Thursday, 21 January 2016

NEJM Week of 10th December 2015 (#20)

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of the 10th December 2015 (#20)
University of Notre Dame Australia
(Fremantle Campus)

Occasional Editorial Comments

None
                                                                                                    
MUST READ SECTION

None

Articles Recommended for Medical Students

IMAGES IN CLINICAL MEDICINE


Cullen’s and Grey Turner’s Signs in Acute Pancreatitis


These signs are talked about frequently but uncommonly seen by students.

Required learning: Acute pancreatitis (presentation, common causes and management – but don’t forget the rare autoimmune pancreatitis associated with the IgG4 syndromes), SIRS, MODS.  
Look for Sister Mary Joseph's nodule in previous Images in Clinical Medicine 

CLINICAL PRACTICE

Thyroid Nodules


A very important area which is a frequent OSCI topic for the head and neck examination.
This area is covered in pathology, various lectures in medicine, surgery and ENT and is one of the case studies covered in MED300 medicine rotation cases.

Recommended learning:

Examination of the head and neck (don’t forget the examination of oral cavity, pharynx, sinuses, larynx and scalp), anatomy of lymphatic drainage and approaches to “lumps in the neck.”

Examination of the thyroid, thyrotoxicosis and approach to thyroid nodules

CLINICAL IMPLICATIONS OF BASIC RESEARCH

The Immune Response — Learning to Leave Well Enough Alone


This article is written by Dr. Jim Rosenbaum who is a rheumatologist and ophthalmologist at the University of Oregon, Portland. He is a world authority on systemic and autoimmune diseases involving the eye and provides a precise overview on concepts of autoimmunity and autoinflammation which is easy to understand.

CORRESPONDENCE

Ischemic Limb Gangrene with Pulses


Recommended learning: Review the causes of ischaemic limb gangrene with and without palpable pulses. Good Figure and case with pictures

Important Articles Related to Mechanisms of Disease and Translational Research

None

Other areas which should be of interest to medical students

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL

Case 38-2015 — A 21-Year-Old Man with Fatigue and Weight Loss

http://www.nejm.org/doi/full/10.1056/NEJMcpc1506821

 

An interesting case of metastatic non-seminomatous germ-cell tumour of the testis with extremely high levels of hCG causing gynaecomastia and thyrotoxicosis with discussion of the mechanisms.


Recommended learning: Review testicular tumours, types and management and swellings within the scrotum.

EDITORIAL

Scabies and Global Control of Neglected Tropical Diseases


ORIGINAL ARTICLE

Mass Drug Administration for Scabies Control in a Population with Endemic Disease

http://www.nejm.org/doi/full/10.1056/NEJMoa1500987

This is a very significant population study (from Sydney, Melbourne, Darwin and Fiji) on scabies and secondary impetigo on three Fijian islands, each with a scabies prevalence ranging from 32.1 to 49%!!  Participants on the three islands were treated respectively with permethrin to a) patients and contacts, b) mass administration of permethrin and c) mass administration of ivermectin. Prevalence of scabies fell respectively to 18.8%, 15.8% and 1.8% at 12 months with a similar proportional fall in the prevalence pf impetigo. This is a major study with significance public health implications for developing countries.
Recommended learning: Identification of scabies infection, the populations affected and the management.

Perspective

My Life as a (Fake) Patient

http://www.nejm.org/doi/full/10.1056/NEJMp1508706



An interesting perspective from a professional standardized patient and when she becomes a real patient.

NEJM Week of 3rd December 2015 (#19)

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of the 3rd December 2015 (#19)
University of Notre Dame Australia
(Fremantle Campus)


Occasional Editorial Comments

  In this issue (Perspective), there is an overview of the Swiss health care system (http://www.nejm.org/doi/full/10.1056/NEJMp1508256 ) in the series International Health Care Systems which began in January 2015 in the Journal. The Australian system was reviewed (http://www.nejm.org/doi/full/10.1056/NEJMp1410737) in the August 6th edition. For those interested in international health care systems and where Australia rates, these are an excellent series of Perspective articles. Check out the Turkish system.
                                   
