Saturday, November 30, 2013

Gastric antral vascular ectasia (GAVE)

Here is a case report and mini-review.

Disease associations include cirrhosis and rheumatic diseases particularly systemic sclerosis. The terminology surrounding GAVE tends to be confusing. Watermelon stomach is a subtype of GAVE associated more with the rheumatic diseases. Portal hypertensive gastropathy, with which GAVE may be confused, is a separate entity.

Friday, November 29, 2013

The Avandia hype: cooler heads prevail

As reported in Medscape:
The US Food and Drug Administration (FDA) is lifting restrictions on the prescribing and use of the diabetes drug rosiglitazone (Avandia, Avandamet, Avandaryl, GlaxoSmithKline) on the basis of recent data that demonstrate no elevated cardiovascular risk.
"Although some scientific uncertainty about the cardiovascular safety of rosiglitazone medicines still remains, in light of the new re-evaluation of the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial, our concern is substantially reduced," the FDA said in a statement.

Finally a more sober assessment. The issue of Avandia and cardiovascular disease was hyped in 2007 when this meta-analysis came out. I tried to apply some perspective but in no time the hype took on a life of its own.

One of the authors of the meta-analysis (Dr. Steve Nissen) didn't seem to mind. In fact, he threw a little fuel to the fire, saying in an interview that Avandia deaths would dwarf the carnage of 911. And his meta-analysis didn't even show a statistically significant increase in deaths attributable to Avandia.

The potential for macrovascular harm from older diabetes drugs had been known for decades but was never hyped in this manner. The screaming was so loud it was hard to have a nuanced discussion though I tried, here and in other posts.

Wednesday, November 27, 2013

Monday, November 25, 2013

Type of bundle branch block and incident risk of heart failure

From a report in Circulation: Heart Failure:
Methods and Results—Cox’s regression was used to evaluate hazard ratios with 95% confidence intervals for HF among 65 975 participants of the Women’s Health Initiative (WHI) study during an average follow-up of 14 years…
Compared with women with no BBB, LBBB, and intraventricular conduction defect were strong predictors of incident HF in multivariable-adjusted risk models (hazard ratio, 3.79; confidence interval, 2.95–4.87 for LBBB and hazard ratio, 3.53; confidence interval, 2.14–5.81 for intraventricular conduction defect). RBBB was not a significant predictor of incident HF in multivariable-adjusted risk model, but the combination of RBBB and left anterior fascicular block was a strong predictor (hazard ratio, 2.96; confidence interval, 1.77–4.93). QRS duration was an independent predictor of incident HF only in LBBB, with more pronounced risk at QRS greater than or equal to 140 ms than at less than 140 ms. QRS nondipolar voltage (RNDPV) was an independent predictor in both RBBB and LBBB and, in addition, in LBBB, QRS/STT angle and ST J-point depression in aVL were independent predictors.

Saturday, November 23, 2013

The Sunshine Act: What’s it all about?

Here’s a nice free full text summary in NEJM explaining its effects on physicians. The article mentions ways physicians can participate in the process and further the cause of transparency. If you really want to get on board with transparency here’s the Facebook challenge: next time you attend a drug company sponsored event, check in. Mention that you are attending a sponsored event and include a brief description of the food and beverages.

Friday, November 22, 2013

Prone ventilation in severe ARDS

Up until publication of this study in NEJM prone positioning was reserved as a rescue modality. This study however showed a robust improvement in mortality when prone ventilation was used selectively for patients defined physiologically as having severe disease.

Thursday, November 21, 2013

Fungal meningitis following epidural steroid injections

Here are two recent reports from NEJM about the outbreak, traced to a compounding pharmacy [1] [2].

Of interest:

61 deaths were reported.

Strokes, mainly posterior circulation territory, were reported as complications.

This was the largest outbreak of health care related infection ever reported in the US.

Two organisms, Aspergillus fumigatus and Exserohilum rostratum, were identified in clinical infections.

Fungal infections of the CNS may be prone to chronicity and relapse, so final outcomes remain unknown in many patients.

