Thursday, June 29, 2017

Language obfuscation: adminspeak


The coming microbial apocalypse: resistance patterns in Mexico 2005-2012


The Tigecycline Evaluation and Surveillance Trial (T.E.S.T) is a global antimicrobial surveillance study of both gram-positive and gram-negative organisms. This report presents data on antimicrobial susceptibility among organisms collected in Mexico between 2005 and 2012 as part of T.E.S.T., and compares rates between 2005–2007 and 2008–2012.


Each center in Mexico submitted at least 200 isolates per collection year; including 65 gram-positive isolates and 135 gram-negative isolates. Minimum inhibitory concentrations (MICs) were determined using Clinical Laboratory Standards Institute (CLSI) broth microdilution methodology and antimicrobial susceptibility was established using the 2013 CLSI-approved breakpoints. For tigecycline US Food and Drug Administration (FDA) breakpoints were applied. Isolates of E. coli and K. pneumoniae with a MIC for ceftriaxone of less than 1 mg/L were screened for ESBL production using the phenotypic confirmatory disk test according to CLSI guidelines.


The rates of some key resistant phenotypes changed during this study: vancomycin resistance among Enterococcus faecium decreased from 28.6 % in 2005–2007 to 19.1 % in 2008–2012, while β-lactamase production among Haemophilus influenzae decreased from 37.6 to 18.9 %. Conversely, methicillin-resistant Staphylococcus aureus increased from 38.1 to 47.9 %, meropenem-resistant Acinetobacter spp. increased from 17.7 to 33.0 % and multidrug-resistant Acinetobacter spp. increased from 25.6 to 49.7 %. The prevalence of other resistant pathogens was stable over the study period, including extended-spectrum β-lactamase-positive Escherichia coli (39.0 %) and Klebsiella pneumoniae (25.0 %). The activity of tigecycline was maintained across the study years with MIC90s of less than or equal to 2 mg/L against Enterococcus spp., S. aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Enterobacter spp., E. coli, K. pneumoniae, Klebsiella oxytoca, Serratia marcescens, H. influenzae, and Acinetobacter spp. All gram-positive organisms were susceptible to tigecycline and susceptibility among gram-negatives ranged from 95.0 % for K. pneumoniae to 99.7 % for E. coli.


Antimicrobial resistance continues to be high in Mexico. Tigecycline was active against gram-positive and gram-negative organisms, including resistant phenotypes, collected during the study.

The picture was mixed, with some resistance rates increasing, others decreasing and a broad range of susceptibility to tigecycline.

Monday, June 19, 2017

Antibiotic stewardship and the coming microbial apocalypse: cognitive factors driving overuse

Is this a “tragedy of the commons?” This is not a conflict between the needs of the individual patient and the good of the commons. There are potential harms to the individual patient from excessive use. From the article:

Our chief moral duty as clinicians is to our individual patients, in defense of physicians who seem to disregard the commons. However, clinicians and patients may be underestimating the individual harms and overestimating the benefits of antibiotics. Although the effects of antibiotics on the host's microbiota are often invisible, evidence that the impact is more deleterious than previously suspected is accumulating (8). Such findings may eventually change our attitude toward individual antibiotic risk to a greater degree than the threat of resistant infections alone. Using antibiotics only when needed is in the best interest of our patients as well as our communities.

According to the editorial, adoption of best practice in the area of overusage is slower than in many other areas of medicine. Why? More from the article:

Long-standing habits are hard to break. Analogous to birth cohort effects, training cohorts may exhibit stable similarities in social practice norms, which are affected by cultural attitudes toward antibiotic benefits versus harms, patient–clinician communication, or perceived expectations, and may result in different thresholds for antibiotic use. Learned practices that are shared, especially between attending physicians and trainees, resist change even when there is no evidence to support the practice. However, physicians are also influenced by their contemporary social networks—the system and social context within which they practice, including the attitudes and behaviors of their surrounding colleagues (10). These networks can be a powerful motivator for change.

