Friday, October 31, 2014

Assessing neurologic prognosis after cardiac arrest

Below are some take home points from a recent review:

Cooling remains accepted as an established modality to improve neurologic outcome but the optimal temperature target is uncertain.

Reference here.

The incorporation of hypothermia into post arrest care has completely changed neuro assessment post cardiac arrest.

In the hypothermia era the assessment is almost always delayed. The optimal timing remains under investigation but is now believed to be 4-5 days post arrest.

When hypothermia is applied it is rarely possible to declare poor neurologic prognosis in the immediate post arrest period.

Doing so would require exam findings of total loss of brain stem function. The authors recommend that such a clinical assessment be supplemented by testing such as EEG.

The motor response at 48-72 hours after sedative withdrawal may be helpful.

A motor response that localizes a painful stimulus is a favorable sign and obviates the need for further evaluation.

Pupillary and corneal responses may be helpful at 72 hours post arrest.

Bilateral absence at that time point is strongly associated with a poor outcome.

Post arrest seizures and myoclonus can be difficult to interpret.

They are often confused with one another. Neither is considered reliable for neurologic prognostication after cardiac arrest. Status myoclonus, a severe and generalized form of post anoxic myoclonus, is a poor prognostic sign and in years past was considered a reliable indicator. That thinking has recently changed after a few reports of occasional favorable outcome.

The use of EEG and imaging modalities was discussed in the review.

Emergency treatment of WPW associated tachycardias

A summary post at Emergency Medicine PharmD.

Thursday, October 30, 2014

Sitagliptin and heart failure exacerbation

This is from a large insurance claims database:

Patients with incident HF were identified from individuals with T2D initially treated with metformin or sulfonylurea and followed over time. Subjects subsequently using sitagliptin were compared with those not using sitagliptin in the 90 days before our primary outcome of all-cause hospital admission or death using a nested case-control analysis after adjustment for demographics and clinical and laboratory data. HF-specific hospital admission or death also was assessed.
Results A total of 7,620 patients with diabetes and incident HF met our inclusion criteria. Mean (SD) age was 54 years (9), and 58% (3,180) were male. Overall, 887 patients (12%) were exposed to sitagliptin therapy (521 patient years of exposure) after incident HF. Our primary composite endpoint occurred in 4,137 patients (54%). After adjustment, sitagliptin users were not at an increased risk for the primary endpoint (7.1% vs. 9.2%, adjusted odds ratio [aOR]: 0.84, 95% confidence interval [CI]: 0.69 to 1.03) or each component (hospital admission 7.5% vs. 9.2%, aOR: 0.93, 95% CI: 0.76 to 1.14; death 6.9% vs. 9.3%, aOR: 1.16, 95% CI: 0.68 to 1.97). However, sitagliptin use was associated with an increased risk of HF hospitalizations (12.5% vs. 9.0%, aOR: 1.84, 95% CI: 1.16 to 2.92).
Conclusions Sitagliptin use was not associated with an increased risk of all-cause hospitalizations or death, but was associated with an increased risk of HF-related hospitalizations among patients with T2D with pre-existing HF.

More from CardioBrief:

The authors said their finding “is likely clinically relevant” and might have an impact on the choice of add-on therapy for heart failure patients with diabetes.
In an accompanying editorial, Deepak Bhatt writes that the findings “add to a small but growing body of evidence that suggests DPP-4 inhibitors as a class of drugs, and possibly diabetes drugs in general, may increase the risk of heart failure.” However, he noted, the “increase in absolute risk, if present at all, appears to be small.”

Wednesday, October 29, 2014

Genotype based warfarin dosing

The latest meta-analysis:

Conclusions and Relevance In this meta-analysis of randomized clinical trials, a genotype-guided dosing strategy did not result in a greater percentage of time that the INR was within the therapeutic range, fewer patients with an INR greater than 4, or a reduction in major bleeding or thromboembolic events compared with clinical dosing algorithms.

Tuesday, October 28, 2014

Facebook “likes” and hospital mortality rates

Findings in a recent study:

With the growth of Facebook, public health researchers are exploring the platform's uses in health care. However, little research has examined the relationship between Facebook and traditional hospital quality measures. The authors conducted an exploratory quantitative analysis of hospitals' Facebook pages to assess whether Facebook "Likes" were associated with hospital quality and patient satisfaction. The 30-day mortality rates and patient recommendation rates were used to quantify hospital quality and patient satisfaction; these variables were correlated with Facebook data for 40 hospitals near New York, NY. The results showed that Facebook "Likes" have a strong negative association with 30-day mortality rates and are positively associated with patient recommendation. These exploratory findings suggest that the number of Facebook "Likes" for a hospital may serve as an indicator of hospital quality and patient satisfaction. These findings have implications for researchers and hospitals looking for a quick and widely available measure of these traditional indicators.

Via Hospital Medicine Virtual Journal Club.

Monday, October 27, 2014

How EMRs, core measures and other “system improvements” degrade patient care

There's a great essay on this subject at Medpage Today. I would just add that it's not so much the computer that degrades care as it is the culture we've built around it.

Saturday, October 25, 2014

Doxycycline: Can it protect against C diff?

