Establishing Meaningful Change Thresholds in Patient-Reported Outcomes Among Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer in ALTA-1L Trial.

OBJECTIVES: An earlier study from the ALTA-1L trial of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer demonstrated that brigatinib produces superior health-related quality of life (QoL) outcomes over crizotinib. This study aimed to derive meaningful change thresholds (MCTs) for European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-LC13 to refine the earlier results. METHODS: Patients from the ALTA-1L trial were administered the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires. Responses were analyzed using anchor-based analysis, graphical analysis, distribution-based analysis, longitudinal responder analysis, and time to deterioration. RESULTS: The patient-reported outcome population comprised 262 patients who completed the EORTC QLQ-C30 at baseline and at least 1 follow-up timepoint. Both anchors (QLQ-C30 items for overall health and QoL) had correlations >0.40 or < -0.40 with all functioning domains, fatigue, pain, appetite loss, and all dyspnea scores. Within-group analysis for most scales found the derived MCT was consistent with a cutoff of 10 points for classifying individual-patient change, except for 3-item dyspnea. The probability of improvement/remaining stable was significantly greater in the brigatinib group over crizotinib for the EORTC QLQ-C30 emotional functioning, appetite loss, and constipation domains. CONCLUSIONS: This study derived MCTs for EORTC QLQ-C30 and QLQ-LC13 domains that may be applied in future studies and again demonstrated the superiority of brigatinib over crizotinib in health-related QoL outcomes in patients with non-small cell lung cancer.

[Special issue PRO] A demonstration of estimands and sensitivity analyses for time-to-deterioration of patient reported outcomes.

In oncology trials, health-related quality of life (HRQoL), specifically patient-reported symptom burden and functional status, can support the interpretation of survival endpoints, such as progression-free survival. However, applying time-to-event endpoints to patient-reported outcomes (PRO) data is challenging. For example, in time-to-deterioration analyses clinical events such as disease progression are common in many settings and are often handled through censoring the patient at the time of occurrence; however, disease progression and HRQoL are often related leading to informative censoring. Special consideration to the definition of events and intercurrent events (ICEs) is necessary. In this work, we demonstrate time-to-deterioration of PRO estimands and sensitivity analyses to answer research questions using composite, hypothetical, and treatment policy strategies applied to a single endpoint of disease-related symptoms. Multiple imputation methods under both the missing-at-random and missing-not-at-random assumptions are used as sensitivity analyses of primary estimands. Hazard ratios ranged from 0.52 to 0.66 over all the estimands and sensitivity analyses modeling a robust treatment effect favoring the treatment in time to disease symptom deterioration or death. Differences in the estimands include how people who experience disease progression or discontinue the randomized treatment due to AEs are accounted for in the analysis. We use the estimand framework to define interpretable and principled approaches for different time-to-deterioration research questions and provide practical recommendations. Reporting the proportions of patient events and patient censoring by reason helps understand the mechanisms that drive the results, allowing for optimal interpretation.

Your Path to Transplant: A randomized controlled trial of a tailored expert system intervention to increase knowledge, attitudes, and pursuit of kidney transplant.

Individually tailoring education over time may help more patients, especially racial/ethnic minorities, get waitlisted and pursue deceased and living donor kidney transplant (DDKT and LDKT, respectively). We enrolled 802 patients pursuing transplant evaluation at the University of California, Los Angeles Transplant Program into a randomized education trial. We compared the effectiveness of Your Path to Transplant (YPT), an individually tailored coaching and education program delivered at 4 time points, with standard of care (SOC) education on improving readiness to pursue DDKT and LDKT, transplant knowledge, taking 15 small transplant-related actions, and pursuing transplant (waitlisting or LDKT rates) over 8 months. Survey outcomes were collected prior to evaluation and at 4 and 8 months. Time to waitlisting or LDKT was assessed with at least 18 months of follow-up. At 8 months, compared to SOC, the YPT group demonstrated increased LDKT readiness (47% vs 33%, P = .003) and transplant knowledge (effect size [ES] = 0.41, P < .001). Transplant pursuit was higher in the YPT group (hazard ratio: 1.44, 95% confidence interval: 1.15-1.79, P = .002). A focused, coordinated education effort can improve transplant-seeking behaviors and waitlisting rates. ClinicalTrials.gov registration: NCT02181114.

