Evidence based approach to the diagnosis of DVT

Clear and concise.

Disruptive behavior

I guess now we’re supposed to call it horizontal violence? Whatever you call it, under today’s broad definition it’s pretty common.  And don’t forget, the Joint Commission standard for this applies to all across the organization, not just the docs.

Top social media posts on derm emergencies

Reported here.

Clots in unusual places

Form a recent review:

Highlights

•The diagnosis of SVT and CVT relies exclusively on imaging tests.

•No clinical algorithms or specific laboratory tests are available.

•Abdominal US, CT and MR with angiography are performed for the diagnosis of SVT.

•Cerebral CT and MR with angiography are performed for the diagnosis of CVT.

•Conventional angiography, once the gold standard, is rarely used nowadays.

Abstract

Splanchnic vein thrombosis (SVT) and cerebral vein thrombosis (CVT) are uncommon manifestation of venous thromboembolism (VTE), occurring less frequently than deep vein thrombosis of the lower extremities and pulmonary embolism.

SVT encompasses portal vein thrombosis, mesenteric vein thrombosis, splenic vein thrombosis and the Budd-Chiari syndrome. It is therefore a heterogeneous disease, with differences in clinical manifestations according to the site of thrombosis.

CVT includes thrombosis of the cortical or deep cerebral veins and thrombosis of the major dural venous sinuses. Clinical presentation is variable, with a wide spectrum of signs and symptoms that can mimic other cerebral diseases.

There are no clinical algorithms or specific laboratory tests that can guide in the identification of SVT and CVT; therefore, the diagnosis relies exclusively on imaging tests. Conventional angiography once was the gold standard for the diagnosis of SVT and CVT, but it is rarely used nowadays. Abdominal ultrasound (US), computed tomography (CT) and magnetic resonance (MR) with angiography are currently used for the diagnosis of SVT; while cerebral CT and MR with angiography are currently used for the diagnosis of CVT. These imaging tests have different sensitivities/specificities and different advantages/disadvantages that should be kept into consideration when choosing the appropriate imaging test based on the suspected site of thrombosis.

This narrative review summarizes the clinical and diagnostic approach to SVT and CVT.

Currently recommended transfusion thresholds may be associated with higher mortality in pneumonia

A hemoglobin target of around 8 may be more appropriate in pneumonia.

An increasing body of research suggests that a one size fits all recommendation may not be appropriate.

Management of recurrent VTE in cancer patients

Here is a recent review. Form the review:

Venous thromboembolism (VTE) occurs in 10–20%% of patients with cancer and is associated with significant mortality and morbidity in these patients. The current standard of care recommended by international guidelines is to use low-molecular-weight heparin (LMWH) for 6 months for the management of cancer-associated thrombosis (CAT), which is based on evidence from randomized controlled trials demonstrating that LMWH significantly reduced the risk of recurrent VTE compared with vitamin K antagonists. However, patients with CAT have a high risk of VTE recurrence of up to 20% despite receiving anticoagulation. Reasons for recurrent VTE may include non-compliance, temporary cessation of therapy due to bleeding or for procedures, inadequate dosing, cancer progression, and the presence of heparin-induced thrombocytopenia. Management of patients with CAT and recurrent VTE is not well defined. Management strategies for recurrent VTE include switching to LMWH if an oral anticoagulant is employed, dose escalation of LMWH, or as a last resort option consider insertion of a vena cava filter. In this review, we discuss the acute, long-term, and extended management of CAT, risk factors for recurrent VTE, and management of recurrent VTE.

Severely elevated BP

Treating it with IV bolus meds just because you can.

Bezlotoxumab (Zinplava) for prevention of recurrent C diff

Here’s a review in P&T on this recently approved agent.