From a recent review:

Conclusions: Doxycycline has been shown to have potential protective effects against the development of CDI. Although further randomized placebo-controlled studies are needed, available data suggest that the use of doxycycline in place of alternative antimicrobials, when appropriate, may be a useful antimicrobial stewardship strategy aimed at reducing the incidence of CDI.

Thursday, October 23, 2014

Wednesday, October 22, 2014

Acute right heart failure

---occurs in a variety of critical illnesses. It is probably under recognized. When recognized specific treatment strategies may suggest themselves and result in improved hemodynamics. Free full text review here.

Tuesday, October 21, 2014

George Lundberg: the EMR is a mess

Still, after all these years.

Statins and diabetes

As Larry Husten at Cardiobrief points out, statin use has been associated with slight elevations in blood sugar leading to a diagnosis of diabetes in small numbers of patients. (This phenomenon, by the way, has been observed in other classes of drugs such as thiazides). The clinical importance has been unclear.

Here is a study that sheds more light on the controversy. The study focused on microvascular disease. This is appropriate since it is well known that statins protect against macrovascular disease in a wide apectrum of patients with and without diabetes. From the paper:

We identified all patients living in Denmark who were aged 40 years or older and were diagnosed with incident diabetes between Jan 1, 1996, and Dec 31, 2009. We obtained patients' data from the Danish Patient Registry and information on drug use from the Danish Registry of Medicinal Product Statistics. We randomly selected 15 679 individuals from the database who had used statins regularly until their diagnosis of diabetes (statin users) and matched them in a 1:3 ratio with 47 037 individuals who had never used statins before diagnosis (non-statin users). Our primary outcome was to compare the cumulative incidence of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, or gangrene of the foot in statin users versus non-statin users. We analysed data with Cox regression models, adjusted for covariates including sex, age at diabetes diagnosis, and method of diabetes diagnosis. To address potential biases between statin users and non-statin users, we made adjustments to our analysis with a propensity score and with other factors. Median follow-up was 2·7 years (range 0—13).

During 215 725 person-years of follow-up, 2866 patients developed diabetic retinopathy, 1406 developed diabetic neuropathy, 1248 developed diabetic nephropathy, and 2392 developed gangrene of the foot. Compared with non-statin users, statin users had a lower cumulative incidence of diabetic retinopathy (hazard ratio 0·60, 95% CI 0·54—0·66; p less than 0·0001), diabetic neuropathy (0·66, 0·57—0·75; p less than 0·0001), and gangrene of the foot (0·88, 0·80—0·97; p=0·010), but not diabetic nephropathy (0·97, 0·85—1·10; p=0·62). These results were similar after adjusting for the competing risk of death, after matching for a propensity score, after adjusting for visits to a family doctor, and by stratification on covariates. The corresponding multivariable adjusted hazard ratio for risk of diabetes in the total population was 1·17 (95% CI 1·14—1·21; p less than 0·0001).

Use of statins before diagnosis of incident diabetes was not associated with an increased risk of microvascular disease. Whether statins are protective against some forms of microvascular disease—a possibility raised by these data—will need to be addressed in other studies similar to ours, in mendelian randomisation studies, and preferably in randomised controlled trials.

Monday, October 20, 2014

Delirium in the elderly: pharmacologic management is a last resort

From a paper in American Family Physician via Hospital Medicine Virtual Journal Club:

Treatment of delirium should focus on identifying and managing the causative medical conditions, providing supportive care, preventing complications, and reinforcing preventive interventions. Pharmacologic interventions should be reserved for patients who are a threat to their own safety or the safety of others and those patients nearing death.

Sunday, October 19, 2014

Comparison of anticoagulation strategies for acute VTE

There are now multiple strategies available. They were compared in a recent systematic review and meta-analysis:

Objective To summarize and compare the efficacy and safety outcomes associated with 8 anticoagulation options (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone) for treatment of venous thromboembolism.
Data Sources A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014.
Study Selection Eligible studies were randomized trials reporting rates of recurrent venous thromboembolism and major bleeding in patients with acute venous thromboembolism. Of the 1197 studies identified, 45 trials including 44 989 patients were included in the analyses.
Data Extraction and Synthesis Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. The data were pooled using network meta-analysis.
Main Outcomes and Measures The primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively.
Results Compared with the LMWH–vitamin K antagonist combination, a treatment strategy using the UFH–vitamin K antagonist combination was associated with an increased risk of recurrent venous thromboembolism (hazard ratio [HR], 1.42; 95% credible interval [CrI], 1.15-1.79). The proportion of patients experiencing recurrent venous thromboembolism during 3 months of treatment were 1.84% (95% CrI, 1.33%-2.51%) for the UFH–vitamin K antagonist combination and 1.30% (95% CrI, 1.02%-1.62%) for the LMWH–vitamin K antagonist combination. Rivaroxaban (HR, 0.55; 95% CrI, 0.35-0.89) and apixaban (HR, 0.31; 95% CrI, 0.15-0.62) were associated with a lower risk of bleeding than was the LMWH–vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49% (95% CrI, 0.29%-0.85%) for rivaroxaban, 0.28% (95% CrI, 0.14%-0.50%) for apixaban, and 0.89% (95% CrI, 0.66%-1.16%) for the LMWH–vitamin K antagonist combination.
Conclusions and Relevance Using meta-analytic pooling, there were no statistically significant differences for efficacy and safety associated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH–vitamin K antagonist combination. However, findings suggest that the UFH–vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding.

