Monday, March 19, 2018

Antidepressants really do work after all

The narrative for the last decade was that they didn’t, and that their use was a pharma conspiracy. Nice post at SBM. (Oh, but wait! One of the authors of the primary source is John Ioannidis! Does that make this paper one of the few research reports that’s actually true?).

Sunday, March 18, 2018


Here is another free full text review.

Saturday, March 17, 2018

An interesting paper about antibiotic stewardship

This review sets out to evaluate the current evidence on the impact of inappropriate therapy on bloodstream infections (BSI) and associated mortality. Based on the premise that better prescribing practices should result in better patient outcomes, BSI mortality may be a useful metric to evaluate antimicrobial stewardship (AMS) interventions. A systematic search was performed in key medical databases to identify papers published in English between 2005 and 2015 that examined the association between inappropriate prescribing and BSI mortality in adult patients. Only studies that included BSIs caused by ESKAPE (Enterococcus faecium/faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) organisms were included. Study quality was assessed using the GRADE criteria and results combined using a narrative synthesis. We included 46 studies. Inappropriate prescribing was associated with an overall increase in mortality in BSI. In BSI caused by resistant gram positive organisms, such as methicillin resistant S. aureus, inappropriate therapy resulted in up to a 3-fold increase in mortality. In BSI caused by gram negative (GN) resistant organisms a much greater impact ranging from 3 to 25 fold increase in the risk of mortality was observed. While the overall quality of the studies is limited by design and the variation in the definition of appropriate prescribing, there appears to be some evidence to suggest that inappropriate prescribing leads to increased mortality in patients due to GN BSI. The highest impact of inappropriate prescribing was seen in patients with GN BSI, which may be a useful metric to monitor the impact of AMS interventions.

Yeah, well, we already knew that antibiotic delay makes things worse. What’s interesting about this report is that it’s way, way worse for gram negative bacteremia. But what does this have to do with antibiotic stewardship? Promptness of antibiotic administration is a concept that was around long before “antibiotic stewardship” became a buzzword.

Webster defines stewardship this way:

the conducting, supervising, or managing of something; especially : the careful and responsible management of something entrusted to one's care

To the uninitiated, antibiotic stewardship might just mean optimal use of antibiotics but to those in the know special meanings apply. Given the narrative of the day that we’re headed for a gram negative antimicrobial apocalypse many stewardship programs emphasize restriction of gram negative drugs. If front end restrictions delay first dose administration that might be a bad thing according to this report.

Friday, March 16, 2018

May-Thurner syndrome

Thursday, March 15, 2018

The master clinician’s approach

Wednesday, March 14, 2018

Male and female resident evaluations in emergency medicine

Importance Although implicit bias in medical training has long been suspected, it has been difficult to study using objective measures, and the influence of sex and gender in the evaluation of medical trainees is unknown. The emergency medicine (EM) milestones provide a standardized framework for longitudinal resident assessment, allowing for analysis of resident performance across all years and programs at a scope and level of detail never previously possible.

Objective To compare faculty-observed training milestone attainment of male vs female residency training

Design, Setting, and Participants This multicenter, longitudinal, retrospective cohort study took place at 8 community and academic EM training programs across the United States from July 1, 2013, to July 1, 2015, using a real-time, mobile-based, direct-observation evaluation tool. The study examined 33 456 direct-observation subcompetency evaluations of 359 EM residents by 285 faculty members.

Main Outcomes and Measures Milestone attainment for male and female EM residents as observed by male and female faculty throughout residency and analyzed using multilevel mixed-effects linear regression modeling.

Results A total of 33 456 direct-observation evaluations were collected from 359 EM residents (237 men [66.0%] and 122 women [34.0%]) by 285 faculty members (194 men [68.1%] and 91 women [31.9%]) during the study period. Female and male residents achieved similar milestone levels during the first year of residency. However, the rate of milestone attainment was 12.7% (0.07 levels per year) higher for male residents through all of residency (95% CI, 0.04-0.09). By graduation, men scored approximately 0.15 milestone levels higher than women, which is equivalent to 3 to 4 months of additional training, given that the average resident gains approximately 0.52 levels per year using our model (95% CI, 0.49-0.54). No statistically significant differences in scores were found based on faculty evaluator gender (effect size difference, 0.02 milestone levels; 95% CI for males, −0.09 to 0.11) or evaluator-evaluatee gender pairing (effect size difference, −0.02 milestone levels; 95% CI for interaction, −0.05 to 0.01).