Acquired von Willebrand disease in severe aortic stenosis: reversal with TAVR

From a recent paper:

Highlights

•Many patients undergoing TAVI exhibit, subclinical von VWF abnormalities

•TAVI leads to a restoration of a loss of HMW VWF multimers

•Reduced markers of VWF function may aid to identify patients at increased risk for periprocedural bleeding

Abstract

Background

In this study, we sought to analyze the incidence and relevance of von Willebrand factor (VWF) abnormalities in patients undergoing transcatheter aortic valve implantation (TAVI), especially on perioperative bleeding. Furthermore, we hypothesized that, similar to aortic valve surgery, TAVI results in a restoration of VWF abnormalities.

Methods and results

We performed a prospective analysis of periinterventional VWF parameters in 74 patients (80 ± 7 years, female in 37.5%) undergoing transfemoral TAVI for severe symptomatic aortic valve stenosis. At baseline, VWF:Ag was 210 ± 90 IU/dl with a mean VWF activity of 166 ± 106 IU/dl; activity-to-antigen ratio was 0.85 ± 0.45. Heyde's syndrome (severe aortic stenosis plus GI bleeding from angiodyplasia) was observed in 2/74 (2.7%). Whereas preprocedural loss of high-molecular-weight (HMW) VWF multimers was found in thirty-six patients (48.6%), none of the patients fulfilled criteria for possible acquired VW syndrome. After TAVI, an increase of both VWF:Ag and activity compared to baseline was observed (p less than 0.01). In patients with HMW multimer loss, post-interventional recovery of multimers occurred in all cases. In the two patients with Heyde's syndrome, a trend towards reduced VWF:Ag was seen, with loss of HMW multimers in one patient. Of interest, all patients suffering from periprocedural major bleeding (5/74; 6.8%) exhibited activity-to-antigen ratios less than 0.7, indicating subclinical VWF dysfunction.

Conclusion

Whereas clinically relevant VWF dysfunction is rare, loss of HMW VWF multimers is common in TAVI patients. Similar to surgery, TAVI leads to a restoration of this loss. Furthermore, VWF parameters may be useful parameter to evaluate risk of periprocedural bleeding.

Varicalla zoster pneumonia: an observational study

Free full text from Critical Care.

All received acyclovir. A small number getting adjunctive steroids had worse outcomes.

A case of Wellen’s syndrome

Report and brief review here.

The Winters formula and the thumb rule

The Winters formula is used to assess the appropriateness of the pCO2 response to metabolic acidosis (and thus determine whether a concomitant respiratory acid base disturbance exists). Here’s an interesting post from the archives of the Renal Fellow Network.

Settled science: female physicians are better docs

So says one of the authors of the much talked about study in his somewhat, shall we say, promotional blog posts. [1] [2]

Asymptomatic (incidentally discovered) microscopic hematuria: what’s the most cost effective way to work it up?

The combination of ultrasound and cystoscopy is the winner.

Rivaroxaban versus warfarin and recurrent VTE

From Lancet Hematology:

Methods

In this propensity-matched cohort study, we linked nationwide Danish health registries to identify all patients with a first hospital diagnosis of unprovoked VTE who were new users of rivaroxaban or warfarin. Excluded patients included those who had not been residents in Denmark for at least 1 year before VTE diagnosis, patients with outpatient VTE diagnosis only, patients with other indications for oral anticoagulation treatment, patients with previous experience of oral anticoagulation, patients who did not have a prescription for rivaroxaban or warfarin within 7 days of VTE, and patients who redeemed prescriptions for both rivaroxaban and warfarin, or other oral anticoagulants. Primary effectiveness outcome was recurrent VTE and primary safety outcome was major bleeding. We used propensity matching and Cox regression to compare rates of the outcomes with rivaroxaban versus standard treatment.

Results

From Dec 9, 2011, to Feb 28, 2016, we identified 29 963 patients with incident VTE. After exclusion, we identified 1734 propensity-matched patients given rivaroxaban (1751 before propensity matching) and 2945 propensity-matched patients given warfarin. The rate of recurrent VTE at 6 months' follow-up was 9·9 incidents per 100 person-years with rivaroxaban versus 13·1 incidents per 100 person-years with warfarin, yielding a hazard ratio (HR) of 0·74 (95% CI 0·56–0·96). The rate of major bleeding was 2·4 per 100 person-years at 6 months in rivaroxaban users versus 2·0 in warfarin users (HR 1·19, 95% CI 0·66–2·13).

