Association Between Laboratory Values and Adverse Events in Adults Post-Hematopoietic Stem Cell Transplant During and After Rehabilitation.

OBJECTIVE: The objective of this study was to examine the relationship between adverse events (AEs) and critical events (CEs) during and after rehabilitation in cancer patients post-hemopoietic stem cell transplant (HSCT) or bone marrow transplant (BMT) and to identify whether particular laboratory values are associated with increased risk of AEs or CEs. DESIGN: A retrospective chart review (2012-2017) of hospitalized patients ages 18-75 years who received a diagnosis of cancer and BMT or HSCT receiving rehabilitation services SETTING: Urban Midwest tertiary, research and academic hospital. PARTICIPANTS: In total, 99 hospitalized adults with HSCT or BMT participated in 300 rehabilitation sessions. INTERVENTIONS: Physical or occupational therapy using a symptom-based approach in which patient symptoms were monitored and therapy was adjusted in real time MAIN OUTCOME MEASURES: Incidence of AEs or CEs occurring during or within 48 hours of rehabilitation. RESULTS: A total of 300 rehabilitation sessions were carried out where 99.7% had 1 or more laboratory values outside reference range. In only 3.3% of therapy sessions an AE occurred during or within 2 hours of rehabilitation. Within 48 hours postrehabilitation, AEs occurred in 22.3% and CEs in 4%. No laboratory value was significantly associated with increased risk of AEs or CEs during rehabilitation. A hemoglobin <8.0 g/dL conferred an increased risk of AEs (odds ratio [OR], 2.85-6.89) depending on timeframe analyzed and overall risk of CE (OR, 3.75). Lower hemoglobin levels (<7.5 g/dL and <7.0 g/dL) did not increase this risk. Low platelets (<25 k/µL) increased the risk of AEs on day 1, 2 and overall (OR, 2.5-2.72) and overall risk of CEs (OR, 6.62). CONCLUSIONS: Our research demonstrates a low rate of AEs and CEs during or within 2 hours of rehabilitation but supports the need to monitor patients when hemoglobin is <8 g/dL or platelets are <25 k/µL due to the increased risk of events.

Characteristics and patterns of pediatric chemotherapy-induced peripheral neuropathy: A systematic review.

This systematic review provides a high-quality synthesis of the empirical evidence regarding chemotherapy-induced peripheral neuropathy (CIPN) characteristics and patterns described in studies of children who received neurotoxic chemotherapy to treat cancer. PubMed, CINAHL, PsycINFO, and Embase were searched for articles published 2009 - 2019, yielding 861. Forty-two papers met the eligibility criteria, including 31 that described characteristics and patterns of vincristine-induced CIPN. Fifty-seven percent of articles were of low to moderate quality; measurement flaws were the most common limitations. The reported CIPN incidence varies widely (2.8%-100%) depending on risk factors (e.g., race) and the measurement approach. Incidence rates of sensory, motor, autonomic CIPN, and pain were 12-28%, 50-72%, 0.8-83% and 5.7-44%, respectively. The evidence suggests that sensory and motor neuropathy, pain, and functional deficits are common and can persist into adulthood. Caucasian race is a risk factor and, contrary to prior thinking, cumulative chemotherapy dosage alone does not predict CIPN severity. The influence of other risk factors is less clear, and studies to date have not explored potential interactions among race, genetics, age, sex, drug metabolism, and nutritional status, among other factors.

Assessment of Pediatric Chemotherapy-Induced Peripheral Neuropathy Using a New Patient-Reported Outcome Measure: The P-CIN.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is commonly experienced by children receiving neurotoxic chemotherapy. No validated pediatric CIPN patient-reported outcome (PRO) measures exist. Purpose: To test sensitivity, internal consistency reliability, content and convergent validity, and feasibility of the Pediatric Chemotherapy-Induced Neuropathy (P-CIN), an electronic PRO measure for assessing CIPN in children who received neurotoxic chemotherapy. Method: Five experts evaluated content validity of the 14-item P-CIN. Children 5 to 17 years old with CIPN (N = 79) completed the P-CIN via tablet computer; a subset (n = 26) also underwent neurological examinations using the Pediatric-Modified Total Neuropathy Score. Following preliminary analyses, one item was deleted and three others modified. The revised P-CIN was retested with patients (n = 6) who also completed the Bruininks-Oseretsky Test of Motor Proficiency motor function assessment. Means, item response ranges, standard deviations, content validity indexes, Cronbach's alphas, and correlation coefficients were calculated. Results: Mean participant age was 11.25 (SD = 4.0) years. Most had acute leukemia (62.5%) and received vincristine (98.7%). Content validity index coefficients ranged from .80 to 1.0 (p = .05). For 9 of 14 items, responses ranged from 0 to 4 or 5; response ranges for toe numbness, pick up a coin, and three of four pain items were 0 to 3. After deleting one item, Cronbach's alpha coefficient was .83. P-CIN scores were strongly associated with Pediatric-Modified Total Neuropathy Score (r = .52, p < .01) and Bruininks-Oseretsky Test of Motor Proficiency (r = -.83, p = .04) scores. Sixty-eight percent of children 6 to 17 years old completed P-CIN independently. Discussion: Preliminary evidence suggests that the 13-item P-CIN is internally consistent, is valid, and can be completed independently by children ≥ 6 years. However, we recommend additional testing.

