Costs and Outcomes with Once-Daily versus Every-6-Hour Intravenous Busulfan in Allogeneic Hematopoietic Cell Transplantation.

The high cost of healthcare in the United States has not been consistently associated with improved health outcomes or quality of care, necessitating a focus on value-based care. We identified busulfan dosing frequency during allogeneic hematopoietic cell transplantation (HCT) conditioning as a potential target for optimization. To improve patient convenience and to decrease the cost of busulfan-based conditioning regimens, our institution changed busulfan dose frequency from every 6 hours (q6h) to once-daily (q24h). We compared costs and patient outcomes between these 2 dosing schedules. In June 2017, our institution transitioned from q6h to q24h busulfan dosing. We compared patients who received busulfan/cyclophosphamide conditioning regimens (BU/CY) for allogeneic HCT in the year before the dosing change (q6h cohort) and those who did so in the year after the dosing change (q24h cohort). The primary outcomes were differences in cost, day +90 mortality, and day +90 relapse. Between June 1, 2016, and June 1, 2018, 104 patients (median age 49 years; range, 20 to 63 years) received BU/CY before allogeneic HCT. Fifty-nine patients (57%) received q6h busulfan and 45 (43%) received q24h busulfan. There were fewer men in the q24h busulfan cohort compared with the q6h busulfan cohort (42% versus 64%; P = .024), but there were no other significant differences between the groups. There was an average annual cost savings of $19,990 per patient with q24h busulfan compared with q6h busulfan, and an annual busulfan cost savings of $899,550. There was a significantly lower day +90 mortality in the q24h busulfan cohort compared to the q6h busulfan cohort (0% versus 10%; P = .028). There were no significant differences in relapse at day +90 or in hospital length of stay. Our data indicate that i.v. busulfan dosing for allogeneic HCT conditioning is a target for improved value-based care. At our institution, patients who received q24h busulfan dosing had similar or superior outcomes compared with those receiving q6h dosing, with an average annual cost reduction of $19,990 per patient and an overall annual reduction in busulfan cost of approximately $900,000. These data support the adoption of q24h i.v. busulfan dosing as a standard of care to improve value-based care in allogeneic HCT.

Advance Directive Utilization Is Associated with Less Aggressive End-of-Life Care in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation.

Allogeneic hematopoietic cell transplantation (HCT) is associated with significant morbidity and mortality, making advance care planning (ACP) and management especially important in this patient population. A paucity of data exists on the utilization of ACP among allogeneic HCT recipients and the relationship between ACP and intensity of healthcare utilization in these patients. We performed a retrospective review of patients receiving allogeneic HCT at our institution from 2008 to 2015 who had subsequently died after HCT. Documentation and timing of advance directive (AD) completion were abstracted from the electronic medical record. Outcomes of interest included use of intensive care unit (ICU) level of care at any time point after HCT, within 30 days of death, and within 14 days of death; use of mechanical ventilation at any time after HCT; and location of death. Univariate logistic regression was performed to explore associations between AD completion and each outcome. Of the 1031 patients who received allogeneic HCT during the study period, 422 decedents (41%) were included in the analysis. Forty-four percent had AD documentation prior to death. Most patients (69%) indicated that if terminally ill, they did not wish to be subjected to life-prolonging treatment attempts. Race/ethnicity was significantly associated with AD documentation, with non-Hispanic white patients documenting ADs more frequently (51%) compared with Hispanic (22%) or Asian patients (35%; P = .0007). Patients with ADs were less likely to use the ICU during the transplant course (41% for patients with ADs versus 52% of patients without ADs; P = .03) and also were less likely to receive mechanical ventilation at any point after transplantation (21% versus 37%, P < .001). AD documentation was also associated with decreased ICU use at the end of life; relative to patients without ADs, patients with ADs were more likely to die at home or in hospital as opposed to in the ICU (odds ratio, .44; 95% confidence interval, .27 to .72). ACP remains underused in allogeneic HCT. Adoption of a systematic practice to standardize AD documentation as part of allogeneic HCT planning has the potential to significantly reduce ICU use and mechanical ventilation while improving quality of care at end of life in HCT recipients.

Geographic scope and accessibility of a centralized, electronic consult program for patients with recent fracture.

INTRODUCTON: Low-trauma, osteoporotic fractures among older men are associated with a significant increase in morbidity and mortality. Despite effective therapies for osteoporosis, several studies have demonstrated that management and treatment after a low trauma fracture remains inadequate, especially among men. Fracture liaison services have been shown to significantly improve osteoporosis evaluation and treatment. However, such programs may be less feasible and accessible in rural areas, with limited availability of specialty services. The study objective was to evaluate a centralized, electronic consult (e-consult) program serving multiple veterans administration medical centers, including the geographic scope, accessibility to rural patients, and impact on osteoporosis evaluation and treatment. METHODS: The e-consult program identified veterans with potential osteoporotic fractures from inpatient and outpatient encounter data, based on ICD9 diagnosis codes (800-829) from the central data warehouse. The medical record of an eligible patient was reviewed by a bone health specialist, and an e-consult note was sent to the patient's primary care provider that specified guideline-based recommendations for further evaluation and management. A bone health nurse liaison then coordinated the ordering and follow-up of laboratory and bone density assessment, osteoporosis education (eg medication administration and side effects, calcium and vitamin D supplementation, falls prevention, and exercise), and adherence follow-up via telephone. Patients were identified as living in a rural area if their ZIP code was not in a US Census Bureau-defined urban area (ie population density greater than approximately 386 persons per square kilometer/1000 persons per square mile). RESULTS: From October 2013 to September 2014, 2775 fractures were identified by a fracture-related ICD9 code. After exclusion of those aged less than 50 years and high-trauma fractures, 321 e-consults were completed. Of those, 171 (53.3%) were for patients residing in a rural or highly rural area. The e-consult program saved a total of 19 187 km (11 917 miles) of travel. For rural patients, bisphosphonates were recommended 51 times, with 33 (64.7%) ordered, and bone density assessments were recommended 109 times with 79 (72.5%) ordered. A nurse liaison significantly improved bisphosphonate ordering (from 39.7% to 75.8%) and bone mineral density testing completion rates (from 37.1% to 63.0%), for both rural and urban patients (p<0.01). CONCLUSIONS: A centralized e-consult program can effectively and efficiently provide specialty bone health services to patients residing in rural areas. The program was able to save substantial travel time and increase the rates of evaluation and treatment for osteoporosis.

Intensive Care Utilization for Hematopoietic Cell Transplant Recipients.

Blood and marrow transplantation (BMT) is a potentially curative therapy for a number of malignant and nonmalignant diseases. Multiple variables, including age, comorbid conditions, disease, disease stage, prior therapies, degree of donor-recipient matching, type of transplantation, and dose intensity of the preparative regimen, affect both morbidity and mortality. Despite tremendous gains in supportive care, BMT remains a high-risk medical therapy. A critically ill BMT recipient may require transfer to an intensive care unit (ICU) and the specialized medical and nursing care that can be provided, such as mechanical ventilation and vasopressor support. Mortality for BMT recipients requiring care in an ICU is high. This paper will describe the experience of the Stanford Blood and Marrow Transplant Program in developing and implementing guidelines to maximize the benefit of intensive care for critically ill BMT recipients.

Management and Treatment Modalities in Traumatic Brain Injury.

Traumatic Brain Injury (TBI) is a very broad diagnosis. Some TBI patients have minimal complaints for a short period of time. Other TBI patients suffer from drastic life-altering, permanent brain damage. One particularly troubling class of TBI patients arises from people who experience one or more concussions in their youth. Later, as adults, the TBI manifests as multiple learning difficulties or even personality changes. As ophthalmic professionals, we are often the first to see potential TBI patients as they complain of visual disturbances. It is of utmost importance to find ways to help these people, but first we have to find the deficits. This paper will discuss some therapeutic measures given to TBI patients and the examinations that will provide vital information.

A Three-Step Letter Advance Directive Procedure to Facilitate Patient-Proxy Alignment in Advance Care Planning.

Background: Little is known about the extent of alignment between hematopoietic stem cell transplant (HSCT) patients and their healthcare proxies with respect to advance care planning (ACP). Aim: To determine if a structured three-step process using the letter advance directive (LAD) could (1) allow for the differences in opinion between patient-proxy dyads to surface and (2) help bridge preexisting discordance about specific treatment choices. Design: Blinded to each other, the HSCT patient (LAD-1) and proxy (LAD-2) each completed the LAD (step 1). They unmasked, compared LAD-1 and LAD-2, and discussed their choices (step 2). They completed a final letter directive (LAD-3) by consensus (step 3). Settings/Participants: Convenience sample of eighty dyads (patient and proxy) at a regional HSCT referral center. Results: The mean patient-proxy concordance was 72.9% for the 12 questions in the LAD. Wanting to be pain free at the end of life was the statement with the most amount of agreement (88.75% in LAD-1, 91.25% in LAD-2, and 90% in LAD-3). Patient-proxy dyads had notable discordance related to specific treatments. The highest discordance was related to ventilator support (46.3% of patients refused it, while 58.8% of proxies refused on behalf of the patient). Overall, proxies were more likely than patients to opt in for dialyses and hospice care but more likely to opt out for cardiac resuscitation and sedation to palliate refractory symptoms. On open discussion, patient-proxy discordance mostly resolved in favor of the patient. Conclusions: The ACP process should allow for patient-proxy differences to surface, facilitate a discussion about the granular details with the goal of reaching consensus. Our three-step approach using the LAD is an effective way to identify areas of patient-proxy concordance and discordance about specific treatment preferences. A structured patient-proxy discussion using the LAD helped reconcile discordance and most often in favor of a patient's original wishes.

The relationship between dyspnea and blood pressure in chronic obstructive pulmonary disease.

BACKGROUND AND RESEARCH OBJECTIVE: Although dyspnea is a frequently encountered clinical symptom, precise clinical evaluation of this sensation remains illusive. Dyspnea has been difficult to evaluate empirically, as severity of mechanical pulmonary impairment does not appear to correlate with subjectively reported levels of dyspnea. The purpose of this study was to describe changes in dyspnea and blood pressure with the use of an incentive spirometry and to examine the relationship of such changes in patients with chronic obstructive pulmonary disease. SUBJECTS AND METHODS: A convenience sample of 60 adults diagnosed with chronic obstructive pulmonary disease was recruited from ambulatory outpatient clinics at a large Veterans hospital. A quantitative single-group, within-subjects repeated-measure design was used to investigate the relationship between the variables following incentive spirometry. Dyspnea levels were recorded with the visual analog scale and arterial blood pressures (beat-to-beat systolic, mean, and diastolic) were continuously recorded with tonometry. RESULTS AND CONCLUSIONS: The first 4 periods following use of the incentive spirometer were found to have statistically significant increases from dyspnea baseline scores (F = 77.4, P < .001). The baseline of each of the arterial blood pressure measurements, systolic, mean, and diastolic, were found to have significant differences with all of the 6 postintervention time points (systolic F = 8.0, P < .001; mean F = 7.1, P < .001; diastolic F = 7.2, P < .001). The changes in dyspnea scores and blood pressure measurements were found to have significant inverse correlations at the immediate postintervention time point (r = -0.32 to -0.35, P < .01). Results provide evidence of an inverse relationship between dyspnea and blood pressure patterns and may indicate significant clinical associations to add to the body of knowledge about the symptom of dyspnea.

Wernicke Encephalopathy.

INTRODUCTION AND PURPOSE: This paper reviews the complaints and associated symptoms/consequences of lacking essential nutrients and vitamins in our central and peripheral nervous systems. This has become important as there has been a rise in malnutrition following the increasing incidence of bariatric surgery for obesity. METHODS: A case report example involving review of the clinical presentation and treatment. RESULTS: A 30-year-old Caucasian woman who had gastric sleeve surgery did not take the recommended capsules as they were too large to swallow. She noted diplopia and oscillopsia 2 months later, which led her to have full orthoptic and neuro-ophthalmic evaluations. After being treated with chewable vitamins with thiamine, she noted a tremendous improvement in her symptoms. CONCLUSION: Wernicke encephalopathy is a disease that was seen more in the 1940s and 1950s, following war times and mostly in underdeveloped countries. However, with the increasing utilization of bariatric surgery for obesity, neurological offices are seeing more patients with neurological impairments. We recommend inquiring about any obesity surgery in one's history and including Wernicke encephalopathy in possible differential diagnoses in those patients who have a recent onset of strabismus or nystagmus, altered mental status, and/or gait ataxia.

Anticoagulation with anisindione in a patient with a warfarin-induced skin eruption.

A 71-year-old woman experienced a pruritic, maculopapular, morbilliform rash on her lower extremities 5 days after starting warfarin for recurrent deep vein thrombosis. The rash extended to her truncal areas and progressively worsened until somewhat painful vesicular lesions developed. Warfarin was discontinued, and subcutaneous injections of enoxaparin were begun; the rash resolved. In addition to a history of deep vein thrombosis, the patient had experienced a hypersensitivity skin reaction to warfarin in the past that necessitated withdrawal of the drug and placement of a vena caval filter. Because no clear consensus exists on whether dyes used in compounding warfarin play a causative role or whether allergic cross-sensitivity occurs among the coumarin derivatives, the patient was rechallenged with a dye-free warfarin 10-mg tablet. The pruritic rash returned along with the vesicular lesions and continued to worsen until the warfarin was discontinued again. The patient subsequently was given oral anticoagulant therapy with anisindione, an indanedione, and her symptoms resolved completely. Health care providers managing patients who are receiving oral anticoagulant therapy should be aware of the maculopapular allergic reactions associated with warfarin and consider alternative treatment options such as anisindione.

Objective improvement from base-in prisms for reading discomfort associated with mini-convergence insufficiency type exophoria in school children.

PURPOSE: To determine whether base-in prism glasses could diminish asthenopia, and improve reading abilities (speed, accuracy and comprehension). METHODS: All patients aged 8-18 years, from one practice, were examined and considered prospectively over a six month period. Ten percent (72) of these 703 patients met initial criteria of an exodeviation greater at near than distance and reading discomfort. At initial examination these 72 were asked to read orally, with and without base-in prisms. If the senior examiner noted they read faster and with fewer mistakes, and the patient reported increased reading comfort, then reading (only) glasses with 2 to 3 diopters base-in prism OU were prescribed. Of the 72, 33 were so treated. After 3 weeks they were given the Gray Oral Reading Test (GORT-3). This test has two equal parts which were administered one with, and one without, prisms. A subjective questionnaire was also administered. RESULTS: The overall mean improvement in reading speed, accuracy and comprehension on the GORT- 3 with base-in prisms, was from the 34th to the 66th percentile. The improvements in reading were "statistically significant" at p<.001. Patients also reported subjective improvement in asthenopic symptoms and headaches. CONCLUSION: Base-in prism glasses improve subjective reading comfort and abilities (speed, accuracy and comprehension) in these patients.

Palliative care of hematopoietic cell transplant recipients and families.

OBJECTIVES: To provide support for the early integration of palliative care into the care of hematopoietic cell transplant (HCT) recipients and families with the goal of improving care. DATA SOURCES: Journal articles and on-line databases. CONCLUSION: Early integration of palliative care for HCT recipients at high risk for complex symptom clusters, non-relapse mortality, or relapse offers an opportunity to clarify goals of care, advanced care planning, and improving the quality of care for both recipients and families. IMPLICATIONS FOR NURSING PRACTICE: The palliative care service can support the HCT nurse in providing complex care to HCT recipients who are faced with significant side effects, toxicities, and complications of transplant.

Osteopetrosis.

Osteopetrosis is a rare disease that occurs when a child has an unequal balance between new bone growth and elimination of old bone. Children with this entity are able to make new bone tissue, but are not able to break down and eliminate old bones, which is essential for normal bone growth. These thickened and enlarged bones are very weak. These children can exhibit: failure to thrive, macrocephaly, anemia, deafness, and blindness. We will present a case of osteopetrosis, esotropia, and amblyopia of a 7-year-old boy and will discuss the pathophysiology and treatment.

The use of PET in assessing tumor response after neoadjuvant chemoradiation for rectal cancer.

PURPOSE: To assess the correlation of 18F-FDG-PET (PET) response to pathological response after neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer. METHODS AND MATERIALS: Twenty patients with locally advanced rectal cancer were identified between 2001 and 2005. The median age was 57 years (range 37-72) with 14 males and 6 females. All patients were staged with endorectal ultrasound and/or MRI, CT, and PET. The clinical staging was T3N0M0 (16), T3N1M0 (2), and T3N0M1 (2). Restaging PET was performed after CRT, and prior to definitive surgery. The response on PET and pathology was assessed and correlated. Patient outcome according to PET response was also assessed. RESULTS: Following CRT, a complete PET response occurred in 7 patients, incomplete response in 10, and no response in 3 patients. At surgery, complete pathological response was recorded in 7 patients, incomplete response in 10 and no response in 3. There was a good correlation of PET and pathological responses in complete responders (5/7 cases) and non-responders (3/3 cases). After a median follow-up of 62 months (range 7-73), twelve patients were alive with no evidence of disease. All patients achieving complete metabolic response were alive with no evidence of disease, while as those who had no metabolic response, all died as a result of metastatic disease. CONCLUSIONS: PET is a promising complementary assessment tool for assessing tumor response after CRT if there is a complete or no response. PET response may also predict for outcome.

The multiple facets of multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is an inflammatory and degenerative entity that may involve the brain, optic nerve, and/or the spinal cord. We reviewed 137 patients, aged 4-54 years old at the time of the diagnosis and will report on the vision, different motility disorders found, visual fields, optic neuritis and RAPD, return of vision following the neuritis, visual evoked potential, nerve fiber layer analysis, and systemic problems such as Uhthoff phenomenon, L'Hermitte sign, urinary urgency, and constipation. METHODS: One hundred thirty-seven patients were given full ophthalmologic and orthoptic evaluations. Particular attention was given to subtle relative afferent pupillary defects (RAPD), oscillopsia, pain with eye movement, and other specialty testing including visual evoked potentials and nerve fiber layer assessment. The immunology, pediatric MS, clinical courses, and treatment are also discussed. Treatment included medication, orthoptic modalities, strabismus procedures, and cooling devices. RESULTS: Motiltiy disorders included exophoria, unilateral Internuclear Ophthalmoplegia (INO), esophoria, and various types of nystagmus. The majority of nonmotility ophthalmic entities included optic neuritis, RAPD, and abnormal nerve fiber layer studies. Most patients were diagnosed based on white matter lesions on the MRI and oligoclonal bands in the spinal fluid after lumbar puncture. The majority of systemic signs were numbness, Uhthoff sign, and balance difficulties. Thirty-four percent of the patients were helped with either convergence therapy, prisms for all kinds of diplopia, and field manipulation. CONCLUSIONS: MS is a multi-factorial entity. It is important to emphasize how important a few extra history questions are, including: any pain with eye movement, any bouncing of the images, and is vision or balance any worse in the heat? The Visual Evoked Potential (VEP) and nerve fiber layer studies are important in the diagnosis of MS. Seventy percent of patients with had eye complaints as their initial symptom. Finally, one-third of all patients were helped with some form of orthoptic therapy.

The effect of dissociation on the sensory status.

The sensory status has been studied for many years. Some feel very strongly that Bagolini striated lenses and the Worth 4 Dot test provide vital information regarding patients' overall ability to maintain fusion and/or alignment. Furthermore, some feel strongly that these tests should be done early in the exam, preferably first, so as not to disturb the patient's tenuous hold on fusion. There are no known documented studies that compare sensory tests taken at the beginning of the exam to those taken at the end of the motility exam. Our study found that obtaining sensory results of Bagolini striated lenses and Worth 4 Dot glasses done at the conclusion of the evaluation produce the same or better fusional abilities when these tests are done prior to dissociation.