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The pathogen inactivation process developed by Cerus and Baxter Healthcare Corporations uses the psoralen, S-59 (amotosalen) in an ex vivo photochemical treatment (PCT) process to inactivate viruses, bacteria, protozoans, and leukocytes in platelet concentrates and plasma. Studies were performed by intravenous infusion of S-59 PCT formulations±compound adsorption device (CAD) treatment and with non-UVA illuminated S-59, using doses that were multiples of potential clinical exposures. The studies comprised full pharmacokinetic, single- and repeated-dose (up to 13 weeks duration) toxicity, safety pharmacology (CNS, renal, and cardiovascular), reproductive toxicity, genotoxicity, carcinogenicity testing in the p53[sup ±] mouse, vein irritation, and phototoxicity. No specific target organ toxicity (clinical or histopathological), reproductive toxicity, or carcinogenicity was observed. S-59 and/or PCT formulations demonstrated CNS, ECG, and phototoxicity only at supraclinical doses. Based on the extremely large safety margins (>30,000-fold expected clinical exposures), the CNS and ECG observations are not considered to have any toxicological relevance. Additionally, after a complete assessment, mutagenicity and phototoxicity results are not considered relevant for the proposed use of INTERCEPT platelets. Thus, the results of an extensive series of and in vivo studies have not demonstrated any toxicologically relevant effects of platelet concentrates prepared by the INTERCEPT system. Human & Experimental Toxicology (2001) 20, 533–550. [ABSTRACT FROM AUTHOR]

Background: The photochemical treatment of platelets employs Helinx™ technology, which uses the psoralen S-59 and UVA light in an ex vivo photochemical treatment (PCT) to inactivate viruses, bacteria, and leukocytes in platelet concentrates while retaining therapeutic function. After UVA and before transfusion, residual S-59 and free S-59 photoproduct levels are lowered by an S-59 compound adsorption device (CAD). A comprehensive preclinical safety program, including carcinogenicity, was conducted based on the broad strategy normally applied to a new pharmaceutical. Methods: Studies were performed by intravenous infusion of S-59 PCT formulations +/-CAD treatment and with unilluminated S-59, with doses that were multiples of potential clinical exposures. The studies completed were single dose and multiple dose (up to 13 weeks duration) toxicity, safety pharmacology (CNS, renal, and cardiovascular), reproductive toxicity, genotoxicity, p53 carcinogenicity, vein irritation, phototoxicity, and toxicokinetics (multiple dose pharmacokinetics). Results: No specific target organ toxicity (clinical or histologic pathology), reproductive toxicity, or carcinogenicity was observed. S-59 and/or PCT formulations demonstrated CNS, electrocardiographic (ECG), and phototoxicity at non-clinical doses. Based on the extremely large safety margins (>30,000-fold expected clinical exposures), the CNS and ECG observations are not considered to be of toxicological relevance. Additionally, after a complete assessment, the results of mutagenicity and phototoxicity studies are not considered to be relevant for the proposed use of the photochemically-treated platelets. Conclusion: The results of an extensive series of studies have thus demonstrated no toxicologically relevant effects of platelets treated with Helinx™ technology. The results of the toxicokinetic analyses from 3-month rat and dog studies with S-59 PCT formulations +/CAD treatment were compared with clinical data. These data indicate that the test articles used in the key toxicology studies provided large multiples of the clinical exposure to S-59, whether the comparison was based on dose, C[sub max], or AUC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate psychometric performance of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) total and individual item scores in patients with psoriatic arthritis (PsA) and to estimate score change thresholds and scores corresponding to different levels of symptom/impact severity., Methods: Data up to week 16 from 1252 patients with active PsA enrolled in two randomised controlled trials of bimekizumab (BE OPTIMAL (NCT03895203) and BE COMPLETE (NCT03896581)) were used to assess construct validity (correlations with other patient-reported outcomes), known-groups validity (based on Minimal Disease Activity index, Disease Activity Index for Psoriatic Arthritis and Psoriatic Arthritis Disease Activity Score), reliability (Cronbach's alpha and intraclass correlation coefficients (ICCs)) and responsiveness (sensitivity