Mode equivalence and acceptability of tablet computer-, interactive voice response system-, and paper-based administration of the U.S. National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Background PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. Methods Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0–4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed. Results 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55–0.90); tablet vs paper: 0.81 (0.62–0.96); IVRS vs paper: 0.78 (0.60–0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = −0.04 [−0.16–0.22]; tablet vs paper = −0.02 [−0.11–0.14]; IVRS vs paper = 0.02 [−0.07–0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/−0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported “no problems” responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper. Conclusions Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration. Trial registration NCT Clinicaltrials.gov identifier: NCT0215863

CIP2A expression predicts recurrences of tamoxifen-treated breast cancer

CIP2A is emerging as an oncoprotein overexpressed commonly across many tumours and generally correlated with higher tumour grade and therapeutic resistance. CIP2A drives an oncogenic potential through inhibiting protein phosphatase 2A, stabilizing MYC, and promoting epithelial-to-mesenchymal transition, although further biological mechanisms for CIP2A are yet to be defined. CIP2A protein expression was studied by immunohistochemistry in oestrogen receptor–positive primary breast cancers (n = 250) obtained from the Leeds Tissue Bank. In total, 51 cases presented with a relapse or metastasis during adjuvant treatment with tamoxifen and were regarded as tamoxifen resistant. CIP2A expression was scored separately for cytoplasmic, nuclear, or membranous staining, and scores were tested for statistically significant relationships with clinicopathological features. Membranous CIP2A was preferentially expressed in cases who experienced a recurrence during tamoxifen treatment thus predicting a worse overall survival (log rank = 8.357, p = 0.004) and disease-free survival (log rank = 21.766, p < 0.001). Cox multivariate analysis indicates that it is an independent prognostic indicator for overall survival (hazard ratio = 4.310, p = 0.013) and disease-free survival (hazard ratio = 5.449, p = 0.002). In this study, we propose the assessment of membranous CIP2A expression as a potential novel prognostic and predictive indicator for tamoxifen resistance and recurrence within oestrogen receptor–positive breast cancer

Protocol of the COSMIN study: COnsensus-based Standards for the selection of health Measurement INstruments

BACKGROUND: Choosing an adequate measurement instrument depends on the proposed use of the instrument, the concept to be measured, the measurement properties (e.g. internal consistency, reproducibility, content and construct validity, responsiveness, and interpretability), the requirements, the burden for subjects, and costs of the available instruments. As far as measurement properties are concerned, there are no sufficiently specific standards for the evaluation of measurement properties of instruments to measure health status, and also no explicit criteria for what constitutes good measurement properties. In this paper we describe the protocol for the COSMIN study, the objective of which is to develop a checklist that contains COnsensus-based Standards for the selection of health Measurement INstruments, including explicit criteria for satisfying these standards. We will focus on evaluative health related patient-reported outcomes (HR-PROs), i.e. patient-reported health measurement instruments used in a longitudinal design as an outcome measure, excluding health care related PROs, such as satisfaction with care or adherence. The COSMIN standards will be made available in the form of an easily applicable checklist. METHOD: An international Delphi study will be performed to reach consensus on which and how measurement properties should be assessed, and on criteria for good measurement properties. Two sources of input will be used for the Delphi study: (1) a systematic review of properties, standards and criteria of measurement properties found in systematic reviews of measurement instruments, and (2) an additional literature search of methodological articles presenting a comprehensive checklist of standards and criteria. The Delphi study will consist of four (written) Delphi rounds, with approximately 30 expert panel members with different backgrounds in clinical medicine, biostatistics, psychology, and epidemiology. The final checklist will subsequently be field-tested by assessing the inter-rater reproducibility of the checklist. DISCUSSION: Since the study will mainly be anonymous, problems that are commonly encountered in face-to-face group meetings, such as the dominance of certain persons in the communication process, will be avoided. By performing a Delphi study and involving many experts, the likelihood that the checklist will have sufficient credibility to be accepted and implemented will increase

Patient-reported outcomes in a trial of exenatide and insulin glargine for the treatment of type 2 diabetes

