Flea Bytes: Oral Edoxaban in VTE Prophylaxis in Cancer Patients

Open label non-inferiority trial of 1046 cancer patients (1050 randomized). Non-inferiority margin of 1.5 (HR 1.5), appears to have been randomly decided upon. Expected event rate of 20%, but had an event rate of 13%. Primary endpoint combined VTE and bleeding events which had a HR of 0.97. However, edoxaban improved VTE risk (not reaching statistical significance) by reducing DVTs, but not pulmonary embolism. Further, it had more bleeding, but the increased bleeding event severity was mostly category 2, while category 3 bleeding was similar. This was mostly upper GI bleeding and the authors note in the discussion section that it was mostly in patients with GI cancers and whined that the dalteparin bleeding rate was lower than previously reported.

My takeaway – edoxaban seems like a reasonable option for VTE prophylaxis in cancer patients, although it might increase bleeding risks.

Source: N Engl J Med 2018; 378:615-624

Flea Bytes: HHV-6 Encephalopathy

HHV-6 reactivation is one of the most common causes (in 30-70% of patients) of encephalitis in allo-SCT. It is a ubiquitous viral infection that remains latent and can reactivate after transplant.

Risk factors: HLA mismatch, T-cell depletion therapy, treatment with glucocorticoids, and the use of cord blood as a source of stem cells; 90% of cases of HHV-6 reactivation occur in patients who with cord-blood transplants.

Encephalitis presents as subacute confusion, but some may have a more progressive course. Anterograde amnesia, personality changes, irritability and seizures. SIADH is common.

CSF analysis shows mild lymphocytic pleocytosis and protein elevation.

Treatment is based on in-vitro susceptibility testing and foscarnet is therapy of choice. Can add ganciclovir if not clinically improving. But need to monitor closely for side effects including bone marrow suppression and electrolyte derangement which can predispose to seizures. Alternative therapy is cidofovir, but watch out for nephrotoxicity.  Duration is 3-6 weeks and you shouldn’t monitor PCR levels to shorten treatment duration.

Notes from: N Engl J Med 2018; 378:659-669

Flea Bytes: Duration of NG Tubes

  • You should consider a PEG in patients who are likely to require > 4-6 weeks of feeding and there is some evidence that you should consider it at 14 days
  • Polyurethane NG tubes (Dobhoff) should be replaced every 2 weeks due to the effects of gastric acid.
  • Long term NG/NJ tubes can be kept in place for 4-6 weeks

Flea Bytes: Treating Aspiration Pneumonia

For most patients: Ampicillin/Sulbactam is sufficient for oral aerobe/anaerobic coverage

For penicillin allergic patients: Clindamycin monotherapy covers oral aerobes/anaerobes

For hospital-acquired aspiration PNA: Coverage of aerobic bacteria, especially GPC and GNR are more important than anaerobes: Pip/Tazo or meropenem monotherapy

In patients with high risk factors for MRSA, can add an agent with MRSA activity but if MRSA is not detected, this agent should be discontinued

Flea Bytes: Heavy Metal Poisoning

How do patients with heavy metal toxicity present?

Here is a quick table:

Lead: Abdominal pain, irritability, fatigue, anemia, (confusion, seizure, encephalopathy at very high levels)

Cadmium: Interstitial Nephritis

Acute: Nausea, vomiting, severe watery diarrhea.

Chronic: Distal polyneuropathy


Acute: Chest pain, cough, dyspnea

Chronic: Mild neuropsychiatric symptoms with predominant tremor

Flea Bytes: Polymixin/Meropenem Synergy

Meta-analysis found in vitro synergy.  Especially in A baumanii. Mechanism unclear

Synergy testing can be done on isolate if available

Can not necessarily infer in vivo synergy (Beta-lactam/aminoglycoside synergy is demonstrated in vitro but NOT in vivo for example).

Systematic Review and Meta-Analysis of In Vitro Synergy of Polymyxins and Carbapenems. Antimicrobial Agents and Chemotherapy. October 2013 Volume 57 Number 10. p.5104 – 5111.

Tidings from the Citadel: Warfarin in Dialysis

Warfarin Use and the Risk for Stroke and Bleeding in Patients With Atrial Fibrillation Undergoing Dialysis – Mitesh Shah et al. Circulation. 2014;129:1196-1203.

A retrospective cohort study

Population based cohort of patients > 65 years who were admitted in Canada – Quebec and Ontario with a primary or secondary diagnosis of atrial fibrillation. Used ICD-9/10 codes to determine diagnosis and complications such as bleeding and stroke complications. Drug prescriptions were identified by database in Canada where patients > 65 have prescription benefit. Warfarin use was identified by a filled prescription within 30-days of AF diagnosis

626 dialysis patients and 204,210 nondialysis patients. Did not separate by stages of CKD, but rather HD or non-HD. Dialysis patients were younger, male, CHF, HTN, DM, CAD, and bleeding history.