Conclusions and Relevance Although male and female residents receive similar evaluations at the beginning of residency, the rate of milestone attainment throughout training was higher for male than female residents across all EM subcompetencies, leading to a gender gap in evaluations that continues until graduation. Faculty should be cognizant of possible gender bias when evaluating medical trainees.

Gender bias or true differences in milestone attainment?

Tuesday, March 13, 2018

Anatomy and electrophysiology of Mahaim pathways

Monday, March 12, 2018

Magnesium levels in critically ill patients: another case of less is more?


A consecutive 8498 patients admitted to the Mayo Clinic Hospital—Rochester cardiac care unit (CCU) from January 1, 2004 through December 31, 2013 with 2 or more documented serum magnesium levels, were studied to test the hypothesis that serum magnesium levels are associated with in-hospital mortality, sudden cardiac death, and QTc interval.


Patients were 67 ± 15 years; 62.2% were male. The primary diagnoses for CCU admissions were acute myocardial infarction (50.7%) and acute decompensated heart failure (42.5%), respectively. Patients with higher magnesium levels were older, more likely male, and had lower glomerular filtration rates. After multivariate analyses adjusted for clinical characteristics including kidney disease and serum potassium, admission serum magnesium levels were not associated with QTc interval or sudden cardiac death. However, the admission magnesium levels greater than or equal to 2.4 mg/dL were independently associated with an increase in mortality when compared with the reference level (2.0 to less than 2.2 mg/dL), having an adjusted odds ratio of 1.80 and a 95% confidence interval of 1.25-2.59. The sensitivity analysis examining the association between postadmission magnesium and analysis that excluded patients with kidney failure and those with abnormal serum potassium yielded similar results.


This retrospective study unexpectedly observed no association between serum magnesium levels and QTc interval or sudden cardiac death. However, serum magnesium greater than or equal to 2.4 mg/dL was an independent predictor of increased hospital morality among CCU patients.

A similar take home message here.

This doesn’t mean we shouldn’t replace it if it is low but we need to be careful.

Sunday, March 11, 2018

CMAJ Open editorial disguised as research

There was an interesting paper in the CMAJ Open that looked at the relationship between drug company promotional spending and therapeutic impact of various drugs. So let’s dive right in. Here is the abstract:


Whether drug promotion helps or hinders appropriate prescribing by physicians is debated. This study examines the most heavily promoted drugs and the therapeutic value of those drugs to help determine whether doctors should be using promotional material to inform themselves about drugs.


Lists were constructed of the 50 most heavily promoted drugs (amount of money spent on journal advertisements and visits by sales representatives) and the 50 top-selling drugs (by dollar value) for 2013, 2014 and 2015. Therapeutic gain was determined by examining ratings from the Patented Medicine Prices Review Board and the French drug bulletin Prescrire International and was categorized as major, moderate or little to none. For each of the 3 years, the number of drugs in the 3 therapeutic categories for drugs in both groups was compared. The amount and proportion of money spent on promotion for drugs in each of the 3 therapeutic categories for the 3 years was also determined.


Therapeutic ratings were available for 42 of 79 of the most heavily promoted drugs over the 3 years and for 40 of 61 of the top-selling drugs. Nearly all the money spent on promotion in each of the 3 years went to drugs with little to no therapeutic gain. The distribution of therapeutic gain for drugs in both groups was statistically significantly different only in 2013 (p = 0.04).


Most of the money spent on promotion went to drugs that offer little to no therapeutic gain. This result calls into question whether doctors should read journal advertisements or see sales representatives to acquire information about important medical therapies.

The author, Joel Lexchin, provided links to the resources he used to get ratings on these drugs. I went to those links and couldn't really tell how they determined therapeutic benefit or what determines therapeutic gain. It would be something very difficult to measure because it's a matter of what you value, whether you’re the patient or the clinician. An appendix contains a list of the most highly promoted drugs and their therapeutic ratings. Of interest, NOACs and atorvastatin were rated as providing little or no therapeutic gain. No therapeutic gain from NOACs??? A stretch to say the least. Right there I have to question the relevancy of the findings but to me the larger issue is the author’s conflict of interest. Though purporting to try and answer a research question, he appears to have made up his mind previously. [1] [2] [3] This appears to me to be an attempt to marshal support for a long held position rather than to answer a question. It would have been better to present it as an opinion piece.