Saturday, October 18, 2014

Cocaine related Aortic Dissection

From the International Registry of Acute Aortic Dissection:

Our study analyzed 3584 patients enrolled in the International Registry of Acute Aortic Dissection from 1996 to 2012. We divided the population on the basis of documented cocaine use (C+) versus noncocaine use (C-) and further stratified the cohorts into type A (33 C+/2332, 1.4%) and type B (30 C+/1252, 2.4%) dissection.

C+ patients presented at a younger age and were more likely to be male and black. Type B dissections were more common among C+ patients than in C- patients. Cocaine-related acute aortic dissection was reported more often at US sites than at European sites (86.4%, 51/63 vs 13.6%, 8/63; P less than .001). Tobacco use was more prevalent in the C+ cohort. No differences were seen in history of hypertension, known atherosclerosis, or time from symptom onset to presentation. Type B C+ patients were more likely to be hypertensive at presentation. C+ patients had significantly smaller ascending aortic diameters at presentation. Acute renal failure was more common in type A C+ patients; however, mortality was significantly lower in type A C+ patients.

Cocaine use is implicated in 1.8% of patients with acute aortic dissection. The typical patient is relatively young and has the additional risk factors of hypertension and tobacco use. In-hospital mortality for those with cocaine-related type A dissection is lower than for those with noncocaine-related dissection, likely due to the younger age at presentation.

Friday, October 17, 2014

The cardiometabolic risks attributable to chronic inflammtory diseases

From Circulation:

Background—This study sought to evaluate whether risks of diabetes mellitus and cardiovascular disease are elevated across a range of organ-specific and multisystem chronic inflammatory disorders.
Methods and Results—A matched cohort study was implemented in the UK Clinical Practice Research Datalink including participants with severe psoriasis (5648), mild psoriasis (85 232), bullous skin diseases (4284), ulcerative colitis (12 203), Crohn’s disease (7628), inflammatory arthritis (27 358), systemic autoimmune disorders (7472), and systemic vasculitis (6283) and in 373 851 matched controls. The main outcome measures were new diagnoses of type 2 diabetes mellitus, stroke, or coronary heart disease... The hazard ratio for pooled multiple failure estimate was 1.20 (95% confidence interval [CI], 1.15–1.26). The highest relative hazards were observed in systemic autoimmune disorders (1.32; 95% CI, 1.16–1.50) and systemic vasculitis (1.29; 95% CI, 1.16–1.44). Hazards were increased in organ-specific disorders, including severe psoriasis (1.29; 95% CI, 1.12–1.47) and ulcerative colitis (1.26; 95% CI, 1.14–1.40). Participants in the highest tertile of C-reactive protein had greater risk of multiple outcomes (1.52; 95% CI, 1.37–1.68).
Conclusions—The risk of cardiovascular diseases and type 2 diabetes mellitus is increased across a range of organ-specific and multisystem chronic inflammatory disorders with evidence that risk is associated with severity of inflammation. Clinical management of patients with chronic inflammatory disorders should seek to reduce cardiovascular risk.

Thursday, October 16, 2014

Brand name versus generic statins

Generic statins had a slight edge in this study, likely due to better adherence:

Measurements: Adherence to statin therapy (measured as the proportion of days covered [PDC] up to 1 year) and a composite outcome comprising hospitalization for an acute coronary syndrome or stroke and all-cause mortality. Hazard ratios (HRs) and absolute rate differences were estimated.
Results: A total of 90 111 patients who initiated a statin during the study was identified; 83 731 (93%) initiated a generic drug, and 6380 (7%) initiated a brand-name drug. The mean age of patients was 75.6 years, and most (61%) were female. The average PDC was 77% for patients in the generic group and 71% for those in the brand-name group (P less than 0.001). An 8% reduction in the rate of the clinical outcome was observed among patients in the generic group versus those in the brand-name group (HR, 0.92 [95% CI, 0.86 to 0.99]). The absolute difference was −1.53 events per 100 person-years (CI, −2.69 to −0.19 events per 100 person-years).
Limitation: Results may not be generalizable to other populations with different incomes or drug benefit structures.
Conclusion: Compared with those initiating brand-name statins, patients initiating generic statins were more likely to adhere and had a lower rate of a composite clinical outcome.

Wednesday, October 15, 2014

What works in ARDS?

Here are results from an umbrella review---a review of all RCTs and meta-analyses:

We searched PubMed, the Cochrane Library, and Web of Knowledge until July 2013. We included RCTs in ARDS published in English. We excluded trials of newborns and children; and those on short-term interventions, ARDS prevention, or post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this field that addressed mortality. Treatment modalities were grouped in five categories: mechanical ventilation strategies and respiratory care, enteral or parenteral therapies, inhaled/intratracheal medications, nutritional support, and hemodynamic monitoring.

