Monday, 28 March 2016

NEJM Review of 3rd March 2016 (#32)

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of the 3rd March 2016 (#32)
University of Notre Dame Australia (Fremantle Campus)


Occasional Editorial Comment


Perspective

Uber’s Message for Health Care


Uber upended the taxi industry by offering an appealing alternative. Its incursion into a highly regulated market suggests that if consumers gain enough from a new solution, it can overcome entrenched interests. Is U.S. health care ripe for disruption by a medical Uber?

The Uber model presents itself as an industry unencumbered by regulation which therefore is able to offer reliable, faster, and more user friendly service than the conventional business model.  There is much controversy, however as questions of uneven charging, passenger safety and drivers’ professionalism come under more scrutiny. While improvements in patient care standards, costs of health care delivery, safety and improved efficiencies are necessary and achievable, these should not be at the cost of fragmenting the current system.  I do not wish to see an unregulated health care industry, nor do I wish to lose medical coverage for pre-existing illnesses to engorge corporate profits should privatization occur.
The conservative government in Australia would dearly love to dismantle and privatize the health care industry as it continues to be in the US even with the improvements due to passage of the Affordable Care Act (Obamacare). Two major goals of the ACA enacted by a Democratic administration in the US (equivalent to the Labor government in Australia) were to provide health insurance coverage for all uninsured Americans at a reasonable cost and to allow coverage for all uninsurable patients with pre-existing conditions. These goals have been in large part achieved, but should a Republican president and congress be elected, this system may well as promised be dismantled.
In this conservative, privatizing, cost-containing, tax-cutting environment in Australia, we must take care when terms like Uberization are bandied about with the aim of obfuscating true discussions on the real cost of health care and the preservation of one of the best health care system in the world.


Must Read Articles


Perspective

Menopause Management — Getting Clinical Care Back on Track


Use of systemic hormone therapy has decreased dramatically among U.S. women since the Women's Health Initiative results were published. But those results are being misapplied to treatment decisions for women in their 40s and 50s who have distressing vasomotor symptoms

This is an excellent discussion on menopause management which emphasizes the concerns that primary care physicians, including obstetricians and gynaecologists, and medical students in the US, (and I am sure also in Australia), have in prescribing HRT to women with moderate or severe menopausal symptoms. In the US, HRT use has fallen by 80% since the initial findings of the Women’s Health Initiative were published in 2002. This indicates that there are large numbers of women suffering from treatable menopausal symptoms because of the incorrect interpretation of the data (well illustrated in the accompanying Figure). The Perspective urges that physicians who treat women with menopausal symptoms interpret the evidence correctly and that medical schools do likewise in educating students. I am sure that if males suffered from menopausal symptoms, prescribing habits would be rapidly reversed.

Recommended learning:
1.     Biology of the menopause and the clinical presentation
2.     Review the complications of the menopause
3.     Review the management of menopausal symptoms and complications


Articles Recommended for Medical Students



CLINICAL PRACTICE

Peripheral Artery Disease


Atherosclerotic peripheral artery disease is associated with a high rate of cardiovascular events and death. Treatment goals include reducing cardiovascular risk and improving functional capacity. Revascularization is indicated for persistent symptoms.

This extensive and excellent review article on peripheral vascular disease is one you need to store in your data base for years to come. The article begins with a very common clinical problem and then addresses each treatment strategy with current evidence-based detail that is not required for the average medical student.  This will be extremely valuable to have on hand when managing a patient with vascular disease as a MED400 student, intern, or resident in order to answer your patient’s or consultant’s questions.

Recommended learning:
1.     Pathology of atherosclerosis and its causes and other unusual causes of peripheral ischaemia
2.     Common causes and basic management of patients with atherosclerotic peripheral vascular disease


ORIGINAL ARTICLE

Trimethoprim–Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess


In this randomized clinical trial in patients presenting to U.S. emergency departments with an acute uncomplicated cutaneous abscess, drainage plus trimethoprim–sulfamethoxazole therapy for a week was associated with modest clinical benefits as compared with drainage alone.


CLINICAL DECISIONS

Skin Abscess


This interactive feature offers a case vignette accompanied by essays that support either incision and drainage alone or incision and drainage followed by a 7-day course of antibiotics.