MUST READ
REVIEW ARTICLE

Cardiac Complications in Patients Undergoing Major Noncardiac Surgery

 http://www.nejm.org/doi/full/10.1056/NEJMra1502824


This is a must read article for MED300 and MED400 students and for all surgeons, anaesthetists, intensivists and all who manage pre- and post-operative patients.

It discusses perioperative cardiac complications in patients undergoing non-cardiac, major surgery.
Cardiac complications are the major cause of death within the first 30 days after surgery. Figure 1 demonstrates the preoperative, intraoperative and postoperative risk factors associated with perioperative cardiac complications.

Perioperative mortality, if it were considered a separate category, would rank as the third most common cause of death in the US.

Questions are raised and evidence produced in areas such as:
1.            Should BNP levels be routinely performed preoperatively in asymptomatic patients with cardiac risk factors as a means to enhance preoperative risk reduction?
2.            Should preoperative and postoperative troponin levels be monitored in asymptomatic patients with cardiac risk factors to predict postoperative ACS in patients on analgesics and who do not usually present with chest pain?

This is an article that should be read in its entirety when appropriate in the medical course, particularly on the medical, surgical and critical care rotations, as it really is “full of pearls.”

Recommended learning: Preoperative anaesthetic risk assessment and diagnosing postoperative ACS.

Articles Recommended for Medical Students

Perspective

Ending the HIV–AIDS Pandemic — Follow the Science


MEDICINE AND SOCIETY

Applying Public Health Principles to the HIV Epidemic — How Are We Doing?


ORIGINAL ARTICLE

On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection


The above articles bring the reader up to speed on:
1.  Current evidence that indicate that HIV should be treated with ARTs regardless of the CD4 count and that the benefits far outweigh the risks (The Perspective by Fauci clearly describes three major large, international randomized trials and progressively addresses the evidence to support the above statement)
2.    The article about on-demand intermittent preexposure prophylaxis using tenofovir + emtricitabine in HIV negative men having sex with men (high risk exposure) showed a relative reduction in HIV risk of 86% compared with placebo.
There are various caveats to consider in this short nine month study (maybe better drug compliance than longer studies) including i) regular use of condoms (the study indicated that drugs were not a substitute for condom use), ii) individual risk assessment where prophylaxis was tailored to the perceived risk (Russian roulette) and iii) the risk of developing drug resistance (not discussed in the study but alluded to in passing by Fauci). Clearly the current evidence suggests that preexposure prophylaxis is an effective public health tool in this high risk group and is cost-effective, though this would be a hard sell to insurance companies.

Recommended learning: Review public health aspects of HIV infection

EDITORIAL

Continuous or Interrupted Chest Compressions for Cardiac Arrest


Trial of Continuous or Interrupted Chest Compressions during CPR

In this trial, over 23,000 patients with out-of-hospital cardiac arrest were assigned to standard CPR with a chest compression-to-ventilation ratio of 30:2 or to continuous chest compressions. There was no significant between-group difference in survival to hospital discharge

For those interesting in analysing the study, read the original article. However, I received more information and the results of the background studies by reading the excellent Editorial. The study found no difference in outcomes in out-of-hospital, non-traumatic, cardiac arrests between the use of continuous chest compressions and chest compression-to-ventilation rate of 30:2. An excellent and comprehensive study with interesting exclusions which improved the quality of the study.

Recommended learning: Management of cardiac arrest, ACLS protocols

ORIGINAL ARTICLE

Acetaminophen for Fever in Critically Ill Patients with Suspected Infection


 This is a study in ICU, critically ill patients with fever, probably due to infection, who were treated with either IV placebo every six hours or IV acetaminophen 1 g every six hours until either discharge from the ICU, cessation of the fever, cessation of antimicrobial therapy or death. The results showed no shortening of time in the ICU and no change in the 90 day death rate in the acetaminophen treated group over placebo.