We identified 159 published RCTs of which 93 had overall mortality reported (n = 20,671 patients)--44 trials (14,426 patients) reported mortality as a primary outcome. A statistically significant survival benefit was observed in eight trials (seven interventions) and two trials reported an adverse effect on survival. Among RCTs with more than 50 deaths in at least one treatment arm (n = 21), two showed a statistically significant mortality benefit of the intervention (lower tidal volumes and prone positioning), one showed a statistically significant mortality benefit only in adjusted analyses (cisatracurium), and one (high-frequency oscillatory ventilation) showed a significant detrimental effect. Across 29 meta-analyses, the most consistent evidence was seen for low tidal volumes and prone positioning in severe ARDS.

Via Intensive care medicine worth knowing.

Sunday, October 12, 2014

Hepatic emergencies

A podcast and show notes from FOAM was linked here at EM Basic.

A few points and questions of interest raised in the post:

Do abnormal coags preclude paracentesis?

It's controversial and ultimately boils down to an assessment of benefit versus risk. Some authorities give a relative contraindication when the INR is greater than 2. Others emphasize clinical bleeding risk (clinical evidence of DIC or fibrinolysis) over laboratory values. Similar controversy exists regarding whether to give blood products in an attempt to reverse coagulopathy prior to paracentesis.

SBP prophylaxis in cirrhotic patients with upper GI bleeding

Some evidence suggests a NNT for mortality of 22 according to the notes.

Is ammonia measurement helpful in diagnosing and monitoring hepatic encephalopathy?

The discussants say categorically no. I think that position is a little extreme, in that controversy surrounds the question. There are data showing that the level of ammonia correlates with the presence or absence of HE and with its severity, even if the correlation is poor. There are caveats in using blood ammonia, and when patients present altered they need a thorough work up even if the ammonia is very high.

Amoxicillin-clavulanate is high on the list of drugs that cause liver injury

This was news to me but per the pod cast and notes the NIH reports it as number one, believed to be due to the clavulanate component. It is a mixed hepatocellular and cholestatic pattern.

And for some more pearls, particularly the interpretation of lab values in liver emergencies, see the slides and lecture notes by Nick Genes linked here. (Note: the acuity classification for liver failure seems to get tweaked just about every time I see a liver talk, and Nick's is no exception).

Saturday, October 11, 2014

Epinephrine in non-shockable cardiac arrest

For the last several years there has been this emerging idea in the resuscitation field that “drugs don't work.” Well, that idea has been challenged by this paper:

119,978 adults from 570 hospitals who had a cardiac arrest in hospital with asystole (55%) or pulseless electrical activity (45%) as the initial rhythm. Of these, 83,490 arrests were excluded because they took place in the emergency department, intensive care unit, or surgical or other specialty unit, 10,775 patients were excluded because of missing or incomplete data, 524 patients were excluded because they had a repeat cardiac arrest, and 85 patients were excluded as they received vasopressin before the first dose of epinephrine. The main study population therefore comprised 25,095 patients. The mean age was 72, and 57% were men.

The primary outcome was survival to hospital discharge. Secondary outcomes included sustained return of spontaneous circulation, 24 hour survival, and survival with favorable neurologic status at hospital discharge.

25,095 adults had in-hospital cardiac arrest with non-shockable rhythms. Median time to administration of the first dose of epinephrine was 3 minutes (interquartile range 1-5 minutes). There was a stepwise decrease in survival with increasing interval of time to epinephrine (analyzed by three minute intervals): adjusted odds ratio 1.0 for 1-3 minutes (reference group); 0.91 (95% confidence interval 0.82 to 1.00; P=0.055) for 4-6 minutes; 0.74 (0.63 to 0.88; P less than 0.001) for 7-9 minutes; and 0.63 (0.52 to 0.76; P less than 0.001) for greater than 9 minutes. A similar stepwise effect was observed across all outcome variables.

In patients with non-shockable cardiac arrest in hospital, earlier administration of epinephrine is associated with a higher probability of return of spontaneous circulation, survival in hospital, and neurologically intact survival.

Via Intensive care medicine worth knowing.

Friday, October 10, 2014

Political trends among U.S. physicians

From 1991 to 2012 there has been a shift from Republican to Democrat and more polarization among specialties.

From JAMA Internal Medicine:

Design, Setting, and Participants We explored partisan differences in physician contributions by sex, for-profit vs nonprofit practice setting, and specialty using multiple regression analysis. We studied the relation between the variation in the mean annual income across specialties and the mean percentage of physicians within each specialty contributing to Republicans...
Results Between the 1991 to 1992 and the 2011 to 2012 election cycles, physician campaign contributions increased from $20 million to $189 million, and the percentage of active physicians contributing increased from 2.6% to 9.4%. Of physicians who contributed during the study period, the mean percentage contributing to Republicans was 57% for men and 31% for women. Since 1996, the percentage of physicians contributing to Republicans has decreased, to less than 50% in the 2007 to 2008 election cycle and again in the 2011 to 2012 election cycle. Contributions to Republicans in 2011 to 2012 were more prevalent among men vs women (52.3% vs 23.6%), physicians practicing in for-profit vs nonprofit organizations (53.2% vs 25.6%), and surgeons vs pediatricians (70.2% vs 22.1%). In 1991 to 1992, these contribution gaps were smaller: for sex, 54.5% vs 30.9%; for organizations, 54.2% vs 40.0%; and for specialty, 65.5% vs 32.7%. The percentage of physicians contributing to Republicans across specialties correlated 0.84 with the mean log earnings of each specialty; specialties with higher mean earnings had higher percentages of physicians contributing to Republicans.