Wednesday, November 20, 2013

Can we prevent ARDS?

According to a recent review prevention is based on early recognition and management of risk factors. Consideration of certain risk factors suggests various preventive strategies, most of which are not based on high level evidence:

Low tidal volume mechanical ventilation
This is of proven benefit for patients with established ARDS who require invasive mechanical ventilation. What about mechanically ventilated patients who do not have ARDS? The review cites evidence that in such patients it is an effective strategy. This evidence has been accumulating for awhile and I summarized it back in 2010.

Prophylactic PEEP
Although “5 of PEEP” is almost a default setting for mechanically ventilated patients these days the evidence on whether it prevents lung injury is mixed.

Fluid management
Direct evidence is not available concerning fluid management as a preventive strategy. If the cutoff for defining ARDS is arbitrary and lung injury exists along a continuum, one might infer benefit based on findings in patients with established ARDS. It is well known that a conservative fluid strategy is beneficial in such patients.

Appropriate sepsis care
Sepsis is a well known precursor to ARDS. Although the particular outcome of ARDS has not been specifically examined, early application of the sepsis bundle is known to improve general outcomes. ARDS is sometimes a late consequence of sepsis. Halting the sepsis progression early might be a preventive measure.

Transfusion strategies
No such strategies have been studied in controlled trials for prevention of ARDS. However, given the increased recognition of transfusion associated lung injury (TRALI), a restrictive transfusion strategy, as is now generally recommended for hospitalized patients, is appealing.

Tuesday, November 19, 2013

Altitude related illness

The topic was recently reviewed in NEJM.

High altitude pulmonary edema, acute mountain sickness and high altitude cerebral edema were discussed. High altitude cerebral edema is a serious condition which can be fatal, and exists on a continuum with acute mountain sickness.

Monday, November 11, 2013

HbA1c, QTc and mortality in DM2 patients with foot ulcers

In this study A1c levels below 7.5 and long QT intervals were associated with increased mortality. There is a poorly understood association between lengthened QT interval and DM which I have cited in previous posts.

Sunday, November 10, 2013

Langerhans cell histiocytosis

This mysterious and somewhat rare condition was formerly given a variety of confusing names. Here is an update.

Saturday, November 09, 2013

Friday, November 08, 2013

Emerging echinocandin resistance in Candida glabrata

From a recent report:

Results. Two hundred ninety-three episodes (313 isolates) of C. glabrata bloodstream infection were analyzed. Resistance to echinocandins increased from 4.9% to 12.3% and to FLC from 18% to 30% between 2001 and 2010, respectively. Among the 78 FLC resistant isolates, 14.1% were resistant to 1 or more echinocandin. Twenty-five (7.9%) isolates harbored a FKS mutation. The predictor of a FKS mutant strain was prior echinocandin therapy (stepwise multivariable analysis, odds ratio, 19.647 [95% confidence interval, 7.19–58.1]). Eighty percent (8/10) of patients infected with FKS mutants demonstrating intermediate or resistant MICs to an echinocandin and treated with an echinocandin failed to respond or responded initially but experienced a recurrence.
Conclusions. Echinocandin resistance is increasing, including among FLC-resistant isolates. The new Clinical and Laboratory Standards Institute clinical breakpoints differentiate wild-type from C. glabrata strains bearing clinically significant FKS1/FKS2 mutations. These observations underscore the importance of knowing the local epidemiology and resistance patterns for Candida within institutions and susceptibility testing of echinocandins for C. glabrata to guide therapeutic decision making.

Species based therapy of candida infections may no longer be enough.

Thursday, November 07, 2013

Novel (target specific) oral anticoagulants: pharmacokinetics and drug interactions

This post contains some more of the key points from Dr. Tracy Minichiello's talk at the recent UCSF Hospital Medicine conference along with additional material I've gathered including this review.