Ensuring the need is met: A 50-year simulation study of the National Kidney Registry's family voucher program.

The National Kidney Registry (NKR) Advanced Donation Program enables living donors the opportunity to donate altruistically, or in advance of a potential recipient's transplant, and to receive a voucher that can be redeemed for a future transplant facilitated by the NKR. Family vouchers allow a donor to identify multiple individuals within their immediate family, with the first person in that group in need of a transplant being prioritized to receive a kidney. An increase in vouchers introduces concerns that demand for future voucher redemptions could exceed the supply of available donors and kidneys. A Monte Carlo simulation model was constructed to estimate the annual number of voucher redemptions relative to the number of kidneys available over a 50-year time horizon under several projected scenarios for growth of the program. In all simulated scenarios, the number of available kidneys exceeded voucher redemptions every year. While not able to account for all real-life scenarios, this simulation study found that the NKR should be able to satisfy the likely redemption of increasing numbers of vouchers under a range of possible scenarios over a 50-year time horizon. This modeling exercise suggests that a donor family's future needs can be satisfied through the voucher program.

Symptom burden trajectories experienced by patients with brain tumors.

BACKGROUND: Survivors of childhood brain tumors experience persistent health concerns across their lifespan. In the current study, the authors evaluated changes in symptom burden over the course of 12 months using pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) measures. METHODS: Data from 202 survivors aged 8 to 21 years and 262 parents of survivors who were aged 5 to 21 years were analyzed. All completed a PROMIS Cognition short form and computerized adaptive tests of pediatric Anxiety, Depressive Symptoms, Fatigue, Mobility, Upper Extremity Function, and Peer Relationships. Approximately one-half of participants (223 participants: 97 survivors of childhood brain tumors and 126 parents) completed the 12-month follow-up. Linear mixed-effects models evaluated group-level symptoms over time. Cox proportional hazard models explored whether symptoms predicted survival, and latent class growth analysis investigated patterns of individual-level symptom changes over time. RESULTS: Linear mixed-effects models demonstrated that patient-reported Cognition and parent-reported Anxiety worsened over time. Latent class growth analysis results indicated that patient and parent reports diverged, both with regard to the number of classes identified and in the trends of these classes. Parents and patients reported similar patterns of depression over time. For the other areas, parents either were more likely to observe different patterns (Peer Relationships and Mobility) or less likely to observe different patterns (Upper Extremity Function, Cognition, Anxiety, and Fatigue). Baseline patient-reported Mobility and Upper Extremity Function were found to be associated with survival. CONCLUSIONS: Survivors of childhood brain tumors demonstrated different trajectory patterns of symptom burden. Along with baseline functioning status and days since treatment, patient-reported Mobility and Upper Extremity Function were associated with survival, suggesting a possible role for patient-reported outcomes in clinical care, especially individualized, tailored assessments such as PROMIS.

Trajectories of health-related quality of life among renal transplant patients associated with graft failure and symptom distress: Analysis of the BENEFIT and BENEFIT-EXT trials.

Understanding the correlation between transplant symptoms, health-related quality of life (HRQoL), and graft outcomes is needed to support patient-focused drug development and posttransplant management. A post-hoc analysis of patient-reported outcomes from the Phase III belatacept trials was conducted in order to investigate the interrelationship between trajectories of HRQoL, symptom experience, and allograft outcomes. HRQoL and symptom experience were evaluated using Short-Form 36 Survey (SF-36) and Modified Transplant Symptom Occurrence and Distress Scale (MTSOSD-59R), respectively. HRQoL was captured in 831 eligible renal transplant patients at baseline, 12, 24, and 36 months posttransplant. Following transplantation, patients reported improvements in all SF-36 subscales compared to baseline. Latent class analysis revealed four trajectories in perceived general health, which were associated with graft failure after adjustment. Compared to patients with good perceived health, patients with fair and poor perceived health had 4.7 (95% confidence interval [CI] 1.5-14.8, P < .01) and 19.8 (95% CI 5.9-66.0, P < .01) times the risk of graft failure, respectively. Using multinomial logistic regression, different sets of symptoms were associated with perceived general health at baseline and 12 months posttransplant. The study supports monitoring HRQoL and symptom experience to capture each patient's health perspective, improve drug development, and optimize posttransplant management.