Thursday, October 09, 2014

ARISE! Everyone got EGDT!

After release of the ProCESS results many bloggers, particularly in the field of emergency medicine, began crowing that early goal directed therapy (EGDT) for septic shock was dead. Many of them openly admitted to having had a death wish on EGDT for some time. My take on ProCESS was a bit different:

What does this all mean?
“Usual care” for sepsis has, over the past decade, incorporated evidence based process improvements, including the principles of EGDT. This is attributable in large part to the Surviving SepsisCampaign, which was once criticized as a marketing campaign disguised as evidencebased medicine.
“Usual care” has now improved to the point where system improvements in the form of bundles may no longer be important...
The real questions addressed by this study concerned which specific components of the resuscitation bundle (EGDT) need to be preserved and which can be dispensed with. It appears now that dobutamine and aggressive transfusion will take a back seat.
That leaves us with the question of the central line. From the ProCESS trial we can conclude that clinical volume assessment is an acceptable alternative to CVP monitoring in many patients. Central venous oxygen saturation is not essential (lactate measurements and clinical parameters are reasonable surrogates).

Now ARISE has been released and the EGDT death wishers have erupted again. I won't go into the details of the paper here. The full text and an appendix detailing what the patients received are available at the link. Suffice it to say: although fewer patients among the controls got a central line (most did though) or received vasoactive drugs (most did in both groups) treatment in the two groups was largely the same.

What was actually being compared in this study? To me it was
strictly protocolized EGDT versus EGDT minus the SVO2 monitor with more room for clinical judgment.

In perspective

What do the Rivers study, ProCESS and ARISE tell us? Here's my take:

Volume assessment remains important but the best way to do so is unknown. Do it via CVP, physical exam or other means, however you will.

Assessment of tissue perfusion is important but the best method is unknown, whether via SVO2, lactate monitoring or bedside clinical examination.

Lower transfusion targets can be applied to septic shock just as in other conditions.

Since publication of the Rivers study “usual care” has risen to the standard of EGDT due to uptake of the Surviving Sepsis guidelines.

Guidelines and pathways must leave room for clinical judgment if evidence is to be applied for all it's worth.

EGDT is not dead. The notion is sound. How best to set resuscitation goals and monitor their achievement is not as simple as some have thought.

Sources of information used by emergency medicine residents

Leaders in academic emergency medicine have been among the more vocal proponents of evidence based medicine. They have also been strong advocates for the use of social media as learning resources. So this survey on how EM residents search for information was interesting:

Outcomes: Of the 401 residents who received the e-mailed survey, 226 (56.3%) completed it. Of these, 97.7% reported spending at least one hour per week engaging in extracurricular education, and 34.5% reported spending two to four hours per week (P less than .001). Time listening to podcasts was the most popular (reported by 35.0% of residents), followed by reading textbooks (33.6%) and searching Google (21.4%; P less than .001). Residents endorsed podcasts as the most beneficial (endorsed by 70.3%) compared with textbooks (endorsed by 54.3%), journals (36.5%), and Google (33.8%; P less than .001). Most respondents reported evaluating the quality of evidence or reviewing references “rarely” or less than half the time. A majority (80.0%) selected the topics they accessed based on recent clinical encounters.
Next Steps: The results suggest that residents are using more open access interactive multimedia tools. Medical educators must engage with current learners to guide appropriate use of these.

It's interesting how trends in the real world, even the academic real world, differ from the “official” positions on EBM in which these types of resources are discouraged.

Wednesday, October 08, 2014

Hospitalist medicine: primary care medicine's deal with the devil

Rob Lamberts, a clinic based physician who some time ago began turning his inpatients over to hospitalist care recently posted in the ACP Hospitalist blog concerning his experience with the model. The picture he paints here is one of fragmented communication, bewildered patients and downright poor care.

We have to be careful about generalizations. This is an anecdote, and not all hospitalist programs function this way. There are some good ones and some bad ones. But I've heard this story before from many settings. Why does this problem persist even as the hospitalist movement has matured over almost two decades? The answer that first comes to mind is the discontinuity of patient care that is built into the model but that's only a small part of the problem. The real problem is that the field of hospital medicine has become so bogged down with useless metrics and artificial quality surrogates that it has neglected the old fashioned basics of excellent patient care.

Catheter directed thrombolysis for DVT

From a recent observational study:

Objectives The primary objective was to compare in-hospital outcomes of CDT plus anticoagulation with those of anticoagulation alone. The secondary objective was to evaluate the temporal trends in the utilization and outcomes of CDT in the treatment of proximal DVT.