This article features a multicentre (n=5) US randomized, double-blind placebo controlled trial on 1013 patients who completed the study and who presented to the ED with cutaneous abscesses (majority 2-5 cm diameter, not requiring hospital admission) that were all incised and drained. The aim of the study was to determine whether a 7-day course of trimethoprim-sulfamethoxazole compared with placebo resulted in higher cure rates, which it did (80.5 versus 73.6%). The causes for cure failure are indicated in Table 1. Cultures from these community-acquired abscesses revealed 45.3% were MRSA, a rate that now appears to have stabilized after an initial sharp rise. Recommended antibiotics for abscesses treated in GP or in the ED are either trimethoprim-sulfamethoxazole or doxycycline.
If you do not wish to read the article, I recommended reading the Clinical Decision article (a point – counterpoint discussion) but focusing on the use of drainage + antibiotics (Howard Gold MD) where practical recommendations for antibiotics are suggested.

Recommended learning: Pathology, presentation and management of cutaneous abscesses, cellulitis and erysipelas.


CLINICAL PROBLEM-SOLVING

Too Much of a Good Thing


A 54-year-old man presented to the emergency department with a 1-month history of edema in the lower legs and a 1-week history of upper abdominal pain. He also reported intermittent nausea, early satiety, and diarrhea but did not have fevers, chills, or vomiting.

This case discussion focuses on the pathology and causes of non-cirrhotic portal hypertension, a very uncommon entity. The selected causes are indicated in Table 2.
The patient under discussion presented with vitamin A poisoning (hypervitaminosis A) as the cause of non-cirrhotic portal hypertension. This case emphasizes the importance of taking a detailed history from the patient, particularly where the cause may not be clinically obvious at presentation. I emphasize to students that “common things are common”, but with the proviso that all relevant facts have been gathered from the patient and that they are compatible the clinical presentation. 
I quote from the Commentary in the article: “Delayed diagnosis of noncirrhotic portal hypertension probably stems from cognitive errors made during clinical decision making, and particularly from premature closure (i.e., failure to consider reasonable alternatives after an initial diagnosis has been made). Arriving at the correct diagnosis in difficult cases requires that clinicians remain open to alternative diagnostic considerations and selective further evaluation, including repeat history taking.”


IMAGES IN CLINICAL MEDICINE

Right Ventricular Infarction


A 61-year-old man with a personal history of smoking and a family history of coronary artery disease presented with what he described as a squeezing pain in the left side of his chest that woke him from sleep. He also had dizziness and diaphoresis

A good illustration of right ventricular myocardial infarction.

Don’t forget: The patient who presents with an acute inferior/posterior myocardial infarction with hypotension (particularly after morphine and/or nitrates), tachycardia, raised JVP but with clear lung fields requires IV fluids, not diuretics.


IMAGES IN CLINICAL MEDICINE

Vertebral-Body Erosion in Thoracic Aortic Aneurysm


A 74-year-old man presented with acute back pain but no neurologic symptoms. He had a history of hypertension, open repair of an aortic infrarenal aneurysm, and end-stage renal failure. CT revealed a thoracic aneurysm and well-corticated erosions of thoracic vertebrae.

An interesting CT scan demonstrating erosion of both T10 and T11 vertebrae by an atherosclerotic thoracic aortic aneurysm. Note the sparing of the disk space which would be involved if infection were the cause.

For those interested in the history of medicine, review the clinical presentations of syphilitic thoracic aortic aneurysms.


Important Articles Related to Mechanisms of Disease and Translational Research



CLINICAL IMPLICATIONS OF BASIC RESEARCH

Burning Fat by Bugging the System


A recent study of mouse models links cold exposure, the microbiome, and remodelling of the intestine to the browning of fat.

I found this to be the most interesting article of the week, unlike the medical students where only 1 in 22 picked this. I was informed by a student whose mother is a practicing endocrinologist in Sydney that, “most endocrinologists (in Sydney) consider that taking cold showers and generally maintaining a colder state overall result in weight loss.”
The study in Cell, 2015, by Chevalier and colleagues, focuses on the generation of beige fat cells in the mouse exposed to the cold. These inducible fat cells, also found recently in humans, can transition between energy dissipation and energy storage. White fat cells, which are associated with the production of an inflammatory response, are abundant in humans and responsible for fat storage. Brown fat cells metabolize fat by mitochondrial activity.
While the data from this study are not yet immediately translatable to humans, the results are fascinating and are illustrated clearly in Figure 1. Cold exposure causes browning of white fat in mice, resulting in increased insulin sensitivity, heat production, and weight loss. The results of the Cell study report that cold exposure in mice also changes the composition of the gut microbiota and results in a large increase in the absorptive surface of the gut. Transplantation of the cold-adapted microbiota from cold-exposed mice to warm recipient mice is sufficient to promote fat browning, weight loss, enhanced insulin sensitivity, and increased intestinal surface area in the recipient mice.
We are in an exponential learning curve about microbiota, not only in the GI tract but also the respiratory tract.  

