Safety and Effectiveness of Ferumoxytol in Hemodialysis Patients at 3 Dialysis Chains in the United States Over a 12-Month Period

Background

Intravenous (IV) iron is the treatment of choice for iron-deficiency anemia (IDA) in patients with dialysis-dependent chronic kidney disease (DD-CKD). However, IV iron products have been associated with serious adverse events (SAEs), including anaphylactoid reactions. Ferumoxytol is an IV iron preparation that can be injected over a short period of time. Although randomized clinical trials support ferumoxytol’s efficacy and safety, additional insights may be drawn from the acquisition of long-term, repeat dosing efficacy and safety data in a real-world setting.

Objective

The goal of this study was to characterize the effectiveness and safety profile of ferumoxytol as administered to adult DD-CKD patients with IDA in a real-world setting. The ability of ferumoxytol to maintain hemoglobin (Hb), transferrin saturation (TSAT), and ferritin treatment targets established by the 2006 Kidney Disease Outcomes Quality Initiative guidelines was determined in 3 medium-sized US-based dialysis chains.

Methods

This retrospective, observational study was conducted to examine laboratory and dosing data for all patients who received any dose of ferumoxytol at 3 US-based dialysis chains over a 12-month period. Investigators and/or physicians from each of the chains also made independent determinations regarding the seriousness of any adverse event (AE). Special attention was paid to the incidence and types of AEs and SAEs that were potentially associated with ferumoxytol.

Results

Over the 12-month observation period, 8666 patients (mean [SD] age in chains A, B and C, 63.9 [14.8], 63.9 [14.9] and 63.6 [15.1], respectively), were treated with 33,358 doses of ferumoxytol across the 3 chains. Treatment with ferumoxytol corresponded to an increased mean monthly Hb level relative to baseline (0.13–0.69 g/dL) and led to an increase in the proportion of patients maintained within the target Hb range of 10 to 12 g/dL (61%–72%). Ferumoxytol was also associated with increases in TSAT and ferritin that stabilized throughout the observation period. Incidence of AEs was similar across the 3 chains; between 0.07% and 1.77% of all patients treated at each chain experienced an AE associated with ferumoxytol administration. SAEs were reported in 0.2% of patients. The most common AEs reported (≥6 patients) were nausea (0.37% of patients), pruritus (0.29%), vomiting (0.25%), hypotension (0.21%), and dyspnea (0.20%). Two patients (0.02%) experienced anaphylactoid reactions. The AE profile of ferumoxytol remained consistent with that reported from controlled clinical trials.

Conclusions

These long-term data, which include repeat dosing in a large number of DD-CKD patients with IDA in a real-world setting, confirm the effectiveness of ferumoxytol in increasing and maintaining Hb levels within the target range and with favorable assessments of long-term safety.     

Impact of a Palliative Care Consultation Team on Cancer-Related Symptoms in Advanced Cancer Patients Referred to an Outpatient Supportive Care Clinic

ContextPatients with advanced cancer may develop severe physical and psychosocial symptoms. There are limited data on the impact of an outpatient palliative consultation (PC) team on cancer-related symptoms.ObjectivesTo study the impact of the PC on symptoms in patients with advanced cancer receiving outpatient palliative care.MethodsFour hundred six consecutive patients referred to a supportive care outpatient center (OPC) from January 2006 to June 2007 with complete Edmonton Symptom Assessment Scale (0–10 scale) at the initial and follow-up visits were reviewed. Patient characteristics, change of symptoms at follow-up visit, and response rate were analyzed. Using logistic regression models, the predictors of improvement of pain and fatigue were assessed.ResultsMedian age was 59 years; 53% were female. Median interval between visits was 15 days. Mean scores at baseline and follow-up visits were fatigue 6.8 and 5.3 (P < 0.0001), pain 5.3 and 4.1 (P < 0.0001), depression 3.2 and 2.5 (P < 0.0001), anxiety 3.7 and 2.8 (P < 0.0001), dyspnea 2.7 and 2.5 (P = 0.05), sleep 5 and 4 (P < 0.0001), and well-being 5.2 and 4.4 (P < 0.0001). Dyspnea (odds ratio and P-value, 0.90, 0.03), nausea (0.92, 0.06), and depression (0.91, 0.04) were associated with improvement in fatigue; drowsiness (1.10, 0.04), and feeling of well-being (0.87, 0.02) were associated with improvement in pain.ConclusionThe initial consult by PC achieved significant symptom improvement in patients receiving treatment in the OPC. Further prospective studies are needed.     

Symptoms of Depression Over Time in Adults With Pediatric-Onset Spinal Cord Injury

Objective

To investigate the prevalence of depressive symptoms in adults with pediatric-onset spinal cord injury (SCI) and explore potential risk factors that may be associated with elevated symptoms.

Design

Longitudinal, cohort survey over a period of 2 to 9 years. Follow-up occurred approximately every year, a total of 868 interviews were conducted, and most participants contributed to at least 3 waves of data (72%; range, 2–8; mean, 4.34±2.16).

Setting

Community.

