Monitoring International Trends posted January 2015

Country-specific events

The NBA is interested in relevant safety issues which arise in particular countries, and also instances of good practice. We monitor health issues in countries from which Australia’s visitors and immigrants come.

1. 
   Towards the end of December the US National Institutes Health (NIH) allowed five studies involving a mouse model for MERS-CoV and two influenza studies to continue after a 2-month moratorium on such “gain of function” studies.
   
2. 
   FDA Commissioner Margaret Hamburg announced in December 2014 that “the agency will take the necessary steps to recommend a change to the blood donor deferral period for men who have sex with men from indefinite deferral to one year since the last sexual contact……..Additionally, in collaboration with the NIH’s National Heart Lung and Blood Institute (NHLBI), the FDA has already taken steps to implement a national blood surveillance system that will help the agency monitor the effect of a policy change and further help to ensure the continued safety of the blood supply……The FDA intends to issue a draft guidance recommending this proposed change in policy in 2015, which will also include an opportunity for public comment”.
   
3. 
   The Solomon Islands Red Cross suspended its blood collection program. The National Referral Hospital was appealing for blood donations.
   
4. 
   In Ireland in 2010, the health service agreed with Alexion on funding for ten patients to receive Soliris (eculizumab), which controls the breakdown of red blood cells. This was a pilot “Access with Evidence” program, and the program is full. Not surprisingly, a patient with paroxysmal nocturnal haemoglobinuria (PNH) who cannot access the program is angry. The drug costs €437,000 per patient per year.
   
5. 
   South Australian pharmacists will be able to vaccinate adults who are not already eligible for a free flu shot as part of the National Immunisation Program.
   

5. Safety and patient blood management

We follow current issues in patient safety and achieving favourable patient outcomes.

Appropriate transfusion

1. 
   A recent meta-analysis¹⁴ has concluded that the use of tranexamic acid in patients undergoing spinal surgery appears to be effective in reducing the amount of blood loss, the volume of blood transfusion, the transfusion rate, and the postoperative partial thromboplastic time. The authors found data too limited for any conclusions regarding safety. They said more high-quality randomized controlled trials are required before a recommendation can be made concerning the administration of tranexamic acid during surgery.
   
2. 
   In a recent meta-analysis¹⁵, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin compared with crystalloid and saline. Furthermore, the 90-day mortality of patients with septic shock decreased significantly.
   
3. 
   Dr Nancy Dunbar, at the Dartmouth-Hitchcock Medical Center¹⁶ in Lebanon, New Hampshire has described how she and others had “figured out how to harness the power of the electronic medical record to embed evidence-based transfusion criteria into the computerized physician order entry process through the best practices alert functionality.” She said pathologists are provided with “real-time” education and reminders with each order. The proportion of two-unit transfusions decreased after the implementation of the electronic best practices alert — from 47 per cent to 15 per cent.
   
4. 
   Research led by Jonathan H. Chen, from the Stanford University Medical Center in California ¹⁷ has found a range of reasons clinicians ignore best practice alerts for blood product transfusions. Acute bleeding was the most common reason, followed by protocolized behaviours on specialty services. Some transfusions occurred in anticipation of surgical intervention and some occurred almost immediately pior to hospital discharge.
   
5. 
   Results of a randomized controlled trial suggest that a liberal blood transfusion strategy did not affect mortality compared with a restrictive transfusion strategy among high-risk elderly patients with a history of, or risk factors for, cardiovascular disease. Jeffrey L. Carson, professor of medicine and chief of the division of general internal medicine at Rutgers Robert Wood Johnson Medical School, and colleagues conducted the FOCUS trial in 2,016 patients recruited from 47 hospitals in the US and Canada between July 2004 and February 2009. Patients were at least 50 years old with a history of risk factors for cardiovascular disease. Patients had postoperative haemoglobin concentrations lower than 100 g/L within 3 days of surgery to repair a hip fracture.
   