Changes in microbiota appear to play a role in autoimmunity, control of infection, malignancy, malnutrition management and maybe now may offer a light into the control of obesity.


Other articles that should be of interest to medical students



Perspective

HISTORY OF MEDICINE

Stroke and t-PA — Triggering New Paradigms of Care


Today, health systems have been reconfigured to permit speedy access to stroke care. But this response is a recent phenomenon, dating to the 1995 publication of a research article on recombinant tissue plasminogen activator.

This offers a brief history of stroke, its frequency, the development of stroke centres and evidence-based optimal stroke management, particularly the more recent use of tPA and endovascular therapy. It is important to note that Melbourne (Peter Bladin), together with Boston (MGH) and Sweden were at the forefront in development of the concept of dedicated stroke units and research.


EDITORIAL

Induction of Labor and Cesarean Delivery


The Editorial summarizes the study in this week’s issue of the Journal ( http://www.nejm.org/doi/full/10.1056/NEJMoa1509117 ) and offers an overview of this area together with future studies. The randomized, controlled trial of 619 primigravid women over 35 years of age and older without any obstetrical complications were offered either expectant management of their pregnancy or were induced in their 39th week of gestation. The frequency of Caesarean section in each group, which was the primary outcome of the study, did not differ, nor were there any adverse short-term effects on maternal or neonatal outcomes.




Sunday, 20 March 2016

NEJM Week of 25th February 2016 (#31)

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of the 25th February 2016 (#31)
University of Notre Dame Australia
(Fremantle Campus)


Occasional Editorial Comment

Editorial comments are in Surgical Training and Duty Hours review.

Once again I must emphasize that the editorial comments are mine alone and do not reflect the opinions of the University of Notre Dame Australia, Fremantle Campus, or the School of Medicine. As such, I reserve the rights to reflect my own opinions and anecdotes as a member of the academic faculty of a learned institution. You may agree with me, disagree or have no opinion (hopefully this may change by reading this blog) but as long as my editorial comments engender an academic discussion, I believe I have fulfilled my role.
The practice of good medicine is also the practice of politics and ultimately the delivery of health care dollars to the system. Australia has one of the best and most desired health care systems in the world and we must all be vigilant in order to protect the current system from self-interested politicians who control health care dollars and who attempt to balance their budget using health care dollars.

But more on this next week when I discuss the Uberization (frequently referred to as “The Sharing Economy”) of the medical system.


Must Read Articles

None


Articles Recommended for Medical Students

Perspective

Dealing with Racist Patients


A patient's refusal of care based on the physician's race or ethnic background can raise thorny ethical, legal, and clinical issues — and can be painful and confusing for physicians. Sound decision making in this context turns on five ethical and practical factors

Although most medical students read this Perspective, perhaps because of the catchy term, “racist”, the majority were not as impressed as several PBL tutors who felt this to be a very informative article. I would regard the medical students’ attitude from a positive point of view, namely that the students are more aware of the problems of interacting with racist patients and they also have experienced the strong focus on various aspects of communication, awareness of indigenous culture, ethical training and professionalism which we seek to imbue at Notre Dame. All agreed with the outlined algorithm and believed this to be “obvious”. Students as a group believed they could cope with a single racist comment directed towards them (most as yet had not experienced this), but felt that if this experience became a repetitive experience that it could affect their ability to deliver effective patient care.  In this circumstance, however, they also felt they would need to reflect on their own attitudes to determine if they were in part responsible for these interactions.

Recommended learning:

Communication with Aboriginal and Torres Strait Islander and immigrant patients and understanding how social and cultural norms may differ.


ORIGINAL ARTICLE

Stopping vs. Continuing Aspirin before Coronary Artery Surgery


In a randomized trial involving 2100 patients undergoing coronary artery surgery, the risk of bleeding within 30 days after surgery was not higher with aspirin than with placebo, nor was the risk of death or thrombosis within 30 days after surgery lower with aspirin than with placebo