Interpretation

In this clinical practice setting, rivaroxaban in patients with unprovoked VTE was associated with reduced risk of recurrent VTE compared with standard treatment, without compromising safety.

A related editorial pointed out the potential confounding effects of return visits for INR monitoring being interpreted as recurrent events.

Cardiac cachexia is associated with sympathetic nerve activity in skeletal muscle

From the AHA meeting abstracts:

Introduction: Cardiac cachexia is associated with poor prognosis in patients with heart failure (HF). Sympathetic overactivation might be implicated in the development of muscle wasting, considering the recent data that carvedilol significantly reversed body weight (BW) loss in HF patients…

Methods: We prospectively evaluated changes in BW in 108 non-edematous HFrEF patients in whom muscle sympathetic nerve activity (MSNA) was measured...

Results... One-year combined event rate was significantly higher in BW loss group...MSNA...was significantly higher in BW loss group than in non-BW loss group. Importantly, MSNA burst incidence had a moderate predictability for significant BW loss by receiver-operating characteristic analysis (area under the curve=0.794).

Conclusion: Sympathetic overactivation determined by MSNA could predict significant BW loss in HFrEF patients.

Herpes zoster ophthalmicus

Free full text review in the green journal.

UTI caused by ESBL producing bacteria

Piperacillin-tazobactam works when the lab tells you the isolate is susceptible to it.

Sleep and cardiovascular disease

From a review:

Abstract:

Purpose of review: Sleep plays many roles in maintenance of cardiovascular health. This review summarizes the literature across several areas of sleep and sleep disorders in relation to cardiometabolic disease risk factors.

Recent findings: Insufficient sleep duration is prevalent in the population and is associated with weight gain and obesity, inflammation, cardiovascular disease, diabetes, and mortality. Insomnia is also highly present and represents an important risk factor for cardiovascular disease, especially when accompanied by short sleep duration. Sleep apnea is a well-characterized risk factor for cardiometabolic disease and cardiovascular mortality. Other issues are relevant as well. For example, sleep disorders in pediatric populations may convey cardiovascular risks. Also, sleep may play an important role in cardiovascular health disparities.

Summary: Sleep and sleep disorders are implicated in cardiometabolic disease risk. This review addresses these and other issues, concluding with recommendations for research and clinical practice.

Intention to treat analysis in RCTs

What is it? Why is it important?

Hypokalemia

Free full text review.

Glucagon in the pathogenesis of DM 2: implications for drug therapy

Free full text review.

Using FOAM in the residency curriculum

Free full text article.

Drug interactions in the ICU

Multiple risk factors were identified in this study. Of particular interest was the lack of consistency among four popular interaction checkers.

Clinical pharmacists as ID docs in the ER?

Here are some interesting findings from the Western Journal of Emergency Medicine:

Introduction

Pneumonia impacts over four million people annually and is the leading cause of infectious disease-related hospitalization and mortality in the United States. Appropriate empiric antimicrobial therapy decreases hospital length of stay and improves mortality. The objective of our study was to test the hypothesis that the presence of an emergency medicine (EM) clinical pharmacist improves the timing and appropriateness of empiric antimicrobial therapy for community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP).

Methods

This was a retrospective observational cohort study of all emergency department (ED) patients presenting to a Midwest 60,000-visit academic ED from July 1, 2008, to March 1, 2016, who presented to the ED with pneumonia and received antimicrobial therapy. The treatment group consisted of patients who presented during the hours an EM pharmacist was present in the ED (Monday-Friday, 0900–1800). The control group included patients presenting during the hours when an EM clinical pharmacist was not physically present in the ED (Monday–Friday, 1800–0900, Saturday/Sunday 0000–2400 day). We defined appropriate empiric antimicrobial therapy using the Infectious Diseases Society of America consensus guidelines on the management of CAP, and management of HCAP.