Design, Setting, and Participants Observational study of patients with a principal discharge diagnosis of proximal or caval DVT from 2005 to 2010 in the Nationwide Inpatient Sample (NIS) database. We compared patients treated with CDT plus anticoagulation with the patients treated with anticoagulation alone…

Results Among a total of 90 618 patients hospitalized for DVT (national estimate of 449 200 hospitalizations), 3649 (4.1%) underwent CDT. The CDT utilization rates increased from 2.3% in 2005 to 5.9% in 2010. Based on the propensity-matched comparison, the in-hospital mortality was not significantly different between the CDT and the anticoagulation groups (1.2% vs 0.9%) (OR, 1.40 [95% CI, 0.88-2.25]) (P = .15). The rates of blood transfusion (11.1% vs 6.5%) (OR, 1.85 [95% CI, 1.57-2.20]) (P less than .001), pulmonary embolism (17.9% vs 11.4%) (OR, 1.69 [95% CI, 1.49-1.94]) (P less than .001), intracranial hemorrhage (0.9% vs 0.3%) (OR, 2.72 [95% CI, 1.40-5.30]) (P = .03), and vena cava filter placement (34.8% vs 15.6%) (OR, 2.89 [95% CI, 2.58-3.23]) (P less than  .001) were significantly higher in the CDT group. The CDT group had longer mean (SD) length of stay (7.2 [5.8] vs 5.0 [4.7] days) (OR, 2.27 [95% CI, 1.49-1.94]) (P less than .001) and higher hospital charges ($85 094 [$69 121] vs $28 164 [$42 067]) (P less than .001) compared with the anticoagulation group.

Conclusions and Relevance In this study, we did not find any difference in the mortality between the CDT and the anticoagulation groups, but evidence of higher adverse events was noted in the CDT group.

Tuesday, October 07, 2014

Meta-analysis of resuscitation fluid types in sepsis

From the Annals of Internal Medicine:

Data Synthesis: 14 studies (18 916 patients) were included with 15 direct comparisons. Network meta-analysis at the 4-node level showed higher mortality with starches than with crystalloids (high confidence) and lower mortality with albumin than with crystalloids (moderate confidence) or starches (moderate confidence). Network meta-analysis at the 6-node level showed lower mortality with albumin than with saline (moderate confidence) and low-molecular-weight starch (low confidence) and with balanced crystalloids than with saline (low confidence) and low- and high-molecular-weight starches (moderate confidence).
Limitations: These trials were heterogeneous in case mix, fluids evaluated, duration of fluid exposure, and risk of bias. Imprecise estimates for several comparisons in this network meta-analysis contribute to low confidence in most estimates of effect.
Conclusion: Among patients with sepsis, resuscitation with balanced crystalloids or albumin compared with other fluids seems to be associated with reduced mortality.

Meta-analysis of albumin administration in sepsis

This new meta-analysis is of interest in light of the recent ALBIOS trial.

From the paper:

Results Eighteen articles reporting on 16 primary clinical trials that included 4190 adults in critical or intensive care with sepsis, severe sepsis, or septic shock. A median of 70.0 g daily of pooled human albumin was received over a median of 3 days by adults with a median age of 60.8 years as part of fluid volume expansion and resuscitation, with or without correction of hypoalbuminaemia. The relative risk of death was similar between albumin groups (that received a median of 175 g in total) and control fluid groups (relative risk 0.94; 95% confidence interval 0.87 to 1.01; P=0.11; I2=0%). Trial sequential analysis corrected the 95% confidence interval for random error (0.85 to 1.02; D2=0%). Eighty eight per cent of the required information size (meta-analysis sample size) of 4894 patients was achieved, and the cumulative effect size measure (z score) entered the futility area, supporting the notion of no relative benefit of albumin (GRADE quality of evidence was moderate). Evidence of no difference was also found when albumin was compared with crystalloid fluid (relative risk 0.93; 0.86 to 1.01; P=0.07; I2=0%) in 3878 patents (GRADE quality of evidence was high; 79.9% of required information size) or colloid fluids in 299 patients (relative risk 1.04; 0.79 to 1.38; P=0.76; I2=0%) (GRADE quality of evidence was very low; 5.8% of required information size). When studies at high risk of bias were excluded in a predefined subgroup analysis, the finding of no mortality benefit remained, and the cumulative z score was just outside the boundary of futility. Overall, the meta-analysis was robust to sensitivity, subgroup, meta-regression, and trial sequential analyses.
Conclusions In this analysis, human albumin solutions as part of fluid volume expansion and resuscitation for critically unwell adults with sepsis of any severity (with or without baseline hypoalbuminaemia) were not robustly effective at reducing all-cause mortality. Albumin seems to be safe in this setting, as a signal towards harm was not detected, but this analysis does not support a recommendation for use.

What do high ferritin levels signify?

It depends on how high. From The Bottom Line:

Bottom line: Out of all adult patients with a least 1 serum ferritin level greater than 1,000μg/L from 2008-2010 (n=627), 153 had a malignancy, and 136 had iron-overload syndromes. Average ferritin level for the 6 patients with either adult-onset Still’s disease, systemic juvenile idiopathic arthritis, or hemophagocytic lyphohistiocytosis/macrophage activation syndrome was 14,242μg/L.

Monday, October 06, 2014

Angiotensin receptor–neprilysin inhibition with LCZ696 in heart failure with systolic dysfunction

From the PARADIGM-HF trial, published in NEJM:

We compared the angiotensin receptor–neprilysin inhibitor LCZ696 with enalapril in patients who had heart failure with a reduced ejection fraction. In previous studies, enalapril improved survival in such patients.

In this double-blind trial, we randomly assigned 8442 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure, but the trial was designed to detect a difference in the rates of death from cardiovascular causes.