First a little background about CYP3A4 and P glycoprotein. CYP3A4 is an important enzyme affecting drug bioavailability and metabolism. Drugs (including the TSOACs) and food (notably grapefruit) may interact via CYP3A4. Unfortunately comprehensive lists of interacting drugs are difficult to find and popular consumer resources may not be updated concerning the TSOACs. I did find this article helpful (click on the pdf link for free full text). It is a bit dated but does contain a long list of applicable drugs. Given the lack of current and comprehensive references your best bet may be to use one of the on line interaction checkers such as the one available via UpToDate.

P glycoprotein is the other big player. P glycoprotein is an ATP-binding cassette (ABC) transporter which extrudes substances out of cells and thus plays a role in drug disposition and bioavailability. All three currently approved TSOACs are susceptible to interactions involving the protein. Again, because comprehensive lists of interacting drugs are not readily available the use of an interaction checker may be necessary. Some background can be found in this paper.

Below are a few of the basics about the kinetics of available TSOACs.

Routes of elimination:

Dabigatran (Pradaxa) 80% renal
Rivaroxaban (Xarelto) 30-60% renal (60% total but half of this is of an inactive metabolite).
Apixaban (Eliquis) 25% renal

Degree of protein binding:

Dabigatran (Pradaxa) 33% (HD effective for removal)
Rivaroxaban (Xarelto) 95% (HD ineffective for removal)
Apixaban (Eliquis) 87% (HD ineffective for removal)

Drug interactions:

Dabigatran (Pradaxa) Via P glycoprotein
Riaroxaban (Xarelto) Via P glycoprotein and CYP3A4
Apixaban (Eliquis) Via P glycoprotein and CYP3A4

Though focused on pulmonary embolism this review is also helpful concerning some of the general aspects of the pharmacokinetics and pharmacodynamics of TSOACs.

Tuesday, November 05, 2013

Novel oral anticoagulants

---which by the way are now referred to as the target specific oral anticoagulants (TOACs)---were the topic of the first talk at the UCSF Hospital Medicine course. Tracy Minichiello, MD, Professor of Medicine at UCSF, covered some pearls and practical aspects of using these agents.

Here I will provide a few basic points about the labeling from her talk along with some additional information from external links.

The agents approved in the US are dabigatran (Pradaxa), rivaroxaban (Xarelto) and Apixaban (Eliquis). All three are approved for non valvular atrial fibrillation. Xarelto has the additional approved indications of VTE prevention and treatment. Elimination is 80% renal for Pradaxa, 30-60% renal for Xarelto and 25% renal for Eliquis.

Renal labeling for Eliquis is unusual and applies only if one of two other characteristics is present:

age greater than or equal to 80 years
body weight less than or equal to 60 kg
serum creatinine greater than or equal to 1.5 mg/dL

No data are available for patients with clearance below 15 or on HD.

Renal labeling for Xarelto is problematic because it is complex (varying significantly based on which indication) and is not contained in its entirety in some readily available references (eg Micromedex and Rxlist). The creatinine clearance cutoff below which use is contraindicated is 30 for for VTE treatment and prevention and 15 for a fib. For VTE treatment or prevention no renal adjustment is called for within the allowable range of renal function though for VTE prevention (only) at clearance of 30-50 the labeling says “use with caution.” (Does that mean we throw caution to the wind for other indications?). For a fib with clearance of 15-50 reduction to 15 mg daily is called for.

Adjustment of Pradaxa to half dose (75mg bid) is recommended for clearance of 15-30. More aggressive renal adjustment recommendations apply if certain interacting drugs are administered. See product labeling for those details. As with Eliquis, no information is available for patients with clearance below 15 or on HD.

Labeling for interacting drugs as well as other practical aspects of the use of TSOAC drugs covered in Dr. Minichiello's talk will be discussed in subsequent posts.

At first glance the TSOACs look like “cleaner” drugs with greater ease of use as compared to warfarin. What I learned from Dr. Minichiello's talk and break out session is that this is not necessarily true despite some advantages. You need to know a great deal about the pharmacokinetics of these agents in order to use them confidently and competently.