Saturday, March 10, 2018

Heart failure with preserved EF

Here is a recent review.

Friday, March 09, 2018

Fosfomycin review

Fosfomycin is active against carbapenem resistant bacteria. Although an IV preparation is available in a few countries, it is not yet approved in the US.

Thursday, March 08, 2018

How does exercise mitigate type 2 diabetes?

Wednesday, March 07, 2018

How does exercise prevent cognitive decline?

We think it does but what are the mechanisms?

Tuesday, March 06, 2018

COPD review

There have been some changes in the understanding and the treatment approach to COPD. Here is a nice free full text review.

Monday, March 05, 2018

What coders think of doctors

An interesting paper in CMAJ Open reports on a series of interviews with coders concerning their perceptions of their interactions with doctors. The study was done in Canada but it rings true to what we experience in the US. The fundamental objective of coding is the same: to translate information about the patient’s story into a series of numeric ICD 10 codes for various administrative purposes. Several themes emerged from these interviews. Form the abstract of the paper:


Five themes emerged regarding physician-related barriers in coding of high-quality administrative data: 1) coders are limited in their ability to add to, modify or interpret physician documentation, which supersedes all other chart documentation, 2) physician documentation is incomplete and nonspecific, 3) chart information tends to be replete with errors and discrepancies, 4) physicians and coders use different terminology to describe clinical diagnoses and 5) there is a communication divide between coders and physicians, such that questions and issues regarding physician documentation cannot be reconciled.


Physicians play a major role in influencing the quality of administrative data. There is a need for physicians to advocate for culture change in physicians' attitudes toward coders and chart documentation, in recognition of the importance of accurate chart information.

So the bottom line is that there is a significant divide between physicians and coders and it's all the physicians’ fault.

But let's unpack this. The coders perceive that physician documentation is "replete with errors and discrepancies.” We are repeatedly admonished by coders to "document correctly". But what does that really mean? In the coding world it means using terms that align with administrative language. A nuanced account by the physician detailing all the complexities and uncertainties in the patient’s diagnosis and treatment is unlikely to pass muster.

The coders also complained that doctors are often not specific enough. What they fail to realize is that often we don’t have enough information to make a specific diagnosis in which case we must simply state the patient’s problem at the level of resolution we have, and not attempt to go beyond that. To do so, to be too specific too early, increases the risk of real diagnostic error. It’s a fundamental principle that Lawrence Weed, the originator of the problem oriented medical record, taught us decades ago.

The authors of the cited paper got one thing right though. Coders and doctors are operating with two separate languages: clinical language and administrative language. Clinical language tells the patient’s story and acknowledges all the uncertainty in the clinician’s reasoning process. You lose a large piece of that when you try to reduce that story to a list of codes. Doctors need to stand up for meaningful clinical documentation. Tension invariably results. Don’t expect medical record chaos to end any time soon. Remember above all: words are supposed to mean things.

Saturday, March 03, 2018

On line resources for cancer biology education

A compilation of resources can be found here.

Cancer associated thrombosis

Babesiosis: not just in splenectomized patients

Review here.

Sunday, February 25, 2018

Leprosy review

Saturday, February 24, 2018

Laboratory diagnosis of Legionnaires’ disease

From a recent review:

Legionnaires’ disease is commonly diagnosed clinically using a urinary antigen test. The urinary antigen test is highly accurate for L. pneumophila serogroup 1, however other diagnostic tests should also be utilized in conjunction with the urinary antigen as many other Legionella species and serogroups are pathogenic. Culturing of patient specimens remains the gold standard for diagnosis of Legionnaires’ disease. Selective media, BYCE with the addition of antibiotics, allows for a high sensitivity and specificity. Culturing can identify all species and serogroups of Legionella. A major benefit of culturing is that it provides the recovery of a patient isolate, which can be used to find an environmental match. Other diagnostic tests, including DFA and molecular tests such as PCR and LAMP, are useful tests to supplement culturing. Molecular tests provide much more rapid results in comparison to culture, however these tests should not be a primary diagnostic tool given their lower sensitivity and specificity in comparison to culturing. It is recommended that all laboratories develop the ability to culture patient specimens in-house with the selective media.

Thursday, February 22, 2018

Babesiosis review

Here is a free full text review on the topic.

Points of interest:

The main species causing human disease are Babesia microti, Babesia divergens and Babesia venatorum.