Putting it together, accurate weighing of the true risks and benefits of antibiotic prescribing will help to make prudent use more justifiable on a rational level. However, physicians also need to feel that judicious prescribing is the right thing to do on an emotional or intuitive level, which often requires social cues and accountability. Interventions must also be designed with the reality of time pressure in mind, and caution must be taken with procedures that require an expenditure of time or cognitive resources. The correlation in Silverman and coworkers' study between high patient volume and antibiotic prescribing is consistent with the notion that physicians seeing patients with acute respiratory infections are practicing under extremely busy circumstances, which often require rapid decision making and intuition as opposed to deliberate, rational thought.

The last sentence points to a major barrier in the pursuit of evidence based medicine.

Sunday, June 18, 2017

Marathon running might be bad for your kidneys

In this study 82% got some degree of AKI most of whom had microscopic changes of tubular injury. It did not closely correlate with rhabdo.

Saturday, June 17, 2017

Where will artificial intelligence take us?

According to Bob Wachter it’ll be well on its way to taking over the diagnostic role of the clinician, and in as little as 5 years:

In about 5 years, Dr Wachter predicted, a physician will be able to dictate a patient note into a computer, and the computer — using artificial intelligence — will review the chart and the literature and offer a likely diagnosis or care path.

I don’t believe it. The simplest and most formulaic attempt at this, computer interpretation of ECGs, has gotten us nowhere in over 40 years.

But no doubt there will be efforts to implement this sort of thing, thus furthering the epidemic of misdiagnosis.

Friday, June 16, 2017

The coming microbial apocalypse---who’s at fault?

...we would be remiss not to mention the biggest driver of multidrug resistant organisms on a massive scale: antibiotic use in our livestock and crops. Both ID pharmacists and ID physicians know that this culprit is causing far more harm than prolonged antibiotic usage in hospitals.

Thursday, June 15, 2017

ADD medicines may help prevent MVAs

Design, Setting, and Participants For this study, a US national cohort of patients with ADHD (n = 2 319 450) was identified from commercial health insurance claims between January 1, 2005, and December 31, 2014, and followed up for emergency department visits for MVCs. The study used within-individual analyses to compare the risk of MVCs during months in which patients received ADHD medication with the risk of MVCs during months in which they did not receive ADHD medication.

Exposures Dispensed prescription of ADHD medications.

Main Outcomes and Measures Emergency department visits for MVCs.

Results Among 2 319 450 patients identified with ADHD, the mean (SD) age was 32.5 (12.8) years, and 51.7% were female. In the within-individual analyses, male patients with ADHD had a 38% (odds ratio, 0.62; 95% CI, 0.56-0.67) lower risk of MVCs in months when receiving ADHD medication compared with months when not receiving medication, and female patients had a 42% (odds ratio, 0.58; 95% CI, 0.53-0.62) lower risk of MVCs in months when receiving ADHD medication. Similar reductions were found across all age groups, across multiple sensitivity analyses, and when considering the long-term association between ADHD medication use and MVCs. Estimates of the population-attributable fraction suggested that up to 22.1% of the MVCs in patients with ADHD could have been avoided if they had received medication during the entire follow-up.

Conclusions and Relevance Among patients with ADHD, rates of MVCs were lower during periods when they received ADHD medication. Considering the high prevalence of ADHD and its association with MVCs, these findings warrant attention to this prevalent and preventable cause of mortality and morbidity.

Wednesday, June 14, 2017

Thiamine deficiency and heart failure: evidence for an association is mounting

From the green journal:

Diuretic therapy is a cornerstone in the management of heart failure. Most studies assessing body thiamine status have reported variable degrees of thiamine deficiency in patients with heart failure, particularly those treated chronically with high doses of furosemide. Thiamine deficiency in patients with heart failure seems predominantly to be due to increased urine volume and urinary flow rate. There is also evidence that furosemide may directly inhibit thiamine uptake at the cellular level. Limited data suggest that thiamine supplementation is capable of increasing left ventricular ejection fraction and improving functional capacity in patients with heart failure and a reduced left ventricular ejection fraction who were treated with diuretics (predominantly furosemide). Therefore, it may be reasonable to provide such patients with thiamine supplementation during heart failure exacerbations.