Long-Term Survivorship Care After Cancer Treatment: A New Emphasis on the Role of Rehabilitation Services.

In May 2018, the National Cancer Policy Forum (NCPF) of the National Academies of Sciences, Engineering, and Medicine (formerly the Institute of Medicine) released a report, Long-Term Survivorship Care After Cancer Treatment: Proceedings of Workshop. NCPF-published reports have historically played a significant role in driving policy and payment model changes in oncology care, in addition to raising awareness about the needs of individuals with cancer. This 2018 report provides a specific set of recommendations for improving symptom management and rehabilitation that suggest the integration of rehabilitation services at the point of cancer diagnosis and throughout the continuum of cancer care to effectively screen for and manage the anticipated functional morbidity associated with cancer treatment. The specificity of these recommendations is of significant relevance to the physical therapy profession and should encourage bold steps to effectively increase the presence of physical therapists as members of interdisciplinary cancer care teams. The profession must act to implement models of prospective care, develop targeted education and training initiatives to assure the knowledge and skills of our workforce for this complex population, and augment the current evidence base with greater attention to health services research aiming to understand the effectiveness of rehabilitation services in improving costs, utilization, and meaningful functional outcomes.

Peripheral neuropathy in children and adolescents treated for cancer.

Peripheral neuropathy is a well recognised treatment-related toxicity in children with cancer, associated with exposure to neurotoxic chemotherapy agents. Acute damage can occur in sensory, motor, or autonomic neurons, with symptoms that are rarely life threatening, but often severe enough to interfere with function during therapy and after treatment ends. The type of neuropathy and specific symptoms are associated with multiple factors including age at time of therapy, genetic predisposition, chemotherapy type and cumulative dose, and exposure to other agents during therapy. In this Review, we describe the peripheral neuropathy phenotype in children during cancer therapy and among survivors who have completed therapy, to summarise genetic and treatment-related risk factors for neuropathy, and to outline strategies to monitor and detect neuropathy during and after therapy. Additionally, we outline strategies for medical management of neuropathy during treatment and potential rehabilitation interventions to prevent or remediate functional loss.

Short-Term Recovery of Balance Control: Association With Chemotherapy-Induced Peripheral Neuropathy in Pediatric Oncology.

PURPOSE: To describe the incidence and short-term recovery of balance control in children and adolescents receiving neurotoxic treatment for noncentral nervous system cancers and to investigate the association of chemotherapy-induced peripheral neuropathy and balance control. METHODS: Sixty-five children and adolescents diagnosed with leukemia, lymphoma, or other solid tumors were tested 3 to 6 months into treatment and 3 and 6 months following treatment using the Bruininks-Oseretsky Balance Subscale and Pediatric Modified Total Neuropathy Scale scores of chemotherapy-induced peripheral neuropathy (CIPN). RESULTS: Seventy-eight percent of the participants scored 1 standard deviation or more below population means on the balance subscale while on treatment, and this improved to 53% by 6 months posttreatment, with the leukemia group performing worse at both time points. On-treatment balance scores were moderately associated with motor CIPN, while at 6 months posttreatment they were more closely associated with sensory CIPN. CONCLUSIONS: Mild to moderate balance impairments improve but can persist, even when CIPN has improved, 6 months after treatment for childhood cancer.