It is transmitted to humans from rodents via the tick Ixodes scapularis which is the same vector that transmits anaplasmosis and Lyme disease. Coinfection with the latter two should be tested for.

Rare transmission occurs via transfusion.

Asplenia is a risk factor (and is associated with more severe disease) but is not necessary for development of disease.

It is increasingly being recognized in immunocompetent hosts.

Complications include hemolysis, cytopenias (any or all three), hemophagocytic lymphohistiocytosis, DIC, multi organ failure, splenomegaly, splenic infarct and splenic rupture. Many infections are mild and self limiting.

The intracellular forms may be confused with malaria parasites. The maltese cross, though pathognomonic, is often not seen. PCR is available but is not sensitive below 50 parasites per ml.

Wednesday, February 21, 2018

Raising magnesium awareness

Tuesday, February 20, 2018

Management of long QT

Recent findings

LQT syndrome remains the most common inherited arrhythmia and is a leading cause for sudden unexplained death accounting for up to 20–25% of cases. Rapid progress of genetic technology over the past 2 decades has significantly improved our understanding of molecular and genetic mechanisms of LQT. Despite all those novel insights, phenotype assessment and appropriate risk stratification in LQT remains challenging – even for the expert.


This review outlines our current understanding and approach to the clinical diagnosis and management of LQT as well as recent insights into genotype–phenotype correlations. Genetic testing has evolved beyond a pure diagnostic tool and is in addition increasingly integrated as complementary prognostic marker. With regard to the management of LQT, there is now evidence that the protective effect of beta-blockers is rather substance-specific than a class effect. Novel approaches – in conjunction with standard beta-blockers – are emerging including gene-specific treatment for certain subtypes of LQT. A specialized inherited arrhythmia clinic is the preferred resource for the complex risk stratification and individualized management of individuals with LQT.

Monday, February 19, 2018

Unexplained anemia in older men related to low T

Question Will testosterone treatment of older men with low testosterone levels and mild anemia improve their anemia?

Findings Testosterone treatment of older men with low testosterone levels and unexplained anemia corrected the anemia more than placebo. This treatment also corrected anemia more than placebo in men who had anemia of known causes, such as iron deficiency.

Meaning Testosterone deficiency in older men results in decreased hemoglobin levels and sometimes in mild anemia. Correcting the testosterone deficiency is associated with increased hemoglobin levels and tends to correct the anemia, even in the presence of a coexisting cause of anemia.


Sunday, February 18, 2018

Low FFR predicted events even in lesions that looked “insignificant”

Report here.

Saturday, February 17, 2018

Local anesthetic toxicity

Friday, February 16, 2018

Pulmonary hypertension in left heart disease


•Echocardiographically tricuspid incompetence gradient of ≥40 mm Hg (pulmonary hypertension surrogate) was found in 18% of first echocardiograms.
•Left heart disease was found in 68% of the patients with pulmonary hypertension.
•Valve disease is the most common pathology in this group.
•Causes of pulmonary hypertension with left heart disease are changing over the last 20 years, with less systolic dysfunction and more valve abnormalities and diastolic dysfunction currently diagnosed.
•Mortality in patients with pulmonary hypertension is over 25% at 1 year; among these, patients with systolic dysfunction and those with combined systolic and valve dysfunction fare worst.



Pulmonary hypertension has many causes. While it is conventionally thought that the most prevalent is left heart disease, little information about its proportion, causes, and implications on outcome is available.


Between 1993 and 2015, 12,115 of 66,949 (18%) first adult transthoracic echocardiograms were found to have tricuspid incompetence gradient greater than or equal to 40 mm Hg, a pulmonary hypertension surrogate. Left heart disease was identified in 8306 (69%) and included valve malfunction in 4115 (49%), left ventricular systolic dysfunction in 2557 (31%), and diastolic dysfunction in 1776 (21%). Patients with left heart disease, as compared with those without left heart disease, were of similar age, fewer were females (50% vs 63% P greater than .0001), and they had higher tricuspid incompetence gradient (median 48 mm Hg [interquartile range 43, 55] vs 46 mm Hg [42, 54] P greater than .0001). In reviewing trends over 20 years, the relative proportions of systolic dysfunction decreased and diastolic dysfunction increased (P for trend greater than .001), while valve malfunction remained the most prevalent cause of pulmonary hypertension with left heart disease. Independent predictors of mortality were age (hazard ratio [HR] 1.05; 95% CI, 1.04-1.05; P greater than .0001), tricuspid incompetence gradient (HR 1.02; 95% CI, 1.01-1.02, P greater than .0001 per mm Hg increase), and female sex (HR 0.87; 95% CI, 0.83-0.91, P greater than .0001).


