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School of Nursing research shows 'culture shift' needed for palliative care
School of Nursing research shows 'culture shift' needed for palliative care

Early palliative care offers statistically beneficial effects on patient survival and family caregiver burden, according to articles published in the Journal of Clinical Oncology.

palliativenursingTwo papers recently published by University of Alabama at Birmingham School of Nursing researchers in the Journal of Clinical Oncology highlight the need for a “culture shift” by clinicians and the general public to engage palliative care services long before a person reaches the final stage of life.

Two articles reporting on 207 advanced cancer patients and 122 of their family caregivers who participated in the ENABLE III Trial (“Early Versus Delayed Initiation of Concurrent Palliative Oncology Care” and “Benefits of Early Versus Delayed Palliative Care to Informal Family Caregivers of Patients With Advanced Cancer”) reveal that palliative care delivered soon after a diagnosis of advanced cancer had statistically beneficial effects on patient survival and family caregiver depression and burden when compared with care provided 12 weeks later. The one-year survival rate for patients was 63 percent for those who received early palliative care, compared with 48 percent in the group whose care was delayed. These results support integration of palliative care for patients and families as soon as possible after diagnosis.

“Palliative care is about providing an extra layer of support so that patients can live well and families can be supported,” said principal investigator Marie Bakitas, D.N.Sc., professor and Marie L. O’Koren Endowed Chair in the School of Nursing. “These data support the importance of providing this care at the same time as medical treatments aimed at fully curing disease. Too often, that is not the case.”

“If patients and clinicians wait to introduce palliative care when a person is actively dying, it limits the full range of services that patients and their families can receive,” said Nick Dionne-Odom, Ph.D., postdoctoral fellow in the School of Nursing and lead author of the family caregiver ENABLE Trial outcomes. “This means palliative care is mistakenly associated solely with end-of-life care. This is unfortunate. Our research shows that integration of palliative care earlier in the cancer trajectory benefits both patients and their family caregivers.”

“These data support the importance of providing this care at the same time as medical treatments aimed at fully curing disease. Too often, that is not the case.”

The investigators say that family caregivers who receive this support and education have greater capacity and skills to deliver high-quality support to patients. Likewise, providing patients with palliative care early eases the burden on families, who deliver the majority of care and psychosocial support in the home. 

“Anyone who has been through cancer with a family member can attest to the physical, psychological and existential burden it places on both parties,” Dionne-Odom said. “Receiving this extra layer of support early and at the same time as curative medical treatments is vital for helping patients and their family caregivers develop the coping and other skills needed for the ups and downs of their journey.”

Bakitas says two other shifts in the view of palliative care also are needed.

“Reimbursement mechanisms need to incentivize this care to be offered regardless of six-month prognosis, which is the current hospice-benefit requirement,” Bakitas said. “Also, increased clinician education is needed to train both specialists and general practitioners in palliative care.”

Both researchers say mechanisms still need to be identified that explain the effects of early palliative care, and they are looking at the impact of depression and biological mechanisms that might contribute to this explanation.

Bakitas recently was awarded a five-year, $3.5 million National Institute of Nursing Research R01 grant to study whether palliative care provided to advanced heart-failure patients while they are well results in a better quality of life, improved mood, and less symptom distress/burden for patients and/or caregivers when compared to usual heart-failure care. It will test this similar intervention using materials and an approach adapted from the ENABLE cancer intervention.

A possible novel therapy for a rare but potentially fatal blood disorder
A possible novel therapy for a rare but potentially fatal blood disorder
Similar to the ancient Greek legend of the Trojan horse, platelets in a transgenic mouse deliver a life-saving enzyme.

xinglong zhengIn a city of 1 million, about 10 to 15 patients a year will come to the emergency department with indistinct complaints that hide a potentially fatal blood disease.

“They usually come in the middle of the night, and the symptoms can be very nonspecific,” said X. Long Zheng, M.D., Ph.D., professor and division director of Laboratory Medicine in the Department of Pathology, University of Alabama at Birmingham School of Medicine. “Headache, blurred vision, malaise and abdominal pain. If misdiagnosed, they can die in one to two days.”

This syndrome — acquired thrombotic thrombocytopenic purpura, or TTP — produces blood clots in small arterioles throughout the body, particularly in the brain, heart, pancreas and kidneys. The most effective treatment thus far is daily plasma exchange, with replacement of all or one and a half times the body’s entire blood volume. Such treatment costs nearly $10,000 a day and may need to be continued for weeks or, in some patients, months.

Zheng and colleagues have now developed a potential novel way to treat acquired TTP. Their approach not only could slash the amount of plasma transfusion needed for TTP patients, but also could become a new emergency therapy for strokes, heart attacks, malignant malaria and pre-eclampsia. All are associated with relative deficiency of plasma ADAMTS13 activity. The work, now a proof-of-concept in a mouse TTP model, has been published online this week in the journal Blood.

TTP is an autoimmune disorder — people produce an autoantibody that inactivates an enzyme called ADAMTS13. Of note, Zheng was the first scientist to clone ADAMTS13. That enzyme normally acts to cleave von Willebrand factor, a large protein involved in blood clotting. The loss of ADAMTS13 activity due to autoantibody in TTP patients allows formation of the destructive microvascular clots in many important organ tissues.

Zheng had an idea of how treat TTP: “Hide the enzyme inside cells where the antibody can’t see it.”

His cells of choice were platelets, tiny blood cells a fifth the diameter of a red blood cell.