The question about stopping aspirin 5-7 days before any elective surgery has revolved around the risk of perioperative bleeding (which should ideally be limited by careful surgical haemostasis) versus the risk of a thrombotic event for which the aspirin has been used prophylactically (prevention of stroke, myocardial infarction or death) or as in this study to limit thrombosis in the grafted tissue (vein or internal mammary artery).
The results of this Australian study out of Melbourne and Adelaide, but also Devon and Quebec City, appear to answer this question in this 2-by-2 factorial trial design.  Tranexamic acid was also employed in addition to aspirin at the second level (see Figure 1). There are many aspects of anticoagulation in this study (see Table 3), but in spite of the complex nature and careful design of the study, the results indicate that for patients given 100 mg aspirin preoperatively compared with those where aspirin was stopped 5-7 days prior to surgery in this multicentre study, there was no significant difference between the groups regarding outcome parameters. This appears to answer the question regarding safety of preoperative aspirin use (1-2 hours) in patients undergoing coronary artery surgery in this carefully monitored study using dedicated surgeons interested in participating in the trial.  However, the question remains, can these results be translated to aspirin use prior to all elective surgeries? Students believed that aspirin should definitely not be given prior to neurosurgery or in patients with known bleeding disorders.

An interesting subgroup analysis would have been to perform bleeding times on all patients within 15 minutes of anaesthesia to see if there were any differences in outcomes between the groups.
I was reacquainted with the use of tranexamic acid (a synthetic ant-fibrinolytic agent containing lysine analogues which binds reversibly to 4-5 active lysine residues in plasminogen and plasmin reducing their abilities to cleave fibrin) in major trauma, severe dysfunctional uterine bleeding (MED300 students have witnessed this in their O&G rotation), and some bleeding disorders.
How will the general surgeons regard this paper in their numerous predicted discussions?



REVIEW ARTICLE

Challenges in the Elimination of Pediatric HIV-1 Infection


Preventing mother-to-child transmission of HIV-1 requires a series of steps in the care of women and their infants during pregnancy, delivery, and the postpartum period. This review outlines the steps and summarizes progress in resource-limited countries and elsewhere

This is an important article as it illustrates the periods during pregnancy, delivery and breast feeding where HIV transmission occurs and how management and transmission in developed countries and “resource-limited countries” (90% in sub-Saharan Africa) differs.
All of the Figures are clear, including Figure 4 which contrasts different management recommendations in the US and “resource-limited countries”.
I admit that I was unaware of the extremely high frequency of HIV transmission to the infant by breast feeding and that by utilizing antiretroviral agents to the lactating mother and extended prophylaxis to breast-feeding infants the risk of post-natal HIV transmission is reduced to < 2%. Obviously there is no risk if the infant is fed only formula.
This article highlights a seminal public health study published in 1994 in the Journal which demonstrated that administration of a single antiretroviral agent zidovudine given to the mother orally during pregnancy, IV during labour and orally to the newborn for 6 weeks (in non-breast fed infants), reduced HIV transmission by up to 70%.


IMAGES IN CLINICAL MEDICINE

Ocular Rosacea


A 58-year-old man presented with recurrent facial flushing and redness, foreign-body sensation, and blurred vision in both eyes. Examination revealed telangiectasia with hyperemia of the eyelid margins, conjunctival hyperemia, and neovascularization of the cornea in both eyes

An interesting series of photographs demonstrating uncommonly recognised ocular acne rosacea and the response to standard therapy.

Recommended learning:
Review the pathology, clinical manifestations and management of the common skin disorder acne rosacea.





Important Articles Related to Mechanisms of Disease and Translational Research

None


Other articles which should be of interest to medical students

Perspective

Leaping without Looking — Duty Hours, Autonomy, and the Risks of Research and Practice


Critics argue, essentially, that there is no ethical way to study residents' duty-hour rules in a randomized fashion. But in assuming that untested practice is safe, we have compromised trainees' freedom to judge for themselves when their patients need them.

ORIGINAL ARTICLE

National Cluster-Randomized Trial of Duty-Hour Flexibility in Surgical Training


In this randomized trial comparing ACGME duty-hour policies with more flexible policies for surgical residents, the flexible policies resulted in noninferior patient outcomes and no significant difference in residents' satisfaction with overall well-being and education quality

EDITORIAL

Surgical Resident Duty-Hour Rules — Weighing the New Evidence


There are three articles discussing surgical resident duty-hour rules:  the first, Perspective, argues both for and against the ethics of a randomized study involving 59 surgical residency training sites in the US in which participants were not informed of the study parameters in order to obtain more valid and meaningful data (I believe this to be a non-issue); the second, the Original Article, provides the data for the study; and the third, Editorial, presents a reasoned analysis by John Birkmeyer, a Professor of Surgery and general surgeon.  He is also an internationally recognized health services researcher and leader in regional collaborative quality improvement at Dartmouth in NH, USA, who provided a critical and reasoned analysis (I would only read the Editorial, unless you have a particular interest in this area) with focus on surgical training practice by postmillennial learners in the US.