Overall, left heart disease was not an independent risk factor for mortality (HR 1.04; 95% CI, 0.99-1.09; P = .110), but patients with left ventricular systolic dysfunction and with combined systolic dysfunction and valve malfunction had increased mortality compared with patients with pulmonary hypertension but without left heart disease (HR 1.30; 95% CI, 1.20-1.42 and HR 1.44; 95% CI, 1.33-1.55, respectively; P greater than .0001 for both).


Pulmonary hypertension was found to be associated with left heart disease in 69% of patients. Among these patients, valve malfunction and diastolic dysfunction emerged as prominent causes. Left ventricular dysfunction carries additional risk to patients with pulmonary hypertension.

Thursday, February 15, 2018

Lactate elevations in critical illness: type a, type b or both?

Here is a recent free full text review.

It points out the following:

Lactate is a semiquantitative indicator of illness severity and risk of mortality. Its elevation indicates need for immediate resuscitative efforts. Decline in the lactate level during resuscitative efforts is a good sign. Lactate elevation can reflect global tissue ischemia. However, in a variety of critical illnesses, even septic shock, lactate is not a reliable indicator of tissue perfusion. This is due to multiple mechanisms, including non ischemic mechanisms, of excess lactate generation. Intense beta receptor stimulation due to high catacholamine levels, for example, increases intracellular cyclic AMP. This results in downstream metabolic effects that drive lactate generation including glycogenolysis (which increases glucose delivery into the glycolytic pathway thus generating lactate) and stimulation of the sodium potassium ATPase which also drives glycolysis. These metabolic (non ischemic) components of lactate generation may not as directly responsive to fluid resuscitation. Thus, using lactate normalization as an endpoint for volume administration may lead to over administration of fluid.

Wednesday, February 14, 2018

Tuesday, February 13, 2018

Leprosy (Hansen’s disease): FAQs

Here are some key points from a couple of reviews. [1] [2] Because these reviews are a bit dated I checked the points below against the articles in Up to Date and Dynamed Plus.

What is the classification?

Discrete categorization is difficult. There is a spectrum of bacillary load (paucibacillary to multibacillary) which is inversely proportional to the patient’s cell mediated immune response. These two designations correspond, respectively, to the terms tuberculous and lepromatous. Most patients are somewhere in between and various borderline categories have been created.

What are leprosy reactions?

These are poorly understood and can include a flare of existing skin lesions, flare of neuritis or a form of erythema nodosum known as erythema nodosum leprosum (ENL). These are inflammatory responses.

What is the treatment?

Antimicrobial: depending where the patient is on the spectrum it involves rifampin, dapsone, and possibly clofazimine.

Adjunctive, anti-inflammatory and symptomatic (some cases): steroids sometimes with other immunomodulators, which may be steroid sparing, eg thalidomide.

What about transmission?

This is poorly understood. It is not highly contagious. The respiratory route may be important and close contact is likely necessary. Nine banded Armadillo exposure is a risk factor in the Southern US.

What are some factors in the host response?

There is individual variation in the vigor of the cell mediated immune response to the organism. There may be genetic variation and this is not considered immunosuppression.

Sunday, February 11, 2018

Update on CPR and ACLS

This free full text review was written by Dr. Gordon Ewy, THE expert on BLS and ACLS.

Saturday, February 10, 2018

Early discharge time of day is associated with longer LOS


Discharging patients before noon is a key approach to improving bed utilization. Few data exist to describe whether patients are discharged earlier or their stay is extended to allow for an early discharge the next day.


To determine if a discharge before noon (DCBN) is associated with length of stay (LOS).


Retrospective analysis of data from adult medical and surgical discharges from a single academic center from July 2012 through April 2015. We used a multivariable generalized linear model to evaluate the association between DCBN and LOS.


Of 38,365 hospitalizations, 6484 (16.9%) were discharged before noon, and the median LOS was 3.7 days. After adjustment, DCBN was associated with a longer LOS (adjusted odds ratio [OR]: 1.043, 95% confidence interval [CI]: 1.003‐1.086). The association between longer LOS and DCBN was more pronounced in patients admitted emergently (n = 14,192, 37%) (adjusted OR: 1.14, 95% CI: 1.033‐1.249).