Early graft losses in paired kidney exchange: Experience from 10 years of the National Kidney Registry.

Cooperative kidney paired donation (KPD) networks account for an increasing proportion of all living donor kidney transplants in the United States. There are sparse data on the rate of primary nonfunction (PNF) losses and their consequences within KPD networks. We studied National Kidney Registry (NKR) transplants (February 14, 2009 to December 31, 2017) and quantified PNF, graft loss within 30 days of transplantation, and graft losses in the first-year posttransplant and assessed potential risk factors. Of 2364 transplants, there were 38 grafts (1.6%) lost within the first year, 13 (0.5%) with PNF. When compared to functioning grafts, there were no clinically significant differences in blood type compatibility, degree of HLA mismatch, number of veins/arteries, cold ischemia, and travel times. Of 13 PNF cases, 2 were due to early venous thrombosis, 2 to arterial thrombosis, and 2 to failure of desensitization and development of antibody-mediated rejection (AMR). Given the low rate of PNF, the NKR created a policy to allocate chain-end kidneys to recipients with PNF following event review and attributable to surgical issues of donor nephrectomy. It is expected that demonstration of low incidence of poor early graft outcomes and the presence of a "safety net" would further encourage program participation in national KPD.

Does recall period matter? Comparing PROMIS® physical function with no recall, 24-hr recall, and 7-day recall.

PURPOSE: To evaluate the influence of recall periods on the assessment of physical function, we compared, in cancer and general population samples, the standard administration of PROMIS Physical Function items without a recall period to administrations with 24-hour and 7-day recall periods. METHODS: We administered 31 items from the PROMIS Physical Function v2.0 item bank to 2400 respondents (n = 1001 with cancer; n = 1399 from the general population). Respondents were randomly assigned to one of three recall conditions (no recall, 24-hours, or 7-days) and one of two "reminder" conditions (with recall periods presented only at the start of the survey or with every item). We assessed items for potential differential item functioning (DIF) by recall time period. We then tested recall and reminder effects with analysis of variance controlling for demographics, English fluency, and co-morbidities. RESULTS: Based on conservative pre-set criteria, no items were flagged for recall time period-related DIF. Using analysis of variance, each condition was compared to the standard PROMIS administration for Physical Function (no recall period). There was no evidence of significant differences among groups in the cancer sample. In the general population sample, only the 24-hour recall condition with reminders was significantly different from the "no recall" PROMIS standard. At the item level, for both samples, the number of items with non-trivial effect size differences across conditions was minimal. CONCLUSIONS: Compared to no recall, the use of a recall period has little to no effect upon PROMIS physical function responses or scores. We recommend that PROMIS Physical Function be administered with the standard PROMIS "no recall" period.

Meaningful differences and validity for the NCCN/FACT-P Symptom Index: An analysis of the ALSYMPCA data.