Clearly the past is the present when older members of the profession expound on their earlier anecdotal residency training experiences and where this can still effect current training policy. One recent experience I had in Perth was at an RACP business meeting dinner sitting next to a learned academic from the East Coast who was involved in formulating RACP policy-making for medical school internship training. This individual argued forcefully for more intrusive internship training for final year medical students so they would be prepared for the rigours of their internship on day one.  His opinion stemmed from an unfortunate initial first three-month experience he had as a new intern thrust into a neurosurgical rotation at a major teaching hospital in Melbourne without any senior residency supervision over this period. Needless to say this was a harrowing experience for him and indelibly imprinted on the plasticity of his neurons.  I feel sure that what was regarded by him as a traumatic event was regarded by his senior neurosurgical consultants and hospital administrators of the day as a valuable learning experience.

My internship training experience, on the other hand, was the polar opposite and one of the most academically informative training experiences in my life at Sydney Hospital (of course excluding medical school training at the University of Sydney and the Royal North Shore Hospital).


It would be assumed that if the two of us were members of an RACP committee discussing internship training policy in medical school, two differing points of view would have been represented. Clearly the role of the Chairperson is to understand the agenda of the members of the committee in order to limit polarizing points of view by providing balance and limit the development of ill-founded policy decisions

 My belief is that the increased focus on internship training in medical school relates directly to the hospital’s expectation that the newly minted intern should be trained one and ready to fully function from day. The rationale is that this is in the patients’ benefit, but my alternative interpretation is that cost containment at the hospital level and passing on the training costs to the Universities. With the reduction in the residency training force, there is less one on one training of interns by residents and registrars and hospitals are requiring more direct clinical patient care by all medical staff, including paid consultants and less time devoted to teaching and supervision. In fact, some hospitals in Perth have requested that Universities provide the salaries for salaried consultants who teach medical students!!! I believe that in Perth we have a wonderful teaching system which is in slow decline for want of expending more dollars on medical training of our future doctors, nurses and health care professionals at the state level.

I have forged a long-term relationship with my favorite mentor Emeritus Professor Solomon Posen who in his nineties is a prolific broadly educated reader and author and who comments periodically on my blog. I will never forget my first medical ward round when I was asked, “Andrews, tell me what you know about chimerism?” Those days (1969 through the seventies) were very different. Virtually no interns were married and few had partners like the current day. Most expected to work until late in the night until their day’s work had been completed and their patients had all been tucked in for the night. Contrast this to the current post-millennial intern: many are married or have partners and children, even in medical school, and their well-being is focused on a life balance between their professional and non-professional commitments.  Who can deny the conclusion of Dr. Birkmeyer in his editorial conclusion that life has changed and current postgraduate medical trainees now live in a different world where they are expected home at a reasonable and predicted time. The myth regarding patient safety between a flexible schedule and those in the standard-policy group, within defined total number of hours worked ACGME defined guidelines, has been exploded. Patient safety did not suffer if a trainee finished work and handed patient-care over to a colleague, nor was the perception of fatigue a perceived problem. If a surgical resident has to miss the surgery, they can catch up on another patient.

Returning to anecdote, when I was an intern at Sydney Hospital in 1969, when we had the weekend off we left at 12:00 md on Saturday and returned at 8:00 am Monday morning – this was regarded as a civilized practice. We handed over the care of our patients in a detailed and meaningful fashion and frequently introduced the patient to our colleague. We would expect that all of our patients would be seen daily and when problems arose they would be handled efficiently. Among some of us, we might even try to find a physical sign or even a treatment error that our colleague had omitted in the chart. However, when I arrived in the US in 1976, I was amazed at the opposite attitude to patient care. Residents and interns regarded their patients as their own personal property and that they were the only ones who could take care of their patients. Many expected to be called at all hours of the day or night if any change occurred in their patients. Rounds would be routinely expected every day. Personally, I regard this practice as a form of intellectual arrogance accepting that a colleague, in general, cannot treat a patient as you do. This attitude is now changing in the US as indicated in the Editorial, with all consultants who treat Medicare patients at Public Facilities expected to see and examine their patients each day and dictate in each patient’s chart for Medicare remuneration for the hospital. This will happen I predict in Australia within the next few years.  Trainee residents now understand that the Consultant is really in charge of the patient, both physically, financially and medico-legally, and are willing now to step back and accept the change in these well-deserved and federally mandated changes in sane work hours in US hospitals.