Participants

Adults (N=214; 133 men; mean age at first interview, 29.52±5.21y; range, 24–42y) who sustained an SCI prior to age 19 (mean age at injury, 13.93±4.37y; range, 0–18y). Participants tended to have complete injuries (71%) and tetraplegia (58%).

Interventions

Not applicable.

Main Outcome Measures

Participants completed measures assessing psychosocial functioning, physical independence, participation, and depression at each time point. Multilevel growth modeling analyses were used to explore depression symptoms across time.

Results

Depression symptoms at initial status were typically minimal (3.07±.24; 95% confidence interval, 2.6–3.54) but fluctuated significantly over time (P<.01). Several factors emerged as significant predictors of depressive symptoms in the final model, including less community participation (P<.01), incomplete injury (P=.02), hazardous drinking (P=.02), bladder incontinence (P=.01), and pain (P=.03). Within individuals, as bowel accidents (P<.01) and pain increased (P<.01), depression scores increased; however, marriage resulted in decreases in depression scores for individuals (P=.02).

Conclusions

These findings suggest that most patients with pediatric-onset SCI are psychologically resilient, but strategies to minimize secondary health complications and foster community participation and engagement should be considered.     

Feasibility and Acceptability to Patients of a Longitudinal System for Evaluating Cancer-Related Symptoms and Quality of Life: Pilot Study of an e/Tablet Data-Collection System in Academic Oncology

Programmed, notebook-style, personal computers (“e/Tablets”) can collect symptom and quality-of-life (QOL) data at the point of care. Patients use an e/Tablet in the clinic waiting area to complete electronic surveys. Information then travels wirelessly to a server, which generates a real-time report for use during the clinical visit. The objective of this study was to determine whether academic oncology patients find e/Tablets logistically acceptable and a satisfactory means of communicating symptoms to providers during repeated clinic visits. Sixty-six metastatic breast cancer patients at Duke Breast Cancer Clinic participated. E/Tablets were customized to electronically administer a satisfaction/acceptability survey, several validated questionnaires, and the Patient Care Monitor (PCM) review of symptoms survey. At each of the four visits within six months, participants completed the patient satisfaction/acceptability survey, which furnished data for the current analysis. Participant demographics were: mean age of 54 years, 77% Caucasian, and 47% with less than a college education. Participants reported that e/Tablets were easy to read (94%), easy to navigate (99%), and had a comfortable weight (90%); they found it easy to respond to questions using the e/Tablet (98%). Seventy-five percent initially indicated satisfaction with PCM for reporting symptoms; this proportion increased over time. By the last visit, 88% of participants indicated that they would recommend the PCM to other patients; 74% felt that the e/Tablet helped them remember symptoms to report to their clinician. E/Tablets offered a feasible and acceptable method for collecting longitudinal patient-reported symptom and QOL data within an academic, tertiary care, breast cancer clinic.     

Cancer-Related Fatigue: State of the Science

Cancer-related fatigue (CRF) is a disabling and distressing symptom that is highly prevalent across the cancer continuum from a patient's diagnosis and treatment through survivorship and end of life. It has a multifactorial etiology and significant individual variability in its clinical expression, determinants, and sequelae. Despite the significance of CRF, it is often underdiagnosed, and management is frequently suboptimal. This review synthesizes the state of the science concerning the features, possible mechanisms, and predictors of CRF; offers recommendations for the evaluation of CRF; and appraises the strength of the evidence for a wide range of pharmacologic and nonpharmacologic interventions to prevent and manage fatigue during and after cancer and its treatment. There is evidence from methodologically rigorous controlled trials that exercise, psycho-educational interventions, and cognitive-behavioral therapy for insomnia are effective in the treatment of CRF, and a wide range of pharmacologic and nonpharmacologic interventions has shown initial promise in single-arm pilot studies with small, heterogeneous samples. Rigorously designed and adequately powered randomized trials are warranted to (1) determine the effectiveness of promising approaches and (2) identify the interventions that are most effective in treating CRF in specific subpopulations (eg, stem cell transplant recipients, older adults, patients with lung or colorectal cancers, survivors, and those at the end of life). Studies to elucidate the biologic expression profiles of CRF, to explicate the mechanisms through which particular interventions impact CRF, and to identify the mediators and moderators of fatigue outcomes will ultimately permit individually tailored approaches for the treatment of CRF.     

The Handgrip Strength Test as a Measure of Function in Breast Cancer Survivors: Relationship to Cancer-Related Symptoms and Physical and Physiologic Parameters