BACKGROUND: The Functional Assessment of Cancer Therapy-Prostate (FACT-P) and the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy-Prostate Symptom Index-17 (NFPSI-17) are 2 commonly used measures for patient-reported outcomes in prostate cancer trials. Their use may be enhanced by a better understanding of how change scores on the measures should be interpreted. METHODS: Using data from the phase 3 Alpharadin in Symptomatic Prostate Cancer Patients trial, this study estimated important change scores on the FACT-P and the NFPSI-17 via a combination of distribution- and anchor-based methods. These data were also used to establish evidence for the validity of the NFPSI-17. RESULTS: The available data suggested the following important difference ranges: 2 to 4 points for the Prostate Cancer Subscale, 5.5 to 8.5 points for the Trial Outcome Index, 1 to 1.5 points for the 3-item Pain Scale, 1 to 2 points for the 4-item Pain Scale, 4 to 6 points for the NFPSI-17, 2 to 3.5 points for NFPSI-Disease-Related Symptoms-Physical, 0.5 points for NFPSI-Disease-Related Symptoms-Emotional, 1 to 1.5 points for NFPSI-Treatment Side Effects, and 0.5 to 1 point for NFPSI-Function/Well-Being. The internal consistency reliability of the NFPSI-17 and most of its subscales was good to excellent (>.70). Significant support was also found for the known groups validity of the NFPSI-17 (and most of its subscales) on the basis of the Eastern Cooperative Oncology Group performance status, the total alkaline phosphatase, the presence of a skeletal-related event during treatment, and the prostate-specific antigen response before the end of treatment. CONCLUSIONS: The secondary analysis supports the continued use of the FACT-P, the NFPSI-17, and its related subscales in future research on the quality of life of patients with symptomatic castration-resistant prostate cancer with bone metastases.

What does risk of future cancer mean to breast cancer patients?

PURPOSE: Newly diagnosed breast cancer patients greatly overestimate their risk of developing contralateral breast cancer (CBC). Better understanding of patient conceptions of risk would facilitate doctor-patient communication and surgical decision making. In this mixed methods study, we prospectively examined breast cancer patients' perceived risk of future cancer and the reported factors that drove their risk perceptions. METHODS: Women age 21-60 diagnosed with breast cancer without a BRCA mutation or known distant metastases completed a study interview between surgical consult and surgical treatment. Participants completed a 12-item Perceived Risk Questionnaire, which assessed 10-year and lifetime risks of ipsilateral local recurrence, CBC, and distant recurrence. Patients provided qualitative explanations for their answers. RESULTS: Sixty-three patients completed study interviews (mean age 50.3). Participants were primarily White (85.7%) and 90.5% had attended college. Patients estimated their 10-year risk of CBC as 22.0%, nearly 4 times the established 10-year risk. Women attributed their risk perceptions to "gut feelings" about future cancer, even when women knew those feelings contradicted medically established risk. Perceptions of risk also reflected beliefs that cancer is random and that risk for local recurrence, CBC, and distant recurrence are the same. CONCLUSIONS: Our findings point to the need for novel ways of presenting factual information regarding both risk of recurrence and of new primary cancers, as well as the necessity of acknowledging cognitive and affective processes many patients use when conceptualizing risk. By differentiating women's intuitive feelings about risk from their knowledge of medically estimated risk, doctors can enhance informed decision making.

Direct Delivery of Kidney Transplant Education to Black and Low-Income Patients Receiving Dialysis: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: Compared with others, black and low-income patients receiving dialysis are less likely to receive kidney transplantation (KT) education within dialysis centers. We examined the efficacy of 2 supplementary KT education approaches delivered directly to patients. STUDY DESIGN: Prospective, 3-arm parallel-group, randomized, controlled trial. SETTINGS & PARTICIPANTS: Adult, black, and white low-income patients receiving dialysis in Missouri. INTERVENTION: Patients were randomly assigned to 1 of 3 educational conditions: (1) standard of care, usual KT education provided in dialysis centers (control); (2) Explore Transplant @ Home patient-guided, 4 modules of KT education sent directly to patients using print, video, and text messages; and (3) Explore Transplant @ Home educator-guided, the patient-guided intervention plus 4 telephonic discussions with an educator. OUTCOMES: Primary: patient knowledge of living (LDKT) and deceased donor KT (DDKT). Secondary: informed decision making, change in attitudes in favor of LDKT and DDKT, and change in the number of new steps taken toward KT. RESULTS: In intent-to-treat analyses, patients randomly assigned to educator- and patient-guided interventions had greater knowledge gains (1.4 point increase) than control patients (0.8 point increase; P=0.02 and P=0.01, respectively). Compared with control patients, more patients randomly assigned to educator- and patient-guided interventions were able to make informed decisions about starting KT evaluation (82% vs 91% and 95%; P=0.003), pursuing DDKT (70% vs 84% and 84%; P=0.003), and pursuing LDKT (73% vs 91% and 92%; P<0.001). LIMITATIONS: Potential contamination because of patient-level randomization; no assessment of clinical end points. CONCLUSIONS: Education presented directly to dialysis patients, with or without coaching by telephone, increased dialysis patients' KT knowledge and informed decision making without increasing educational burden on providers. FUNDING SOURCE: This project was funded by the National Institutes of Health and Health Resources and Services Administration. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02268682.

