Risk of chemotherapy-associated thromboembolism

A risk score model was developed to predict chemotherapy-associated venous thromboembolism (VTE). Initial risk factors included were site of the malignancy, platelet count >350,000/microL, hemoglobin concentration <10 g/dL, leukocyte count >11,000/microL, and body mass index ≥35 kg/m2 [1].

This model was expanded to include two additional variables: soluble P-selectin and D-dimer levels, with resulting scores varying from zero to eight [2]. 

In a retrospective study, the cumulative VTE probability after six months was 35, 20, 10, and 1 percent for those with the highest (≥5), high-intermediate (4), low-intermediate (3), and lowest (zero) scores, respectively.


Source:

1. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111:4902.
2. Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood 2010; 116:5377.

Updated Guidelines for erythropoiesis stimulating agents (ESAs)

Clinical practice guidelines for use of erythropoiesis stimulating agents (ESAs) from the American Society of Hematology (ASH) and the American Society of Clinical Oncology (ASCO) were updated in 2010 :

• ESAs should NOT be used for patients with cancer and anemia unassociated with chemotherapy. Use of ESAs in patients with lower-risk myelodysplastic syndromes to avoid transfusion is an exception to this recommendation. 

• For patients undergoing myelosuppressive chemotherapy who have a hemoglobin value of <10 g/dL, clinicians should discuss potential benefits and harms of ESAs compared with red blood cell transfusion. 

• The hemoglobin should be increased to the lowest concentration needed to avoid transfusion. ESAs should be discontinued if there is no response within six to eight weeks.

Source:

1. Rizzo JD, Brouwers M, Hurley P, et al. American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. Blood 2010; 116:4045.
2. Rizzo JD, Brouwers M, Hurley P, et al. American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. J Clin Oncol 2010; 28:4996.

Updated Practice Parameters for Allergen Immunotherapy

Practice parameters for allergen immunotherapy have been updated by the Joint Task Force (a panel of experts from three American professional allergy organizations).

Most recommendations are similar to the 2007 version. Changes include:

• the addition of atopic dermatitis as a condition that may respond to immunotherapy and the use of venom immunotherapy to prevent recurrent, and
• bothersome large local reactions to insect stings.

The new parameters also emphasize the importance of measuring baseline tryptase in patients with moderate to severe anaphylaxis to insect stings, to detect underlying mast cell disorders


Source:
Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol 2011; 127:S1.

Eribulin for Metastatic Breast Cancer

Eribulin mesylate, a synthetic analogue of halichondrin B, a substance derived from a marine sponge, inhibits the polymerization of tubulin and microtubules. Phase II studies observed a significant level of activity in heavily pretreated patients with advanced breast cancer. 

Preliminary results of the phase III EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) trial were presented at the 2010 American Society of Clinical Oncology meeting [59]. In this trial, 762 heavily pretreated patients were randomly assigned to either eribulin (1.4 mg/m2 days 1 and 8 every 21 days) or other treatment of the physician’s and patient’s choice. Treatment with eribulin compared to alternative therapy significantly improved median overall survival (the primary endpoint, 13.1 versus 10.7 months). The primary toxicity with eribulin was neutropenia, with grade 3 and 4 neutropenia in 45 percent of patients, and grade 3 and 4 febrile neutropenia in 4 percent.

In November 2010, based upon results from the phase III EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) trial, the US FDA approved eribulin for treatment of metastatic breast cancer in patients who have previously received an anthracycline and taxane in the adjuvant or metastatic setting and at least two prior metastatic chemotherapy regimens.

Source:

• Cortes J, Vahdat L, Blum JL, et al. Phase II study of the halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine. J Clin Oncol 2010; 28:3922.
• Twelves, C, Loesch, JL, Blum, LT, et al. A phase III study (EMBRACE) of eribulin mesylate versus treatment of physician's choice in patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 2010; 28:18s.
• Vahdat LT, Pruitt B, Fabian CJ, et al. Phase II study of eribulin mesylate, a halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 2009; 27:2954.

