Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease

Oral medicine acceptance in infants and toddlers: measurement properties of the caregiver-administered Children’s acceptance tool (CareCAT)

BACKGROUND: Developing age-appropriate medications remains a challenge in particular for the population of infants and toddlers, as they are not able to reliably self-report if they would accept and consequently take an oral medicine. Therefore, it is common to use caregivers as proxies when assessing medicine acceptance. The outcome measures used in this research field differ and most importantly lack validation, implying a persisting gap in knowledge and controversy in the field. The newly developed Caregiver-administered Children’s Acceptance Tool (CareCAT) is based on a 5-point nominal scale, with descriptors of medication acceptance behavior. This crosssectional study assessed the measurement properties of the tool with regards to the user’s understanding and its intra- and inter-rater reliability. METHODS: Participating caregivers were enrolled at a primary healthcare facility where their children (median age 6 months) had been prescribed oral antibiotics. Caregivers, trained observers and the tool developer observed and scored on the CareCAT tool what behavior children exhibited when receiving the medicine (n = 104). The videorecords of this process served as replicate observations (n = 69). After using the tool caregivers were asked to explain their observations and the tool descriptors in their own words. The tool’s reliability was assessed by percentage agreement and Cohen’s unweighted kappa coefficients of agreement for nominal scales. RESULTS: The study found that caregivers using CareCAT had a satisfactory understanding of the tool’s descriptors. Using its dichotomized scores the tool reliably was strong for acceptance behavior (agreement inter-rater 84–88%, kappa 0.66–0.76; intra-rater 87–89%, kappa 0.68–0.72) and completeness of medicine ingestion (agreement inter-rater 82–86%, kappa 0.59–0.67; intra-rater 85–93%, kappa 0.50–0.70). CONCLUSIONS: The CareCAT is a low-cost, easy-to-use and reliable instrument, which is relevant to assess acceptance behavior and completeness of medicine ingestion, both of which are of significant importance for developing age-appropriate medications in infants and toddlers

The impact of ADHD on the health and well-being of ADHD children and their siblings

Childhood attention-deficit/hyperactivity disorder (ADHD) has been associated with reduced health and well-being of patients and their families. The authors undertook a large UK survey-based observational study of the burden associated with childhood ADHD. The impact of ADHD on both the patient (N = 476) and their siblings (N = 337) on health-related quality of life (HRQoL) and happiness was quantified using multiple standard measures [e.g. child health utility-9D (CHU-9D), EuroQol-5D-Youth]. In the analysis, careful statistical adjustments were made to ensure a like-for-like comparison of ADHD families with two different control groups. We controlled for carers' ADHD symptoms, their employment and relationship status and siblings' ADHD symptoms. ADHD was associated with a significant deficit in the patient's HRQoL (with a CHU-9D score of around 6 % lower). Children with ADHD also have less sleep and were less happy with their family and their lives overall. No consistent decrement to the HRQoL of the siblings was identified across the models, except that related to their own conduct problems. The siblings do, however, report lower happiness with life overall and with their family, even when controlling for the siblings own ADHD symptoms. We also find evidence of elevated bullying between siblings in families with a child with ADHD. Overall, the current results suggest that the reduction in quality of life caused by ADHD is experienced both by the child with ADHD and their siblings

Diabetes MILES – The Netherlands: rationale, design and sample characteristics of a national survey examining the psychosocial aspects of living with diabetes in Dutch adults

Background : As the number of people with diabetes is increasing rapidly worldwide, a more thorough understanding of the psychosocial aspects of living with this condition has become an important health care priority. While our knowledge has grown substantially over the past two decades with respect to the physical, emotional and social difficulties that people with diabetes may encounter, many important issues remain to be elucidated. Under the umbrella of the Diabetes MILES (Management and Impact for Long-term Empowerment and Success) Study International Collaborative, Diabetes MILES &ndash; The Netherlands aims to examine how Dutch adults with diabetes manage their condition and how it affects their lives. Topics of special interest in Diabetes MILES - The Netherlands include subtypes of depression, Type D personality, mindfulness, sleep and sexual functioning. Methods/design : Diabetes MILES &ndash; The Netherlands was designed as a national online observational study among adults with diabetes. In addition to a main set of self-report measures, the survey consisted of five complementary modules to which participants were allocated randomly. From September to October 2011, a total of 3,960 individuals with diabetes (40% type 1, 53% type 2) completed the battery of questionnaires covering a broad range of topics, including general health, self-management, emotional well-being and contact with health care providers. People with self-reported type 1 diabetes (specifically those on insulin pump therapy) were over-represented, as were those using insulin among respondents with self-reported type 2 diabetes. People from ethnic minorities were under-represented. The sex distribution was fairly equal in the total sample, participants spanned a broad age range (19&ndash;90 years), and diabetes duration ranged from recent diagnosis to living with the condition for over fifty years. Discussion : The Diabetes MILES Study enables detailed investigation of the psychosocial aspects of living with diabetes and an opportunity to put these findings in an international context. With several papers planned resulting from a pooled Australian-Dutch dataset and data collections planned in other countries, the Diabetes MILES Study International Collaborative will contribute substantially to identifying potentially unmet needs of those living with diabetes and to inform clinical research and care across the globe. <br /