Short-term recovery of chemotherapy-induced peripheral neuropathy after treatment for pediatric non-CNS cancer.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent side effect of pediatric cancer treatment. The presentation of CIPN, trajectory and completeness of recovery over the first 6 months postchemotherapy, and the influence of patient and treatment characteristics on recovery are described. PATIENTS AND METHODS: Sixty-seven children and adolescents treated for non-CNS cancers were evaluated for CIPN using the pediatric modified total neuropathy score (ped-mTNS) while on treatment and 3 and 6 months postchemotherapy. Differences between diagnostic groups and treatment type were evaluated as well as change in scores over time. Risk factors for on-treatment and persistent CIPN at 6 months were identified. RESULTS: Overall, ped-mTNSs were in the abnormal range for 86.5% during treatment and scores decreased over time (initial 9.3 ± 0.6, 6 months 4.3 ± 0.4; F = 38.14, P < 0.001). By 6 months posttreatment, mean scores and percentage of children with abnormal scores were reduced to 2.4 ± 0.3 and 11.5%, respectively, in the ALL group, but remained higher at 5.7 ± 0.7 and 57%, respectively, for lymphoma, and 5.2 ± 1.0 and 60%, respectively, for other solid tumors. At 6 months posttreatment, light touch deficits and foot strength deficits remained in 19.4 and 59.7%, respectively, compared with only 4.9 and 9.8% of the control population. Subjects who were older at exposure, female, or who received etoposide in addition to vincristine were at higher risk for on-treatment CIPN. On-treatment sensory abnormalities were associated with increased risk of persistent CIPN. CONCLUSION: While CIPN improves in most pediatric patients, significant numbers, especially those treated for lymphoma or other solid tumors, have remaining neuropathic signs and symptoms 6 months posttreatment.

The pediatric-modified total neuropathy score: a reliable and valid measure of chemotherapy-induced peripheral neuropathy in children with non-CNS cancers.

BACKGROUND: Neurotoxicity is a common side-effect of cancer treatment, but no scales have been validated for the pediatric population. The objective of this study was to test the reliability and validity of the pediatric modified-Total Neuropathy Scale (ped-mTNS) to measure chemotherapy-induced peripheral neuropathy in school-aged children. METHODS: Forty-one subjects aged 5-18 years undergoing chemotherapy with vincristine or cisplatin and 41 age- and gender-matched controls completed study measures. Subjects were tested with the ped-mTNS at a specified time during treatment. Standardized measures of balance and hand function were completed concurrently. Internal consistency of the ped-mTNS was evaluated using Chronbach's alpha. Validity was tested by comparing case and control ped-mTNS scores as well as testing the hypothesis that ped-mTNS scores would be associated with scores on tests of balance and manual dexterity. Inter-rater and test-retest reliability were each assessed in a subset of 10 subjects. RESULTS: Twenty-three subjects with acute lymphoblastic leukemia, six with lymphoma, and 12 with solid tumors completed measures along with 41 age- and gender-matched controls. Internal consistency was acceptable with a Chronbach's alpha of 0.76. Children undergoing treatment for cancer had significantly worse scores on the ped-mTNS compared to controls (subjects, 8.7 ± 4.2; controls, 1.4 ± 0.9; p < 0.001). As hypothesized, scores on the ped-mTNS were associated with measures of balance and manual dexterity. Inter-rater and test-retest reliability was acceptable (intraclass correlation coefficients >0.9 each). CONCLUSIONS: The ped-mTNS is a reliable and valid measure of chemotherapy-induced peripheral neuropathy in school-aged children that is associated with relevant functional limitations.

Physical activity among adult survivors of childhood lower-extremity sarcoma.

INTRODUCTION: Adult survivors of childhood lower-extremity sarcoma are largely physically inactive, a behavior which potentially compounds their health burden. Altering this behavior requires understanding those factors that contribute to their physical inactivity. Therefore, this investigation sought to identify factors associated with inactivity in this subpopulation of cancer survivors. METHODS: Demographic, personal, treatment, and physical activity information from adult survivors of childhood lower-extremity sarcomas was obtained from the Childhood Cancer Survivor Study (CCSS) cohort. Generalized linear models were used to identify variables that best identified those individuals who were physically inactive. RESULTS: Only 41% of survivors met Center for Disease Control (CDC) activity guidelines. Survivors were 1.20 (95% confidence intervals (CI) 1.11-1.30) more likely compared to CCSS sibling cohort and 1.12 (95% CI 1.10-1.15) times more likely than the general population to fail to meet CDC guidelines. Significant predictors of physical inactivity included female sex, hemipelvectomy surgery, and platinum and vinca alkaloid chemotherapy. CONCLUSIONS: The primary findings of this study are that survivors of childhood onset lower-extremity sarcoma are (1) highly likely to be physically inactive and (2) less likely than their siblings or the general population to regularly exercise. This study has identified treatment-related risk factors associated with inactivity that will help health and wellness practitioners develop successful exercise interventions to help these survivors achieve recommended levels of physical activity for health. IMPLICATIONS FOR CANCER SURVIVORS: These results suggest that physical activity interventions for adult survivors of childhood lower-extremity sarcomas should be sex specific and responsive to unique physical late effects experienced by these survivors.