The trial was stopped early, according to prespecified rules, after a median follow-up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. At the time of study closure, the primary outcome had occurred in 914 patients (21.8%) in the LCZ696 group and 1117 patients (26.5%) in the enalapril group (hazard ratio in the LCZ696 group, 0.80; 95% confidence interval [CI], 0.73 to 0.87; P less than 0.001). A total of 711 patients (17.0%) receiving LCZ696 and 835 patients (19.8%) receiving enalapril died (hazard ratio for death from any cause, 0.84; 95% CI, 0.76 to 0.93; P less than 0.001); of these patients, 558 (13.3%) and 693 (16.5%), respectively, died from cardiovascular causes (hazard ratio, 0.80; 95% CI, 0.71 to 0.89; P less than 0.001). As compared with enalapril, LCZ696 also reduced the risk of hospitalization for heart failure by 21% (P less than 0.001) and decreased the symptoms and physical limitations of heart failure (P=0.001). The LCZ696 group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment, hyperkalemia, and cough than the enalapril group.

LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure. (Funded by Novartis; PARADIGM-HF number, NCT01035255.)

Ebola virus review

From a free full text review in Intensive Care Medicine:

It is transmitted by direct contact through broken skin or mucous membranes with blood, urine, saliva, faeces, vomit, and other body fluids of symptomatic infected patients or convalescent persons, or through contaminated needle sticks [1, 2. The current outbreak in West Africa probably began in December 2013 in Guinea [3], and is causing unprecedented concerns for the following reasons: (1) it is due to a strain with 97 % homology with Zaire ebolavirus, the most virulent species, with prior fatality rates as high as 90 %; (2) as of August 22, 2014, four countries have been involved, with 2,615 suspected cases, 1,528 laboratory-confirmed cases, and 1,427 related deaths, which is already many more than the largest epidemic reported to date (425 cases in Uganda, 2000–2001), and the situation is unlikely to be resolved soon [4, 5]; (3) the 2014 West Africa outbreak affects rural as well as urban areas, and recently reached the most populous African country (Nigeria); and (4) experienced governmental and non-governmental organizations, including Médecins Sans Frontières, have been active on the field since March 2014 [3], but have failed to control the epidemic.
Many factors contributed to this failure, including population poverty and authorities’ distrust, disease denial in the context of strong religious beliefs, porous borders, weaknesses in public health systems, and inadequate salaries and lack of adequate protection for health care workers.

Use of on line resources by medical professionals

This article focuses on social media and has tutorial videos for Twitter and RSS readers. Almost all of these resources are free. Users can be overwhelmed because, like primary journal articles, they are now proliferating exponentially. As far as I can tell emergency medicine physicians are the leaders in the promotion and adoption of this technology. Despite that, recognition by academic medicine remains poor overall.

There is a lot of discussion on how to organize and vet these resources but nothing is settled. This is nothing new. In my nine years in the blogosphere I have seen many such efforts come and go. Nothing will ever be settled except for this: caveat emptor. Ultimate responsibility lies with the user. It's a jungle, but so too with books and journals.

Via Clinical Cases and Images.

Sunday, October 05, 2014

Competing views on Twitter for scientific topics

An interesting discussion was linked at Clinical Cases and Images. I can see both sides. For me it is a great repository of links to direct readers to primary sources. But I was particularly interested in this comment:

Twitter is ill-suited for nuanced, in-depth scientific discussions. The tweets are only 140-characters after all, and it is difficult to follow a conversation because every single tweet is a separate web page. Tweet materials that appeal to a general audience, rather than complex scientific papers.

Should scientific discussions ever be anything but nuanced and in-depth? I am a little concerned that Twitter is extending the sound bite culture of the TV watching general audiences into the professional arena. Not so good in my view.

Saturday, October 04, 2014

Does pneumococcal vaccine help? It's complicated.

I love vaccinations. But I have to be honest about the pneumococcal polysaccharide vaccine (PPV) that's been the focus of a publicly reported core measure for years. The evidence is weak. And why? Because so is the vaccine itself, compared to the newer conjugate vaccine as noted in a recent review post at Clinical Correlations:

In the late 1990s, Prevnar 7 was introduced to the US market; it covalently attached the capsular polysaccharide to the highly immunogenic modified diphtheria toxin protein [1]. The result was a more robust immune response that proved effective in children [7]. Coverage was later expanded by 6 serotypes for the development of Prevnar 13, a 13-valent pneumococcal conjugate vaccine (PCV13) [8]. The vaccination was approved for universal use in children to protect against the 13 most common disease-causing S. pneumoniae serotypes in this population [7]. Twelve of the serotypes in PCV13 are also included in the PPSV23 vaccination, serotype 8 is covered by PPSV23 but not PCV13, serotype 6A is covered by PCV13 but not PPSV 23 [5,3].
In 2012, the ACIP recommended the use of PCV13 for specific adult patients, given the vaccination’s vigorous and long-lasting immune response [9]. PPSV23 provides T-cell independent antigens that produce IgG antibodies but have limited immune memory. The stronger immune activation by PCV13 provides T-cell stimulation resulting in higher titers of IgG, memory cell activation, and IgA antibodies that protect mucosal surfaces [9,10]. Studies comparing IgG levels after PCV and PPSV administration have shown much higher titer levels after PCV injection [9,10,11].

