Venetoclax combinations delay the time to deterioration of HRQoL in unfit patients with acute myeloid leukemia.

Phase 3 trials Viale-A and Viale-C evaluated health-related quality of life (HRQoL) in patients with AML unfit for intensive chemotherapy who received venetoclax (VEN) + (AZA) (Viale-A) or low-dose cytarabine (LDAC) (Viale-C) or placebo (PBO) + AZA or LDAC. Patient-reported outcomes included: EORTC QLQ-C30 global health status (GHS/QoL) and physical functioning (PF), PROMIS Cancer Fatigue Short Form 7a (Fatigue), and EQ-5D-5L health status visual analog scale (HS-VAS). Time to deterioration (TTD), defined as worsening from baseline in meaningful change thresholds (MCT) of ≥10, 5, or 7 points for GHS/QoL or PF, fatigue, and HS-VAS, respectively, was assessed; differences between groups were analyzed using Kaplan-Meier and unadjusted log-rank analyses. VEN + AZA vs PBO + AZA patients had longer TTD in GHS/QoL (P = 0.066) and fatigue (P = 0.189), and significantly longer TTD in PF (P = 0.028) and HS-VAS (P < 0.001). VEN + LDAC vs PBO + LDAC patients had significantly longer TTD in GHS/QoL (P = 0.011), PF (P = 0.020), and fatigue (P = 0.004), and a trend in HS-VAS (P = 0.057). Approximately 43%, 35%, 32%, and 18% of patients treated with VEN + AZA, AZA + PBO, VEN + LDAC, or LDAC + PBO, respectively, saw improvements >MCT in GHS/QoL. Overall, VEN may positively impact HRQoL in patients with AML ineligible for intensive chemotherapy, leading to longer preservation of functioning and overall health status.

Correction to: Development of a conceptual model and patient-reported outcome measures for assessing symptoms and functioning in patients with heart failure.

The article Development of a conceptual model and patient-reported outcome measures for assessing symptoms and functioning in patients with heart failure.

Development of a conceptual model and patient-reported outcome measures for assessing symptoms and functioning in patients with heart failure.

PURPOSE: Heart failure (HF) is a common condition that places considerable burden on patients. We aimed to develop a patient-reported outcome (PRO) measure to assess the symptoms and impacts of HF. METHODS: Phase 1: a targeted literature review, expert interviews, and concept elicitation (CE) interviews with patients with HF (n = 26) were used to develop a conceptual model of the core symptoms and impacts of HF. To capture these concepts, three new fit-for-purpose PRO questionnaires were constructed in accordance with US Food and Drug Administration PRO guidance. Phase 2: three 'waves' of cognitive interviews were conducted with patients with HF (n = 28) to validate and refine the questionnaires. RESULTS: Three key symptoms-shortness of breath, oedema, and fatigue-were identified across the literature review, expert interviews and CE interviews. Several additional symptoms, cognitive changes and impacts of HF were reported in the CE interviews and included in the conceptual model. A 10-item symptom questionnaire (Heart Failure-Daily Symptom Diary) was constructed; cognitive testing showed that the final PRO measure was easy to understand/complete and relevant to patients with HF, confirming content validity. Two HF impact questionnaires were developed (Assessing Dyspnoea's Impact on Mobility and Sleep and Heart Failure-Functional Status Assessment), but required refinement to ensure patient understanding. CONCLUSIONS: Patient input contributed to the development of a PRO instrument for assessing physical and cognitive symptoms important to patients with HF using novel measurement strategies. Inclusion of daily metrics offers differentiation from other qualified instruments and may provide clinical insight for improving lifestyles. Additionally, two draft PRO measures may, after further validation, be useful to assess the impacts of HF.

Validity and reliability of the Colorado Adult Joint Assessment Scale in adults with moderate-severe hemophilia A.