Dialysis vs Non-Dialysis: CHADS2 >/= 2: 72% versus 55% (indication for anti-coagulation); HAS-BLED >/=3: 85% versus 25%. Similar rates of warfarin prescription (46% vs 51%)

image (3)

In non-dialysis patients, warfarin users had a lower incidence of stroke (2.19 vs 2.51/100 person-years)

In dialysis patients, stroke incidence was similar for warfarin and non-warfarin users: 3.37 versus 2.91/100 person-years.

After adjusting for confounders – warfarin use had a HR of 1.14 in diaylsis patients. While in non-dialysis patients had a HR 0.87 with warfarin use.

After adjusting for confounders, warfarin use, was associated with a 44% higher risk for bleeding event in dialysis patients and 19% higher risk in nondialysis patients.


image (4)

Flea Bytes: Calf DVTs

Randomized double blind placebo-control trial that faced slow recruitment thus faces the problem of being underpowered to detect a difference.

Outpatients without cancer or prior VTE with symptomatic calf DVT. Assigned 1:1 to receive nadroparin or placebo daily for 6 weeks. All were given compression stockings and followed for 90 days.

Primary outcome was extension to proximal vein, contralateral proximal DVT, or systemic embolism by day 42.

Safety outcome – non-major bleeding by day 42.
122 patients in nadroparin and 130 placebo.

Primary outcome 3% in the nadroparin and 5% in placebo. 5 patients had bleeding in nadroparin arm with 1 major bleeding event.

Need more information before change in practice.

Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial – M Righini et al; Lancet Haematology, The, 2016-12-01, Volume 3, Issue 12, Pages e556-e562.

Flea Bytes: Enhancing Teaching Effectiveness

Enhancing Teaching Effectiveness and Vitality in the Ambulatory SettingKelley M Skeff, MD, PhD

The Stanford Method

Seven-component Framework to Enhance Teaching Effectiveness

1. Establishing a Positive Learning Climate
-Reflects the degree of stimulation, enthusiasm, comfort, and excitement
-Demonstrate enthusiasm for the content being taught and for teaching itself
-Assess if the setting is conductive to teaching

2. Control of the Teaching Session
-Task-management approaches a teacher uses to focus and pace a session
-Time is limited, need to organize the session to manage time well
-Focus on several areas including ongoing disease processes, cost of care, and health maintenance (outpatient). Also need to evaluate and supervise house officers. can’t focus on all aspects and need to respect the time limitations for learners and patients.

3. Communication of Goals
– Expectation setting: educational experiences they should have, attitudes, knowledge and skills that should be acquired.
– Define specific observable behaviors you’d like to see

4. Enhance Understanding and Retention
– Attitudes: learners should have opportunities to consider and discuss their present attitudes, conceptualize their role, and discuss and set their own goals in a supportive environment.
– Knowledge: present material in clear and organized manner, emphasize key points to be remembered, and actively involve the learner in the process.

5. Evaluation
– Formative evaluation – conducted throughout education experience – helps plan future education experiences to help the learn master desired goals
– Summative evaluation – assessing learners final competence.

6. Feedback
– provide information to improve performance.
– inform, reinforce, or praise when performance is acceptable to excellent
– inform and constructively criticize when performance is needing improvement
– referencing stated expectations can provide the standard for feedback
– ensure time for feedback

7. Self-directed Learning

Flea Bytes: Hepatic Cysts

More common in women, 1.5:1 female to male ratio. 5% of people have cysts on autopsy and 5% of these are neoplastic. The majority of liver cysts (90%) are asymptomatic. Found incidentally on US or CT. Neoplastic cysts are mostly solitary. US imaging is most helpful and CT scan are used in specific cases. US helps determine content of the cysts. Certain cysts are responsive to estrogen.

Location in the liver does not help differentiate neoplastic from non-neoplastic.

Non-neoplastic cysts: wall is smooth, no septa, and no debris. Presence of these suggests the possibility of biliary cystadenoma or cystadenocarcinoma.

Liver tests are normal. In cases of congenital polycystic liver disease alkaline phosphatase maybe elevated.

Surgical removal and histologic sectioning is the only way to determine if neoplastic or not.

First must rule out Echinococcus – endemic worldwide and associated with rural areas with sheep. Test with ELIZA which is 90% sensitive. If surgery is not an option can consider aspiration. Mucin in cystic fluid is concerning for malignancy, but absence does not rule out malignancy. Also can check CEA and CA 19-9 in the aspirate, but inadequate NPV.

Monitor cysts that are 1-2cm, but if they grow to 2-5 consider, and definitely > 5 cm must consider surgery.

If all of the cyst tissue is removed, recurrence is unlikely, however if any part of the cyst wall is left behind recurrence can be up to 50%.

Advances in Hepatology: Current Developments in the Treatment of Hepatitis and Hepatobiliary Disease: Managment of Heaptic Cysts – Jorge L Herrera