Assessment of change in quality of life, carcinoid syndrome symptoms and healthcare resource utilization in patients with carcinoid syndrome.

BACKGROUND: There is limited information on changes over time in carcinoid syndrome (CS) symptoms and quality of life (QoL). This study assessed change in CS symptoms and QoL in patients treated with somatostatin analogs (SSAs) using the Functional Assessment of Cancer Therapy-General (FACT-G) and Patient-Reported Outcomes Measurement Information System (PROMIS)-29 instruments. METHODS: Patients ≥18 years old with CS symptoms and treated with SSA or non-SSA agents in the United States were recruited through a patient advocacy group to complete a two-part, anonymous online survey. Time point (T) 1 survey was fielded from July-October 2016, and T2 survey followed 6 months later. Clinical characteristics and SSA treatment duration were assessed at T1. FACT-G and PROMIS-29 QoL surveys were administered and CS symptoms were assessed at T1 and T2; proportions of patients not experiencing symptoms were compared by McNemar's test. Healthcare resource utilization (HRU) was assessed for the T1-T2 interval, and mean difference in QoL score from T1 to T2 by SSA duration was calculated. RESULTS: Of 117 participants at T1, 89 (76%) completed the T2 survey and served as the study sample; 11 (13%) were treated with SSAs for > 0-2 years, 37 (42%) for > 2-5 years, and 39 (45%) for > 5 years. A higher proportion of patients at T2 vs. T1 reported the following symptoms as not applicable: diarrhea (16% vs. 7%, p < 0.05), flushing (28% vs. 18%, p < 0.05), wheezing (78% vs 66%, p = 0.008). Most patients (89%) had a physical exam and a mean of 7.2 healthcare provider visits between T1 and T2. Patients treated with SSAs for ≤2 years had a mean positive change of 3.7 in their FACT-G total score between surveys, and 6.0 in an additional set of CS-specific questions. Patients receiving SSAs for > 2 years did not appear to associate with a clinically meaningful improvement in QoL score as assessed by FACT-G between T1 and T2; patients also had no clinically meaningful improvement as assessed by PROMIS-29. CONCLUSIONS: There may be clinically important improvement in QoL as measured by FACT-G in patients in earlier years of receiving SSA, which may not appear in later years of SSA treatment.

Using the Patient-Reported Outcomes Measurement Information System (PROMIS) to measure symptom burden reported by patients with brain tumors.

BACKGROUND: Children with brain tumors can experience symptom burden throughout their disease continuum. The aim of the study was to evaluate symptom burden reported by children with brain tumors and factors that potentially were associated with their symptoms. METHODS: Data from 199 children with brain tumors aged 7-22 (mean age = 14 years; 52% males; 76% white) were analyzed. Symptom burden was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) via computerized adaptive testing (CAT)-anxiety, depression, fatigue, mobility, upper extremity function, peer relationship, and cognition. Patients and parents completed Symptom Distress Scales (SDS). Test statistics and ANOVA were used to evaluate relationships between PROMIS measures and potentially influential variables. RESULTS: Significant results (P < 0.01) showing impact of symptom burden included: PROMIS measures correlated with SDSs reported by patients and parents on all comparisons. Fatigue, mobility, and upper extremity function were associated with Karnofsky functional performance status, number of treatment modalities (0-3), and time since last treatment (≤1 year, >1 year). Fatigue and cognition were associated with educational program (regular classroom without an individualized education plan vs those that had an individualized education plan); mobility and upper extremity function were associated with time since last radiation. Mobility, upper extremity function, and anxiety were associated with time since last chemotherapy. CONCLUSIONS: Significant associations were found between PROMIS and SDS as well as clinical and demographic characteristics. Brief-yet-precise PROMIS CATs can be used to systematically assess symptom burden experienced by children with brain tumors.