BACKGROUND: The Colorado Adult Joint Assessment Scale (CAJAS) is designed to assess joint health in adults with hemophilia. The CAJAS comprises nine items (swelling, muscle atrophy, axial deformity, crepitus, range of motion, contracture, instability, strength, gait) and assesses six joints. OBJECTIVE: To assess CAJAS content validity and psychometric properties. PATIENTS/METHODS: Data were obtained from the Trial to Evaluate the Effect of Secondary Prophylaxis With rFVIII Therapy in Severe Hemophilia A Adult and/or Adolescent Subjects Compared to That of Episodic Treatment (SPINART) study and a separate CAJAS validation study. CAJAS assessments in SPINART were performed by physical therapists (PTs) from the United States, Romania, Bulgaria, and Argentina. In the validation study, content validity was assessed from interviews with six PTs at three US hemophilia centers; cultural equivalence was assessed with seven non-US PTs from SPINART. Reliability data were collected from 30 subjects at four US centers. Test-retest reliability was evaluated by having the same PT perform CAJAS examinations at two visits, 7-10 days apart. Inter-rater reliability was assessed by comparing CAJAS scores of two different PTs performing separate examinations of the same patient several hours apart at the same visit. Psychometric properties were assessed using SPINART and validation study data. RESULTS: The CAJAS demonstrated good content validity. Test-retest reliability was high (intraclass correlation coefficient, 0.98), as was inter-rater reliability (intraclass correlation coefficient, 0.88). Internal consistency reliability was strong (α = .90). The CAJAS demonstrated good convergent/divergent validity, known-groups validity, and ability to detect change. CONCLUSIONS: The CAJAS is a valid and reliable measure of joint health in adults with moderate-severe hemophilia and is appropriate for use in clinical practice.

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.

Patient-Reported Outcome and Observer-Reported Outcome Assessment in Rare Disease Clinical Trials: An ISPOR COA Emerging Good Practices Task Force Report.

BACKGROUND: Rare diseases (RDs) affect a small number of people within a population. About 5000 to 8000 distinct RDs have been identified, with an estimated 6% to 8% of people worldwide suffering from an RD. Approximately 75% of RDs affect children. Frequently, these conditions are heterogeneous; many are progressive. Regulatory incentives have increased orphan drug designations and approvals. OBJECTIVE: To develop emerging good practices for RD outcomes research addressing the challenges inherent in identifying, selecting, developing, adapting, and implementing patient-reported outcome (PRO) and observer-reported outcome (ObsRO) assessments for use in RD clinical trials. GOOD PRACTICES FOR OUTCOMES RESEARCH: This report outlines the challenges and potential solutions in determining clinical outcomes for RD trials. It follows the US Food and Drug Administration Roadmap to Patient-Focused Outcome Measurement in Clinical Trials. The Roadmap consists of three columns: 1) Understanding the Disease or Condition, 2) Conceptualizing Treatment Benefit, and 3) Selecting/Developing the Outcome Measure. Challenges in column 1 include factors such as incomplete natural history data and heterogeneity of disease presentation and patient experience. Solutions include using several information sources, for example, clinical experts and patient advocacy groups, to construct the condition's natural history and understand treatment patterns. Challenges in column 2 include understanding and measuring treatment benefit from the patient's perspective, especially given challenges in defining the context of use such as variations in age or disease severity/progression. Solutions include focusing on common symptoms across patient subgroups, identifying short-term outcomes, and using multiple types of COA instruments to measure the same constructs. Challenges in column 3 center around the small patient population and heterogeneity of the condition or study sample. Few disease-specific instruments for RDs exist. Strategies include adapting existing instruments developed for a similar condition or that contain symptoms of importance to the RD patient population, or using a generic instrument validated for the context of use. CONCLUSIONS: This report provides state-of-the-art solutions to patient-reported outcome (PRO) and observer-reported outcome (ObsRO) assessments challenges in clinical trials of patients with RDs. These recommended solutions are both pragmatic and creative and posed with clear recognition of the global regulatory context used in RD clinical development programs.

An overview of current trends and gaps in patient-reported outcome measures used in haemophilia.

AIM: This review summarises the importance, recent progress and issues in measuring patient-reported outcomes (PROs) in haemophilia research. METHODS: A critical review of recent advances and trends in measuring haemophilia-related PROs was conducted, using current regulatory guidelines and methodological recommendations to evaluate these instruments. RESULTS: Although regulators, payers and policymakers increasingly consider the patient's perspective to be important in treatment decision-making, to date, few haemophilia intervention studies have meaningfully applied PRO endpoints. Condition-specific PRO instruments have been developed, but most are not fully validated; sensitivity to subgroup differences and changes over time is unclear. Generic PROs and instruments developed for other conditions have been used to measure health-related quality of life (HRQL) in haemophilia patients, but little evidence of their validity for this purpose exists. Haemophilia presents a number of challenges to developing valid, reliable and responsive PRO instruments, including the rarity of the disorder; necessitating research in multiple counties to attain sufficient sample size; the chronic nature of the condition; acute exacerbations of illness; age and geographical region variations with respect to treatment; differences in treatment regimens, range of disease severity and phenotypes; and changes in patients' perceived health status over time. Given that haemophilia begins at birth, the illness has an impact on the lives of caregivers, although the extent of the impact is largely unknown. CONCLUSIONS: Patient perspectives are crucial to understanding the best and most cost-effective haemophilia treatment approaches. More research is needed on the ability of current disease-specific and generic PRO instruments to capture responsiveness to treatments over time and subgroup differences in outcomes. Inclusion of PROs in clinical trials is necessary to answer these questions.