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL

Case 6-2016 — A 10-Year-Old Boy with Abdominal Cramping and Fevers


A 10-year-old boy was seen in the gastroenterology clinic because of abdominal cramping and fevers. Abdominal imaging studies revealed circumferential thickening of a segment of the colonic wall and mesenteric lymphadenopathy. A diagnostic procedure was performed.

While the case presented is a very uncommon presentation, the discussion revolves around the differential diagnosis of an infiltrative lesion involving the right colonic wall in a 10-year-old boy. As usual, most considerations focus on either a primary inflammatory process (particularly autoimmune processes), a primary infectious cause or, a malignancy.
For those particularly interested in the specific details of the hereditary basis of colorectal cancer and recent genetic developments, this offers a detailed discussion.

Recommended learning:
Differential diagnosis of abdominal pain in children
Review of the pathology, genetics, epidemiology, prevention, presentation and management of colorectal cancer in adults



Tuesday, 1 March 2016

NEJM Week of 18th February 2016 (#30)

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of the 18th February 2016 (#30)
University of Notre Dame Australia
(Fremantle Campus)


Occasional Editorial Comment
None

Must Read Articles
Perspective

The Doctor’s New Dilemma

http://www.nejm.org/doi/full/10.1056/NEJMp1513708

 

A central primary care dilemma is that engaging with patients as people makes us fall behind in administrative tasks and feel more burned out, but not engaging means avoiding intimacy that would not only help the patient but keep us from feeling burned out

 

To chat or not to chat, that is the question?  

The above summary of the Perspective is the crux of the matter. Do you engage your patient at the onset talking generally about the book next to their bed, about their occupation, about their travels or their family? The presenting complaint may not be what the patient really wants to talk about.  Invariably, after I introduce myself to the patient and find out their presenting complaint, I will ask a few general questions such as where they live; where were they born; what do they do; do they have a family and support system, reading or travel? This only takes a matter of minutes but allows the process of building early rapport. Frequently with this “chit-chat” up front, the real reason, if not obvious, for their visit may become apparent.  Unfortunately, in this day and age, “time is money” which tends to blunt this essential interaction.

As a profession, we must rally against forces trying to reduce this essential patient-doctor interaction.  We must work through our professional organizations and government to ensure a just remuneration for services rendered by all primary care physicians (I am excluding most proceduralists and surgeons) to be based on realist and justifiable time spent with the patient. Just wait for a politician or their family to be seen and they will both demand and expect extra time to be spent with them.


 

IMAGES IN CLINICAL MEDICINE

Geographic Tongue

http://www.nejm.org/doi/full/10.1056/NEJMicm1502932

 

A 73-year-old man was referred by his primary care physician, who noted a “weird” red lesion that had been moving across the dorsum of the man's tongue for approximately 3 months. The patient was a former smoker with essential hypertension, hypercholesterolemia, and hyperuricemia.

 

Students frequently mention geographic tongue, usually as not being present, when they are describing the tongue in the mouth examination.  Now, I am sure that many will now be able to recognise this entity when present in their patient.

 


Articles Recommended for Medical Students


Perspective

Zika Virus in the Americas — Yet Another Arbovirus Threat

http://www.nejm.org/doi/full/10.1056/NEJMp1600297

 

The explosive pandemic of Zika virus infection in South and Central America is the most recent of four unexpected arrivals of important arthropod-borne viral diseases in the Western Hemisphere over the past 20 years. Is this an important new disease-emergence pattern?

 

As the Perspective indicates, this “explosive epidemic occurring throughout South America, Central America and the Caribbean, is now potentially threatening the United States.” Suddenly last week, President Obama requested the US congress to appropriate $1.8 billion dollars to combat this epidemic. As the Perspective indicates, there is much that is unknown about this arbovirus (a virus spread by arthropods, such as mosquitoes and ticks and probably by sexual intercourse – why are some and not others affected?). It has been difficult to get an early handle on this epidemic as the Brazilian Health Authorities have been reluctant to share their data with the CDC for fear they will lose control of their investigations, the results of which they fear will be cannibalized in publications and research dollars by the CDC! Talk about mutual collaboration. As with dengue, chickungunya and West Nile virus, global warming may well play a role as the vector travels and mutations occur in the viruses.

An excellent, large case-control study (pregnant women with and without active viral infection) is underway with results available within nine months.