Recommended learning: Management of fever in the ICU patient

CLINICAL PROBLEM-SOLVING

Back to Nature

http://www.nejm.org/doi/full/10.1056/NEJMcps1407030

 

The clinical problem is a presumed infection in an immunosuppressed young male resulting in hilar adenopathy, a hilar mass and small pleural effusions.
This is a good exercise in clinical reasoning but with an unusual organism causing the problem.

Recommended learning: Biological warfare, bioterrorism, causes of hilar adenopathy in the acutely ill patient


Important Articles Related to Mechanisms of Disease and Translational Research

None
                                                                                  Other areas which should be of interest to medical students
Perspective

Tenuous Tether


This is a piece of medical history beginning with Laennec and his use of the first stethoscope, which was a major improvement over listening directly with the ear to the lungs (usually in a patient with cavitatory tuberculosis), through echocardiography and the electronic stethoscope and now visual representation of the murmur and heart sounds on a computer screen at the bedside! An interesting read.

ORIGINAL ARTICLE

Intensive Supportive Care plus Immunosuppression in IgA Nephropathy


This open-label trial randomly assigned patients with IgA nephropathy to supportive care or supportive care plus immunosuppression. The added immunosuppression did not significantly improve outcomes; more adverse events occurred, with no change in the rate of decrease in eGFR
.

This is an important article on the most common cause of glomerulonephritis in the developed world.
This is a three year study comparing two groups of patients with primary IgA nephropathy after a six week run-in period with specific criteria prior to randomization (age 18 to 70 years; proteinuria level between 0.75 – 3.0 /day of urinary protein excretion plus arterial hypertension (defined by the use of antihypertensive medication or by an ambulatory blood pressure ≥140/90 mm Hg), impaired renal function (defined as an eGFR > 30 and < 90 ml/minute/1.73 m2), or both. Exclusion criteria were secondary and rapidly progressive, crescentic IgA nephropathy, other chronic renal diseases, and any prior immunosuppressive therapy). The two groups were either intensive comprehensive supportive therapy (ACE/ARBs, quit smoking, dietary advice, and statins for lipid control) or intensive comprehensive supportive therapy + immunosuppression (in 2007when the study was commenced, corticosteroids for 3 years + oral cyclophosphamide for 3 months followed by azathioprine for the remainder of the 3 years).

The results showed no difference in outcomes between the groups with no change in the rate of decrease in the eGFR, but more adverse effects in the immunosuppression group.

Recommended learning: Review pathology and course of IgA nephropathy and other causes of acute glomerulonephritis

NEJM Week of 26th November 2015 (#18)

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of the 26th November 2015 (#18)
University of Notre Dame Australia
(Fremantle Campus)


Occasional Editorial Comments

The five articles below on BP control are a MUST READ with very practical applications and must be considered in the context of local Australian guidelines. They will be a fertile ground for much discussion and in all likelihood there may not be an agreed upon practical resolution. Such is life and you will just have live with it.

Today I could recommend virtually every article in the Journal, but have to restrain myself to a practical approach and not risk scaring off the medical student with too much excitement and information.

However, it is a good idea each week to review the entire contents of the Journal in case I have omitted something of particular interest to you.

Don’t forget that there are Podcasts each week with summaries of articles the Editorial Board regard as the most significant and there is a host of practical procedures demonstrated in the NEJM video library (this week how to  insert an intracranial-pressure monitor!!!).                                                                                                                                                                                                                                                                                                                                                                                                               
MUST READ
Perspective
FOCUS ON RESEARCH

Time to Reassess Blood-Pressure Goals


Hypertension is a major public health problem, but experts disagree on blood-pressure targets. For many patients, the SPRINT study suggests, target blood pressure in treating hypertension should be lower than is now recommended, but achieving that goal won't be easy

EDITORIAL

A SPRINT to the Finish


EDITORIAL

Redefining Blood-Pressure Targets — SPRINT Starts the Marathon


ORIGINAL ARTICLE

A Randomized Trial of Intensive versus Standard Blood-Pressure Control

The SPRINT Research Group

Patients at increased cardiovascular risk but without diabetes were assigned to intensive treatment of systolic BP (target, <120 mm Hg) or standard treatment (target, <140 mm Hg). After a median of 3.26 years, the rate of cardiovascular events was significantly lower with intensive treatment.

