Differential effects of secukinumab vs. ustekinumab for treatment of psoriasis on quality of life, work productivity and activity impairment: a structural equation modelling analysis.

BACKGROUND: The appearance and lifelong, chronic nature of psoriasis result in considerable burden to patients, such as sleep impairment, depressive symptoms, negative self-esteem and reduced work productivity. OBJECTIVES: To examine direct and indirect (mediated) effects of secukinumab vs. ustekinumab on quality of life, work productivity and activity impairment based on psoriasis severity and symptoms. METHODS: Analyses were based on data from the CLEAR study. Structural equation modelling examined the effects of secukinumab vs. ustekinumab on the Dermatology Life Quality Index (DLQI) and on the Work Productivity and Activity Impairment (WPAI) questionnaire using Psoriasis Area and Severity Index (PASI) severity and symptoms (pain, itching and scaling) as potential mediators. Analyses were conducted primarily for patients achieving a PASI 90 response (90% or greater reduction in PASI from baseline) at week 16 (repeated at week 52) and for PASI 50, 75 and 100. RESULTS: Results at weeks 16 and 52 showed that the effect of treatment on change in DLQI score was mediated by the PASI 90 response and by improvements in itching, pain, and scaling. Achieving any PASI response as early as week 16 directly resulted in significantly better WPAI scores. At week 52, both PASI response and improvement in scaling directly resulted in significantly better WPAI scores. Pain, itching and scaling were correlated (r = 0·51-0·68); improvement in any of these had a significant effect (directly or indirectly) on WPAI. All results favoured secukinumab over ustekinumab. CONCLUSIONS: The results underscore the important role of both PASI response and reduction in symptoms on improvements in health-related quality of life and work and daily activity in favour of secukinumab vs. ustekinumab.

A (Latent) Class of Their Own: Response Patterns in Trading Off Quantity and Quality of Life in Time Trade-Off Exercises.

BACKGROUND: Conflicting results regarding associations of time trade-off (TTO) valuations with respondent characteristics have been reported, mostly on the basis of regression analyses. Alternative approaches, such as the latent class analysis (LCA), may add to the further understanding of variations in TTO responses. OBJECTIVES: To identify whether subgroups of respondents can be identified on the basis of their responses to TTO exercises and to investigate which respondent characteristics are associated with membership of the identified subgroups. METHODS: Members of the Dutch general public, aged 18 to 65 years, completed a Web-based questionnaire concerning sociodemographic characteristics, three TTO exercises valuing health states described using the domains of the EuroQol five-dimensional questionnaire, and preference for quality versus quantity of life. LCA was used to identify patterns in the responses. Predictive variables were included in the final LCA model to identify the particular respondent characteristics that predict subgroup membership. RESULTS: The sample consisted of 1067 respondents. Four latent classes were identified in the responses to TTO exercises. Two were high traders, focusing on quality of life and trading off a relatively high number of years. The other two were low traders, focusing on length of life. Predictive analyses revealed significant differences between subgroups in terms of age, sex, subjective life expectancy, and preference for quantity over quality of life. CONCLUSIONS: We showed that distinct classes of respondents can be discerned in TTO responses from the general public, distinguishing subgroups of low and high traders. More research in this area should confirm our findings and investigate their implications for health state valuation exercises.

Analysis of disease activity categories in chronic spontaneous/idiopathic urticaria.