The vitamin C cocktail for severe sepsis and septic shock

I know I’m a little late with this. Here’s the paper published in Chest. Form the paper:


In this retrospective before-after clinical study, we compared the outcome and clinical course of consecutive septic patients treated with intravenous vitamin C, hydrocortisone and thiamine during a 7-month period (treatment group) compared to a control group treated in our ICU during the preceding 7 months. The primary outcome was hospital survival. A propensity score was generated to adjust the primary outcome.


There were 47 patients in both treatment and control groups with no significant differences in baseline characteristics between the two groups. The hospital mortality was 8.5% (4 of 47) in the treatment group compared to 40.4% (19 of 47) in the control group (p less than 0.001). The propensity adjusted odds of mortality in the patients treated with the vitamin C protocol was 0.13 (95% CI 0.04-0.48, p=002). The SOFA score decreased in all patients in the treatment group with none developing progressive organ failure. Vasopressors were weaned off all patients in the treatment group, a mean of 18.3 ± 9.8 hours after starting treatment with vitamin C protocol. The mean duration of vasopressor use was 54.9 ± 28.4 hours in the control group (p less than 0.001).


Our results suggest that the early use of intravenous vitamin C, together with corticosteroids and thiamine may prove to be effective in preventing progressive organ dysfunction including acute kidney injury and reducing the mortality of patients with severe sepsis and septic shock. Additional studies are required to confirm these preliminary findings.

A post at the Skeptics’ Guide to EM has a nice discussion and critical appraisal, and several notables from the FOAM community weighed in. The participants were unanimous in saying that this study is only hypothesis generating and should not change practice at the moment.

The problems with this study are obvious. Issues that concerned me in particular were:

1) There were three interventions. If the effect is true, which one(s) worked?
2) It seems too good to be true.
3) What are we to make of the 40.4% mortality in the control group?

Some would ask why not just give it to septic patients, since it is harmless, right? Others would counter that you could say the same thing about homeopathy. But wait, homeopathy has no plausible mechanism of action. Vitamin C does. Several, in fact.

It’s interesting that the folks at East Virginia don’t feel there is equipoise for a randomized controlled trial. As experience accumulates I expect to see more and more low level evidence published, from that institution and elsewhere. If that experience repeatedly and consistently points toward a therapeutic effect, especially a very large one as suggested in this study, then we may never feel there’s equipoise and it will gradually become accepted into sepsis care. More likely we’ll see results that are not so good, leading eventually to a randomized trial. My bottom line today is that, while it would be difficult to fault someone for incorporating this into sepsis care, the Marik study should be considered hypothesis generating only, in need of further study, and not a mandate for practice change.

ACP puts out its own guideline for hypertension in the elderly

In short, the target is systolic below 150, and consider below 140 if high cardiovascular risk is present.

As to the choice of pharmacologic agents they don’t write anything in stone:

Effective pharmacologic options include antihypertensive medications, such as thiazide-type diuretics (adverse effects include electrolyte disturbances, gastrointestinal discomfort, rashes and other allergic reactions, sexual dysfunction in men, photosensitivity reactions, and orthostatic hypotension), ACEIs (adverse effects include cough and hyperkalemia), ARBs (adverse effects include dizziness, cough, and hyperkalemia), calcium-channel blockers (adverse effects include dizziness, headache, edema, and constipation), and β-blockers (adverse effects include fatigue and sexual dysfunction).

