Familial hypocalciuric hypercalcemia

Linked here are some reviews on this topic. [1] [2] [3] [4]

Why is it important? Because it looks a lot like primary hyperparathyroidism. A significant number of cases per year get confused with hyperparathyroidism and as a result undergo inappropriate (and failed) surgery. It’s very tricky. There are ways to make the distinction, as outlined in the articles. If you are about to diagnose primary hyperparathyroidism and refer a patient for surgery pause and ask yourself: am I missing familial hypocalciuric hypercalcemia?

How can we end the HIV pandemic? Detect and treat everyone we can!

The topic is reviewed here.

Here’s what’s key, according to the article:

Together, these studies demonstrate that when ART effectively suppresses a person’s viral load to undetectable levels, the risk for sexual transmission of HIV to an uninfected sexual partner is essentially zero.

Conflict of interest concerns misdirected: JAMA report

Another of the articles in JAMA’s theme issue on COI makes a case that the focus of concern has been wrong:

Much current research and debate involving conflicts of interest in medicine focus on the appropriate level of physician interaction with firms in industries related to health care, such as pharmaceutical and medical device companies. The influential article by Brennan et al1 that led academic medical centers to take the lead in tackling problems caused by conflicts of interest focused almost exclusively on interactions between physicians and pharmaceutical companies. The 2009 Institute of Medicine report Conflict of Interest in Medical Research, Education, and Practice also limited its coverage of conflicts to interactions between physicians and pharmaceutical, medical device, and biotechnology companies. The American Medical Student Association “scorecard” grades conflict of interest policies at medical schools purely on the basis of how they regulate physician-industry relations.

Although these interactions may influence physicians in ways unrelated or even detrimental to patient care, only a small percentage of physicians have substantial financial relationships with pharmaceutical or device companies.2 In contrast, every physician is paid for providing patient-directed services via a system set by the physician’s practice group and supported by insurers, government, individuals, and others who reimburse for care. While a minority of physicians receive direct payments from industry, the average primary care physician sees roughly 2000 patients per year who are, directly and via insurance, billed an average of $5000…

The nearly singular emphasis on physician-industry relationships has been way out of proportion, a point I have been making for years on this blog and in other forums.

Exogenous insulin antibody syndrome

Though reduced, it didn’t completely go away when we went from animal to human insulins.

Early cath post out of hospital cardiac arrest improves survival

Read here.

Review of the pathogenesis of DM 1

From the review:

Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of β cells of the endocrine pancreas. Pathogenesis of T1DM is different from that of type 2 diabetes mellitus, where both insulin resistance and reduced secretion of insulin by the β cells play a synergistic role. We will present genetic, environmental and immunologic factors that destroy β cells of the endocrine pancreas and lead to insulin deficiency. The process of autoimmune destruction takes place in genetically susceptible individuals under the triggering effect of one or more environmental factors and usually progresses over a period of many months to years, during which period patients are asymptomatic and euglycemic, but positive for relevant autoantibodies. Symptomatic hyperglycemia and frank diabetes occur after a long latency period, which reflects the large percentage of β cells that need to be destroyed before overt diabetes become evident.

Dieulafoy’s lesions: free full text review

Read it here.

Drug induced eosinophilic pneumonia

This Medicine paper, available as free full text, is a review of case reports. It provides not only a review of drug induced EP (daptomycin is the most important drug) but also a nice overview of the eosinophilic pneumonias in general.

Mechanisms of sudden cardiac death related to cigarette smoking

This study focuses on repolarization abnormalities, particularly prolongation of the Tp-e.

Animations in cell biology

Free educational resources here.

Should patients admitted with inflammatory bowel disease exacerbation be tested for C diff?

The American College of Gastroenterology guidelines (which as of a few weeks ago are no longer the newest ones) recommend testing. More recently there was this study:

To evaluate the frequency, possible risk factors, and outcome of Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD) patients.