BACKGROUND: Measurement of disease activity guides treatment of chronic spontaneous urticaria (CSU). A weekly Urticaria Activity Score - here, the average of twice-daily patient assessment of itch and hives scores summed over 1 week (UAS7TD ) - measures severity from 0 to 42. Insufficient evidence exists on whether disease activity states, defined by categorical UAS7TD scores, correlate with other patient-reported outcomes and treatment response. OBJECTIVES: To evaluate and compare categorical UAS7TD scores with selected measures of disease-related quality of life and impact. METHODS: Data from three randomized clinical trials of omalizumab in CSU were pooled. Continuous UAS7TD scores were categorized into five disease activity states: urticaria-free, well-controlled, mild, moderate and severe urticaria. Total scores from the Dermatology Life Quality Index; the Chronic Urticaria Quality of Life questionnaire; and questions on sleep and daily activity interference, presence of angioedema and diphenhydramine use were compared within categorized UAS7TD disease-state scores, using anova for analysis at different time points and mixed-effects regressions for analysis of all data pooled. RESULTS: Pooled analyses showed that categorical UAS7TD disease states accurately predicted differences among treated patients with CSU with different levels of disease activity. A consistent pattern existed between categories, with higher-activity disease states associated with significantly higher impact and an increase in angioedema frequency. Results at different treatment time points were consistent. CONCLUSIONS: Categorical UAS7TD disease states can discriminate between measures when considering the impact of urticaria activity. Using five categorical disease states could simplify clinical assessment and monitoring of treatment efficacy.

Self-report quality of life as a predictor of hospitalization for patients with LV dysfunction: a life course approach.

For this secondary data analysis of a large clinical drug study, researchers investigated the independent prognostic utility of self-report quality-of-life measures versus clinical measures for assessing patient risk for heart-failure-related hospitalization. The experience of heart failure varies over the life course; hence, four age groups were investigated. Quality-of-life measures, specifically health-related quality-of-life and psychosocial quality-of-life measures, were found to be independent and significant predictors of heart-failure-related hospitalizations, as compared to traditional clinical indicators. In addition, the psychosocial quality-of-life measure varied by age group in its importance as a predictor of hospitalization, suggesting differential relevance over the life course. Specifically, psychosocial quality of life was most strongly predictive of hospitalization for those ages 21-44, was less predictive for those ages 45-54, and was nonsignificant for those 55-64 years of age and those 65 and over. Including self-report quality-of-life measures provides a more complete picture of the factors associated with risk of hospitalization at different points in the life course for individuals with heart failure. These findings suggest that researchers and practitioners could use self-report quality-of-life measures as additional prognostic indicators of a patient's condition and risk for heart-failure-related hospitalization, especially for younger patients.

Social support and caregiver distress: a replication analysis.

OBJECTIVES: Prior studies have conceptualized and operationalized social support in different ways, making it difficult to determine if the inconsistencies in findings are due to differences in study design, samples, conceptualization, or measurement. The present study examined the replicability of models of social support and caregiver distress across 4 community-based caregiving studies representative of many conducted in the past 10 years. The goal was to identify areas of consistency in findings across the data sets. METHODS: The authors analyzed 3 models specifying patterns of relationship between social support and depression (main effect, mediation effect, and moderation effect) separately within data sets using hierarchical ordinary least squares regression. Results were compared across data sets. RESULTS: The replication analysis confirmed the robustness of behavior problems and caregiver health as important contributors to caregiver distress. Results of hypotheses examining the pattern of relationship between social support and distress were inconsistent, however. Only 1 type of social support was associated with distress in the expected direction: Less emotional support was associated with higher levels of distress in 2 of the 4 data sets. DISCUSSION: More complex theoretical models that incorporate common measures to represent the linkages between types of stressor, types of support, and their interactions are needed to foster replicability and generalizability of research results.

Retinoid-dependent gene expression regulates early morphological events in the development of the murine retina.

Endogenous retinoids have been implicated in the axial patterning of the embryonic vertebrate retina; however, no studies have directly examined how asymmetric retinoid-dependent gene expression regulates early morphological events in the development of the retina. Here we used a line of indicator mice that possess a retinoid-dependent transgene to examine the relationship between retinoic acid (RA)-dependent gene expression and events occurring during early eye morphogenesis, such as the closure of the optic disc. We found that retinoid-regulated gene expression shifts along the dorsal/ventral axis of the embryonic retina; at embryonic day (E) E11.5 transgene expression is restricted to the neuroepithelium in dorsal retina, and by E14.5 only immature cells located in ventral retina and the dorsal retinal margins demonstrate transgene activation. By manipulating RA levels, we were not only able to systemically alter RA-dependent gene expression along the dorsal/ventral axis, but also to affect retinal morphology. In particular, reducing RA availability resulted in the abnormal closure of the optic fissure. These results indicate that asymmetric levels of RA regulate early RA-dependent gene expression in the eye and demonstrate that the normal pattern of retinoid-dependent gene transcription along the dorsal/ventral axis is critical for the proper development of the vertebrate retina.