Pediatric intestinal transplantation: Analysis of the intestinal transplant registry.

The ITR serves as an international database for centers around the world to contribute to current knowledge about intestinal transplant outcomes. Led by the IRTA and managed by the Terasaki Research Institute, the ITR collects data annually and uses these data to generate reports that guide management strategies and policy statements. The aim of this manuscript was to analyze outcomes specific to pediatric intestinal transplantation. Outcome data for children transplanted from 1985 to 2017 were analyzed and predictive factors assessed. A total of 2010 children received 2080 intestine containing allografts during this period. Overall, 1-year and 5-year patient and graft survival were 72.7%/66.1% and 57.2/48.8%, respectively. One-year conditional survival was most strongly associated with being a first-time transplant recipient and liver-inclusive grafts. Patient survival was most strongly associated with elective status of transplantation as compared with hospitalized status. Enteral autonomy following transplantation has continued to improve by era with colonic inclusion demonstrating additional incremental improvement in enteral autonomy and freedom from intravenous fluid. While PTLD and technical complications contribute less to graft loss than in earlier eras, rejection remains the largest contributor to long-term graft loss. Re-transplantation is linked with significantly worse conditional graft survival, and sepsis remains the largest contributor to patient death. Newer data elements are focusing on impact of donor variables, donor and recipient tissue typing, and impact of the development of de novo antibodies.

A randomized controlled trial of Explore Transplant at Home to improve transplant knowledge and decision-making for CKD 3-5 patients at Kaiser Permanente Southern California.

BACKGROUND: Five-year survival on dialysis is only 40%, compared to 74% with a deceased donor kidney transplant (DDKT) and 87% with a living donor kidney transplant (LDKT). An American Society of Transplantation (AST) Consensus Conference recommended that patients with chronic kidney disease (CKD) Stages 3-5 have the opportunity to learn about and decide which treatment option is right for them, particularly about LDKT. However, early education about LDKT and DDKT outside of transplant centers is inconsistent and often poor, with patients in CKD 3 and 4 and ethnic/racial minorities even less likely to receive it. A new randomized control trial (RCT), in partnership with Kaiser Permanente Southern California (KPSC), will assess knowledge gaps and the effectiveness of a supplementary video-guided, print and technology-based education intervention for English- and Spanish-speaking patients in CKD Stages 3, 4, and 5 to increase LDKT knowledge and decision-making. To date, no published LDKT educational interventions have studied such a large and diverse CKD population. METHODS: In this RCT, 1200 English and Spanish-speaking CKD Stage 3-5 patients will be randomly assigned to one of two education conditions: ET@Home or KPSC standard of care education. Randomization will be stratified by CKD stage and primary language spoken. Those in the ET@Home condition will receive brochures, postcards, DVDs, and text messages delivering educational content in modules over a six-month period. Baseline data collection will measure demographics, transplant derailers, and the amount of previous CKD and transplant education they have received. Changes in CKD and transplant knowledge, ability to make an informed decision about transplant, and self-efficacy to pursue LDKT will be captured with surveys administered at baseline and at six months. DISCUSSION: At the conclusion of the study, investigators will understand key knowledge gaps for patients along the CKD continuum and between patients who speak different languages and have assessed the effectiveness of both English- and Spanish-language supplementary education in increasing KPSC patients' knowledge about the opportunities for and risks and benefits of LDKT. We hope this program will reduce disparities in access to transplant. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03389932; date registered: 12/26/2017.

A survey comparison of educational interventions for teaching pneumatic otoscopy to medical students.

