The Fatigue Associated with Depression Questionnaire (FAsD): responsiveness and responder definition

PURPOSE: The Fatigue Associated with Depression Questionnaire (FAsD) was developed to assess fatigue and its impact among patients with depression. The purpose of this study was to examine the questionnaire’s responsiveness to change and identify a responder definition for interpretation of treatment-related changes. METHODS: Data were collected at baseline and at 6 weeks from patients with depression starting treatment with a new antidepressant. RESULTS: Of the 96 participants, 55.2% were women, with a mean age of 43.4 years. The total score and both subscales demonstrated statistically significant change with moderate to large effect sizes (absolute values ≥0.76). FAsD change scores were significantly correlated with change on the Brief Fatigue Inventory (r ≥ 0.73; p < 0.001). FAsD mean change scores discriminated among patient subgroups differing by degree of improvement in patient- and clinician-reported fatigue and depression. Responder definition for the two subscales and total score (0.67, 0.57, 0.62) was estimated primarily based on mean change among patients who reported a small but important improvement in fatigue. DISCUSSION: The FAsD was responsive to change, and the responder definition may be used when interpreting treatment-related change. Results add to previous findings suggesting the FAsD is a useful measure of fatigue among patients with depression

Development and Validation of the Questionnaire for Adaptive Hyperactivity and Goal Achievement (AHGA)

Objective: This paper illustrates the preliminary psychometric properties of the Questionnaire for Adaptive Hyperactivity and Goal Achievement (AHGA), aimed at measuring adaptive characteristics of hyperactivity and goal pursuit in older adults. Methods: The 12-item scale was administered to a sample of 120 subjects (older adults) between February 2022 and June 2022. The reliability of AHGA was measured using Cronbach’s alpha, and factor structure was established using parallel analysis (PA) and principal component analysis (PCA). Convergent validity was tested against the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). Results: All included subjects have an average age of 74.1±5.1 years. AHGA reliability was good (Cronbach’s alpha: 0.713 [95%CI: 0.630 to 0.783]). Factor analysis suggested two main components: goal achievement and hyperactivity, which explained 41% of the variance in the data. The results support the convergent validity of the scale: AHGA measures adaptive characteristics of hyperactivity and goal pursuit, in contrast to BRIAN, which measures pathological characteristics. Conclusion: The reported findings represent an innovative approach to hyperthymic features by embracing a broader spectrum concept that conceptualizes the potential transition between pathological and adaptive aspects as a continuum

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

Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

BACKGROUND: The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) has previously been associated with various types of adenocarcinoma. METHODS: MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA), anti-MIF antibody or MIF anti-sense) on cell growth and cytokine expression were analyzed. RESULTS: Human bladder cancer cells (HT-1376) secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44. CONCLUSIONS: This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma

Global impression of perceived difficulties in children and adolescents with attention-deficit/hyperactivity disorder: Reliability and validity of a new instrument assessing perceived difficulties from a patient, parent and physician perspective over the day

<p>Abstract</p> <p>Background</p> <p>The objective of this analysis was to evaluate the psychometric properties of a brief scale developed to assess the degree of difficulties in children with Attention-Deficit/Hyperactivity Disorder (ADHD). The Global Impression of Perceived Difficulties (GIPD) scale reflects overall impairment, psychosocial functioning and Quality of Life (QoL) as rated by patient, parents and physician at various times of the day.</p> <p>Methods</p> <p>In two open-label studies, ADHD-patients aged 6–17 years were treated with atomoxetine (target-dose 0.5–1.2 mg/kg/day). ADHD-related difficulties were assessed up to week 24 using the GIPD. Data from both studies were combined to validate the scale.</p> <p>Results</p> <p>Overall, 421 patients received atomoxetine. GIPD scores improved over time. All three GIPD-versions (patient, parent, physician) were internally consistent; all items showed at least moderate item-total correlation. The scale showed good test-retest reliability over a two-week period from all three perspectives. Good convergent and discriminant validity was shown.</p> <p>Conclusion</p> <p>GIPD is an internally consistent, reliable and valid measure to assess difficulties in children with ADHD at various times of the day and can be used as indicator for psychosocial impairment and QoL. The scale is sensitive to treatment-related change.</p

Atomoxetine treatment and ADHD-related difficulties as assessed by adolescent patients, their parents and physicians