Health state utilities associated with attributes of treatments for hepatitis C

BACKGROUND: Cost-utility analyses are frequently conducted to compare treatments for hepatitis C, which are often associated with complex regimens and serious adverse events. Thus, the purpose of this study was to estimate the utility associated with treatment administration and adverse events of hepatitis C treatments. DESIGN: Health states were drafted based on literature review and clinician interviews. General population participants in the UK valued the health states in time trade-off (TTO) interviews with 10- and 1-year time horizons. The 14 health states described hepatitis C with variations in treatment regimen and adverse events. RESULTS: A total of 182 participants completed interviews (50 % female; mean age = 39.3 years). Utilities for health states describing treatment regimens without injections ranged from 0.80 (1 tablet) to 0.79 (7 tablets). Utilities for health states describing oral plus injectable regimens were 0.77 (7 tablets), 0.75 (12 tablets), and 0.71 (18 tablets). Addition of a weekly injection had a disutility of −0.02. A requirement to take medication with fatty food had a disutility of −0.04. Adverse events were associated with substantial disutilities: mild anemia, −0.12; severe anemia, −0.32; flu-like symptoms, −0.21; mild rash, −0.13; severe rash, −0.48; depression, −0.47. One-year TTO scores were similar to these 10-year values. CONCLUSIONS: Adverse events and greater treatment regimen complexity were associated with lower utility scores, suggesting a perceived decrease in quality of life beyond the impact of hepatitis C. The resulting utilities may be used in models estimating and comparing the value of treatments for hepatitis C. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10198-014-0649-6) contains supplementary material, which is available to authorized users

Meaningful health outcomes for paediatric neurodisability: stakeholder prioritisation and appropriateness of patient reported outcome measures

BACKGROUND: Health services are increasingly focused on measuring and monitoring outcomes, particularly those that reflect patients' priorities. To be meaningful, outcomes measured should be valued by patients and carers, be consistent with what health professionals seek to achieve, and be robust in terms of measurement properties. The aim of this study was (i) to seek a shared vision between families and clinicians regarding key aspects of health as outcomes, beyond mortality and morbidity, for children with neurodisability, and (ii) to appraise which multidimensional patient reported outcome measures (PROMs) could be used to assess salient health domains. METHODS: Relevant outcomes were identified from (i) qualitative research with children and young people with neurodisability and parent carers, (ii) Delphi survey with health professionals, and (iii) systematic review of PROMs. The International Classification of Functioning Disability and Health provided a common language to code aspects of health. A subset of stakeholders participated in a prioritisation meeting incorporating a Q-sorting task to discuss and rank aspects of health. RESULTS: A total of 33 pertinent aspects of health were identified. Fifteen stakeholders from the qualitative and Delphi studies participated in the prioritisation meeting: 3 young people, 5 parent carers, and 7 health professionals. Aspects of health that emerged as more important for families and targets for health professionals were: communication, emotional wellbeing, pain, sleep, mobility, self-care, independence, mental health, community and social life, behaviour, toileting and safety. Whilst available PROMs measure many aspects of health in the ICF, no single PROM captures all the key domains prioritised as for children and young people with neurodisability. The paucity of scales for assessing communication was notable. CONCLUSIONS: We propose a core suite of key outcome domains for children with neurodisability that could be used in evaluative research, audit and as health service performance indicators. Future work could appraise domain-specific PROMs for these aspects of health; a single measure assessing the key aspects of health that could be applied across paediatric neurodisability remains to be developed

The PedsQL™ as a patient-reported outcome in children and adolescents with Attention-Deficit/Hyperactivity Disorder: a population-based study

