Psychometric Validation of the Psoriasis Symptoms and Impacts Measure (P-SIM), a Novel Patient-Reported Outcome Instrument for Patients with Plaque Psoriasis, Using Data from the BE VIVID and BE READY Phase 3 Trials

From Springer Nature via Jisc Publications RouterHistory: received 2021-05-27, registration 2021-06-16, accepted 2021-06-16, pub-electronic 2021-07-14, online 2021-07-14, pub-print 2021-10Publication status: PublishedFunder: UCB PharmaAbstract: Introduction: Plaque psoriasis can significantly impact patients’ quality of life. We assessed psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), developed to capture patients’ experiences of signs, symptoms and impacts of psoriasis. Methods: Pooled, blinded, 16-week data from 1002 patients in the BE VIVID and BE READY bimekizumab phase 3 trials were analysed. The suitability of the P-SIM missing score rule (weekly scores considered missing if ≥ 4 daily scores were missing) was assessed. Test–retest reliability was evaluated using intraclass correlation coefficients (ICCs). Convergent validity was assessed between P-SIM and relevant patient-reported outcome (PRO) (Dermatology Life Quality Index [DLQI], DLQI item 1 [skin symptoms], Patient Global Assessment of Psoriasis) and clinician-reported outcome (ClinRO) scores (Psoriasis Area and Severity Index [PASI], Investigator’s Global Assessment [IGA]) at baseline and week 16. Known-groups validity was assessed, comparing P-SIM scores between patient subgroups predefined using PASI/IGA scores. Sensitivity to change over 16 weeks was evaluated; responder definition (RD) thresholds were explored. Results: The missing score rule used did not impact P-SIM scores. Test–retest reliability analyses demonstrated excellent score reproducibility (ICC 0.91–0.98). Inter-item correlations at baseline and week 16 were strong (> 0.5), apart from “choice of clothing” with “skin pain” and “burning” at baseline (both 0.49). All P-SIM scores were moderately to strongly correlated with other outcomes, demonstrating convergent validity, apart from ClinROs (PASI, IGA) at baseline that had low variability. P-SIM scores discriminated known groups at week 16, confirming known-groups validity. Changes from baseline to week 16 in P-SIM and other clinically relevant outcomes were strongly correlated (> 0.5; weaker with ClinROs), establishing sensitivity to change. Anchor-based RD analyses determined a four-point P-SIM item score decrease as indicative of marked clinically meaningful improvement. Conclusion: P-SIM scores demonstrated good reliability, validity and sensitivity to change. A four-point RD threshold could be used to assess 16-week treatment effects. Trial Registration: BE VIVID: NCT03370133; BE READY: NCT03410992

Validation of the Hidradenitis Suppurativa Investigator Global Assessment

Importance Few simplified instruments exist for use in hidradenitis suppurativa (HS) trials. Objective To assess psychometric properties of the Hidradenitis Suppurativa Investigator Global Assessment (HS-IGA) score using a clinical trial data set. Design, Setting, and Participants This retrospective analysis of a phase 2 randomized double-blind, placebo-controlled, active-reference arm trial (UCB HS0001) included adults with moderate-to-severe HS. Exposures Trial participants were randomized at baseline to receive bimekizumab, adalimumab, or placebo. Main Outcomes and Measures The HS-IGA score at prespecified time points up to 12 weeks after randomization. Results The HS-IGA score showed strong convergent validity with IHS4 and HS-PhGA scores at baseline (Spearman correlation, 0.86 [P < .001] and 0.74 [P < .001], respectively) and at week 12 (Spearman correlation, 0.73 [P < .001] and 0.64 [P < .001], respectively). The HS-IGA scores assessed during predosing visits at screening and baseline showed good test-retest reliability (intraclass correlation coefficient [ICC] = 0.92). At week 12, HS-IGA responders were significantly associated with HiSCR-(50/75/90) responders (χ2 = 18.45; P < .001; χ2 = 18.11; P < .001; and χ2 = 20.83; P < .001, respectively). The HS-IGA score was predictive of HiSCR-50/75/90 and HS-PhGA response at week 12 (AUC, 0.69, 0.73, 0.85, and 0.71, respectively). However, the HS-IGA as a measure of disease activity showed low predictive validity with patient-reported outcomes at week 12. Conclusions and Relevance The HS-IGA score demonstrated good psychometric properties compared with existing measures and may be considered for use as an end point in clinical trials for HS

Radiofrequency and Microwave Ablation Compared to Systemic Chemotherapy and to Partial Hepatectomy in the Treatment of Colorectal Liver Metastases:A Systematic Review and Meta-Analysis

To assess safety and outcome of radiofrequency ablation (RFA) and microwave ablation (MWA) as compared to systemic chemotherapy and partial hepatectomy (PH) in the treatment of colorectal liver metastases (CRLM). MEDLINE, Embase and the Cochrane Library were searched. Randomized trials and comparative observational studies with multivariate analysis and/or matching were included. Guidelines from National Guideline Clearinghouse and Guidelines International Network were assessed using the AGREE II instrument. The search revealed 3530 records; 328 were selected for full-text review; 48 were included: 8 systematic reviews, 2 randomized studies, 26 comparative observational studies, 2 guideline-articles and 10 case series; in addition 13 guidelines were evaluated. Literature to assess the effectiveness of ablation was limited. RFA + systemic chemotherapy was superior to chemotherapy alone. PH was superior to RFA alone but not to RFA + PH or to MWA. Compared to PH, RFA showed fewer complications, MWA did not. Outcomes were subject to residual confounding since ablation was only employed for unresectable disease. The results from the EORTC-CLOCC trial, the comparable survival for ablation + PH versus PH alone, the potential to induce long-term disease control and the low complication rate argue in favour of ablation over chemotherapy alone. Further randomized comparisons of ablation to current-day chemotherapy alone should therefore be considered unethical. Hence, the highest achievable level of evidence for unresectable CRLM seems reached. The apparent selection bias from previous studies and the superior safety profile mandate the setup of randomized controlled trials comparing ablation to surgery