Telavancin for Hospital-Acquired Pneumonia

Telavancin is an intravenous semisynthetic lipoglycopeptide antibiotic that is broadly active against both aerobic and anaerobic gram-positive bacteria, including streptococci, methicillin-susceptible S. aureus, methicillin-resistant S. aureus (MRSA), and some vancomycin-resistant enterococci.

In two randomized trials (the ATTAIN studies) in patients with hospital-acquired pneumonia due to gram-positive bacteria, especially MRSA, telavancin was noninferior to vancomycin in terms of clinical response.

Among patients with monomicrobial S. aureus infection, the cure rates were higher in patients who received telavancin, particularly among those with an MRSA isolate with reduced susceptibility to vancomycin.

These results suggest that telavancin is particularly useful for patients with MRSA isolates with reduced susceptibility to vancomycin. However, telavancin has not been approved by the US Food and Drug Administration for the treatment of pneumonia.

Source:

1. Pfaller MA, Mendes RE, Sader HS, Jones RN. Telavancin activity against Gram-positive bacteria isolated from respiratory tract specimens of patients with nosocomial pneumonia. J Antimicrob Chemother 2010; 65:2396.
2. Rubinstein E, Lalani T, Corey GR, et al. Telavancin versus vancomycin for hospital-acquired pneumonia due to gram-positive pathogens. Clin Infect Dis 2011; 52:31.

Sulfonylureas and post-MI mortality

The impact of antidiabetic medications on clinical outcomes in patients developing acute myocardial infarction (MI) is controversial.

In some studies, the use of early generation sulfonylurea drugs compared with no sulfonylureas or metformin is associated with increased mortality after myocardial infarction.

The newer sulfonylureas, gliclazide and glimepiride, are selective for the pancreatic sulfonylurea receptors over the cardiac receptors and do not appear to be associated with increased cardiovascular mortality compared with other diabetes medications.

In a study of 1310 patients with diabetes who were hospitalized for myocardial infarction, in-hospital mortality rates were significantly lower in patients previously treated with sulfonylureas compared with other oral medications, insulin, or no medication.

Among the sulfonylurea-treated patients, mortality was significantly lower in patients receiving gliclazide or glimepiride compared with glyburide, which is not selective for the pancreatic sulfonylurea receptors.

Source:

Zeller M, Danchin N, Simon D, et al. Impact of type of preadmission sulfonylureas on mortality and cardiovascular outcomes in diabetic patients with acute myocardial infarction. J Clin Endocrinol Metab 2010; 95:4993.

Platelet Transfusion for Severe Hemorrhage

A more aggressive approach to platelet transfusions may reduce mortality in trauma patients with severe hemorrhage.

In a retrospective study of 657 patients requiring massive blood transfusion, better survival rates were found in patients with higher platelet to packed red blood cell (PRBC) transfusion ratios. The mortality was significantly lower for patients who received the highest apheresis platelet to PRBC ratio (≥1:6) compared to those with the lowest ratio (<1:18), after controlling for such factors as injury severity, initial blood pressure, and transfusion of other blood products.

For injured patients requiring a massive transfusion, as the apheresis platelet-to-red cell ratio increased, a stepwise improvement in survival was seen. Prospective evaluation of the role of platelet transfusion in massively transfused patients is warranted.


Source: 

Inaba K, Lustenberger T, Rhee P, et al. The impact of platelet transfusion in massively transfused trauma patients. J Am Coll Surg 2010; 211:573.

Basic and Advanced Life Support: 2010 Resuscitation Guidelines for Pediatric and Adult

Based upon extensive review of clinical and laboratory evidence, the American Heart Association (AHA) and the International Liaison Committee on Resuscitation (ILCOR) published updated guidelines for basic life support (BLS) and advanced life support (ALS) interventions in children and adults in 2010.