<p>Abstract</p> <p>Background</p> <p>The degree of ADHD-related difficulties – reflecting overall impairment, social functioning, and quality of life – may be perceived differently by adolescent patients, parents and physicians. The primary aim of this study was to investigate ADHD-related difficulties during atomoxetine treatment, as perceived by the three different raters. Secondary objectives focused on effectiveness and tolerability of atomoxetine treatment in a population of adolescent patients with ADHD.</p> <p>Methods</p> <p>Adolescents with ADHD, aged 12–17 years, received open-label atomoxetine (0.5–1.2 mg/kg/day) up to 24 weeks. ADHD-related difficulties at various times of the day were rated using the Global Impression of Perceived Difficulties (GIPD) instrument. Inter-rater agreement was analyzed using Cohen's Kappa with 95% confidence intervals (95% CI). ADHD-Rating Scale (ADHD-RS) and Clinical Global Impression Severity (GGI-S) scores were assessed by the investigator; and spontaneous adverse events, vital signs and laboratory parameters were collected for tolerability assessments.</p> <p>Results</p> <p>159 patients received atomoxetine. Patients' baseline mean GIPD total ratings were significantly lower than parents' and physicians' scores (12.5 [95%CI 11.6;13.5] vs. 17.2 [16.2;18.2] and 18.8 [17.8;19.8]). For all raters, GIPD scores significantly improved over time. Changes were greatest within the first two weeks. Kappa coefficients varied between 0.186 [0.112;0.259] and 0.662 [0.529;0.795], with strongest agreements between parent and physician assessments, and significant improvements of patient/physician agreements over time (based on 95% CIs). ADHD-RS and CGI-S scores significantly improved over the course of the study (based on 95% CIs). Tolerability results were consistent with earlier reports.</p> <p>Conclusion</p> <p>ADHD-related difficulties were perceived differently by the raters in this open-label trial, but consistently improved during atomoxetine treatment. The GIPD instrument appeared sensitive to treatment-related change. These primarily quantitative findings may guide future studies to more systematically investigate the clinical and practical relevance of the differences observed. Additionally, in order to further validate these results, placebo- and comparator-controlled trials are recommended as well as inclusion of healthy controls and other patient populations.</p> <p>Trial Registration</p> <p><b>Clinical Trial Registry</b>: ClinicalTrials.gov: NCT00191737</p

The normalisation of drug supply: The social<i>supply</i>of drugs as the “other side” of the history of normalisation

Aims: Describes how the relative normalisation of recreational drug use in the UK has been productive of, and fused with, the relatively normalised and non-commercial social supply of recreational drugs. Methods: Semi-structured interviews with 60 social suppliers of recreational drugs in two studies (involving a student population n = 30 and general population sample n = 30). Respondents were recruited via purposive snowball sampling and local advertising. Findings: Both samples provided strong evidence of the normalised supply of recreational drugs in micro-sites of friendship and close social networks. Many social suppliers described “drift” into social supply and normalised use was suggested to be productive of supply relationships that both suppliers and consumers regard as something less than “real” dealing in order to reinforce their preconceptions of themselves as relatively non-deviant. Some evidence for a broader acceptance of social supply is also presented. Conclusions: The fairly recent context of relative normalisation of recreational drug use has coalesced with the social supply of recreational drugs in micro-sites of use and exchange whereby a range of “social” supply acts (sometimes even involving large amounts of drugs/money) have become accepted as something closer to gift-giving or friendship exchange dynamics within social networks rather than dealing proper. To some degree, there is increasing sensitivity to this within the criminal justice system

Epstein-Barr Virus Evades CD4+ T Cell Responses in Lytic Cycle through BZLF1-mediated Downregulation of CD74 and the Cooperation of vBcl-2

Evasion of immune T cell responses is crucial for viruses to establish persistence in the infected host. Immune evasion mechanisms of Epstein-Barr virus (EBV) in the context of MHC-I antigen presentation have been well studied. In contrast, viral interference with MHC-II antigen presentation is less well understood, not only for EBV but also for other persistent viruses. Here we show that the EBV encoded BZLF1 can interfere with recognition by immune CD4+ effector T cells. This impaired T cell recognition occurred in the absence of a reduction in the expression of surface MHC-II, but correlated with a marked downregulation of surface CD74 on the target cells. Furthermore, impaired CD4+ T cell recognition was also observed with target cells where CD74 expression was downregulated by shRNA-mediated inhibition. BZLF1 downregulated surface CD74 via a post-transcriptional mechanism distinct from its previously reported effect on the CIITA promoter. In addition to being a chaperone for MHC-II αβ dimers, CD74 also functions as a surface receptor for macrophage Migration Inhibitory Factor and enhances cell survival through transcriptional upregulation of Bcl-2 family members. The immune-evasion function of BZLF1 therefore comes at a cost of induced toxicity. However, during EBV lytic cycle induced by BZLF1 expression, this toxicity can be overcome by expression of the vBcl-2, BHRF1, at an early stage of lytic infection. We conclude that by inhibiting apoptosis, the vBcl-2 not only maintains cell viability to allow sufficient time for synthesis and accumulation of infectious virus progeny, but also enables BZLF1 to effect its immune evasion function