The weakness of the evidence in favor of PPV was illustrated in a Cochrane review linked at the Clinical Correlations post:

Main results
Twenty-five studies met our inclusion criteria (18 RCTs involving 64,852 participants and seven non-RCTs involving 62,294 participants). Meta-analysis of the RCTs found strong evidence of PPV efficacy against IPD with no statistical heterogeneity (OR 0.26, 95% CI 0.14 to 0.45; random-effects model, I2 statistic = 0%). There was efficacy against all-cause pneumonia in low-income (OR 0.54, 95% CI 0.43 to 0.67, I2 statistic = 19%) but not high-income countries in either the general population (OR 0.71, 95% CI 0.45 to 1.12, I2 statistic = 93%) or in adults with chronic illness (OR 0.93, 95% CI 0.73 to 1.19, I2 statistic = 10%). PPV was not associated with substantial reductions in all-cause mortality (OR 0.90, 95% CI 0.74 to 1.09; random-effects model, I2 statistic = 69%). Vaccine efficacy against primary outcomes appeared poorer in adults with chronic illness. Non-RCTs provided evidence for protection against IPD in populations for whom the vaccine is currently utilised (OR 0.48, 95% CI 0.37 to 0.61; random-effects model, I2 statistic = 31%). This review did not consider adverse events as it was outside the scope of the review.

Authors' conclusions
This meta-analysis provides evidence supporting the recommendation for PPV to prevent IPD in adults. The evidence from RCTs is less clear with respect to adults with chronic illness. This might be because of lack of effect or lack of power in the studies. The meta-analysis does not provide evidence to support the routine use of PPV to prevent all-cause pneumonia or mortality.

Weak. Modest at best. It doesn't really prevent pneumonia, at least in the patients we see, nor does it lower mortality. For invasive disease the relative risk reduction looks robust but the absolute risk reduction is low. The NNT must be very very high.

Patients I admit with pneumonia seem to exhibit more skepticism than many of today's policy makers. “I got the shot. How could I now have pneumonia?” they ask.

I believe pneumococcal vaccination is the right thing to do but there's no bang for the buck with PPV. Making PPV a core measure was poorly informed. If vaccination is to remain a core measure I believe PCV should be the singular focus but there remains some debate around that question.

Friday, October 03, 2014

Ebola precautions in U.S. hospitals

Many hospitals, apparently, are going beyond the current evidence based recommendations to meet the Ebola threat.

From a recent Annals of Internal Medicine piece:

The CDC recommends placing patients with suspected or confirmed Ebola in a single-patient room and instituting contact and droplet precautions (1). These entail donning a fluid-impermeable gown, gloves, a surgical mask, and either goggles or a face shield. If the patient has “copious” secretions, the CDC also recommends shoe and leg coverings. If an aerosol-generating procedure is planned (such as intubation or bronchoscopy), the CDC recommends wearing an N95 mask and placing the patient in a negative-pressure room. Despite this guidance, many hospitals are planning to place all patients in negative-pressure rooms at all times, to compel all personnel to wear full-body hazardous material (HazMat) suits, and to require N95 masks or powered air-purifying respirators rather than surgical masks at all times...
Sharing airspace with an infected patient is not a risk factor. Transmission requires direct physical contact and is inefficient...
Exceeding these recommendations may paradoxically increase risk. Introducing new and unfamiliar forms of personal protective equipment could lead to self-contamination during removal of such gear. Requiring HazMat suits and respirators will probably decrease the frequency of provider–patient contacts, inhibit providers' ability to examine patients, and curtail the use of diagnostic tests.

Nonspecific ST-T changes: nonspecific but not necessarily insignificant

The point is illustrated in this post at the ECG Interpretation blog.

Two important points were made:

We should not be so dismissive about the common ECG reading “NSST-T abnormality.”

ST segment flattening, even if the segment is isoelectric, is abnormal and suggests ischemia.
Barney Marriott was fond of saying that the ST segment “should never hug the baseline.”

Thursday, October 02, 2014

The beta blocker contraindication in cocaine associated chest pain: a myth?

From a recent study:

Beta blockers are indicated for management of acute coronary syndromes, but they generally are withheld in patients with cocaine-associated chest pain because of concerns for adverse outcomes related to the unique physiological effects of cocaine. Because few clinical studies have evaluated this interaction, we identified patients with toxicology screen results positive for cocaine treated for chest pain at 2 academic hospitals...patients treated with β blockers experienced similar peak troponin levels, individual adverse events, and rates of the composite primary end point (15.9% vs 12.3%, p = 0.32). The primary end point also was similar after propensity score analysis (odds ratio 1.37, 95% confidence interval 0.64 to 2.93, p = 0.42), including specific comparisons of beta-1 selective (odds ratio 1.83, 95% confidence interval 0.79 to 4.24) and nonselective (odds ratio 0.90, 95% confidence interval 0.33 to 2.42) β blockers, when compared with patients not receiving β blockers. In conclusion, no differences in outcomes were observed between patients treated versus not treated with β-blocker therapy in the setting of cocaine-related chest pain.