Results

A total of 406 patients were included in the final analysis (103 treatment patients and 303 control patients). During the hours the EM pharmacist was present, patients were significantly more likely to receive appropriate empiric antimicrobial therapy (58.3% vs. 38.3%; p less than 0.001). Regardless of pneumonia type, patients seen while an EM pharmacist was present were significantly more likely to receive appropriate antimicrobial therapy (CAP, 77.7% vs. 52.9% p=0.008, HCAP, 47.7% vs. 28.8%, p=0.005). There were no significant differences in clinical outcomes.

Conclusion

The presence of an EM clinical pharmacist significantly increases the likelihood of appropriate empiric antimicrobial therapy for patients presenting to the ED with pneumonia.

The physical presence of clinical pharmacists in the ER was associated with more appropriate antibiotics according to this study, but we don’t know the nature of their involvement in treatment decisions. The HCAP designation used in the report is now considered obsolete and no longer recognized in the guidelines although it was appropriate for the time frame of the study. The major error in the control group was in categorization of patients as either CAP or HCAP. The strong implication is that pharmacists were better at diagnosing the type of pneumonia than the docs. There is something very wrong here.

IV bolus diltiazem followed by immediate release oral for patients presenting with rapid atrial fibrillation

This seemed to work as well as the traditional bolus-drip method in a small study and has potential to conserve resources.

Delafloxacin

Here’s that new fluoroquinolone everyone’s talking about.

Product labeling: Baxdela.

Are we practicing EBM in the treatment of ARDS?

Far from it, it seems. Just over a quarter of patients with ARDS in the study got low tidal volume ventilation. Moreover, only about half the patients meeting ARDS criteria were acknowledged as such.

Exercise, Parkinson disease and dementia

From a recent Mayo Clinic review:

Parkinson disease is a slowly progressive neurodegenerative condition; after many years, dementia or medication-refractory motor symptoms may develop.

A myriad of animal studies document a direct, favorable effect of aerobic-type exercise on the brain; this includes liberation of neurotrophic hormones and enhancement of a variety of neuroplasticity mechanisms. Exercise tends to protect animals from neurotoxins that induce parkinsonism.

Long-term exercise and fitness in healthy humans is associated with greater volumes of cerebral cortex and hippocampus and less age-related white matter pathology.

Midlife exercise is associated with a significantly reduced later risk of Parkinson disease.

Conclusion from this evidence: Regular aerobic-type exercise tending to lead to fitness is the single strategy with compelling evidence for slowing Parkinson disease progression. All patients with Parkinson disease should be encouraged to engage in regular such exercise.

Dealing with drug allergy

Drug Allergy: An Updated Practice Parameter is an official document promulgated by a collaboration of three professional societies. Although it is a bit dated it is the latest such edition written by the collaboration. Moreover, for penicillin allergy an update was published in Mayo Clinic Proceedings only months ago. The Mayo update generally follows the recommendations of this document. Below are some key points.

The overall classification of drug induced disease encompasses all types of adverse reactions, not just allergic reactions.

From the document:

ADRs are broadly categorized into predictable (type A) and unpredictable (type B) reactions. Predictable reactions are usually dose dependent, are related to the known pharmacologic actions of the drug…

Unpredictable reactions are generally dose independent, are unrelated to the pharmacologic actions of the drug, and occur only in susceptible individuals. Unpredictable reactions are subdivided into drug intolerance, drug idiosyncrasy, drug allergy, and pseudoallergic reactions.

Allergic reactions are defined as immunologic reactions. Although the Gell-Coombs classification remains the framework for thinking about allergic reactions, the current classification has been extended beyond that.