to change). Clinically meaningful within-patient improvement thresholds were estimated by anchor-based and distribution-based analyses, and symptom/impact severity thresholds were estimated by receiver operating characteristic curve analyses., Results: The mean (SD) PsAID-12 total score at baseline was 4.19 (1.94). PsAID-12 scores demonstrated good convergent validity and good known-groups validity. Internal consistency reliability (Cronbach's alpha 0.95) and test-retest reliability (ICC ≥ 0.70) were also good. Responsiveness was acceptable (correlations ≥0.30 for most scores). Improvement thresholds were estimated at 1.5-2 points for the PsAID-12 total score and 2 or 3 points for item scores. Thresholds for different levels of symptom/impact severity could be derived for most PsAID-12 items., Conclusions: The PsAID-12 demonstrated robust psychometric properties in a large sample of patients with active PsA, supporting its use as a fit-for-purpose patient-reported outcome in this population. Furthermore, thresholds for score interpretation were derived., Competing Interests: Competing interests: LG: Grants from AbbVie, Biogen, Eli Lilly, Novartis, Sandoz and UCB Pharma; consulting fees from AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Sandoz and UCB Pharma. A-MO: Research grants to Johns Hopkins University from AbbVie, Amgen and Janssen; consulting fees from BMS, Janssen, Sanofi and UCB Pharma. LCC: Grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma; consultant for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake Pharma, Novartis, Pfizer, and UCB Pharma; speaking fees from AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, medac, Novartis, Pfizer, and UCB Pharma. DG: Consultant and/or received grant support from Abbvie, Amgen, BMS, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB Pharma. AO: Grant/research support from AbbVie, Amgen, Janssen, Novartis and Pfizer, consultant of AbbVie, Amgen, BMS, Celgene, CorEvitas, Eli Lilly, GSK, Gilead, Janssen, Novartis, Pfizer, Takeda and UCB Pharma. CGP: Employed by Evidera, a part of Thermo Fisher Scientific, which received funding for this research from UCB Pharma. VC, VT and JL: Employees and stockholders of UCB Pharma. BI: Employee of UCB Pharma; shareholder of AbbVie, GlaxoSmithKline and UCB Pharma. MdW: Over the last five years Stichting Tools has received fees for lectures or consultancy provided by MdW from Celgene, Eli Lilly, Janssen-Cilag, Pfizer and UCB Pharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Hidradenitis suppurativa (HS) has a profound negative impact on patients' health-related quality of life (HRQoL). Here we summarize the evidence on HRQoL and Patient Reported Outcomes (PROs) in patients with HS in real-world settings by conducting a systematic literature review (SLR) of observational studies., Methods: Data sources included MEDLINE, Embase & PsycINFO between January 1, 2010 and August 29, 2021, and conference proceedings between 2019 and 2021. Identified abstracts were reviewed and screened independently by two reviewers. Eligibility criteria included patients with HS of any severity, sample size ≥ 100, reporting PROs including HRQoL measures. Included studies were critically appraised., Results: Fifty-eight observational studies matched inclusion criteria. Dermatology Life Quality Index (DLQI) was the most commonly utilized instrument: 57% of included studies reported mean baseline DLQI scores, ranging between 8.4 and 16.9, indicating a very large impact on the patients' HRQoL. Higher scores were reported with increasing disease severity and among female patients. Pain was assessed mostly by an 11-point (0-10) numeric rating scale (NRS) with a mean baseline score ranging from 3.6 to 7.7 indicating moderate to high pain levels. There was a negative impact of HS on patients' psychological well-being, based on PRO scores related to depression and anxiety. A high proportion of sexual dysfunction was reported, with a larger impact on women than men. Work productivity and leisure activity were consistently found to be impaired in patients with HS., Conclusions: All included studies reported a negative impact of HS on patients' lives. A diverse set of disease- and non-disease-specific PRO instruments were utilized highlighting the need for more consistent use of HS-specific validated PRO instruments to assess the impact of HS on the different aspects of patients' HRQoL to allow for data to be more meaningfully interpreted and compared in real-world settings. Patients with HS need better disease management approaches that address the observed low quality of life., (© 2024. The Author(s).)