If you have witnessed the quantity of toxins being sprayed, inhaled and ingested by the inhabitants (they drink the water in buckets that have been sprayed) to remove the mosquito larvae, how will this toxic exposure be excluded as a risk factor for disease and foetal abnormalities?

What is the association between the virus and microcephaly and Guillain-Barre syndrome? Stay tuned.

 

 

ORIGINAL ARTICLE

Clinical Management of Ebola Virus Disease in the United States and Europe

http://www.nejm.org/doi/full/10.1056/NEJMoa1504874

 

Since the beginning of the current Ebola epidemic, several patients with Ebola virus disease have been cared for in the United States and Europe. In this report, the clinical course and care of these 27 patients are described.\

 

This article describes the management of 27 patients with Ebola infection acquired in West Africa (#24) and in the US or Europe (#3). Of the 27 patients, 22 were health care personnel and all were treated in the US or Europe. Compared with management in West Africa (survival rates from 26 – 63%), the survival rate in this group was 81.5% (five died). This improved survival rate was attributable to “close monitoring, and aggressive supportive care that included intravenous fluid hydration, correction of electrolyte abnormalities, nutritional support and critical care management for respiratory and renal failure.”

Of the 27 patients, 23 received a variety of investigational therapies which will undoubtedly be described in the future in more detail when combined with data from the West African experiences.

 

However if a new drug, biological therapy or vaccine is found to be effective which the drug companies will be willing to expend the enormous cost of producing a drug with limited use? If it is a vaccine, who will be vaccinated, when will they be vaccinated and who will bear the costs?

 

Maybe, the WHO could develop its own Pharmaceutical Research and Development Company to produce drugs and vaccines that multinational Pharma does not deem profitable for shareholders. Again, who would pay the bill, but just a thought?


REVIEW ARTICLE

Statin-Associated Autoimmune Myopathy

http://www.nejm.org/doi/full/10.1056/NEJMra1515161

 

Statins are widely used and lower the risk of death from cardiovascular causes. In a fraction of patients, an autoimmune myopathy may develop, characterized by the development of autoantibodies to the target enzyme, HMG-CoA reductase

 

This is an important Review Article on muscle disease associated with statin therapy. Although the article focuses on a very rare autoimmune necrotizing myopathy with antibodies directed against HMG-CoA reductase (incidence of 1 in 50,000 patients treated), the basic information for medical students regarding statin use is contained in the first paragraph, in particular in reference 1 (Ganga et al, 2014), which is a large systemic review which found that mild musculoskeletal symptoms, such as myalgias, occur equally in controls and patients treated with statins.

This will raise many discussions between those with extreme views who believe statins are “poisons” and those that believe statins should be in the water supply.


 

ORIGINAL ARTICLE

A Randomized Trial Comparing Skin Antiseptic Agents at Caesarean Delivery

http://www.nejm.org/doi/full/10.1056/NEJMoa1511048

 

In this single-center trial comparing chlorhexidine–alcohol with iodine–alcohol for skin antisepsis before caesarean delivery, the use of chlorhexidine–alcohol resulted in a risk of surgical-site infection that was significantly lower than that associated with iodine–alcohol.

 

This is a clearly defined study with defined outcomes, performed in a single centre, comparing chlorhexidine-alcohol with iodine-alcohol for preoperative skin antisepsis in patients undergoing Caesarean section at the University of Washington Medical Center in St. Louis, MO.

The results indicated that chlorhexidine-alcohol was superior to iodine-alcohol in reducing the rate of superficial surgical-site infections (3% versus 4.9%) and deep skin infection (1.0% versus 2.4%).

Can the results of this study be generalized? The Introduction should be read at a minimum to provide good background for the study.

 

A discussion should be generated with your surgical tutors regarding the results of this study.

 


Important Articles Related to Mechanisms of Disease and Translational Research

CLINICAL IMPLICATIONS OF BASIC RESEARCH

Epigenetic Modulators and the New Immunotherapies

http://www.nejm.org/doi/full/10.1056/NEJMcibr1514673

 

A couple of recent studies suggest that DNA methyltransferase inhibitors, currently used in the treatment of hematologic cancers, increase the sensitivity of tumour cells to immune-checkpoint–inhibitor therapy