Becoming a patient with heart failure.

OBJECTIVE: The purpose of this study was to gain a better understanding of the process of becoming a patient with heart failure, a process of identity formation. Are there clues in the patients' stories about heart failure that might give us a better idea of how patients adjust to heart failure and what heart failure means to them? Meanings that individuals attach to events or situations are central to development of identity and subsequent behaviors. DESIGN AND SETTING: Qualitative methods involving detailed interviews and grounded theory method were used in an outpatient cardiology department of a large health care facility in northeast Ohio. PATIENTS: Twenty-one patients with a diagnosis of heart failure were conveniently selected and interviewed for this research. Patients were selected on the basis of having a left ventricular ejection fraction of 35% or less and New York Heart Association class II, III, or IV. Other possible selection criteria (eg, VO(2Max ), walk test, or dyspnea) were not available for all patients and thus did not constitute consistent selection criteria. A broad net was cast for patients with varying characteristics to see if common processes and experiences existed regardless of the differences in clinical indicators. METHODS: Patients were interviewed in the examining room as part of a regularly scheduled visit with their cardiologists. All interviews were tape recorded and fully transcribed. Field notes and relevant patient chart data (eg, age, sex, race, marital status, cause of heart failure, comorbidities, history of hospitalization, New York Heart Association functional class, left ventricular ejection fraction) were included in the transcribed interviews. The transcribed interview was read and responses were given initial conceptual codes. These coded passages were categorized according to more abstract categories or concepts and underlying processes that encompass them. This process continues until all relevant passages have been categorized and subsumed under higher-order (more abstract or general) categories. RESULTS: The process of becoming a patient with heart failure involves a gradual process of taking on a new identity. Five distinct phases of this process of identity formation emerged from the data: a crisis event, the diagnosis, the patient's and family's response to the diagnosis, their acceptance and adjustment to life with this condition, and making the decision to get on with life. CONCLUSIONS: Most research on heart failure has focused on patients or their families farther along in the trajectory of this condition. We know little about the psychosocial experience of the early phases of this condition. Becoming a patient with heart failure is a process of searching for a meaning to this condition (what is it? what does it mean for the future?) and a process of taking on a new identity and appropriate role behaviors. This process takes place over a period of time. This suggests that the formation of individual identities evolve as new information becomes available, as meanings are attached to the new circumstances, and as a process of negotiating new roles among family members (and among patient, family members, and clinicians) takes place. The findings of this study suggest possible interventions that may positively affect the patient's condition and the quality of family life.

Outcomes of antiemetic therapy after the administration of high-dose antineoplastic agents.

Patterns of antiemetic therapy and its outcomes in patients undergoing high-dose antineoplastic therapy were studied. The study, conducted at a cancer center, included both a retrospective evaluation of patients undergoing highly emetogenic high-dose chemotherapy with peripheral blood stem-cell rescue between November 1994 and December 1995 and a concurrent evaluation of patients treated between January and May 1996. During the study period the recommended antiemetic regimen for highly emetogenic chemotherapy was a single dose of granisetron 1 mg i.v. daily 30 minutes before treatment on days of chemotherapy. Severity of nausea and vomiting during both the acute phase (from day 1 of chemotherapy to 24 hours after its completion) and delayed phase (from 24 hours to five days after the end of chemotherapy) was graded according to the Common Toxicity Criteria Grading Scale. A total of 59 patients were evaluable; 41 were reviewed retrospectively, and 18 were reviewed concurrently. On day 1 of the acute phase, 53 patients (90%) had no vomiting and 51 patients (86%) had no nausea. The frequency and severity of nausea and vomiting increased on successive acute-phase days, and it was necessary to add other antiemetics. Nausea and vomiting continued to be significant problems throughout the delayed phase; 32 (54%) of the patients had a maximum of grade 3 nausea, and 29 patients (49%) had a maximum of grade 2 vomiting. Substantial numbers of patients who received selective serotonin type 3 receptor antagonists before high-dose antineoplastic agents had significant nausea and vomiting that required the addition of other antiemetics.

