Response shift, recall bias and their effect on measuring change in health-related quality of life amongst older hospital patients

Background: Assessments of change in subjective patient reported outcomes such as health-related quality of life (HRQoL) are a key component of many clinical and research evaluations. However, conventional longitudinal evaluation of change may not agree with patient perceived change if patients' understanding of the subjective construct under evaluation changes over time (response shift) or if patients' have inaccurate recollection (recall bias). This study examined whether older adults' perception of change is in agreement with conventional longitudinal evaluation of change in their HRQoL over the duration of their hospital stay. It also investigated this level of agreement after adjusting patient perceived change for recall bias that patients may have experienced. Methods: A prospective longitudinal cohort design nested within a larger randomised controlled trial was implemented. 103 hospitalised older adults participated in this investigation at a tertiary hospital facility. The EQ-5D utility and Visual Analogue Scale (VAS) scores were used to evaluate HRQoL. Participants completed EQ-5D reports as soon as they were medically stable (within three days of admission) then again immediately prior to discharge. Three methods of change score calculation were used (conventional change, patient perceived change and patient perceived change adjusted for recall bias). Agreement was primarily investigated using intraclass correlation coefficients (ICC) and limits of agreement. Results: Overall 101 (98%) participants completed both admission and discharge assessments. The mean (SD) age was 73.3 (11.2). The median (IQR) length of stay was 38 (20-60) days. For agreement between conventional longitudinal change and patient perceived change: ICCs were 0.34 and 0.40 for EQ-5D utility and VAS respectively. For agreement between conventional longitudinal change and patient perceived change adjusted for recall bias: ICCs were 0.98 and 0.90 respectively. Discrepancy between conventional longitudinal change and patient perceived change was considered clinically meaningful for 84 (83.2%) of participants, after adjusting for recall bias this reduced to 8 (7.9%). Conclusions: Agreement between conventional change and patient perceived change was not strong. A large proportion of this disagreement could be attributed to recall bias. To overcome the invalidating effect of response shift (on conventional change) and recall bias (on patient perceived change) a method of adjusting patient perceived change for recall bias has been described.

Reference bias : presentation of extreme health states prior to EQ-VAS improves health-related quality of life scores. A randomised crossover trial.

Background: Clinical practice and clinical research has made a concerted effort to move beyond the use of clinical indicators alone and embrace patient focused care through the use of patient reported outcomes such as healthrelated quality of life. However, unless patients give consistent consideration to the health states that give meaning to measurement scales used to evaluate these constructs, longitudinal comparison of these measures may be invalid. This study aimed to investigate whether patients give consideration to a standard health state rating scale (EQ-VAS) and whether consideration of good and poor health state descriptors immediately changes their selfreport. Methods: A randomised crossover trial was implemented amongst hospitalised older adults (n = 151). Patients were asked to consider descriptions of extremely good (Description-A) and poor (Description-B) health states. The EQ-VAS was administered as a self-report at baseline, after the first descriptors (A or B), then again after the remaining descriptors (B or A respectively). At baseline patients were also asked if they had considered either EQVAS anchors. Results: Overall 106/151 (70%) participants changed their self-evaluation by ≥5 points on the 100 point VAS, with a mean (SD) change of +4.5 (12) points (p < 0.001). A total of 74/151 (49%) participants did not consider the best health VAS anchor, of the 77 who did 59 (77%) thought the good health descriptors were more extreme (better) then they had previously considered. Similarly 85/151 (66%) participants did not consider the worst health anchor of the 66 who did 63 (95%) thought the poor health descriptors were more extreme (worse) then they had previously considered. Conclusions: Health state self-reports may not be well considered. An immediate significant shift in response can be elicited by exposure to a mere description of an extreme health state despite no actual change in underlying health state occurring. Caution should be exercised in research and clinical settings when interpreting subjective patient reported outcomes that are dependent on brief anchors for meaning. Trial Registration: Australian and New Zealand Clinical Trials Registry (#ACTRN12607000606482) http://www.anzctr. org.au

Evidence of disagreement between patient-perceived change and conventional longitudinal evaluation of change in health-related quality of life among older adults

Objective: To identify agreement levels between conventional longitudinal evaluation of change (post–pre) and patient-perceived change (post–then test) in health-related quality of life. Design: A prospective cohort investigation with two assessment points (baseline and six-month follow-up) was implemented. Setting: Community rehabilitation setting. Subjects: Frail older adults accessing community-based rehabilitation services. Intervention: Nil as part of this investigation. Main measures: Conventional longitudinal change in health-related quality of life was considered the difference between standard EQ-5D assessments completed at baseline and follow-up. To evaluate patient-perceived change a ‘then test’ was also completed at the follow-up assessment. This required participants to report (from their current perspective) how they believe their health-related quality of life was at baseline (using the EQ-5D). Patient-perceived change was considered the difference between ‘then test’ and standard follow-up EQ-5D assessments. Results: The mean (SD) age of participants was 78.8 (7.3). Of the 70 participants 62 (89%) of data sets were complete and included in analysis. Agreement between conventional (post–pre) and patient-perceived (post–then test) change was low to moderate (EQ-5D utility intraclass correlation coefficient (ICC)¼0.41, EQ-5D visual analogue scale (VAS) ICC¼0.21). Neither approach inferred greater change than the other (utility P¼0.925, VAS P¼0.506). Mean (95% confidence interval (CI)) conventional change in EQ-5D utility and VAS were 0.140 (0.045,0.236) and 8.8 (3.3,14.3) respectively, while patient-perceived change was 0.147 (0.055,0.238) and 6.4 (1.7,11.1) respectively. Conclusions: Substantial disagreement exists between conventional longitudinal evaluation of change in health-related quality of life and patient-perceived change in health-related quality of life (as measured using a then test) within individuals.