The anemia impact measure (AIM): development and content validation of a patient-reported outcome measure of anemia symptoms and symptom impacts in cancer patients receiving chemotherapy.

PURPOSE: To develop a patient-reported outcome instrument for measuring anemia symptoms and their impact in patients with chemotherapy-induced anemia (CIA). METHODS: Qualitative research was conducted using six focus groups and 24 interviews with 46 CIA patients, eight interviews in patients receiving chemotherapy with no CIA history and two interviews in patients successfully treated for CIA. Atlas.ti 5.0 was used to organize key concepts. Cognitive interviews with 16 CIA patients and assessment of relevance of each item to CIA by 10 clinicians were also conducted to evaluate content validity. RESULTS: Most CIA patients were white (76%) and female (83%), and the average age was 60 years. The most common cancer types were breast cancer (54%) and lung cancer (17%). Tiredness was the most prevalent symptom and rated as the most important by 83% of CIA patients; weakness, shortness of breath, lightheadedness, and dizziness were ranked next in importance. The final anemia impact measure (AIM) contains: (1) daily CIA symptom diary (9 items), and (2) impact of CIA-related tiredness (29 items covering daily living activities, social activities, cognitive function, and emotions). Cognitive interviews found that the AIM was relevant and easy to understand. CONCLUSIONS: The AIM assesses important patient-perceived CIA symptoms and their impact and was developed using extensive patient qualitative data.

Quality of life and disability in patients with treatment-failure gout.

OBJECTIVE: The relationship between self-reported quality of life and disability and disease severity was evaluated in subjects with treatment-failure gout (n = 110) in a prospective, 52-week, observational study. METHODS: Subjects had symptomatic crystal-proven gout of at least 2 years' duration and intolerance or refractoriness to conventional urate-lowering therapy. Serum uric acid (sUA) concentration, swollen and tender joint counts, frequency and severity of gout flares, tophus assessments, comorbidities, and patient-reported outcomes data [Medical Outcomes Study Short Form-36 (SF-36), Health Assessment Questionnaire-Damage Index] were collected. Analyses included correlations of patient-reported outcomes with clinical variables and changes in clinical status. RESULTS: Mean age of study subjects was 59 years. Mean scores on SF-36 physical functioning subscales were 34.2-46.8, analogous to persons aged >or= 75 years in the general population. Subjects with more severe gout at baseline had worse health-related quality of life (HRQOL) in all areas (p < 0.02 for all measures), compared to patients with mild-moderate disease. Number of flares reported in past year, number of tender joints, swollen joints, and tophi correlated significantly with some or all HRQOL and disability measures. sUA was not significantly correlated with any HRQOL or disability measure. Subjects with comorbidities experienced worse physical, but not mental, functioning. CONCLUSION: Severe gout is associated with poor HRQOL and disability, especially for patients who experience more gout flares and have a greater number of involved joints. Subject perceptions of gout-related functioning and pain severity appear to be highly sensitive indicators of HRQOL and disability.

Factors associated with retirement-related job lock in older workers with recent occupational injury.

PURPOSES: Job lock (inability to leave a job due to financial or benefits needs) has been found to significantly restrict job mobility. However, it has not been studied in terms of inability to retire. This study evaluated the relationship between health, work environment, and retirement-related job lock in workers > or =55 with recent occupational injuries. METHODS: Workers completed a mailed, self-report survey about their pre- and post-injury health and functioning, work environment, and retirement plans. Bivariate and multivariate analyses determined those factors associated with retirement-related job lock. RESULTS: Over half of the respondents wanted to retire but could not because they needed job-related income or benefits. Factors associated with retirement-related job lock were indicative of poorer health and mental function and dissatisfaction with the workplace social environment. No injury-related factors were significant. CONCLUSIONS: Retirement-related job lock was common in older workers with occupational injuries, and appears to be primarily due to difficulties at work, combined with health conditions that may impair work abilities. Workers wishing to retire but unable to do so may be at risk for work-related injuries, as well as decrements in work function and premature retirement resulting in insufficient income and health benefits.

Understanding the role of sex differences in work injuries: implications for primary care practice.