Balance interventions for diabetic peripheral neuropathy: a systematic review.

Diabetic Peripheral Neuropathy (DPN) is a complication of diabetes experienced by more than 30% of all diabetic patients. It causes decreased sensation, proprioception, reflexes, and strength in the lower extremities, leading to balance dysfunction. The purpose of this study was to assess the effectiveness of interventions used by physical therapists to minimize balance dysfunction in people with DPN. Currently, no systematic review exists that explores the effectiveness of these interventions. When conducting this systematic review, we searched the electronic databases CINAHL, EMBASE, Cochrane Review, and Medline using specific search terms for the period from inception of each database to June 2009. Two independent reviewers analyzed the abstracts obtained to determine whether the article focused on balance interventions that are within the scope of physical therapy practice. All study designs were eligible for review with the exception of case reports and systematic reviews. The Delphi criteria was used to assess methodological quality. This literature search and methods assessment resulted in 2213 titles, 82 abstracts, and 6 articles, including 1 randomized controlled trial eligible for inclusion. The 6 articles contained 4 physical therapy interventions including monochromatic infrared energy therapy, vibrating insoles, lower extremity strengthening exercises, and use of a cane. Upon thorough analysis of outcome measures, statistical significance, and clinical relevance, the intervention of lower extremity strengthening exercises was given a fair recommendation for clinical use in treating balance dysfunction in patients with DPN. All others had insufficient evidence to either support or refute their effect on balance in this population.

Cancer rehabilitation with a focus on evidence-based outpatient physical and occupational therapy interventions.

Cancer rehabilitation is an important part of survivorship as a distinct phase of treatment. Although cancer rehabilitation may involve many disciplines, this article specifically covers evidence-based treatment in physical and occupational therapy. Patients may need physical and occupational therapy services for a variety of cancer-related or cancer-treatment-related problems, including pain, fatigue, deconditioning, and difficulty with gait. They may also have problems resuming their previous level of function, which can impact on activities of daily living, instrumental activities of daily living, return to previous home and community activity levels, and return to work. This review discusses the role of physical and occupational therapy in helping cancer patients improve pain and musculoskeletal issues, deconditioning and endurance effects, fatigue, balance and falls, and lymphedema and psychosocial problems.

Physical performance limitations among adult survivors of childhood brain tumors.

BACKGROUND: Young adult survivors of childhood brain tumors (BTs) may have late effects that compromise physical performance and everyday task participation. The objective of this study was to evaluate muscle strength, fitness, physical performance, and task participation among adult survivors of childhood BTs. METHODS: In-home evaluations and interviews were conducted for 156 participants (54% men). Results on measures of muscle strength, fitness, physical performance, and participation were compared between BT survivors and members of a population-based comparison group by using chi-square statistics and 2-sample t tests. Associations between late effects and physical performance and between physical performance and participation were evaluated in regression models. RESULTS: : The median age of BT survivors was 22 years (range, 18-58 years) at the time of the current evaluation, and they had survived for a median of 14.7 years (range, 6.5-45.9 years) postdiagnosis. Survivors had lower estimates of grip strength (women, 24.7 + or - 9.2 kg vs 31.5 + or - 5.8 kg; men, 39.0 + or - 12.2 kg vs 53.0 + or - 10.1 kg), knee extension strength (women, 246.6 + or - 95.5 Newtons [N] vs 331.5 + or - 5.8 N; men, 304.7 + or - 116.4 N vs 466.6 + or - 92.1 N), and peak oxygen uptake (women, 25.1 + or - 8.8 mL/kg per minute vs 31.3 + or - 5.1 mL/kg per minute; men, 24.6 + or - 9.5 mL/kg per minute vs 33.2 + or - 3.4 mL/kg per minute) than members of the population-based comparison group. Physical performance was lower among survivors and was associated with not living independently (odds ratio [OR], 5.0; 95% confidence interval [CI], 2.0-12.2) and not attending college (OR, 2.3; 95% CI 1.2-4.4). CONCLUSIONS: Muscle strength and fitness values among BT survivors were similar to those among individuals aged > or = 60 years and were associated with physical performance limitations. Physical performance limitations were associated with poor outcomes in home and school environments. The current data indicated an opportunity for interventions targeted at improving long-term physical function in this survivor population.