OBJECTIVE: The aim of this study was to examine the relationship of muscular strength, as measured by the handgrip strength (HGS) test, with pain, fitness, fatigue, mood, and autonomic nervous system function in breast cancer survivors. DESIGN: A cross-sectional study comprising 95 breast cancer survivors was conducted. HGS; heart rate variability; pressure pain threshold of the neck, shoulder, hand, and tibia of the affected side; and fitness level (6-min walk test, neck-shoulder mobility, vertical jump, sit-to-stand test, and trunk curl test) were assessed as outcomes. Participants completed the Fatigue Piper Scale and Profile of Mood States questionnaires and the neck-shoulder visual analog scale. Correlation was conducted to examine the relationship of HGS with pain, fitness, fatigue, and mood. RESULTS: We observed a fair relationship of HGS with shoulder pain and a moderate to fair relationship with fitness (all P < 0.01; ρ range, 0.24-0.56). The relationship between HGS and heart rate variability (high-frequency domain) was weak (P = 0.049, ρ = 0.23). Likewise, the relationship between HGS and Profile of Mood States subscales ranged from weak to fair (all P < 0.001; ρ range, -0.22 to -0.36). HGS showed a weak relationship with Fatigue Piper Scale (all P < 0.01; ρ range, -0.28 to -0.35). Passive shoulder flexion, fatigue, and vertical jump were independent and significant predictors of HGS (P < 0.01; R = 0.466). CONCLUSIONS: These results suggest that the HGS test might be an important correlate of health in breast cancer survivors. This finding suggests that HGS could be recommended as an adjuvant method of evaluation, which may help with efficiency of clinical practice. Further research on breast cancer patients is needed to confirm or refute these findings.     

Feeling Better and Smoking Less: The Relationship Between Trauma Symptoms and Smoking Over Time

Although it is well documented that individuals who have experienced traumatic events smoke cigarettes at significantly higher rates than individuals without exposure to trauma, the longitudinal relationship between smoking and trauma-related symptoms remains unclear. The present study examined this issue among 288 female veterans receiving treatment for trauma-related disorders over a period of up to 3 years. Consistent with previous cross-sectional research, across time points more symptomatology was associated with higher rates of smoking. Longitudinally, decreases in symptoms of negative affect over time were associated with decreases in smoking.

康复期劳教戒毒人员身心症状分析

目的 探讨康复期劳教戒毒人员的身心状况及其相关机制.方法 采用自编的<康复期劳教戒毒人员临床症状调查表>和<艾森克个性问卷>对1 004例康复期劳教戒毒的阿片类物质依赖者进行测评,并对相关症状进行分析.结果 康复期劳教戒毒人员主要躯体症状为全身乏力、健忘、关节酸痛、心慌和四肢不适;主要心理症状为心理渴求、失眠及焦虑,艾森克自评问卷分析显示,心理渴求群组P分和E分与对照组有非常显著性差异(P<0.01),失眠人群和焦虑人群的N分均明显偏高(P<0.01).结论 康复期劳教戒毒人员的躯体症状主要为全身乏力、健忘、关节酸痛、心慌和四肢不适,其原因可能是神经内分泌系统失衡和神经系统的可塑性改变;而心理症状则是吗啡精神依赖物质的活性作用与该人群人格特征共同决定的.     

Perceived Burdensomeness as an Indicator of Suicidal Symptoms

The Interpersonal-Psychological Theory of Suicidal Behavior proposes precursors to serious suicidality, including the perception that one is a burden on loved ones. The purpose of the present study was to evaluate the association of perceived burdensomeness and key suicide-related variables in 343 adult outpatients of the Florida State University Psychology Clinic (187 female; 156 male). Participants completed the Beck Scale for Suicide Ideation and the Beck Depression Inventory, as well as items on perceived burdensomeness and hopelessness. Perceived burdensomeness remained a significant predictor of suicidality indicators (i.e., attempt status and BSSI scores) above and beyond the contribution one of the most robust predictors of suicidality, hopelessness. Results suggest that both burdensomeness and hopelessness display predictive power with regards to suicidal behavior and that perceived burdensomeness displayed the signature of a resilient suicide risk factor. Thus, targeting perceived burdensomeness in the assessment of suicidal behavior may aid in treatment and prevention efforts.

Population Pharmacokinetics of Oxycodone in Patients With Cancer-Related Pain

ABSTRACT

Oxycodone is an opioid widely prescribed to cancer patients for pain relief. However, the pharmacokinetics of oxycodone has not been sufficiently examined. Therefore the aim of this work was to study population pharmacokinetics of oxycodone in patients with cancer pain. The authors analyzed 108 serum oxycodone samples of 33 individuals with nonlinear mixed-effects model (NONMEM). Population pharmacokinetics was calculated using the one-compartment model of clearance, volume of distribution, bioavailability, absorption constant rate, and lag time. An exponential error model was used to determine interindividual variability and a relative error model was applied to assess residual variability. Population pharmacokinetics of oxycodone at the end point were as follows: CL(L/h) = 10.7 × [1 + (2 ? Child-Pugh Classification)] (Class: A = 0, B = 1, C = 2); V_d (L) = 193; k_a (h^?1) = 0.336; T_lag (h) = 0.859; F (%) = 63.9. Interindividual variability was CL: 30.5%, V_d: 44.6%, and F: 37.0%, and residual variability was 16.2%. As the total clearance in patients with liver dysfunction (Child-Pugh class B) was reduced to 33.3%, serum concentration of oxycodone increased by 1.5. Therefore, it became clear that dose adjustments are essential when treating patients with liver dysfunction. These findings suggest that population parameters are useful for evaluating pharmacokinetics of oxycodone in patients with cancer pain.