PURPOSE: Primary care physicians care for work-injured women and men, yet there is little information on sex differences in outcomes and factors contributing to post-injury outcomes to guide their evaluation and recommendations. METHODS: Two self-administered questionnaires were sent to a large sample of women and men with work injuries reported to the New Hampshire (USA) Department of Labour between November 2000 and March 2002. Factors associated with the work injury and outcomes were assessed. RESULTS: A total of 3001 persons (1448 women and 1553 men) completed the first questionnaire and 67% completed the second questionnaire. Work-injured women were significantly younger, more educated, more likely to be single, had more pre-injury comorbidities, and worked in less physically demanding occupations as compared to work-injured men. Women's injuries were more often a result of routine job tasks and of gradual onset. Women had worse long-term outcomes including job stability and post-injury income. In multivariate analyses, being female was independently associated with a negative employer response and greater future work concerns. CONCLUSIONS: Women and men differ in terms of work injury circumstances and factors contributing to post-injury outcomes. Primary care providers should consider sex when evaluating and treating work-injured adults.

A historical look at alcohol abuse trends in army and civilian populations, 1980-1995.

OBJECTIVES: The purpose of this study was to compare civilian and Army alcohol-related hospitalization trends and to plot temporal changes in rates relative to alcohol-related legislation and social policies. METHOD: We compared population-based civilian and Army annual hospitalization rates for overall alcohol-related diagnoses and for alcohol-related diagnostic subgroups (1980-1995) and plotted them against civilian and military substance abuse regulations. Civilian data were adjusted to Army age, gender, and race. RESULTS: Although overall civilian and Army alcohol hospitalization rates were similar, alcohol subgroup rates varied. Simultaneous drug and alcohol abuse (polyabuse) rates were higher among civilians (16.6 per 10,000) than Army soldiers (5.1 per 10,000). Army rates for dependent alcohol-related disorders were higher and increased. Army nondependent alcohol disorders tracked with alcohol-related regulations as rates fell 69% between 1985 and 1995. CONCLUSION: Army and civilian alcohol abuse trends vary by abuse type. Without longitudinal, diagnosis-specific subgroup analyses, these trends would not have emerged. Army policies and screening may explain divergent nondependent alcohol abuse and lower polyabuse rates.

Factors affecting the organizational responses of employers to workers with injuries.

The organizational responses of employers to work-related injuries is one of several significant influences on return-to-work outcomes. Thus, understanding the factors that lead to better or worse organizational responses to work injuries may ultimately help to improve success in this area. The purpose of this study was to systematically explore factors that might influence the organizational responses of employers to injured workers, based on employee perceptions. Cross-sectional survey data were collected from 2,943 subjects with work-related injuries which had occurred less than eight weeks prior to survey completion. Measured variables included pre-injury demographic and job factors, injury circumstances, and a measure of post-injury events that comprised the organizational response. Multivariate linear regression results show that age, gender, job dissatisfaction before injury, prior difficulty performing job tasks, injury severity, back injury and lost time were all associated with negative organizational responses, suggesting potential opportunities for intervention.

Early retirement due to occupational injury: who is at risk?

BACKGROUND: As the workforce is rapidly ageing, research on the consequences of occupational injuries in older workers is becoming more important. One adverse outcome unique to older workers, early retirement, has significant negative social and economic consequences for workers and employers. Although linked to poor worker health, the roles of workplace factors and occupational injury have not been well-defined. METHOD: Changes in retirement plans attributed to an occupational injury were studied in a population-based sample of 1,449 New Hampshire workers aged

The use of sentinel injury deaths to evaluate the quality of multiple source reporting for occupational injuries.

PURPOSE: This study sought to develop an efficient method for evaluating the validity and completeness of routinely available sources of occupational injury fatality data. METHODS: Deaths due to falls from elevations, machinery, and electrocutions were selected as sentinel injuries likely to have occurred at work. Deaths from these injuries were identified from Maryland vital statistics over 7 years. The work-relatedness of these injuries and sensitivity of reporting were determined from death certificates, medical examiner reports, the National Traumatic Occupational Fatality System (NTOF), the Maryland Occupational Safety and Health Administration (MOSH), and Workers' Compensation (WC) data. RESULTS: A total of 527 deaths were identified for ages 16 and above, of which, 45% were work-related. Identification of work-related deaths varied by source: medical examiner (100%), death certificates (89%), NTOF (68%), MOSH (59%), and WC (44%). Reporting differed by age, cause of injury, year, occupation, and industry. CONCLUSIONS: Examination of work-relatedness for deaths from certain causes is an efficient means of evaluating the quality of occupational injury reporting source data. These sentinel injuries uncovered significant underreporting in sources used by national surveillance systems, resulted in improved NTOF reporting, and suggest the need to make more use of medical examiner data when available.