The normal function of a platelet is to stop bleeding from blood vessels. “When the platelet sticks to the injured site, it gets activated, changes its shape and releases its contents,” said Zheng. “It’s like a mini-bomb.”

Zheng reasoned that, if he could fill the platelets with ADAMTS13, the platelets would then carry the enzyme right to the place it was most needed to dissolve the TTP clots.

For the proof-of-concept, his research group developed transgenic mice that expressed functional recombinant human ADAMTS13 (rADAMTS13) in mouse platelets.

The group then showed that:

  • The platelets with the human rADAMTS13 had normal agglutination and aggregation.
  • The platelets released rADAMTS13 upon stimulation with clot inducers.
  • The mice with rADAMTS13 inside platelets were significantly protected in a vascular injury model of thrombus formation.
  • The same mice were protected against bacterial toxin or recombinant von Willebrand factor-induced TTP due to hereditary deficiency of ADAMTS13, a genetic disease where an offspring makes little or no ADAMTS13 (although hereditary TTP is much rarer than acquired TTP).
  • These mice were also protected against antibody-mediated TTP after being challenged by recombinant von Willebrand factor.

All of these findings of the study, they conclude, “suggest that platelets may be ideal carriers for antithrombic ADAMTS13, allowing its release at high concentrations at the site of thrombus formation without being inactivated by the potential circulating anti-ADAMTS13 inhibitors.”

Of course, genetic engineering or biochemical approaches would not be used to apply this proof-of-concept to human TTP patients. Zheng says one approach will be to learn how to pack ADAMTS13 inside the human platelets during the time that bags of donated blood sit at room temperature for three days as they are tested for multiple infectious disease markers. These packed platelets would then be tested to learn how many ADAMTS13-loaded platelets need to be transfused to get anti-blood clot and anti-TTP effects in patients with acquired TTP. Platelets do not have nuclei, and they lack the blood type ABO antigen markers found on red blood cells.

The co-authors of the paper, “Platelet-delivered ADAMTS13 inhibits arterial thrombosis and prevents murine models of thrombotic thrombocytopenic purpura,” include Drs. Brandy Pickens, Yingying Mao, Dengju Li, Don Siegel and Douglas Cines from the departments of Pathology and Laboratory Medicine, University of Pennsylvania; and Dr. Mortimer Poncz from the Division of Hematology, Children’s Hospital of Philadelphia.

Zheng has recently joined faculty at the University of Alabama at Birmingham. He has been an NIH-sponsored investigator of TTP since 2003.

Trussville couple prepares for April birth of baby with serious heart defect
Trussville couple prepares for April birth of baby with serious heart defect
The future for babies born with hypoplastic left-heart syndrome depends to a great extent upon additional cardiac issues that may not be fully known until after birth.
The UAB/Children's of Alabama fetal team enables caregivers to combine the best of OB, cardiology and surgery to give HLHS babies the best chances to have the best outcomes they can have.

Crystal and James Burford are preparing for the birth of their son, Jeremiah James, on April 8, with the knowledge that Baby J.J. will be fighting for his life from the moment he arrives.

J.J. was diagnosed with hypoplastic left-heart syndrome by physicians in UAB’s Division of Maternal-Fetal Medicine this past fall. Children born with HLHS have underdeveloped features on the left side of their heart, and it cannot pump oxygen-rich blood to the body properly.

More on the surgery and the challenges faced by the Burfords and other families dealing with HLHS is explained in this video.

The Burfords are allowing UAB News to follow their journey to their April 8 due date and beyond, in part to bring awareness to a condition that affects 960 babies born in the United States each year.

“We see approximately 10-20 babies who have hypoplastic left-heart syndrome or related variants every year,” said Waldemar Carlo, M.D., pediatric cardiologist at Children’s of Alabama and assistant professor in the UAB School of Medicine Department of Pediatrics.

Although treatments for HLHS have improved in recent years, there is no cure. Nationwide, only 75 percent of babies born with HLHS survive to age 1, Carlo says.

Follow their story from the beginning.

“Survival depends to a great extent upon the rest of the problems that may or may not be present and additional cardiac issues that may not be fully elucidated until the baby is born,” said Bennett Pearce, M.D., pediatric cardiologist at Children’s of Alabama and professor in the UAB School of MedicineDivision of Pediatric Cardiology. “We make a diagnosis before birth, and we refine the diagnosis after birth.”

Treatments include three major surgeries — the first occurring within one week of birth.

A successful first surgery is better ensured by bringing the baby as close to a full 40-week term pregnancy as possible, says UAB Maternal-Fetal Medicine physician Richard Davis, M.D.

“In some ways it is a catch-22: You want these babies to stay in the uterus as long as they can, as long as they are growing and have normal fluid levels; but too much prenatal surveillance can sometimes lead to false results, and an additional problem may be indicated that may prompt thinking that an earlier delivery is necessary when, in fact, there are no additional issues,” Davis said. “Our goal is to get these babies to 39 or 40 weeks so they are big, strong babies for surgery. It’s important to tell the mothers that because they often think, ‘Let’s treat the baby as soon as we can.’ But amazingly, these hearts are very stable in the uterus.”

The fetal team comprises physicians and nurses from the high-risk Maternal-Fetal Medicine group, plus pediatric cardiology, cardiac ICU, cardiac surgery and neonatology.

“Our fetal team enables us to combine the best of OB, cardiology and surgery to give these babies the best chances to have the best outcomes they can have,” Carlo said. “We have a great deal of experience in dealing with this type of cardiac physiology and with the surgeries and post-operative care required in these little babies.”

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