Localization of protein kinase C to UV-sensitive photoreceptors in the mouse retina.

The present study has identified a population of cone photoreceptors in the murine retina that are uniquely immunoreactive for protein kinase C (PKC). Wavelength-sensitive cone subtypes are segregated along the dorso-ventral axis in the mouse retina with ventral retina occupied exclusively by ultraviolet wavelength-sensitive (UVWS) cones, and dorsal retina dominated by middle wavelength-sensitive cones. PKC-positive cones are found primarily in the ventral retina, and double-label immunocytochemistry using a short wavelength-sensitive opsin antibody confirms that they specifically correspond to the UVWS cone subtype. The PKC antibody, as documented in other mammals, also identifies rod bipolar cells in the mouse retina. UVWS cones and bipolar cells have previously been shown to share transcriptional regulatory elements, as observed in transgenic mice encoding a portion of the human SWS-opsin promoter controlling the lacZ reporter gene. In such mice, the transgene product, beta-galactosidase, is expressed in populations of both cones and bipolar cells. The present study confirms that lacZ-expressing photoreceptors are indeed PKC-positive photoreceptors, but that the lacZ-expressing bipolar cells are not the PKC-positive rod bipolar cells. These cells must correspond to a type of cone bipolar cell.

Caregiver burden and generic well-being: opposite sides of the same coin?

Caregiver burden is one of the most commonly used variables in caregiving research, both as a predictor and as an outcome. It has been suggested that caregiver burden can be measured in terms of discrete dimensions of well-being and that burden and well-being represent opposite sides of the same coin. The goal of this study was to explore this issue further by comparing commonly used dimensions of burden with parallel dimensions of well-being, both as outcome variables and as predictors of other outcomes, in a sample of caregivers. The findings suggest that burden may tap a unique domain of caregiving outcomes that is not represented by more objective indicators of these effects. Dismissing burden as an unnecessary or redundant construct seems premature.

Never-married elderly. A reassessment with implications for long-term care policy.

Researchers are beginning to look more closely at the lives of never-married elderly. As yet, there is no clear consensus regarding the lives and social support networks of the never-married elderly. In particular, are never-married elderly at greater risk for institutionalization than other marital groups? Findings from past research are mixed. Part of the difficulty lies in grouping never-married elderly with other unmarried elderly, or focusing on the presence or absence of a spouse. This article reexamines the life situation of never-married elderly in terms of health, social interaction, and household and family structure. The never married are compared with married, widowed, and divorced/separated elderly persons on these three dimensions. The findings suggest that never-married elderly are socially active, are not socially isolated, and may not be at high risk for institutionalization compared to other marital groups.

Constitutive production of interleukin 2 activity by a T cell hybridoma.

Several laboratories have recently confirmed the importance that interleukin 2 (IL-2, formerly referred to as T cell growth factor) plays not only in the maintenance of cultured functional T cell lines but also as a potent regulator of immune responses. Despite the development of preparative IL-2 purification procedures, as well as identification of IL-2 producer tumor cell lines, simple sources of lectin-free IL-2 containing conditioned medium remain undefined. In hopes of establishing such a source of mitogen-free IL-2, we elected to fuse the high titer IL-2 producer tumor cell line, LBRM-33, with a drugmarked T cell lymphoma. In this communication we report the successful isolation of a T cell hybridoma that constitutively synthesizes and secretes biologically active IL-2. Hybridoma conditioned medium contained approximately 10 to 100 times the amount of IL-2 produced by conventional T cell mitogen-stimulated murine splenocyte preparations. In addition to providing a simple means for producing IL-2 containing conditioned medium without the presence of contaminating lectin, we hope that constitutive IL-2 producer hybrid cell lines will prove interesting as vehicles for dissection of the molecular events involved in IL-2 biosynthesis.