BACKGROUND: Though pneumatic otoscopy improves accurate diagnosis of ear disease, trainees lack proficiency. We evaluated the effect of three different training techniques on medical students' subsequent reported use of basic and pneumatic otoscopy in patient encounters. METHODS: Pediatric clerkship students participated in an ear exam workshop with randomization to one of three educational interventions: task trainer (Life/form®, Fort Atkinson WI), instructional video, or peer practice. Each student received an insufflator bulb and logbook to record otoscopic exams and completed an 18-item anonymous survey at clerkship conclusion. RESULTS: 115 of 150 students (77%) completed the survey. There was no significant difference in number of basic or pneumatic otoscopic exams performed based on method of training. Most students (68-72%) felt more likely to perform pneumatic otoscopy after training. Though the majority of students performed basic otoscopy on patients when an ear exam was indicated, they used pneumatic otoscopy less than 10% of the time. Students reported significant barriers to otoscopy: time, access to equipment, cerumen impaction, patient hold, and anxiety. Student comments described a culture where insufflation was neither practiced nor valued by supervising physicians. CONCLUSION: Training in pneumatic otoscopy can increase student comfort, but barriers exist to using the skill in clinical practice.

Validity and usefulness of a single-item measure of patient-reported bother from side effects of cancer therapy.

BACKGROUND: The improving efficacy of cancer treatment has resulted in an increasing array of treatment-related symptoms and associated burdens imposed on individuals undergoing aggressive treatment of their disease. Often, clinical trials compare therapies that have different types, and severities, of adverse effects. Whether rated by clinicians or patients themselves, it can be difficult to know which side effect profile is more disruptive or bothersome to patients. A simple summary index of bother can help to adjudicate the variability in adverse effects across treatments being compared with each other. METHODS: Across 4 studies, a total of 5765 patients enrolled in cooperative group studies and industry-sponsored clinical trials were the subjects of the current study. Patients were diagnosed with a range of primary cancer sites, including bladder, brain, breast, colon/rectum, head/neck, hepatobiliary, kidney, lung, ovary, pancreas, and prostate as well as leukemia and lymphoma. All patients were administered the Functional Assessment of Cancer Therapy-General version (FACT-G). The single item "I am bothered by side effects of treatment" (GP5), rated on a 5-point Likert scale, is part of the FACT-G. To determine its validity as a useful summary measure from the patient perspective, it was correlated with individual and aggregated clinician-rated adverse events and patient reports of their general ability to enjoy life. RESULTS: Analyses of pharmaceutical trials demonstrated that mean GP5 scores ("I am bothered by side effects of treatment") significantly differed by maximum adverse event grade (P<.001) in all trials, with a clear trend toward increasing GP5 scores with level of increasing adverse event grade. Effect sizes ranged from 0.13 to 0.46. Analyses of cooperative group trials demonstrated a significant correlation between GP5 and item GF3 ("I am able to enjoy life") in the predicted direction. CONCLUSIONS: The single FACT-G item "I am bothered by side effects of treatment" is significantly associated with clinician-reported adverse events and with patients' ability to enjoy their lives. It has promise as an overall summary measure of the burden of a given set of treatment toxicities compared with another. Future research can identify the contribution of individual side effects compared with one another in terms of how each may contribute to overall bother. Cancer 2018;124:991-7. © 2017 American Cancer Society.

Prophylactic Seizure Medication and Health-Related Quality of Life After Intracerebral Hemorrhage.