CLINICAL DECISIONS

Excellent clinical vignette on BP control discussing various options based on evidence.

The above five publications occupying half of the Journal relate to the Spring Research Group study comparing Intensive (< 120 mm Hg systolic) versus Standard (<140 mm Hg systolic) BP control in a randomized, non-diabetic, controlled, open-labelled trial in 102 centres in the US and Puerto Rico.

The overall results indicate the lower systolic BP group (intensive) had better outcomes, although:
1.     Not all patients in either group attained the set BP goal
2.     There was a significant increase in adverse events in the intensive group.

I recommend that you review the paper, but pay particular attention to the Perspective article written by Chobanian who provides a reasoned analysis of the study and then read the two Editorials. Most agree that the lower the BP overall within reason, the better the outcomes. However most of the disagreement relates to how this is achieved and to what levels.
The Clinical Decision Making article also makes for interesting  reading.                                                                                                                                                    
If the standard of less than 140/90 is sought in the non-diabetic patient, in the US less than 50% have controlled BP and only 10% in the non-Western world. How can we improve on this with a lower control level of 120 mm Hg?  
Hypertension is the leading cause of death worldwide. Can the physician expect patients to be compliant with up to three BP medications to achieve this result? Read the Chobanian Perspective.


Articles Recommended for Medical Students

ORIGINAL ARTICLE

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages


This is the first large multicentre, randomized, placebo-controlled trial looking at progesterone vaginal suppositories versus placebo for the first trimester in women with recurrent miscarriage (loss of three or more pregnancies).

There was no difference in pregnancy outcomes in the progesterone group versus the placebo group.
Recommended learning: Review the physiology of the menstrual cycle, the role of progesterone during pregnancy and miscarriages in general.


CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL

Case 37-2015 — A 76-Year-Old Man with Fevers, Leukopenia, and Pulmonary Infiltrates (and non-caseating granulomata on lung biopsy)


Interesting bedtime reading and clinical reasoning.
I have seen two cases of polyarthritis of similar origin, though rare.

Recommended learning: Causes on non-caseating granulomata


Important Articles Related to Mechanisms of Disease and Translational Research

ORIGINAL ARTICLE

Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes


This is an article describing a new inhibitor of the sodium-glucose cotransporter 2 in the kidney which results in increased excretion of glucose by the kidney.
The outcome results of the study are positive but I would not spend much time reviewing the article unless you are particularly interested.
I would use this as a probe to review the following:

Recommended learning:
1.     Renal tubular physiology, particularly reviewing glucose transport in the normal and in DKA (recent reviews in the NEJM)

2.     Review the mechanisms of action and the underlying physiology of the groups of non-insulin therapies used to treat diabetes mellitus:
a.     Sulfonlyureas
b.    Metformin (new data on the MOA in NEJM search)
c.     Thiazolidinediones (data  in NEJM 12-12 2015 suggests that these drugs may also have a place as antagonists of the PPAR- nuclear receptor [glitazone receptor] in removing resistant stem cell clones in patients with CML treated with tyrosine kinase inhibitors)
d.    DPP-4 inhibitors
e.     Glucagon-like peptide-1 analogues
f.      Inhibitors of the Na-glucose co-transporter 2
g.    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.
As we learn more about cell biology and immune-pharmaco-genetics, many more indications for older therapies will become apparent.