BACKGROUND: Patient-reported measures can be used to examine whether drug differences other than clinical efficacy have an impact on outcomes that may be important to patients. Although exenatide and insulin glargine appear to have similar efficacy for treatment of type 2 diabetes, there are several differences between the two treatments that could influence outcomes from the patient's perspective. The purpose of the current study was to examine whether the two drugs were comparable as assessed by patient-reported outcomes using data from a clinical trial in which these injectable medications were added to pre-existing oral treatment regimens. METHODS: Patients were randomized to either twice daily exenatide or once daily insulin glargine during a 26-week international trial. At baseline and endpoint, five patient-reported outcome measures were administered: the Vitality Scale of the SF-36, The Diabetes Symptom Checklist – Revised (DSC-R), the EuroQol EQ-5D, the Treatment Flexibility Scale (TFS), and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Change from baseline to endpoint was analyzed within each treatment group. Group differences were examined with General linear models (GLMs), controlling for country and baseline scores. RESULTS: A total of 549 patients with type 2 diabetes were enrolled in the trial, and current analyses were conducted with data from the 455 per protocol patients (228 exenatide and 227 insulin glargine). The sample was primarily Caucasian (79.6%), with slightly more men (55.2%) than women, and with a mean age of 58.5 years. Paired t-tests found that both treatment groups demonstrated statistically significant baseline to endpoint change on several of the health outcomes instruments including the DSC-R, DTSQ, and the SF-36 Vitality subscale. GLMs found no statistically significant differences between groups in change on the health outcomes instruments. CONCLUSION: This analysis found that both exenatide and insulin glargine were associated with significant improvements in patient-reported outcomes when added to oral medications among patients with type 2 diabetes. Despite an additional daily injection and a higher rate of gastrointestinal adverse events, treatment satisfaction in the exenatide group was comparable to that of the glargine group, possibly because of weight reduction observed in patients treated with exenatide

Health promotion through self-care and community participation: Elements of a proposed programme in the developing countries

BACKGROUND: The concepts of health promotion, self-care and community participation emerged during 1970s, primarily out of concerns about the limitation of professional health system. Since then there have been rapid growth in these areas in the developed world, and there is evidence of effectiveness of such interventions. These areas are still in infancy in the developing countries. There is a window of opportunity for promoting self care and community participation for health promotion. DISCUSSION: A broad outline is proposed for designing a health promotion programme in developing countries, following key strategies of the Ottawa Charter for health promotion and principles of self care and community participation. Supportive policies may be framed. Self care clearinghouses may be set up at provincial level to co-ordinate the programme activities in consultation with district and national teams. Self care may be promoted in the schools and workplaces. For developing personal skills of individuals, self care information, generated through a participatory process, may be disseminated using a wide range of print and audio-visual tools and information technology based tools. One such potential tool may be a personally held self care manual and health record, to be designed jointly by the community and professionals. Its first part may contain basic self care information and the second part may contain outlines of different personally-held health records to be used to record important health and disease related events of an individual. Periodic monitoring and evaluation of the programme may be done. Studies from different parts of the world indicate the effectiveness and cost-effectiveness of self care interventions. The proposed outline has potential for health promotion and cost reduction of health services in the developing countries, and may be adapted in different situations. SUMMARY: Self care, community participation and health promotion are emerging but dominant areas in the developed countries. Elements of a programme for health promotion in the developing countries following key principles of self care and community participation are proposed. Demonstration programmes may be initiated to assess the feasibility and effectiveness of this programme before large scale implementation

Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008

<p>Abstract</p> <p>Background</p> <p>Health-related quality of life and survival are two important outcome measures in cancer research and practice. The aim of this paper is to examine the relationship between quality of life data and survival time in cancer patients.</p> <p>Methods</p> <p>A review was undertaken of all the full publications in the English language biomedical journals between 1982 and 2008. The search was limited to cancer, and included the combination of keywords 'quality of life', 'patient reported-outcomes' 'prognostic', 'predictor', 'predictive' and 'survival' that appeared in the titles of the publications. In addition, each study was examined to ensure that it used multivariate analysis. Purely psychological studies were excluded. A manual search was also performed to include additional papers of potential interest.</p> <p>Results</p> <p>A total of 451 citations were identified in this rapid and systematic review of the literature. Of these, 104 citations on the relationship between quality of life and survival were found to be relevant and were further examined. The findings are summarized under different headings: heterogeneous samples of cancer patients, lung cancer, breast cancer, gastro-oesophageal cancers, colorectal cancer, head and neck cancer, melanoma and other cancers. With few exceptions, the findings showed that quality of life data or some aspects of quality of life measures were significant independent predictors of survival duration. Global quality of life, functioning domains and symptom scores - such as appetite loss, fatigue and pain - were the most important indicators, individually or in combination, for predicting survival times in cancer patients after adjusting for one or more demographic and known clinical prognostic factors.</p> <p>Conclusion</p> <p>This review provides evidence for a positive relationship between quality of life data or some quality of life measures and the survival duration of cancer patients. Pre-treatment (baseline) quality of life data appeared to provide the most reliable information for helping clinicians to establish prognostic criteria for treating their cancer patients. It is recommended that future studies should use valid instruments, apply sound methodological approaches and adequate multivariate statistical analyses adjusted for socio-demographic characteristics and known clinical prognostic factors with a satisfactory validation strategy. This strategy is likely to yield more accurate and specific quality of life-related prognostic variables for specific cancers.</p

Is complementary and alternative medicine (CAM) cost-effective? a systematic review

BACKGROUND: Out-of-pocket expenditures of over $34 billion per year in the US are an apparent testament to a widely held belief that complementary and alternative medicine (CAM) therapies have benefits that outweigh their costs. However, regardless of public opinion, there is often little more than anecdotal evidence on the health and economic implications of CAM therapies. The objectives of this study are to present an overview of economic evaluation and to expand upon a previous review to examine the current scope and quality of CAM economic evaluations. METHODS: The data sources used were Medline, AMED, Alt-HealthWatch, and the Complementary and Alternative Medicine Citation Index; January 1999 to October 2004. Papers that reported original data on specific CAM therapies from any form of standard economic analysis were included. Full economic evaluations were subjected to two types of quality review. The first was a 35-item checklist for reporting quality, and the second was a set of four criteria for study quality (randomization, prospective collection of economic data, comparison to usual care, and no blinding). RESULTS: A total of 56 economic evaluations (39 full evaluations) of CAM were found covering a range of therapies applied to a variety of conditions. The reporting quality of the full evaluations was poor for certain items, but was comparable to the quality found by systematic reviews of economic evaluations in conventional medicine. Regarding study quality, 14 (36%) studies were found to meet all four criteria. These exemplary studies indicate CAM therapies that may be considered cost-effective compared to usual care for various conditions: acupuncture for migraine, manual therapy for neck pain, spa therapy for Parkinson's, self-administered stress management for cancer patients undergoing chemotherapy, pre- and post-operative oral nutritional supplementation for lower gastrointestinal tract surgery, biofeedback for patients with "functional" disorders (eg, irritable bowel syndrome), and guided imagery, relaxation therapy, and potassium-rich diet for cardiac patients. CONCLUSION: Whereas the number and quality of economic evaluations of CAM have increased in recent years and more CAM therapies have been shown to be of good value, the majority of CAM therapies still remain to be evaluated

Whole organisms or pure compounds? entourage effect versus drug specificity

As the therapeutic use of sacred plants and fungi becomes increasingly accepted by Western medicine, a tug of war has been taking place between those who advocate the traditional consumption of whole organisms and those who defend exclusively the utilization of purified compounds. The attempt to reduce organisms to single active principles is challenged by the sheer complexity of traditional medicine. Ayahuasca, for example, is a concoction of at least two plant species containing multiple psychoactive substances with complex interactions. Similarly, cannabis contains dozens of psychoactive substances whose specific combinations in different strains correspond to different types of therapeutic and cognitive effects. The “entourage effect” refers to the synergistic effects of the multiple compounds present in whole organisms, which may potentiate clinical efficacy while attenuating side effects. In opposition to this view, mainstream pharmacology is adamant about the need to use purified substances, presumably more specific and safe. In this chapter, I will review the evidence on both sides to discuss the scientific, economic, and political implications of this controversy. The evidence indicates that it is time to embrace the therapeutic complexity of psychedelics.2019-07-3