well as the absence of any significant
adverse effects. Wyeth was also stunned by the 12-month data which showed that
methotrexate in these doses was as effective at treating RA as their new agent
Enbrel. However, there is a happy ending for Wyeth, in that the 2-year data
showed that Enbrel fared statistically better than methotrexate alone in
treating active RA. This has been the most important study of therapeutics in
RA (funded would you believe by a pharmaceutical company), in that it taught
rheumatologists how to use methotrexate and introduced the first biological
agent in the treatment of RA. We have come a long way since then in treating
RA.
The current study introduces the new oral agent
baricitinib, an inhibitor of the intracellular Janus kinases, JAK1 and JAK2. Patients in this 52-week study (1307
patients, phase 3, double-blinded, placebo- and active-controlled trial of
moderate to severe active RA who had failed to respond to methotrexate) were
maintained on methotrexate (placebo) while other groups were treated with methotrexate
together with either adalimumab (a monoclonal antibody against TNFa, standard
therapy) or the study drug, baricitinib.
All data points studied, including radiological
progression, over the 52-week study (see Figure 1) showed that baricitinib +
methotrexate statistically outperformed adalimumab + methotrexate. The withdrawal rate was slightly greater with
baricitinib than adalimumab and adalimumab produced a greater increase in
haemoglobin level than baricitinib (Table 2).
Recommended learning: Review the basic groups of drugs used to
treat rheumatoid arthritis.
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL
Case
5-2017 — A 19-Year-Old Man with Hematuria and a Retroperitoneal Mass
A
19-year-old man presented with a 2-day history of hematuria, without pain,
after hiking. Imaging revealed a well-circumscribed 4.6-cm retroperitoneal
mass. A procedure was performed.
This CPC involves the differential diagnosis of a South
American patient presenting with painless haematuria. He was found to have a mass which was anterior
and medial to the right psoas muscle, anterior to the right common femoral
artery and which produced mild medial deviation of the ureter. In the
discussion, the cause of the haematuria was attributed to either vigorous
exercise or the close proximity of the mass to the ureter (I do not really
understand the pathology unless there was invasion of the thick muscular wall
of the ureter). Why did the patient not also have a cystoscopy or tuberculin skin
test/interferon g release assay and culture/PCR of urine for TB?
New and Novel Therapies
ORIGINAL ARTICLE
Osimertinib
or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer
In
a randomized trial involving patients with non–small-cell lung cancer with
mutant EGFR (T790M) in whom a tyrosine kinase inhibitor had failed, osimertinib
was associated with significantly longer progression-free survival than
platinum therapy plus pemetrexed.
Patients with advanced non-small cell lung cancer and
sensitizing mutations of the epidermal growth factor receptor generally respond
well to first -line EGFR tyrosine kinase inhibitors. After 9 – 13 months, the majority recur with
60% developing a new EGFR resistance mutation inhibiting optimal binding of the
first-line EGFR inhibitor. Osimertinib binds to both the sensitising and
resistance EGFR mutations, again inhibiting down-stream signalling.
When osimertinib was compared with platinum +
pemetrexed (folic acid antimetabolite inhibiting both purine and pyrimidine
synthesis) in patients with advanced disease with both mutations, the former therapy
improved disease-free survival over the latter group (10.1 months vs 4.4
months) as well as in the objective response rate (71% vs 31%). In 144 patients with CNS metastases, progression-free
survival was also increased with osimertinib (8.5 months vs 4.2 months). Grade
3 or higher adverse effects were lower in the osimertinib group than in the
platinum + pemetrexed group (23% vs 47%).
Articles Some Medical Students Found Interesting
IMAGES IN CLINICAL MEDICINE
Eosinophilic
Otitis Media
A
50-year-old man presented with a 6-month history of pain, otorrhea, and
progressive hearing loss in both ears. Polypoid masses were found in both
external ear canals.
This is an interesting case of otitis media.