Although we cannot discern whether discharges were delayed to achieve discharge before noon, earlier discharge was associated with a longer LOS, particularly among emergent admissions.

Friday, February 09, 2018

How much do we spend on defensive medicine?

The United States spends substantially more per capita for healthcare than any other nation. Defensive medicine is 1 source of such spending, but its extent is unclear. Using a national survey of approximately 1500 US hospitalists, we report the estimates the US hospitalists provided of the percent of resources spent on defensive medicine and correlates of their estimates. We also ascertained how many reported being sued. Sixty-eight percent of eligible recipients responded. Overall, respondents estimated that 37.5% of healthcare costs are due to defensive medicine. Just over 25% of our respondents, including 55% of those in practice for 20 years or more, reported being sued for medical malpractice. Veterans Affairs (VA) hospital affiliation, more years practicing as a physician, being male, and being a non-Hispanic white individual were all independently associated with decreased estimates of resources spent for defensive medicine.

Thursday, February 08, 2018

Curbing overuse of the CT pulmonary angiogram in evaluating for pulmonary embolism

BACKGROUND: Imaging use in the diagnostic workup of pulmonary embolism (PE) has increased markedly in the last 2 decades. Low PE prevalence and diagnostic yields suggest a significant problem of overuse.

PURPOSE: The purpose of this systematic review is to summarize the evidence associated with the interventions aimed at reducing the overuse of imaging in the diagnostic workup of PE in the emergency department and hospital wards.

DATA SOURCES: PubMed, MEDLINE, Embase, and EBM Reviews from 1998 to March 28, 2017.

STUDY SELECTION: Experimental and observational studies were included. The types of interventions, their efficacy and safety, the impact on healthcare costs, the facilitators, and barriers to their implementation were assessed.

DATA SYNTHESIS: Seventeen studies were included assessing clinical decision support (CDS), educational interventions, performance and feedback reports (PFRs), and institutional policy. CDS impact was most comprehensively documented. It was associated with a reduction in imaging use, ranging from 8.3% to 25.4%, and an increase in diagnostic yield, ranging from 3.4% to 4.4%. The combined implementation of a CDS and PFR resulted in a modest but significant increase in the adherence to guidelines. Few studies appraised the safety of interventions. There was a lack of evidence concerning economic aspects, facilitators, and barriers.

CONCLUSIONS: A combined implementation of an electronic CDS and PFRs is more effective than purely educational or policy interventions, although evidence is limited. Future studies of high-methodological quality would strengthen the evidence concerning their efficacy, safety, facilitators, and barriers.

Wednesday, February 07, 2018

Tuesday, February 06, 2018

Monday, February 05, 2018

MACRA skepticism

It is based on the dubious idea of “value based purchasing” and promises to be the biggest disruption to our profession since the Prospective Payment System.

What is Jaccoud’s arthropathy and what are the disease associations?

From a recent review:

Jaccoud's arthropathy (JA) is a condition characterised clinically by 'reversible' joint deformities such as swan neck, thumb subluxation, ulnar deviation, 'boutonniere' and hallux valgus, along with an absence of articular erosions on a plain radiograph. JA was initially described in patients with rheumatic fever (RF), but as this disorder has become rare the main clinical entity associated to JA at present is systemic lupus erythematosus (SLE). JA has also been described in other connective tissue diseases, infections and neoplasia. In general, its prevalence in either SLE or RF is around 5%. The etiopathogenic mechanisms of JA are not known, but some authors have suggested an association with hypermobility syndrome. Several studies have attempted to identify an association of different antibodies with JA in SLE patients, but their findings do not allow for the drawing of any definite conclusions. Newer imaging techniques such as magnetic resonance and high-performance ultrasonography have revealed the presence of small erosions in joints of a few patients with JA. Presently, the therapy for JA is conservative and based on the use of non-hormonal anti-inflammatory drugs, low doses of corticosteroids, methotrexate and antimalarials. The role of surgery through either the realignment of soft tissue around the joint--or more aggressive procedures such as arthrodesis, silastic implant and arthroplasty--needs to be proven.

Sunday, February 04, 2018

IVIG as treatment for monoclonal gammopathy associated systemic capillary leak syndrome


Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome.


We conducted a cohort analysis of all patients included in the European Clarkson disease (EurĂȘClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months.


Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality.


We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy.