Magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor in a patient with von Willebrand disease: perioperative optimization for patients with coagulopathies. Illustrative case.

BACKGROUND: Essential tremor (ET) is one of the most common movement disorders worldwide. In medically refractory ET, deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus is the current standard of care. However, DBS carries an inherent 2% to 3% risk of hemorrhage, a risk that can be much higher in patients with concomitant coagulopathy. Magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy is a surgical alternative that is highly effective in treating ET, with no reports of intracranial hemorrhage to date. OBSERVATIONS: This is the first documented case of successful MRgFUS thalamotomy in a patient with von Willebrand disease (VWD). A 60-year-old left-handed male had medically refractory ET, VWD type 2B, and a family history of clinically significant hemorrhage after DBS. He underwent right-sided MRgFUS thalamotomy and received a perioperative course of VONVENDI (recombinant von Willebrand factor) to ensure appropriate hemostasis. Postprocedure imaging confirmed a focal lesion in the right thalamus without evidence of hemorrhage. The patient reported 90% improvement of his left-hand tremor and significant improvement in his quality of life without obvious side effects. LESSONS: MRgFUS thalamotomy with peri- and postoperative hematological management is a promising alternative to DBS for patients with underlying coagulopathies.

How I treat anemia in older adults.

ABSTRACT: With the global growing older adult population, clinicians face the common, yet complex challenge of how to evaluate and manage anemia in this population. Older age predisposes to common causes of anemia such as nutritional deficiencies, inflammatory disorders, chronic kidney disease, and hematologic malignancies. Failure to diagnose and appropriately manage anemia may result in decreased quality of life, impaired cognition, impaired mobility, and increased mortality. Anemia diagnosis in older adults presents a diagnostic conundrum because anemia may have a single cause, may be multifactorial, or may have no apparent cause even after an extensive evaluation. We believe a systematic approach to diagnosis ensures appropriate testing and avoids the pitfall of undertreatment and overtreatment. In this article we present our recommended approach through common scenarios for the management of anemia in the older adult.

Cognitive-motor dual-task interference in adults with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a genetic disorder that causes physical and cognitive impairment due to hemolysis, painful vaso-occlusion episodes, joint avascular necrosis, and strokes. As individuals with SCD age and develop conditions impacting their physical and cognitive function, their ability to multitask successfully and safely may decline. Cognitive-motor dual-task interference occurs when there is deterioration in one or both tasks while dual-tasking relative to single-tasking. Dual-task assessment (DTA) is a valuable measure of physical and cognitive function; however, there is limited data on DTA in adults with SCD. RESEARCH QUESTION: Is DTA a feasible and safe method of measuring physical and cognitive function in adults with SCD? What patterns of cognitive-motor interference occur in adults with SCD? METHODS: We enrolled 40 adults with SCD (mean age 44 years, range 20-71) in a single-center prospective cohort study. We used usual gait speed as the measure of motor performance and verbal fluency (F, A, and S) as the measure of cognitive performance. We measured feasibility as the proportion of consented participants able to complete the DTA. We calculated the relative dual-task effect (DTE %) for each task and identified patterns of dual-task interference. RESULTS: Most consented participants completed the DTA (91%, 40/44) and there were no adverse events. There were 3 main dual-task interference patterns for the first trial using letter 'A': Motor Interference (53%, n = 21), Mutual Interference (23%, n = 9), and Cognitive-Priority Tradeoff (15%, n = 6). For the second trial using letter 'S', there were two main dual-task interference patterns: Cognitive-Priority Tradeoff (53%, n = 21) and Motor Interference (25%, n = 10). STATEMENT OF SIGNIFICANCE: DTA was feasible and safe in adults with SCD. We identified specific patterns of cognitive-motor interference. This study supports further evaluation of DTA as a potentially useful tool to measure physical and cognitive function in ambulatory adults with SCD.

Management of Older Adults with Sickle Cell Disease: Considerations for Current and Emerging Therapies.

People with sickle cell disease (SCD) are living longer than ever before, with the median survival increasing from age 14 years in 1973, beyond age 40 years in the 1990s, and as high as 61 years in recent cohorts from academic centers. Improvements in survival have been attributed to initiatives, such as newborn screening, penicillin prophylaxis, vaccination against encapsulated organisms, better detection and treatment of splenic sequestration, and improved transfusion support. There are an estimated 100,000 people living with SCD in the United States and millions of people with SCD globally. Given that the number of older adults with SCD will likely continue to increase as survival improves, better evidence on how to manage this population is needed. When managing older adults with SCD (defined herein as age ≥ 40 years), healthcare providers should consider the potential pitfalls of extrapolating evidence from existing studies on current and emerging therapies that have typically been conducted with participants at mean ages far below 40 years. Older adults with SCD have historically had little to no representation in clinical trials; therefore, more guidance is needed on how to use current and emerging therapies in this population. This article summarizes the available evidence for managing older adults with SCD and discusses potential challenges to using approved and emerging drugs in this population.

Characterising the prevalence of overweight and obese status among adults with sickle cell disease.

Individuals with sickle cell disease (SCD) have historically been considered underweight. Despite increasing body mass index (BMI) in the general population, the prevalence of overweight and obese status remains unclear in the adult SCD population. Our primary aim was to determine the prevalence of overweight and obese status and to identify associations between BMI, demographic, and clinical characteristics. We conducted an analysis of abstracted electronic health record data and patient-reported outcomes from the Sickle Cell Disease Implementation Consortium registry; individuals aged 20-45 years were included. The median (interquartile range) BMI for the 1664 adults in this analysis was 23.9 (21.1-28) kg/m2 . In this cohort, 42.9% had a BMI of >25 kg/m2 (Centers for Disease Control and Prevention definition of overweight/obese). In multivariable analysis, higher odds of being overweight or obese were associated with female gender, older age, college education, private insurance, and hypertension diagnosis. Higher odds of a BMI of >25 kg/m2 were observed in individuals with HbSC or HbSß+ thalassaemia regardless of hydroxycarbamide (hydroxyurea) exposure (odds ratio [OR] 3.4, p < 0.0001) and HbSS or HbSß0 thalassaemia exposed to hydroxycarbamide (OR 1.6, p = 0.0003) compared to those with HbSS or HbSß0 thalassaemia with no hydroxycarbamide exposure. These data highlight the importance of early identification, prevention, and intervention for increasing BMI to reduce obesity-related complications that may impact SCD-related complications.

"Death is as Much Part of Life as Living": Attitudes and Experiences Preparing for Death from Older Adults with Sickle Cell Disease.

The life-limiting and unpredictable nature of sickle cell disease (SCD) is well-established, yet there is limited literature on end-of-life planning. The purpose of this study was to describe perspectives about preparing for death for older adults with SCD. We enrolled 19 older adults with SCD (age ≥ 50 years) into this qualitative descriptive study. Theme 1 was "anticipation of early death," with sub-themes: (a) informed of early death and (b) making plans for death. Theme 2 was "near death experiences." Theme 3 was "differences in level of comfort with death" with subthemes: (a) death as a part of life and (b) differences in level of comfort discussing death. Theme 4 was "influence of spirituality" with subthemes: (a) God controls the timing of death and (b) belief in the afterlife. These results will inform interventions to improve the quality of patient-provider communication to provide goal-concordant end-of-life care for adults with SCD.

The Sickle Cell Disease Functional Assessment (SCD-FA) tool: a feasibility pilot study.

BACKGROUND: The life expectancy for individuals with sickle cell disease (SCD) has greatly increased over the last 50 years. Adults with SCD experience multiple complications such as cardiopulmonary disease, strokes, and avascular necrosis that lead to limitations that geriatric populations often experience. There are no dedicated instruments to measure functional decline and functional age to determine risk of future adverse outcomes in older adults with SCD. The objective of this study was to assess the feasibility of performing the Sickle Cell Disease Functional Assessment (SCD-FA). METHODS: We enrolled 40 adults with SCD (20 younger adults aged 18-49 years as a comparison group and 20 older adults aged 50 years and older) in a single-center prospective cohort study. Participants were recruited from a comprehensive sickle cell clinic in an academic center in the southeastern United States. We included measures validated in an oncology geriatric assessment enriched with additional physical performance measures: usual gait speed, seated grip strength, Timed Up and Go, six-minute walk test, and 30-second chair stand. We also included an additional cognitive measure, which was the Montreal Cognitive Assessment, and additional patient-reported measures at the intersection of sickle cell disease and geriatrics. The primary outcome was the proportion completing the assessment. Secondary outcomes were the proportion consenting, duration of the assessment, acceptability, and adverse events. RESULTS: Eighty percent (44/55) of individuals approached consented, 91% (40/44) completed the SCD-FA in its entirety, and the median duration was 89 min (IQR 80-98). There were no identified adverse events. On the acceptability survey, 95% (38/40) reported the length as appropriate, 2.5% (1/40) reported a question as upsetting, and 5% (2/40) reported portions as difficult. Exploratory analyses of physical function showed 63% (25/40) had a slow usual gait speed (< 1.2 m/s). CONCLUSION: The SCD-FA is feasible, acceptable, and safe and physical performance tests identified functional impairments in adults with SCD. These findings will inform the next phase of the study where we will assess the validity of the SCD-FA to predict patient-important outcomes in a larger sample of adults with SCD.

Optimizing management of sickle cell disease in patients undergoing surgery.

Individuals with sickle cell disease (SCD) are likely to be referred for surgery at some point in their lifetime due to a high incidence of musculoskeletal and intrabdominal complications such as avascular necrosis and gallbladder disease. Preoperative optimization is a multidisciplinary process that involves a hematologist with SCD expertise, an anesthesiologist, and the surgical team. The type and risk classification of the surgery, disease severity, medications, baseline hemoglobin, transfusion history, and history of prior surgical complications are often documented. Clinicians should consider perioperative risk assessment that includes determining the patient's functional status and cardiovascular risk and screening for obstructive sleep apnea. Many patients will require preoperative transfusion to reduce the risk of postoperative complications such as acute chest syndrome and vaso-occlusive pain crises. The hematologist should consider the patient's preoperative transfusion requirements and ensure that the surgical team has an appropriate plan for postoperative observation and management. This often includes follow-up laboratory studies, a postoperative pain management plan, and venous thromboembolism prophylaxis. The transfusion plan should be patient-specific and take into account the SCD genotype, baseline hemoglobin, disease severity, risk classification of the surgery, and history of prior surgical complications. In the intraoperative and postoperative period, dehydration, hypothermia, hypotension, hypoxia, and acidosis should be avoided, and incentive spirometry should be utilized to minimize complications such as acute chest syndrome. In this review we discuss preoperative, intraoperative, and postoperative strategies to optimize patients with SCD undergoing surgery.

Adherence to Iron Chelation Therapy with Deferasirox Formulations among Patients with Sickle Cell Disease and ß-thalassemia.

BACKGROUND: Individuals with hemoglobinopathies experience complications that often require management with multiple transfusions. These chronic transfusions can lead to iron overload, which places them at increased risk of organ damage, malignancy, and even death. Deferasirox is the most common iron chelator used to treat iron overload due to its safety, efficacy, and oral administration. The first formulation of deferasirox, a dispersible tablet for oral suspension (DT) called Exjade®, was associated with adherence challenges due to complaints from poor taste and side effects such as abdominal discomfort. A new film-coated tablet formulation (FCT) called Jadenu® was subsequently developed to overcome these challenges. OBJECTIVE: The objective of this study was to compare adherence rates between formulations of deferasirox (DT versus FCT) and describe associations between adherence to chelation therapy and changes in hematological parameters among patients with SCD and ß-thalassemia. METHODS: In this retrospective study of 20 children and adults with sickle cell disease (SCD) and ß-thalassemia with iron overload, we compared adherence rates for deferasirox DT versus deferasirox FCT. We reviewed data from the electronic medical record and pharmacy expense reports between 2014 and 2018. We calculated the mean medication possession ratio (MPR) and analyzed the mean paired difference in MPR and ferritin levels using paired sample t-test. RESULTS: The overall mean MPR was 0.15 (0.25) for deferasirox DT and 0.44 (0.32) for deferasirox FCT. The mean paired difference in MPR when transitioning from deferasirox DT to deferasirox FCT was +0.29, p-value < 0.01 (95% CI: 0.19, 0.39). The mean paired difference in ferritin while on deferasirox DT compared to ferritin 6 months after transitioning to deferasirox FCT was -306 ng/mL p-value = 0.14 (95% CI: 719, 113). CONCLUSION: There was significant improvement in adherence to iron chelation therapy when patients transitioned from deferasirox DT to deferasirox FCT.

Geriatric assessment for older adults with sickle cell disease: protocol for a prospective cohort pilot study.

BACKGROUND: The life expectancy for people with sickle cell disease (SCD) has improved tremendously over the last 50 years. This population experiences hemolysis and vaso-occlusion in multiple organs that lead to complications such as cardiopulmonary disease, strokes, and avascular necrosis. These complications can limit mobility and aerobic endurance, similar to limitations that often occur in geriatric populations. These sickle-cell and age-related events lead to frequent hospitalization, which further increases the risk of functional decline. We have few tools to measure functional decline in people with SCD. The purpose of this paper is to describe a protocol to evaluate the feasibility of sickle cell disease geriatric assessment (SCD-GA). METHODS/DESIGN: We will enroll 40 adults with SCD (20 age 18-49.99 years and 20 age ≥ 50 years) in a prospective cohort study to assess the feasibility of SCD-GA. The SCD-GA includes validated measures from the oncology geriatric assessment enriched with additional physical and cognitive measures. The SCD-GA will be performed at the first study visit, at 10 to 20 days after hospitalization, and at 12 months (exit visit). With input from a multidisciplinary team of sickle cell specialists, geriatricians, and experts in physical function and physical activity, we selected assessments across 7 domains: functional status (11 measures), comorbid medical conditions (1 measure), psychological state (1 measure), social support (2 measures), weight status (2 measures), cognition (3 measures), and medications (1 measure). We will measure the proportion completing the assessment with feasibility as the primary outcome. Secondary outcomes include the proportion consenting and completing all study visits, duration of the assessment, acceptability, and adverse events. DISCUSSION: We present the protocol and rationale for selection of the measures included in SCD-GA. We also outline the methods to determine feasibility and subsequently to optimize the SCD-GA in preparation for a larger multicenter validation study of the SCD-GA.