Effects of &beta;-Hydroxy &beta;-Methylbutyrate Supplementation on Working Memory and Hippocampal Long-Term Potentiation in Rodents

&beta;-hydroxy &beta;-methylbutyrate (HMB), a metabolite of the essential amino acid leucine, has been shown to preserve muscle mass and strength during aging. The signaling mechanism by which HMB elicits its favorable effects on protein metabolism in skeletal muscle is also preserved in the brain. However, there are only a few studies, all at relatively high doses, addressing the effect of HMB supplementation on cognition. This study evaluated the effects of different doses of HMB on the potentiation of hippocampal synapses following the experimental induction of long-term potentiation (LTP) in the hippocampus of behaving rats, as well as on working memory test (delayed matching-to-position, DMTP) in mice. HMB doses in rats were 225 (low), 450 (medium), and 900 (high) mg/kg body weight/day and were double in mice. Rats who received medium or high HMB doses improved LTP, suggesting that HMB administration enhances mechanisms related to neuronal plasticity. In the DMTP test, mice that received any of the tested doses of HMB performed better than the control group in the overall test with particularities depending on the dose and the task phase

Living with disabling chronic pain: results from a face-to-face cross-sectional population-based study.

To estimate the prevalence of disabling chronic pain (DCP) in Spanish adults, to analyse its characteristics, to determine its multimorbidity and to identify its associated factors. 2011 Andalusian Health Survey, a cross-sectional population survey based on face-to-face home interviews. 6507 people aged 16 years or older and living in Andalusia, Spain. The response variable was disabling chronic pain. Multivariate multinomial logistic regression models were used to analyse the association of factors with disabling chronic pain. The sample design was considered throughout the statistical analysis. The prevalence of disabling chronic pain in the Spanish adult population was 11.36% (95% CI 11.23 to 11.49), while that of non-disabling chronic pain was 5.67% (95% CI 5.57 to 5.77). Disabling chronic pain was associated with high multimorbidity (especially in women (51%) and in the elderly (70%) with three or more additional chronic diseases), as well as with disadvantaged social status (such as female gender (OR=2.12), advanced age (OR10-year increase=1.28), unemployment (OR=1.33), manual work (OR=1.26), low income (OR=1.14) and reduced emotional social support (OR=1.04)). Other influential factors were tobacco consumption (OR=1.42), sleeping ≤7 hours (OR=1.2)], environmental or work conditions (OR=1.16) and quality of life (ORmental=1.21, ORphysical=2.37). The population with disabling chronic pain was associated with multimorbidity, vulnerable social status and an impaired quality of life. In contrast, the population with non-disabling chronic pain showed almost no differences when compared with the population without chronic pain. The association between DCP and mental disorders highlights the need for psychosocial services in the management of chronic pain

Maternal Diabetes and Cognitive Performance in the Offspring: A Systematic Review and Meta-Analysis.

Diabetes during gestation is one of the most common pregnancy complications associated with adverse health effects for the mother and the child. Maternal diabetes has been proposed to negatively affect the cognitive abilities of the child, but experimental research assessing its impact is conflicting. The main aim of our study was to compare the cognitive function in children of diabetic and healthy pregnant women.A systematic review and meta-analysis was conducted through a literature search using different electronic databases from the index date to January 31, 2015. We included studies that assessed the cognitive abilities in children (up to 14 years) of diabetic and non-diabetic mothers using standardized and validated neuropsychological tests.Of 7,698 references reviewed, 12 studies involving 6,140 infants met our inclusion criteria and contributed to meta-analysis. A random effect model was used to compute the standardized mean differences and 95% confidence interval (CI) were calculated. Infants (1-2 years) of diabetic mothers had significantly lower scores of mental and psychomotor development compared to control infants. The effect size for mental development was -0.41 (95% CI -0.59, -0.24; p<0.0001) and for psychomotor development was -0.31 (95% CI -0.55, -0.07; p = 0.0125) with non-significant heterogeneity. Diabetes during pregnancy could be associated with decreased intelligence quotient scores in school-age children, although studies showed significant heterogeneity.The association between maternal diabetes and deleterious effects on mental/psychomotor development and overall intellectual function in the offspring must be taken with caution. Results are based on observational cohorts and a direct causal influence of intrauterine hyperglycemia remains uncertain. Therefore, more trials that include larger populations are warranted to elucidate whether gestational diabetes mellitus (GDM) has a negative impact on offspring central nervous system (CNS)

Study flowchart showing the number of studies identified, screened, assessed for eligibility and included in the qualitative and quantitative analysis [17].

<p>*Further information regarding the excluded studies can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142583#pone.0142583.s010" target="_blank">S2 Text</a>.</p