I must state from the onset that no student considered this article for review as they believed it was not important and too difficult to understand. I had to agree with them. However!
Immune-checkpoint inhibitors in the treatment of melanoma and renal cell cancer have been introduced in the Journal over the last six months of 2015 and we will undoubtedly be hearing much more about them in the future in oncology.
Activated T cells are capable of killing tumour cells. If T cells express immune checkpoint receptors on their surface, the T cell is either inactivated (by the binding of CTLA-4 to its ligand CD80/B7-1 on the tumour cell) or undergoes apoptosis (by binding of PD-1 to its ligands PD-L1 and PD-L2 on the tumour cells). These interactions thus render the activated T cell unable to kill the specific tumour cells. If these checkpoint receptors on the surface of T cells can be blocked by specific inhibitors (in the reviewed study by Chiappinelli et al, Cell 2015 by an antibody directed against CTLA-4), the activated T cell rebounds and is able to kill the tumour cells.
The authors of the Cell article, in combination with anti-CTLA-4, added a drug (azacitidine – inhibits DNA methylation) to treat the melanoma cells. This resulted in activation of endogenous retroviral dsRNA and subsequent release of b-interferon which induced class I MHC expression with tumour antigen on the surface of the tumour cell. This then resulted in tumour cell death by the specific activated T cell.

Other articles which should be of interest to medical students

 ORIGINAL ARTICLE

Effects of Testosterone Treatment in Older Men

http://www.nejm.org/doi/full/10.1056/NEJMoa1506119

 

In this study, men 65 years of age or older with low serum testosterone and symptoms of hypoandrogenism received testosterone or placebo for a year. Testosterone had a moderate benefit in sexual function and some benefit in mood but no benefit in vitality or walking distance

 

EDITORIAL

Establishing a Framework — Does Testosterone Supplementation Help Older Men?

http://www.nejm.org/doi/full/10.1056/NEJMe1600196

 

 Neither the students nor I were impressed with the results with this extensive study, although we all understood the rationale and need for this study. The major problem with this testosterone replacement study was the method of selection of patients. It was reminiscent of the biblical quotation: many are called but few are chosen.

Apart from raising the testosterone level with testosterone replacement therapy (as a gel) over 12 months in this super-highly-selected group (790 from a pool of 51,085) of men which bore no semblance to reality, we gleaned the following:

1.     This population of men with an average age of 72 did not represent any valid patient population due to multiple exclusion criteria and thus limiting any generalizability of any conclusions made,

2.     Any improvement in sexual function in this very fit patient group only lasted for about nine months, then waned, but testosterone could not compete with the benefits provided by phosphodiesterase 5 inhibitors,

3.     There were minimal improvements in physical performance, mood and depression. Further, any potential long-term benefits such as improvement in risk of falls and increased bone density were not able to be studied, and

4.     Potential adverse effects of testosterone therapy in the elderly were not able to be addressed

 

 

 

VIDEOS IN CLINICAL MEDICINE

Removal of Foreign Bodies from the Ear and Nose

http://www.nejm.org/doi/full/10.1056/NEJMvcm1207469

 

This video depicts the clinical presentation of patients with a foreign body in the external auditory canal or the nasal passage and describes the most effective techniques for smooth and safe retrieval.

 

An interesting video, when you finally get it to work. It should be viewed by MED400 students doing their ENT rotation. Store this link. You will get very interesting pointers on what to avoid with buzzing insects and beans in body orifices.


 

IMAGES IN CLINICAL MEDICINE

Central Pontine Myelinolysis

http://www.nejm.org/doi/full/10.1056/NEJMicm1504134

 

A 35-year-old man presented with acute alcoholic hepatitis and encephalopathy. His sodium level was 119 mmol per liter. Over the next 5 days his condition improved with supportive treatment, including lactulose, vitamins and normal saline for hypovolemia




I have included a link to superior demonstrations of this rare condition should you be interested.


CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL

Case 5-2016 — A 43-Year-Old Man with Altered Mental Status and a History of Alcohol Use

http://www.nejm.org/doi/full/10.1056/NEJMcpc1509361

 

A 43-year-old man with a history of alcohol use presented with altered mental status. The initial blood pressure was 236/158 mm Hg; imaging studies of the head revealed ventriculomegaly and a mass at the foramen of Monro. A diagnostic procedure was performed.

 

Several students read this CPC which is a very unusual presentation of rare primary cerebral mucormycosis in an alcoholic male. This fungus affects immunosuppressed patients and the prototype infection is invasion of the nasal sinuses with extension into the brain in a poorly controlled diabetic. This fungus requires functional neutrophils for its normal control. It invades blood vessels resulting in distal ischemia and extensive tissue necrosis. In addition to antifungal therapy, aggressive surgery is indicated.

A Figure demonstrates normal CSF flow.