A. Pediatric Guidelines

A. 1. Basic Life Support (BLS)

The 2010 international resuscitation guidelines emphasize the importance of hard, fast chest compression, with full chest recoil and minimal interruptions. The major changes for basic cardiopulmonary resuscitation (CPR) from previous guidelines published in 2005 include:

• Initiate CPR in infants or children who are unresponsive and not breathing (or only gasping). 
• If no pulse is definitely identified within 10 seconds, give compressions before performing airway or breathing maneuvers.  
• The use of conventional CPR (compressions with ventilation) rather than compression-only CPR in infants and children with cardiac arrest is reaffirmed, regardless of whether the arrest occurs within or outside of the hospital. Compression-only CPR is only appropriate in adults. 
• For infants and children <8 years of age, a manual defibrillator or an AED with a pediatric dose attenuating system should be used whenever possible. However, if a manual defibrillator or an AED with a pediatric dose attenuating system is not available, then use of an AED without a dose attenuator is now acceptable. 

A. 2. Advanced Life Support (ALS) 

The 2010 international resuscitation guidelines reaffirm the ALS approach to arrhythmias and cardiac arrest in children. The major changes for pediatric advanced life support from previous guidelines published in 2005 include:

• Beyond the newborn period, cuffed endotracheal (ET) tubes are equally as safe as uncuffed tubes, and are favored in some clinical circumstances. Monitoring should ensure that cuff pressures do not exceed 20 cm H2O.
• Evidence is insufficient to routinely recommend cricoid pressure (Sellick maneuver) in infants and children undergoing endotracheal intubation. If it is used, cricoid pressure should be removed if airway obstruction occurs when ventilation is required or if there is difficulty viewing the larynx.
• Etomidate should not be used routinely for rapid sequence intubation or sedation in children with septic shock. Ketamine, if available and not contraindicated, is preferable.

B. Adult Guidelines 

The 2010 international resuscitation guidelines for basic and advanced cardiac life support continue to emphasize the critical importance of performing excellent cardiopulmonary resuscitation (CPR) without interruption and providing early defibrillation for amenable arrhythmias. 

B.1. Basic Life Support (BLS) 

The major changes for adult CPR from previous guidelines published in 2005 include the following:

• Begin chest compressions immediately for any unresponsive adult who is not breathing, is breathing abnormally (eg, gasping), or in whom a pulse cannot be readily palpated within 10 seconds. The new fundamental sequence for BLS is chest compressions, airway opening, and then rescue breathing (“C-A-B”).
• Encourage compression-only CPR for lay rescuers.
• Ensure that excellent chest compressions are performed: rate ≥100 per minute; compression of at least 5 cm (2 inches) with each down-stroke; full recoil between compressions; minimize interruptions.

B.2 Advanced Cardiac Life Support (ACLS) 

The major changes for ACLS from previous guidelines published in 2005 include the following:

• Successful ACLS depends upon excellent CPR. Real-time monitoring and optimization of CPR is strongly encouraged.
• Intravenous infusion of a chronotropic agent (dopamine or epinephrine) is recommended for unstable bradycardia as an equally effective treatment compared to external pacing.
• Adenosine may be used for the diagnosis and treatment of stable patients with undifferentiated, regular, wide-complex tachycardia with a monomorphic QRS waveform.
• The management of pulseless electrical activity and asystole have been combined into a single algorithm.
• Atropine is no longer a recommended treatment for pulseless electrical activity or asystole.
• Quantitative waveform capnography is recommended for confirmation and monitoring of proper endotracheal tube placement.
• Systematic care provided by a multidisciplinary team is important to the survival of patients with a return of spontaneous circulation following cardiac arrest.

Fever and Neutropenia Guidelines

Updated guidelines from the Infectious Diseases Society of America (IDSA) for the use of antimicrobial agents in neutropenic patients with cancer have been published.

This document updates and expands the initial IDSA Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations.

These guidelines emphasize the importance of categorizing neutropenic patients with fever as high-risk versus low-risk for severe infection. All neutropenic patients with fever require immediate broad-spectrum empiric antibiotic therapy to treat both gram-negative and gram-positive bacteria.


Source:
Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis 2011; 52:e56.

Wormwood (Artemisia absinthium) and IgA nephropathy

Inhibition of the renin-angiotensin system is a widely accepted approach to treat immunoglobulin A (IgA) nephropathy. Tumor necrosis factor α (TNF-α) is considered to be involved in the pathophysiologic process of this disorder. Recent in vitro and clinical observations that wormwood (Artemisia absinthium) can decrease TNF-α levels.