Other areas which should be of interest to medical students

REVIEW ARTICLE

Treatment of Tuberculosis


This is a good review article on tuberculosis, particularly involving therapeutic choices. It offers very little discussion on research advances but discusses all available medications extensively.
An excellent Figure demonstrating the cellular Sites of Active of the various medications.
Store this article in your data base and review when we do the case of TB in the MED300 discussion cases.

Recommended learning: Review the epidemiology of TB, the immunohistopathology, medications and public health issues in particular in the immigrant and Aboriginal populations. 

CLINICAL IMPLICATIONS OF BASIC RESEARCH

Resolvin Infectious Inflammation by Targeting the Host Response


Of course I had to bring up this article. A very interesting update on the role of Resolvins in acute inflammation and targeting host immune responses in patients with sepsis. Not routine reading.
Maybe I will mention Resolvins in passing in the MED100 lecture I give on acute inflammation (you may wish to review the Figure)


Recommended learning: Review SIRS; sepsis and arachidonic metabolism

Wednesday, 20 January 2016

NEJM Week of 19th November 2015 (#17)

 

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of the 19th November 2015 (#17)
University of Notre Dame Australia
(Fremantle campus)

Occasional Editorial Comments

While many articles in this issue may be of great interest to selected groups (malarial vaccine, agent to treat RSV, sub-clinical leaflet thrombosis in biosynthetic aortic valves), I have not included these as recommendations.

Articles Recommended for Medical Students

CLINICAL PRACTICE

Generalized Anxiety Disorder

http://www.nejm.org/doi/full/10.1056/NEJMcp1502514

Persistent anxiety and uncontrollable worry for at least 6 months characterize generalized anxiety disorder. First-line treatments are cognitive behavioral therapy or pharmacotherapy with a selective serotonin-reuptake or serotonin–norepinephrine reuptake inhibitor.

 

This is a very good review on generalized anxiety disorder, developed in the context of a clinical scenario. The management section is covered well as is the section on areas of uncertainty. This is recommended reading particularly for MED400 but also for all other years as many medical students may suffer intermittently from this disorder.

 

Recommended learning: Generalized anxiety disorder, acute anxiety reactions


Perspective (must read)
BECOMING A PHYSICIAN

Graduate Medical Education in the Freddie Gray Era


In the wake of the death of Freddie Gray and the protests over unjust treatment of black Americans, the internal medicine residency program at Johns Hopkins launched a curriculum aiming to provide tools for improving population health and reducing health disparities

This is a heart-lifting article that details what was achieved in the general area of public health in a specific residency training program in the US (Baltimore, Johns Hopkins). My words cannot add to those in the article, but suffice it to say there is a strong parallel between the poor in some areas of Baltimore and the Aboriginal population in Australia. You should read every word in this article.


Important Articles Related to Mechanisms of Disease and Translational Research

None

Other areas which could be of interest to medical students

ORIGINAL ARTICLE

Prospective Validation of a 21-Gene Expression Assay in Breast Cancer


Patients with early-stage estrogen-receptor–positive, node-negative breast cancer whose 21-gene Oncotype DX profile suggested a low risk of recurrence were safely treated with endocrine therapy alone and were spared exposure to adjuvant chemotherapy

EDITORIAL

Biology before Anatomy in Early Breast Cancer — Precisely the Point


This is a reverse-transcriptase-PCR 21-gene assay using RNA extracted from formalin-fixed paraffin-embedded tissue looking at various genes associated with breast cancer. At this stage from an enormous clinical and pathological data base, this is an assay looking for validation. At last the authors appear to have found a patient super-subset in which the assay may be useful with incredible restrictive parameters. Using multiple arbitrary parameters (I read this to generate a positive statistical outcome), the authors derive a ”recurrence score” which, if it falls between 0-10, indicate that at 5 years patients will have an extremely low rate of recurrence (local and distal) and a 98% survival rate. These patients who were HR positive by definition, required endocrine therapy alone.
Genetic studies in cancer, with some obvious exceptions, have a long way to go before they can predict specific treatment responsiveness and predict the subsequent outcomes. This is one study on a very long journey.