Monday, November 04, 2013

The Mediterranean diet protects against CKD

I never cease to be amazed. From a recent report:

Results Compared with low adherents, medium and high adherents were 23% and 42% less likely to have CKD, respectively (adjusted odds ratio [95% confidence interval]=0.77 [0.57 to 1.05] and 0.58 [0.38 to 0.87], respectively, P for trend=0.04). Among those individuals with CKD, phosphate intake and net endogenous acid production were progressively lower across increasing adherence groups. No differences were observed regarding other cardiometabolic risk factors across adherence groups. As many as 168 (33%) CKD individuals died during follow-up. Compared with low adherents, proportional hazards regression associated medium and high adherents to a 25% and 23% lower mortality risk, respectively (adjusted hazard ratio [95% confidence interval]=0.75 [0.52 to 1.06] and 0.77 [0.44 to 1.36], respectively, P for trend=0.10). Sensitivity analyses showed significant and stronger associations when only adequate dietary reporters were considered.
Conclusions Adherence to a Mediterranean dietary pattern is associated with lower likelihood of CKD in elderly men. A greater adherence to this diet independently predicted survival in those patients with manifest CKD. Clinical trials are warranted to test the hypothesis that following such a diet could improve outcomes (independent of other healthy lifestyles) in CKD patients.

Saturday, November 02, 2013

Hospital medicine CME

Today I'm in San Francisco having just completed UCSF's 17th Annual Hospital Medicine course. First a shout-out to Bob Wachter, course director, for putting together another great meeting. Offerings of this quality are getting harder to find because for the last decade they have been under attack by the CME thought police. The CME thought police operate under several wrong headed assumptions a few of which I'll mention here:

Industry sponsored CME is corrupt and can't be good. This meeting is one of many counter examples.

CME should not take place in a nice relaxing setting. Resort-based CME is now considered a no-no by many institutions which have discontinued their off campus activities.

CME is only worthwhile if it can be tied in a measurable way to physician behavior. And a close corollary..

Didactic CME should be abandoned because it cannot be linked directly to measurable outcomes. Though the benefits of traditional didactic CME are not as concrete as the thought police would like my own career long learning experience strongly convinces me of its value.

Many attendees Tweeted the conference. I was not among them. For me Tweets are a little too sound-bitey to do justice to the course content. But unlike the CME thought police I respect differences in learning needs among individuals and make no presumption about what style of information sharing is best for others. So if Tweets work for you search #UCSFMHP13 and find Tweets aplenty from the conference.  I may blog portions of the content once I have some down time if I'm still as pumped up and expansive as I am now.

Inverse relationship between length of stay and readmission rate for heart failure

From a report in Circulation: Heart Failure:

Patients treated in countries with longer lengths of stay for heart failure hospitalizations had significantly lower rates of readmission within 30 days of randomization. Findings were similar among sites in the United States, where each 1-day increase in the mean length of stay at the site level was independently associated with a lower risk of all-cause and heart failure readmission.

The authors cite the unintended consequences of DRGs:

Since 1984, when the current reimbursement model was introduced in the United States, there have been strong incentives to reduce lengths of stay to maximize hospital profitability. The consequent reduction in hospital lengths of stay has been accompanied by increases in postdischarge readmission rates,17 which may have resulted in greater overall costs among patients with heart failure.

Friday, November 01, 2013

Strategies associated with reduced heart failure readmissions

From a recent study:

Strategies that were associated with lower hospital RSRRs included the following: (1) partnering with community physicians or physician groups to reduce readmission (0.33% percentage point lower RSRRs; P=0.017), (2) partnering with local hospitals to reduce readmissions (0.34 percentage point; P=0.020), (3) having nurses responsible for medication reconciliation (0.18 percentage point; P=0.002), (4) arranging follow-up appointments before discharge (0.19 percentage point; P=0.037), (5) having a process in place to send all discharge paper or electronic summaries directly to the patient’s primary physician (0.21 percentage point; P=0.004), and (6) assigning staff to follow up on test results that return after the patient is discharged (0.26 percentage point; P=0.049).