Herbal drug wormwood markedly decreased protein excretion among ten patients who had biopsy-proven IgA nephropathy and creatinine clearances greater than 90 mL/min. The decrease in protein excretion was also observed six months after stopping the herbal supplement. Thujone-free wormwood with its favorable safety profile can be an alternative supplement to manage proteinuria in patients with IgA nephropathy. 


Source: 

Krebs S, Omer B, Omer TN, Fliser D. Wormwood (Artemisia absinthium) for poorly responsive early-stage IgA nephropathy: a pilot uncontrolled trial. Am J Kidney Dis 2010; 56:1095.

Combination ARB and ACE inhibitor therapy and cancer risk

The risk of cancer from antihypertensive drugs has been much debated, with a recent analysis showing increased risk with angiotensin-receptor blockers (ARBs).

A large meta-analysis (>300,000 patients from 70 randomized trials) found that combination therapy with angiotensin-receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACE inhibitors) was associated with a significant increase in cancer incidence, but there was no increase in cancer incidence with ARBs or ACE inhibitors when used alone. Cancer death was not significantly increased. 

A possible increase in cancer risk with the use of combination therapy provides additional rationale to not simultaneously treat with ARBs and ACE inhibitors unless there is a compelling reason for dual therapy.


Source: 

Bangalore S, Kumar S, Kjeldsen SE, et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. Lancet Oncol 2011; 12:65.

Maintenance Therapy for ANCA-associated Vasculitis

Current remission maintenance therapies for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) are limited by partial efficacy and toxicity.

The IMPROVE trial, a multicenter trial, demonstrated that mycophenolate mofetil was less effective than azathioprine for maintaining disease remission among 156 patients with newly diagnosed ANCA-associated vasculitis.

After induction of remission with cyclophosphamide and glucocorticoids, patients received either azathioprine (starting at 2 mg/kg per day, then reduced to 1.5 and 1.0 mg/kg per day after 12 and 18 months, respectively) or MMF (starting at 2000 mg per day and reduced to 1500 and 1000 mg per day after 12 and 18 months respectively). Both agents were withdrawn after 42 months of treatment. At a median follow-up of 39 months, relapses were significantly less frequent among those who received azathioprine (38 versus 55 percent, adjusted hazard ratio 0.56, 95% CI 0.34-0.91).

The rate of adverse events was not significantly different for those who received azathioprine (16 versus 8 percent, respectively).

Keywords: 

antibodies, antineutrophil cytoplasmic, azathioprine, drug reaction, adverse, inflammation, mycophenolate mofetil, patient safety, randomized trials, recurrence, survival, vasculitis.

Source: 

Hiemstra TF, Walsh M, Mahr A, et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA 2010; 304:2381.

2010 CDC Updated Guidelines for Treatment of Sexually Transmitted Diseases (STDs)

In 2010 the Centers for Disease Control and Prevention (CDC) updated guidelines for treatment of sexually transmitted diseases (STDs).

The following recommendations, represent some of the revisions from 2006 CDC guidelines:

• A single dose of azithromycin (1 gram orally) has been shown to be clinically effective for treatment of chlamydial infections in pregnancy. The previous recommendation for amoxicillin 500 mg orally three times a day for seven days is also recommended and is an equally effective, but less convenient, approach. Pregnant women should be retested for chlamydia three weeks after treatment, and women treated in the first trimester should be retested three months later. 

• Diagnostic evaluation for cervicitis has been expanded to include testing for C trachomatis and N gonorrhoeae by nucleic acid amplification, and testing for bacterial vaginosis and trichomoniasis. 

• Treatment options for bacterial vaginosis have been expanded. 

• Treatment options for genital warts have been expanded and include: waiting for spontaneous resolution, podofilox 0.5 percent solution or gel, imiquimod 5 percent cream, or sinecatechins 15 percent ointment. 

• The dose of ceftriaxone for treatment of gonorrhea has been increased from 125 mg to 250 mg intramuscularly in a single injection.