Ace those board exams

Pain is not a vital sign

Tuesday, June 13, 2017

Troponin: what the hospitalist needs to know

Here is a review in JACC. There is an audio file which nicely summarizes the article.

Monday, June 12, 2017

Travelers diarrhea

From a BMJ review:

Enterotoxic Escherichia coli (ETEC) is the most common cause of acute travellers’ diarrhoea globally

Chronic (greater than 14 days) diarrhoea is less likely to be caused by bacterial pathogens

Prophylactic antibiotic use is only recommended for patients vulnerable to severe sequelae after a short period of diarrhoea, such as those with ileostomies or immune suppression

A short course (1-3 days) of antibiotics taken at the onset of travellers’ diarrhoea reduces the duration of the illness from 3 days to 1.5 days

Sunday, June 11, 2017

Cognitive function after TAVR

In this study published in JACC the signal was mixed.

Saturday, June 10, 2017

A critical look at stress ulcer prophylaxis

From a recent review:

Conclusions: Many stress ulcer prophylaxis recommendations are based on older studies at risk of bias, which may not be applicable to modern practice. Stress ulcer prophylaxis should be limited to patients considered to be at high risk for clinically important bleeding. When evaluating only the trials at low risk for bias, the evidence does not clearly support lower bleeding rates with proton pump inhibitors over histamine 2 receptor antagonists; however, proton pump inhibitors appear to be the dominant drug class used worldwide today. The current rate of upper gastrointestinal bleeding and the relative adverse effects of acid suppression on infectious risk may drive not only the effectiveness, but also the cost-effectiveness of stress ulcer prophylaxis today. Research is currently underway to better address these issues.

Friday, June 09, 2017

Can we prevent critical illness related weakness?

Data Synthesis: Ten studies met the inclusion criteria. The current body of evidence does not support the use of any pharmacological agent in this setting, although maintaining euglycemia may reduce the prevalence of critical illness polyneuropathy.

Although efforts to achieve and maintain euglycemia are not generally recommended in critically ill patients there is emerging evidence that it may be beneficial in preventing critical illness related weakness.

Thursday, June 08, 2017

Proton pump inhibitors and the risk of CKD and ESRD

It was previously known that PPI use was associated with AKI through the mechanism of acute interstitial nephritis. Now a new study shows an association with CKD and ESRD. From the paper:

We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (n=173,321) and new users of histamine H2-receptor antagonists (H2 blockers; n=20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H2 blockers group, had an increased risk of incident eGFR less than 60 ml/min per 1.73 m2 and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline greater than 30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31–90, 91–180, 181–360, and 361–720 days compared with those exposed for less than or equal to 30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H2 blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD.

Wednesday, June 07, 2017

Pioglitazone and bladder cancer

This BMJ study adds strength to the association:

Design Population based cohort study.

Setting General practices contributing data to the United Kingdom Clinical Practice Research Datalink.

Participants A cohort of 145 806 patients newly treated with antidiabetic drugs between 1 January 2000 and 31 July 2013, with follow-up until 31 July 2014.

Main outcome measures The use of pioglitazone was treated as a time varying variable, with use lagged by one year for latency purposes. Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% confidence intervals of incident bladder cancer associated with pioglitazone overall and by both cumulative duration of use and cumulative dose. Similar analyses were conducted for rosiglitazone, a thiazolidinedione not previously associated with an increased risk of bladder cancer.

Results The cohort generated 689 616 person years of follow-up, during which 622 patients were newly diagnosed as having bladder cancer (crude incidence 90.2 per 100 000 person years). Compared with other antidiabetic drugs, pioglitazone was associated with an increased risk of bladder cancer (121.0 v 88.9 per 100 000 person years; hazard ratio 1.63, 95% confidence interval 1.22 to 2.19). Conversely, rosiglitazone was not associated with an increased risk of bladder cancer (86.2 v 88.9 per 100 000 person years; 1.10, 0.83 to 1.47). Duration-response and dose-response relations were observed for pioglitazone but not for rosiglitazone.