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common chronic mental health condition in children and adolescents. The application of health-related quality of life (HRQOL) as a pediatric population health measure may facilitate risk assessment and resource allocation, the identification of health disparities, and the determination of health outcomes from interventions and policy decisions for children and adolescents with ADHD at the local community, state, and national health level. METHODS: An analysis from an existing statewide database to determine the feasibility, reliability, and validity of the 23-item PedsQL™ 4.0 (Pediatric Quality of Life Inventory™) Generic Core Scales as a patient-reported outcome (PRO) measure of pediatric population health for children and adolescents with ADHD. The PedsQL™ 4.0 Generic Core Scales (Physical, Emotional, Social, School Functioning) were completed by families through a statewide mail survey to evaluate the HRQOL of new enrollees in the State of California State's Children's Health Insurance Program (SCHIP). Seventy-two children ages 5–16 self-reported their HRQOL. RESULTS: The PedsQL™ 4.0 evidenced minimal missing responses, achieved excellent reliability for the Total Scale Score (α = 0.92 child self-report, 0.92 parent proxy-report), and distinguished between healthy children and children with ADHD. Children with ADHD self-reported severely impaired psychosocial functioning, comparable to children with newly-diagnosed cancer and children with cerebral palsy. CONCLUSION: The results suggest that population health monitoring may identify children with ADHD at risk for adverse HRQOL. The implications of measuring pediatric HRQOL for evaluating the population health outcomes of children with ADHD internationally are discussed

Measuring Health Utilities in Children and Adolescents: A Systematic Review of the Literature.

BACKGROUND: The objective of this review was to evaluate the use of all direct and indirect methods used to estimate health utilities in both children and adolescents. Utilities measured pre- and post-intervention are combined with the time over which health states are experienced to calculate quality-adjusted life years (QALYs). Cost-utility analyses (CUAs) estimate the cost-effectiveness of health technologies based on their costs and benefits using QALYs as a measure of benefit. The accurate measurement of QALYs is dependent on using appropriate methods to elicit health utilities. OBJECTIVE: We sought studies that measured health utilities directly from patients or their proxies. We did not exclude those studies that also included adults in the analysis, but excluded those studies focused only on adults. METHODS AND FINDINGS: We evaluated 90 studies from a total of 1,780 selected from the databases. 47 (52%) studies were CUAs incorporated into randomised clinical trials; 23 (26%) were health-state utility assessments; 8 (9%) validated methods and 12 (13%) compared existing or new methods. 22 unique direct or indirect calculation methods were used a total of 137 times. Direct calculation through standard gamble, time trade-off and visual analogue scale was used 32 times. The EuroQol EQ-5D was the most frequently-used single method, selected for 41 studies. 15 of the methods used were generic methods and the remaining 7 were disease-specific. 48 of the 90 studies (53%) used some form of proxy, with 26 (29%) using proxies exclusively to estimate health utilities. CONCLUSIONS: Several child- and adolescent-specific methods are still being developed and validated, leaving many studies using methods that have not been designed or validated for use in children or adolescents. Several studies failed to justify using proxy respondents rather than administering the methods directly to the patients. Only two studies examined missing responses to the methods administered with respect to the patients' ages

Systematic review of quality of life and functional outcomes in randomized placebo-controlled studies of medications for attention-deficit/hyperactivity disorder

Children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) experience functional impairment and poor health-related quality of life (HRQoL) in addition to symptoms of inattention/hyperactivity-impulsivity. To synthesize qualitatively the published evidence from randomized, double-blind, placebo-controlled trials of the effectiveness of pharmacotherapy on functional impairment or HRQoL in patients with ADHD, a systematic PubMed searching and screening strategy was designed to identify journal articles meeting pre-specified criteria. Post hoc analyses and meta-analyses were excluded. HRQoL outcomes, functional outcomes and the principal ADHD symptom-based outcome were extracted from included studies. An effect size of 0.5 versus placebo was used as a threshold for potential clinical relevance (unreported effect sizes were calculated when possible). Of 291 records screened, 35 articles describing 34 studies were included. HRQoL/functioning was usually self-rated in adults and proxy-rated in children/adolescents. Baseline data indicated substantial HRQoL deficits in children/adolescents. Placebo-adjusted effects of medication on ADHD symptoms, HRQoL and functioning, respectively, were statistically or nominally significant in 18/18, 10/12 and 7/9 studies in children/adolescents and 14/16, 9/11 and 9/10 studies in adults. Effect sizes were ≥0.5 versus placebo for symptoms, HRQoL and functioning, respectively, in 14/16, 7/9 and 4/8 studies in children/adolescents; and 6/12, 1/6 and 1/8 studies in adults. Effect sizes were typically larger for stimulants than for non-stimulants, for symptoms than for HRQoL/functioning, and for children/adolescents than for adults. The efficacy of ADHD medication extends beyond symptom control and may help reduce the related but distinct functional impairments and HRQoL deficits in patients with ADHD