Outcomes in work-related injuries: a comparison of older and younger workers.

BACKGROUND: The "graying of the workforce" has generated concerns about the physical capacity of older workers to maintain their health and productivity on the job, especially after an injury occurs. There is little detailed research on age-related differences in work outcomes after an occupational injury. METHODS: A self-report survey about occupational, health, and financial outcomes, and related factors was administered 2-8 weeks post-injury to workers aged < 55 and > or = 55 who had lost time due to a work injury. RESULTS: Despite more severe injuries in older workers, most outcomes were similar in both age groups. In multivariate models, age was unrelated or inversely related to poor outcomes. Injury severity, physical functioning, and problems upon return to work were associated with adverse work injury outcomes. CONCLUSIONS: Older workers appear to fare better than younger workers after a work injury; their relative advantage may be primarily due to longer workplace attachment and the healthy worker effect.

Occupational upper extremity conditions: a detailed analysis of work-related outcomes.

While work-related upper extremity conditions (WRUECs) cause almost 25% of lost time cases in the US, little is known about their long-term occupational consequences. A self-report survey was mailed to New Hampshire workers reporting a WRUEC one year prior to the study. Of the 72 (52%) valid respondents, 60% had lost > or = 1 week of work and 90% had returned to work. Almost 70% reported acute injury onset, and 26% had experienced a recurrence of their WRUEC. Both gradual-onset injuries and recurrences had worse outcomes. Recurrence was related to shorter job tenure, lower job satisfaction, and less satisfaction with medical care and insurer responses. Results imply that a single measure is insufficient to assess occupational outcomes subsequent to a WRUEC. The importance of secondary prevention was highlighted. There is a need for focus on gradual-onset injuries, as well as those acute-onset injuries with risk for recurrence.

Occupational risks and injuries in non-agricultural immigrant Latino workers.

BACKGROUND: To investigate occupational health in urban immigrant Latino workers, using a community-based method. METHODS: A survey was administered through consecutively selected door-to-door interviews. RESULTS: Response rate was 80% (n = 427). Average time in the US was 7.6 years, and average job tenure was 2.8 years. Twenty-five reported exposures to over 10 different hazards, and 18% thought these hazards had harmed their health. Only 31% received any job safety training; 55% had no workers' compensation coverage. Of the 47 (11%) with a work injury in the past 3 years, 27% reported difficulty obtaining treatment, 91% lost time from work (median = 13 days) and 29% had to change jobs because of the injury. The annual occupational injury rate was 12.2/100 full-time workers, compared to an expected rate of 7.1. CONCLUSIONS: Urban immigrant workers have increased risk of occupational injuries, with adverse outcomes.

Work-related outcomes in occupational low back pain: a multidimensional analysis.

OBJECTIVES: This pilot study explored a broad range of work-related outcomes for occupational low back injuries. METHODS: A model of occupational outcomes and a survey instrument were developed on the basis of interviews, expert opinion, and literature reviews. New Hampshire workers who had an occupational back injury a year before the study were sampled from first reports of injury and sent a mailed survey about their postinjury experiences and related factors. RESULTS: Of 251 randomly selected cases, a valid address could be identified for 121, and 99 patients responded. Almost 60% of the respondents had lost 1 week of work or more. At 1 year after injury, half of the respondents had returned to their preinjury job and employer, and 20% were unemployed, half of them because of the injury. Most working respondents reported no decrease in their work capacity. However, 68% still had pain exacerbated by work, and 47% worried that their condition would worsen with continued work. Reinjury occurred in 42% of the respondents. The work-related outcome measures were largely independent of each other. Exploratory multivariate analyses demonstrated unique patterns of factors associated with each outcome. Reinjury risk was significantly greater in respondents whose employers offered accommodations or whose postinjury jobs had greater ergonomic risk. The small sample size limited the ability to achieve statistically significant results in multivariate analyses. CONCLUSIONS: Simply measuring return to work did not appear to capture the full range of job-related consequences from occupational back injuries in this pilot evaluation. Timing of return to work, occupational ergonomic risks, and appropriate job modifications appeared to be particularly important in a safe return to the job after an occupational low back injury. Results suggest opportunities to address risk factors that may improve work outcomes.