OBJECTIVES: Prophylactic levetiracetam is currently used in ~40% of patients with intracerebral hemorrhage, and the potential impact of levetircetam on health-related quality of life is unknown. We tested the hypothesis that prophylactic levetiracetam is independently associated with differences in cognitive function health-related quality of life. DESIGN: Patients with intracerebral hemorrhage were enrolled in a prospective cohort study. We performed mixed models for T-scores of health-related quality of life, referenced to the U.S. population at 50 ± 10, accounting for severity of injury and time to follow-up. SETTING: Academic medical center. PATIENTS: One-hundred forty-two survivors of intracerebral hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: T-scores of Neuro-Quality of Life Cognitive Function v2.0 was the primary outcome, whereas Neuro-Quality of Life Mobility v1.0 and modified Rankin Scale (a global functional scale) were secondary measures. We prospectively documented if prophylactic levetiracetam was administered and retrieved administration data from the electronic health record. Patients who received prophylactic levetiracetam had worse cognitive function health-related quality of life (T-score 5.1 points lower; p = 0.01) after adjustment for age (p = 0.3), National Institutes of Health Stroke Scale (p < 0.000001), lobar hematoma (p = 0.9), and time of assessment; statistical models controlling for prophylactic levetiracetam and the Intracerebral Hemorrhage Score, a global measure of intracerebral hemorrhage severity, yielded similar results. Lower T-scores of cognitive function health-related quality of life at 3 months were correlated with more total levetiracetam dosage (p = 0.01) and more administered doses of levetiracetam in the hospital (p = 0.03). Patients who received prophylactic levetiracetam were more likely to have a lobar hematoma (27/38 vs 19/104; p < 0.001), undergo electroencephalography monitoring (15/38 vs 21/104; p = 0.02), but not more likely to have clinical seizures (4/38 vs 7/104; p = 0.5). Levetiracetam was not independently associated with the modified Rankin Scale scores or mobility health-related quality of life (p > 0.1). CONCLUSIONS: Prophylactic levetiracetam was independently associated with lower cognitive function health-related quality of life at follow-up after intracerebral hemorrhage.

Cold therapy to prevent paclitaxel-induced peripheral neuropathy.

PURPOSE: This case-control study was designed to assess the efficacy of cryotherapy to prevent paclitaxel-induced painful peripheral neuropathy in women with breast cancer. METHODS: Participants served as their own paired control, with randomization of the cooled glove/sock to either the dominant or the non-dominant hand/foot, worn for 15 min prior to, during, and 15 min after completion of the paclitaxel infusion. Outcome measures included the Neuropathic Pain Symptom Inventory, the Brief Pain Inventory, and quantitative sensory testing. Data were measured at each of six time points-baseline, post-treatment (approximately 2 weeks after the last paclitaxel infusion), and at the first, fifth, ninth, and final weekly paclitaxel treatments. RESULTS: Of 29 randomized participants, 20 (69%) received at least one cryotherapy treatment, and 11 (38%) received all four cryotherapy treatments. Ten (34%) participants could not tolerate the cryotherapy, and six (21%) declined further participation at some point during the trial. Only seven participants (24%) were available for the final post-chemotherapy QST and questionnaires. There were no significant differences in measures of neuropathy or pain between treated and untreated hands or feet. CONCLUSIONS: Strategies to prevent painful peripheral neuropathy are urgently needed. In this current trial, dropout due to discomfort precluded adequate power to fully understand the potential benefits of cryotherapy. Much more research is needed to discover safe and effective preventive strategies that can be easily implemented within busy infusion centers.

Fever Burden and Health-Related Quality of Life After Intracerebral Hemorrhage.

BACKGROUND: Fever is associated with worse functional outcomes after intracerebral hemorrhage (ICH); however, there are few prospective data to quantify the relationship with health-related quality of life (HRQoL). We tested the hypothesis that increased burden of fever is independently associated with decreased HRQoL at follow-up. METHODS: In this prospective observational cohort study of 106 ICH patients admitted to a tertiary care hospital between 2011 and 2015, we recorded the highest core temperature each calendar day for 14 days after ICH onset. Fever burden was defined as the number of days with a fever ≥ 100.4 °F (38 °C). HRQoL outcomes were measured with Neuro-QoL domains of Cognitive Function and Mobility at 28 days, 3 months, and 1 year. Results were analyzed using mixed effects regression analysis. RESULTS: Each additional day with a fever was independently associated with lower Mobility HRQoL (T-score - 0.9, [- 1.6 to - 0.2]; p = 0.01) and Cognitive Function HRQoL (T-score - 1.3 [- 2.0 to - 0.6]; p = 0.001) after correction for National Institutes of Health Stroke Scale score on admission, age, and time to follow-up. CONCLUSIONS: Each additional day with a fever was predictive of worse HRQoL domains of Cognitive Function and Mobility after ICH up to 1 year. These data extend previous evidence on the negative association of fever and functional outcomes to the domains of Cognitive Function and Mobility HRQoL. HRQoL outcomes may be a sensitive and powerful way to measure the efficacy of fever control in future research.