There has been an upsurge of CDI in patients with IBD who has been associated with increased morbidity and mortality. Various risk factors have been found to predispose IBD patients to CDI.

A retrospective case–control study on IBD patients admitted with exacerbation and tested for CDI at the Tel Aviv Medical Center in 2008 to 2013. Epidemiologic, laboratory, and prognostic data were retrieved from electronic files and compared between patients who tested positive (CDI+) or negative (CDI−) for CDI.

CDI was identified in 28 of 311 (7.31%) IBD patients hospitalized with diarrhea. IBD-specific risk factors (univariate analysis) for CDI included: use of systemic steroids therapy (odds ratio [OR] = 3.6, 95% confidence interval [CI] 1.2–10.6) and combinations of ≥2 immunomodulator medications (OR = 2.6, 95% CI 1.1–6.3). Additional risk factors for CDI that are common in the general population were hospitalization in the preceding 2 months (OR = 6.0, 95% CI 2.6–14.1), use of antacids (OR = 3.8, 95% CI 1.7–8.4), and high Charlson comorbidity score (OR = 2.5, 95% CI 1.1–5.7). A multivariate analysis confirmed that only hospitalization within the preceding 2 months and use of antacids were significant risk factors for CDI. The prognosis of CDI+ patients was similar to that of CDI− patients.

Hospitalized IBD patients with exacerbation treated with antacids or recently hospitalized are at increased risk for CDI and should be tested and empirically treated until confirmation or exclusion of the infection.

White board notes: Sjogren’s syndrome

Below are key points drawn from a recent NEJM review on the topic as well as E Medicine’s chapter.

Of related interest: pulmonary manifestations of rheumatic diseases [1] [2]

Types of AV block that can cause syncope, and their characteristics

From a recent review:

Current literature reveals three types of paroxysmal atrioventricular block (AVB) that can cause syncope:

Intrinsic paroxysmal atrioventricular block is due to an intrinsic disease of the AV conduction system; this type of “cardiac syncope” is also called Stokes-Adams attack;

Extrinsic vagal paroxysmal atrioventricular block is linked to the effect of the parasympathetic nervous system on cardiac conduction and is one of the mechanisms involved in “reflex syncope.”

Extrinsic idiopathic paroxysmal atrioventricular block is associated with low levels of endogenous adenosine and is supposed to be one of the mechanisms involved in “low-adenosine syncope.”

These three types of paroxysmal AVB present different clinical and electrocardiographic features. Additionally, the efficacy of cardiac pacing and theophylline therapy to prevent syncopal recurrences is also different for these three types of AVB.

Also noteworthy:

Intrinsic AVB, they type we are most familiar with, can take the form of either phase 3 or, less commonly, phase 4 block. Vagally mediated AVB is characterized by sinus slowing leading up to and during the AVB, and evidence that pacing is helpful is lacking. Extrinsic idiopathic paroxysmal AVB due to low baseline adenosine levels is a more recently described entity.

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?).

Babesiosis

Here is another free full text review.

An interesting paper about antibiotic stewardship

From the paper:

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.

May-Thurner syndrome

Free full text review.

The master clinician’s approach

Definitely worth the read.

Male and female resident evaluations in emergency medicine

From JAMA Internal 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?

Anatomy and electrophysiology of Mahaim pathways

Free full text.

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

From the green journal:

Methods

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.

Results

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.

Conclusion

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.

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:

Background:

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.

Methods:

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.

Results:

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).

Interpretation:

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.

Heart failure with preserved EF

Here is a recent review.

Fosfomycin review

Here is a free full text 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.

How does exercise mitigate type 2 diabetes?

There are multiple mechanisms.

How does exercise prevent cognitive decline?

We think it does but what are the mechanisms?

COPD review

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

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:

Results:

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.

Interpretation:

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.

On line resources for cancer biology education

A compilation of resources can be found here.

Cancer associated thrombosis

Free review.

Babesiosis: not just in splenectomized patients

Review here.