6. 
   A Johns Hopkins-led study¹⁸ was the first US-wide review of nearly 100,000 combined hospital admissions for three rare blood cell disorders: thrombotic thrombocytopenic purpura (TTP), heparin-induced thrombocytopenia (HIT) and immune thrombocytopenic purpura (ITP). It found that one in every 13 hospitalized patients with heparin-induced thrombocytopenia and one in every 10 hospitalized patients with thrombotic thrombocytopenic purpura received a platelet transfusion. Platelet transfusions were associated with increased odds of dying in the hospital, fivefold for patients with heparin-induced thrombocytopenia and double for patients with thrombotic thrombocytopenic purpura. The most serious complications were arterial blood clots. Aaron Tobian of the Johns Hopkins University School of Medicine commented: “There was some suggestion that transfusion may be harmful in these conditions, but it really was not known until now. Our study is the first one to show that platelet transfusions are frequently administered to patients with ITP, HIT and TTP, and that they’re associated with higher odds of arterial blood clots and mortality in TTP and HIT.”
   
7. 
   Various transfusion ratio concepts of packed red blood cells (pRBCs), fresh frozen plasma (FFP) and platelets (PLTs) have been used in trauma care. A recent study¹⁹ assessed the haemostatic potential of two predefined ratios using an in vitro thrombelastometric approach. It concluded the coagulation functionality of the 1:1:1 ratio predominated over the 3:1:1: ratio.The January issue of Anesthesiology, the journal of the American Society of Anesthesiologists, published studies on two specific risks associated with blood transfusions. Senior author of both studies wasDaryl Kor, associate professor of anesthesiology at Mayo Clinic in Rochester, Minnesota.
   
8. 
   The January issue of Anesthesiology reported on studies of the two most significant causes of post-transfusion mortality in the US: transfusion related acute lung injury (TRALI) ²⁰and transfusion associated circulatory overload(TACO). Senior author for both papers was an associate professor of anesthesiology at the Mayo Clinic, Rochester, Minnesota. The studies emphasised that both conditions were under-recognised and under-reported. Researchers say postoperative TRALI is significantly underreported and more common than previously thought, with an overall rate of 1.4 percent.
   

Other.

9. 
   A study in the Netherlands²¹ claims to have found a way to improve the prognosis for patients with the most severe and disabling strokes. If doctors can directly remove large clots blocking blood vessels in the brain, they can save brain tissue from dying, so patients can return to an independent life. The researchers used a new type of snare to grab the clots. It is a stent (in this case a small wire cage), on the end of a catheter that is inserted in the groin and passed through an artery to the brain. When it arrives at the clot, the stent is opened and pushed into the clot, which it snags.
   
10. 
    A study²² based on Danish health care system registries has found that people with atrial fibrillation who take nonsteroidal anti-inflammatory drugs while on an antithrombotic therapeutic regimen may be at risk for serious bleeding or thromboembolisms.
    
11. 
    A poster session on Health Services and Outcomes Research during the 56th Annual Meeting of the American Society of Hematology (ASH) in San Francisco estimated payers in the US would see a reduction in overall medical costs if patients switched to newer, novel oral anticoagulants. The study considered ten clinical trials involving dabigatran, rivaroxaban, and apixaban. The study’s lead author, Alpesh N. Amin, consults for Bristol-Myers Squibb and for Pfizer, joint makers of apixaban. 
    
12. 
    Portola Pharmaceuticals announced that its experimental drug andexanet alfa met the main goal (of reversing the effect of Johnson and Johnson and Bayer’s anticoagulant drug Xarelto) in a late-stage study in healthy volunteers aged 50-75 years. Further data is expected in mid-2015. Portola announced last October that the drug reversed the effect of Eliquis, an anti-clotting drug by Bristol-Myers Squibb Co and Pfizer Inc.
    
13. 
    A study report²³ at the ASH annual meeting said patients who suffered unprovoked pulmonary embolism had a significant reduction in the composite risk for recurrent venous thromboembolism and major bleeding when they received anticoagulation for an additional 18 months, but that the benefits associated with extended anticoagulation did not persist after treatment ceased.
    
14. 
    Germany’s Pieris began a Phase I clinical trial of its anaemia drug PRS-080, which sequesters hepcidin, usually regarded as the master negative regulator of iron metabolism. Pieris CEO Stephen Yoder said: "Underpinned by a six million Euro grant from the European Commission, this Phase I clinical trial will bring PRS-080 one step closer to patients not adequately responding to current anaemia therapy.
    

6.