Conclusion The results of this large population based study indicate that pioglitazone is associated with an increased risk of bladder cancer. The absence of an association with rosiglitazone suggests that the increased risk is drug specific and not a class effect.

This is unfortunate because pioglitazone was one of only two diabetes drugs (the other being metformin) associated with better macrovascular outcomes.

Tuesday, June 06, 2017

Pimping: is it good teaching?

Academic Life in Emergency Medicine presents a hypothetical case of pimping on rounds that didn't go well. The follow up discussion lacked clarity because of confusion on just what pimping is. One of the discussants, for example, expounded what was wrong with pimping then went on to suggest ways to pimp more effectively. If pimping is merely teaching by asking questions then it is the Socratic method. It can be either abusive or constructive. Here's a discussion of Socratic teaching from The Pathology Guy.

Monday, June 05, 2017

Purpuric and petechial rashes

Key points from a  BMJ review:

Purpura represents bleeding into the skin or mucosal surfaces. Lesions are considered petechial if they are 2 mm or less in diameter.

The differential is wide and ranges from life threatening to more benign causes. The most feared cause is meningococcemia. That condition, if suspected clinically, warrants immediate administration of parenteral antibiotics pending hospitalization and further evaluation.

Sunday, June 04, 2017

4-factor PCC versus FFP to reverse warfarin in CNS bleeds

A paper in Lancet Neurology offers the highest level evidence to date in favor of 4-factor PCC over FFP for this indication, though it is not a game changer as I'll explain below. From the abstract:


We did an investigator-initiated, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Patients aged at least 18 years with VKA-ICH who presented within 12 h after symptom onset with an INR of at least 2·0 were randomly assigned (1:1) by numbered sealed envelopes to 20 mL/kg of intravenous FFP or 30 IU/kg of intravenous four-factor PCC within 1 h after initial cerebral CT scan. The primary endpoint was the proportion of patients with INR 1·2 or lower within 3 h of treatment initiation. Masking of treatment was not possible, but the primary analysis was observer masked. Analyses were done using a treated-as-randomised approach. This trial is registered with EudraCT, number 2008-005653-37, and, number NCT00928915.


Between Aug 7, 2009, and Jan 9, 2015, 54 patients were randomly assigned (26 to FFP and 28 to PCC) and 50 received study drug (23 FFP and 27 PCC). The trial was terminated on Feb 6, 2015, after inclusion of 50 patients after a safety analysis because of safety concerns. Two (9%) of 23 patients in the FFP group versus 18 (67%) of 27 in the PCC group reached the primary endpoint (adjusted odds ratio 30·6, 95% CI 4·7–197·9; p=0·0003). 13 patients died: eight (35%) of 23 in the FFP group (five from haematoma expansion, all occurring within 48 h after symptom onset) and five (19%) of 27 in the PCC group (none from haematoma expansion), the first of which occurred on day 5 after start of treatment. Three thromboembolic events occurred within 3 days (one in the FFP group and two in the PCC group), and six after day 12 (one and five). 43 serious adverse events (20 in the FFP group and 23 in the PCC group) occurred in 26 patients. Six serious adverse events were judged to be FFP related (four cases of haematoma expansion, one anaphylactic reaction, and one ischaemic stroke) and two PCC related (ischaemic stroke and pulmonary embolism).


In patients with VKA-related intracranial hemorrhage, four-factor PCC might be superior to FFP with respect to normalising the INR, and faster INR normalisation seemed to be associated with smaller haematoma expansion. Although an effect of PCC on clinical outcomes remains to be shown, our data favour the use of PCC over FFP in intracranial haemorrhage related to VKA.

Here are the specifics from the body of the paper regarding hematoma expansion:

Haematoma expansion at 3 h was higher in the FFP than in the PCC group (adjusted difference 16·9 mL, 95% CI 2·5–31·3; p=0·023; table 2 ).