A framework for assessment in oncology rehabilitation.

Although the incidence of cancer in the United States is high, improvements in early diagnosis and treatment have significantly increased survival rates in recent years. Many survivors of cancer experience lasting, adverse effects caused by either their disease or its treatment. Physical therapy interventions, both established and new, often can reverse or ameliorate the impairments (body function and structure) found in these patients, improving their ability to carry out daily tasks and actions (activity) and to participate in life situations (participation). Measuring the efficacy of physical therapy interventions in each of these dimensions is challenging but essential for developing and delivering optimal care for these patients. This article describes the acute and long-term effects of cancer and its treatment and the use of the World Health Organization's International Classification of Functioning, Disability and Health (ICF) as a basis for selection of assessment or outcome tools and diagnostic or screening tools in this population.

Re-organization of P2X3 receptor localization on epidermal nerve fibers in a murine model of cancer pain.

To determine whether ATP and P2X3 receptors contribute to bone-cancer pain in a mouse model, immunohistochemical techniques were used to identify whether changes in the labeling of P2X3 receptors on epidermal nerve fibers (ENFs) occurred during tumor development. C3H mice were injected with osteolytic fibrosarcoma cells in and around the calcaneus bone. These mice exhibited mechanical hyperalgesia by day 10 post-implantation as assessed using von Frey monofilaments. Biopsies of the plantar skin overlying the tumor were obtained at days 10, 14, and 18 post-implantation. Confocal images were analyzed for the number of PGP 9.5, P2X3, and CGRP immunoreactive (ir) ENFs. The overall ENF population (PGP-ir) decreased progressively over time, whereas the subsets of P2X3-ir fibers demonstrated a modest increase and CGRP-ir nerve fibers remained fairly constant. Importantly, the proportion of CGRP-ir fibers that labeled for P2X3 increased from approximately 6% in control animals to nearly 30% at day 14 following tumor cell implantation. These studies demonstrate increased expression of P2X3 receptors on CGRP-ir ENFs during tumor growth and suggest a role for ATP in cancer-related pain.

Distribution and development of dopamine- and octopamine-synthesizing neurons in the medicinal leech.

Although the medicinal leech is a well-studied system in which many neurons and circuits have been identified with precision, descriptions of the distributions of some of the major biogenic amines, such as dopamine (DA) and octopamine (OA), have yet to be completed. In the European medicinal leech Hirudo medicinalis and the American medicinal leech Macrobdella decora,we have presented the first immunohistochemical study of DA neurons in the entire central nervous system, and of OA-immunoreactive (ir) neurons in the head and tail brains. Dopaminergic neurons were identified using the glyoxylic acid method and antisera to DA and its rate-limiting synthetic enzyme tyrosine hydroxylase (TH). Octopaminergic neurons were recognized using a highly specific antiserum raised against OA. An antibody raised against DA-beta-hydroxylase (DbetaH), the mammalian enzyme that converts DA to norepinephrine (NE), was found to immunostain OA-ir neurons. This antibody appears to cross-react with the closely related invertebrate enzyme tyramine-beta-hydroxylase, which converts tyramine to OA, suggesting that the OA-ir cells are indeed octopaminergic, capable of synthesizing OA. Because the DbetaH antiserum selectively immunostained the OA-ir neurons, but not the DA-synthesizing cells, our results also indicate that the DA-ir neurons synthesize DA and not NE as their end product. The expression of TH immunoreactivity was found to emerge relatively early in development, on embryonic day 9 (47-48% of development). In contrast, OA expression remained absent as late as embryonic day 20. Higher order processes of some of the dopaminergic and octopaminergic neurons in the adult brain were observed to project to a region previously described as a neurohemal complex. Several TH-ir processes were also seen in the stomatogastric nerve ring, suggesting that DA may play a role in the regulation of biting behavior. By mapping the distributions and developmental expression pattern of DA and OA neurons in the leech, we aim to gain a better understanding of the functional roles of aminergic neurons and how they influence behavior.