Differences in the symptom experience of older oncology outpatients

Context The relatively low number of older patients in cancer trials limits knowledge of how older adults experience symptoms associated with cancer and its treatment. Objectives This study evaluated for differences in the symptom experience across four older age groups (60–64, 65–69, 70–74, ≥75 years). Methods Demographic, clinical, and symptom data from 330 patients aged >60 years who participated in one Australian and two U.S. studies were evaluated. The Memorial Symptom Assessment Scale was used to evaluate the occurrence, severity, frequency, and distress of 32 symptoms commonly associated with cancer and its treatment. Results On average, regardless of the age group, patients reported 10 concurrent symptoms. The most prevalent symptoms were physical in nature. Worrying was the most common psychological symptom. For 28 (87.5%) of the 32 Memorial Symptom Assessment Scale symptoms, no age-related differences were found in symptom occurrence rates. For symptom severity ratings, an age-related trend was found for difficulty swallowing. As age increased, severity of difficulty swallowing decreased. For symptom frequency, age-related trends were found for feeling irritable and diarrhea, with both decreasing in frequency as age increased. For symptom distress, age-related trends were found for lack of energy, shortness of breath, feeling bloated, and difficulty swallowing. As age increased, these symptoms received lower average distress ratings. Conclusion Additional research is warranted to examine how age differences in symptom experience are influenced by treatment differences, aging-related changes in biological or psychological processes, or age-related response shift.

Modulation of the Chlamydia trachomatis In vitro transcriptome response by the sex hormones estradiol and progesterone

BACKGROUND:Chlamydia trachomatis is a major cause of sexually transmitted disease in humans. Previous studies in both humans and animal models of chlamydial genital tract infection have suggested that the hormonal status of the genital tract epithelium at the time of exposure can influence the outcome of the chlamydial infection. We performed a whole genome transcriptional profiling study of C. trachomatis infection in ECC-1 cells under progesterone or estradiol treatment.RESULTS:Both hormone treatments caused a significant shift in the sub-set of genes expressed (25% of the transcriptome altered by more than 2-fold). Overall, estradiol treatment resulted in the down-regulation of 151 genes, including those associated with lipid and nucleotide metabolism. Of particular interest was the up-regulation in estradiol-supplemented cultures of six genes (omcB, trpB, cydA, cydB, pyk and yggV), which suggest a stress response similar to that reported previously in other models of chlamydial persistence. We also observed morphological changes consistent with a persistence response. By comparison, progesterone supplementation resulted in a general up-regulation of an energy utilising response.CONCLUSION:Our data shows for the first time, that the treatment of chlamydial host cells with key reproductive hormones such as progesterone and estradiol, results in significantly altered chlamydial gene expression profiles. It is likely that these chlamydial expression patterns are survival responses, evolved by the pathogen to enable it to overcome the host's innate immune response. The induction of chlamydial persistence is probably a key component of this survival response.

Shift

Shift was an exhibition held in October 2008, and was the culmination of a 10 month artist in residence held at Metro Arts, Brisbane in 2008. A number of works were produced and exhibited, and were a response to the ambient urban landscape of inner city Brisbane. The research component contributes to the discussion of the form and display of digital animation, and builds upon strategies of presentation developed from series of works completed in 2005-2007 as part of an MA (research) at QUT, Brisbane. For the two week exhibition, one interactive kiosk and several large scale digital prints were produced, and also a site specific digital animation sequence was projected onto urban landscape features next to the gallery.

Demand response for residential appliances via Customer Reward Scheme

This paper proposes a reward based demand response algorithm for residential customers to shave network peaks. Customer survey information is used to calculate various criteria indices reflecting their priority and flexibility. Criteria indices and sensitivity based house ranking is used for appropriate load selection in the feeder for demand response. Customer Rewards (CR) are paid based on load shift and voltage improvement due to load adjustment. The proposed algorithm can be deployed in residential distribution networks using a two-level hierarchical control scheme. Realistic residential load model consisting of non-controllable and controllable appliances is considered in this study. The effectiveness of the proposed demand response scheme on the annual load growth of the feeder is also investigated. Simulation results show that reduced peak demand, improved network voltage performance, and customer satisfaction can be achieved.

Induction of a Th1 immune response and suppression of IgE via immunotherapy with a recombinant hybrid molecule encapsulated in liposome-protamine-DNA nanoparticles in a model of experimental allergy

Liposome-protamine-DNA nanoparticles (LPD) are safe, effective, and non-toxic adjuvants that induce Th1-like immune responses. We hypothesized that encapsulation of allergens into liposomes could be an appropriate option for immunotherapy. The present study evaluated the immunotherapeutic potential of a recombinant hybrid molecule (rHM) encapsulated in LPD nanoparticles in a murine model of Chenopodium album allergy. BALB/c mice were sensitized with the allergen in alum, and the immunotherapy procedure was performed by subcutaneous injections of LPD-rHM, rHM, or empty LPD at weekly intervals. Sensitized mice developed a Th2-biased immune response characterized by strong specific IgG1 and IgE production, IL-4, and the transcription factor GATA3 in spleen cell cultures. Treatment with the LPD-rHM resulted in a reduction in IgE and a marked increase in IgG2a. The LPD-rHM induced allergen-specific responses with relatively high interferon-gamma production, as well as expression of the transcription factor T-bet in stimulated splenocytes. In addition, lymphoproliferative responses were higher in the LPD-rHM-treated mice than in the other groups. Removal of the nanoparticles from the rHM resulted in a decrease in the allergen's immunogenicity. These results indicate that the rHM complexed with LPD nanoparticles has a marked suppressive effect on the allergic response and caused a shift toward a Th1 pathway.