Categories outside the C-G classification include these below. Form the paper:

Hypersensitivity vasculitis Cutaneous or visceral vasculitis Hydralazine, penicillamine, propylthiouracil

DRESS Cutaneous, fever, eosinophilia, hepatic dysfunction, lymphadenopathy Anticonvulsants, sulfonamides, minocycline, allopurinol

Pulmonary drug hypersensitivity Pneumonitis, fibrosis Nitrofurantoin, bleomycin, methotrexate

Systemic drug-induced lupus erythematosus Arthralgias, myalgias, fever, malaise Hydralazine, procainamide, isoniazid

Cutaneous drug-induced lupus erythematosus Erythematous/scaly plaques in photodistribution Hydrochlorothiazide, calcium channel blockers, ACE inhibitors

Drug-induced granulomatous disease Churg-Strauss syndrome, Wegener's granulomatosis Propylthiouracil, leukotriene modifiers

Immunologic hepatitis Hepatitis, cholestatic jaundice Para-aminosalicylic acid, sulfonamides, phenothiazines

Blistering disorders Erythema multiforme, SJS, TEN Sulfonamides, cephalosporins, imidazole anticonvulsants, NSAIDs

Serum sickness–like reactions Erythema multiforme, arthralgias Cefaclor, cefprozil

Immunologic nephropathy Interstitial nephritis, membranous glomerulonephritis Penicillin, sulfonamides, gold, penicillamine, allopurinol

It should be mentioned that some of the categories listed above are poorly understood and may not represent purely immunologic mechanisms.

What is “desensitization?”

More from the paper:

What has often been referred to as drug desensitization is more appropriately described in this parameter as a temporary induction of drug tolerance. Drug tolerance is defined as a state in which a patient with a drug allergy will tolerate a drug without an adverse reaction. Drug tolerance does not indicate either a permanent state of tolerance or that the mechanism involved was immunologic tolerance. Induction of drug tolerance procedures modify a patient's response to a drug to temporarily allow treatment with it safely. They are indicated only in situations where an alternate non–cross-reacting medication cannot be used. Induction of drug tolerance can involve IgE immune mechanisms, non-IgE immune mechanisms, pharmacologic mechanisms, and undefined mechanisms ( Table 2 ). All procedures to induce drug tolerance involve administration of incremental doses of the drug. Through various mechanisms, these procedures induce a temporary state of tolerance to the drug, which is maintained only as long as the patient continues to take the specific drug.

Remember that this technique is recommend only when there is no reasonable alternative, and it doesn’t induce permanent tolerance.

There is also the idea of graded challenge, which is different from tolerance induction (desensitization). Graded challenge is essentially the administration of a test dose.

Remember this, too, from the paper:

Graded challenge (or induction of drug tolerance) should almost never be performed if the reaction history is consistent with a severe non–IgE-mediated reaction, such as SJS, TEN, interstitial nephritis, hepatitis, or hemolytic anemia.

The recommendations for dealing with beta lactam type I allergy are complex

If the allergic history is that of an anaphylactoid reaction there is almost no avoiding the use of special techniques such as skin testing or tolerance induction, were one to strictly follow the document recommendations. Clinical rules cannot assure safe administration of an antibiotic. Consider assessment of side chain similarity for the assessment of safety of cephalosporin administration, for example. Although side chain assessment can be of help in the assessment of risk, in the document there is no recommendation for using it as an assurance of safety. On the other hand, in a couple of cases it can be used to mandate avoidance (such as the use of aztreonam in a patient with an anaphylactoid reaction to ceftazidime).

The application of the special techniques of skin testing, test dosing and tolerance induction is complex and has many contingencies noted in the document and therefore requires expertise.

Practical aspects for the clinician in dealing with type 1 beta lactam allergy

Despite the complexities noted above one can be informed by data on absolute risk. For example, according to the Mayo paper, cross-reactivity between PCN and carbapenems is likely less than 1%, with similar risk for aztreonam. What should one do, for example, when confronted with a patient in septic shock with concern for pseudomonas and ESBL producing bacteria? Considering a mortality increase of 5-10% per hour of non coverage, can you get an allergist on site and skin testing done in time or does the risk of delay exceed a less than 1% chance of a reaction from a carbapenem?

Overview of mechanical ventilation and respiratory failure

Powerpoint from ATS.