Not mentioned in the abstract was a non statistically significant trend toward reduced 90 day mortality in the PCC group.

Why not a game changer? Because 4-factor PCC was already favored over FFP in the 2012 ACCP guidelines, not only for CNS bleeds but for any serious bleed without regard to body area.

Saturday, June 03, 2017

Your patient with a device needs MRI. Now what?

Here is a nice review in JACC.

Some key sections from the text:

Due to concerns of electromagnetic interference with older generators, pacemakers implanted before 1998 and ICDs implanted before 2000 are excluded. Patients with temporary leads, epicardial leads, abandoned leads, and implants within 4 weeks are also excluded and are discussed in greater detail in a separate section…

The mode of pacing is then adjusted, depending on whether or not the patient is pacemaker-dependent. In order to mitigate risk of inhibition of pacing due to detection of radiofrequency or gradient signals, pacing is set to asynchronous pacing (VOO or DOO) in pacemaker-dependent patients. To avoid inappropriate sensing of radiofrequency pulses and therefore inappropriate tracking in patients who are not pacemaker-dependent, pacing is set to a nontracking mode (VVI or DDI). For similar reasons, settings such as rate response, premature ventricular contraction response, ventricular sense response, and atrial fibrillation response are deactivated. To minimize asynchronous pacing and risk of inducing arrhythmia, magnet mode and noise reversion are deactivated. For ICDs, tachyarrhythmia monitoring is deactivated to avoid battery drainage and tachyarrhythmia therapies are deactivated to avoid antitachycardia pacing or shocks.

During the MR, electrocardiograms are recorded and blood pressure and oxygen saturation are monitored. Because no specific imaging sequences are known to increase patient risk, any imaging protocol can be performed, as needed. As discussed later, additional sequences or adjustment may be made to limit image artifacts from the device. Post examination, the original programming is restored, and lead parameters are compared to baseline values and adjusted, if necessary. A follow-up device interrogation is then performed at 3 to 6 months.

Friday, June 02, 2017

Post arrest neurologic prognostication

This, one of many reviews on the topic, though directed to neurologists, contains some points of interest to hospitalists.

Combined modalities of assessment are required. No single category by itself (eg physical exam, imaging, EEG, biomarkers) is enough.

Optimal timing of assessment is influenced by whether hypothermia was used and the anticipated washout times of any sedatives or paralytics. The review doesn't make a clear categorization in this regard the way, for example, the new ACLS guidelines do.

Adverse physical findings should be viewed in terms of their false positive rates for poor neurologic outcome. Examples follow.

Fixed pupils after 72 hours have a false positive rate of 0.5%, 95% CI 0-2.

Absent corneals after 72 hours have a false positive rate of 5%, CI 0-25.

Myoclonus must be interpreted in the context of the EEG and requires expertise.

Absent or extensor posturing to pain after 72 hours has a false positive rate of 10-24%, CI 6-48%

The use of EEG and imaging is complex and requires expertise.

The use of biomarkers is discussed. These are novel markers not available with rapid turnaround in many community hospitals.

Thursday, June 01, 2017

Repair of moderate ischemic mitral regurgitation at the time of CABG


In a trial comparing coronary-artery bypass grafting (CABG) alone with CABG plus mitral-valve repair in patients with moderate ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI) or survival after 1 year. Concomitant mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation, but patients had more adverse events. We now report 2-year outcomes.

We randomly assigned 301 patients to undergo either CABG alone or the combined procedure. Patients were followed for 2 years for clinical and echocardiographic outcomes…


In patients with moderate ischemic mitral regurgitation undergoing CABG, the addition of mitral-valve repair did not lead to significant differences in left ventricular reverse remodeling at 2 years. Mitral-valve repair provided a more durable correction of mitral regurgitation but did not significantly improve survival or reduce overall adverse events or readmissions and was associated with an early hazard of increased neurologic events and supraventricular arrhythmias.