Background: Hidradenitis suppurativa (HS), a chronic skin condition that causes pain and physical dysfunction, can impact significantly on quality of life. Disease-specific tools have been designed to assess the impact of HS on patients, including the HS Symptom Daily Diary (HSSDD), the HS Symptom Questionnaire (HSSQ), and the HS Quality of Life (HiSQOL©) questionnaire, which have been developed into electronic instruments (eHSSDD, eHSSQ, and eHiSQOL©)., Objectives: The objective of this study was to establish the content validity of the electronic version of the HSSDD and HSSQ, and the acceptability and usability of the HSSDD, HSSQ, and HiSQOL©, using concept elicitation and cognitive debriefing interviews., Methods: This was a non-interventional qualitative video interview study involving participants aged ≥18 years with moderate to severe HS recruited from a single clinical site in the USA. Interviews gathered feedback on participants' symptom experience, followed by training and completion of the eHSSDD, eHSSQ, and eHiSQOL© questionnaires on electronic handheld devices. Participants were then interviewed on the content of the eHSSDD and eHSSQ and the acceptability and usability of all three instruments. Interviews were transcribed and qualitatively analysed., Results: Twenty participants with moderate to severe HS (median age: 41.5 [range: 20.0-64.0]; n = 16/20 female) were included. All participants found the eHSSDD, eHSSQ, and eHiSQOL© instructions clear and described the instruments as "easy", "simple" and "self-explanatory". Overall understanding of individual items within the eHSSDD and eHSSQ was high; however, 6/20 participants had difficulty in understanding the average skin pain item in the eHSSDD. All participants were able to accurately recall their symptoms within the recall periods of the eHSSDD and eHSSQ, although 4/20 participants found the 24-h recall period of the eHSSDD limiting. Completion time was quick across all instruments, and usability was high, with the majority of participants reporting no difficulty in completing questionnaires on electronic devices., Conclusion: The concepts covered in the eHSSDD and eHSSQ are relevant and important to patients, supporting their content validity. The findings also provide evidence of acceptability and usability of the eHSSDD, eHSSQ, and eHiSQOL©. A limitation was that all participants were recruited from a single site, which may have introduced selection bias and thus limited the generalisability of results., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

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.

Background: Given the chronic nature of psoriasis and the loss of response that can be observed with therapies over time, it is important to understand the long-term efficacy of new treatments., Objectives: To evaluate maintenance of Week 16 responses with bimekizumab (BKZ) treatment through Year 3, in patients with moderate-to-severe plaque psoriasis., Methods: Data were pooled from BKZ-treated patients in the 52-week (BE VIVID) and 56-week (BE READY and BE SURE) phase III studies, and their ongoing open-label extension (OLE), BE BRIGHT. Efficacy outcomes are reported through 3 years of BKZ treatment in patients with an efficacy response at Week 16. Missing data were imputed primarily using modified nonresponder imputation (mNRI), with nonresponder imputation and observed case data also reported., Results: A total of 989 patients were randomized to BKZ at baseline in BE VIVID, BE READY and BE SURE. At Week 16, 693 patients achieved ≥ 90% reduction from baseline in Psoriasis Area and Severity Index (PASI 90), 503 achieved 100% reduction from baseline in PASI (PASI 100), 694 achieved absolute PASI ≤ 2 and 597 achieved body surface area (BSA) ≤ 1%, and continued into the OLE. Of these, 93.0% maintained PASI 90, 80.8% maintained PASI 100, 94.0% maintained PASI ≤ 2 and 90.3% maintained BSA ≤ 1% responses through to 3 years of BKZ treatment (mNRI). Among Week 16 PASI 90 responders, 96.8% and 72.5% also achieved Investigator's Global Assessment 0/1 and PASI 100 at Week 16, respectively, and 92.2% and 73.4% achieved these responses at Year 3 (mNRI). Among Week 16 PASI 100 responders, 76.3% also achieved Dermatology Life Quality Index (DLQI) 0/1 at Week 16, and DLQI 0/1 response increased with continuous BKZ treatment to 89.0% at Year 3 (mNRI)., Conclusions: High levels of clinical response were maintained through to 3 years of BKZ treatment in the vast majority of Week 16 responders. Long-term treatment with BKZ was efficacious, with important benefits for health-related quality of life, in patients with moderate-to-severe plaque psoriasis., Competing Interests: Conflicts of interest B.S.: Consultant (honoraria) from AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Connect Biopharma, Dermavant, Eli Lilly, EPI Health, Evelo Biosciences, Immunic Therapeutics, Janssen, LEO Pharma, Maruho, Meiji Seika Pharma, Mindera Health, Novartis, Ono, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB Pharma, Union Therapeutics, Ventyxbio and vTv Therapeutics; Stock options in Connect Biopharma and Mindera Health; Speaker for AbbVie, Eli Lilly, Janssen, Regeneron and Sanofi; Scientific Co-Director (consulting fee) from CorEvitas (formerly Corrona) Psoriasis Registry; Investigator for AbbVie, Cara Therapeutics, CorEvitas Psoriasis Registry, Dermavant, Dermira and Novartis; Editor-in-Chief (honorarium) of Journal of Psoriasis and Psoriatic Arthritis. Y.T.: Honoraria and/or grants from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Eli Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical and UCB Pharma. U.M.: Served as advisor and/or clinical study investigator for, and/or received honoraria and/or grants from AbbVie, Almirall, Aristea, Boehringer Ingelheim, Celgene, Dr Reddy’s Laboratories, Eli Lilly, Foamix, Formycon, Forward Pharma, Janssen, LEO Pharma, Medac, Novartis, Phi-Stone, Pierre Fabre, Sanofi and UCB Pharma. M.L.: Employee of Mount Sinai and receives research funds from AbbVie, Amgen, Arcutis, Avotres Therapeutics, Boehringer Ingelheim, Cara Therapeutics, Dermavant, Eli Lilly, Incyte, Janssen, LLC, Ortho Dermatologics, Regeneron and UCB Pharma; Consultant for Aditum Bio, Almirall, AltruBio, AnaptysBio, Arcutis, Aristea, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, CorEvitas (formerly Corrona), Dermavant, Dr Reddy’s Laboratories, Evelo Biosciences, Evommune, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima, LEO Pharma, Meiji Seika Pharma, Mindera Health, Pfizer, Seanergy and Verrica. P.F.: Grant support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Sanofi and Sun Pharma; Investigator for AbbVie, Akaal, Amgen, Arcutis, Argenx, Aslan, AstraZeneca, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Eli Lilly, Evelo Biosciences, Galderma, Genentech, Geneseq, GenesisCare, GSK, Hexima, Janssen, Kymab, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi, Sun Pharma, Teva, UCB Pharma and Valeant; served on advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Mayne Pharma, Merck, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma and Valeant; served as a consultant for Aslan, Bristol Myers Squibb, Eli Lilly, Galderma, GenesisCare, Janssen, LEO Pharma, Mayne Pharma, MedImmune, Novartis, Pfizer, Roche, UCB Pharma and Wintermute; received travel grants from AbbVie, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Roche, Sun Pharma and Sanofi; served as a speaker for or received honoraria from AbbVie, Amgen, Celgene, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Roche, Sanofi, Sun Pharma and Valeant. R.G.L.: Principal Investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer and UCB Pharma; served on scientific advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer and UCB Pharma; provided lectures for AbbVie, Amgen, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis and Pfizer. R.B.W.: Consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi and UCB Pharma; research grants to his institution from AbbVie, Almirall, Janssen, LEO Pharma, Novartis and UCB Pharma; honoraria from Astellas, DiCE, GSK and Union. M.W., V.V., B. Szilagyi.: Employees and shareholders of UCB Pharma. V.C.: Employee of UCB Pharma. C.P.: Consulting fees and/or grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen Cilag, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Sanofi and UCB Pharma., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Aim: The present pilot RCT aimed to investigate the influence of a connective tissue graft (CTG) in combination with the immediate implant placement (IIP) on hard and soft tissue healing, without a bone replacement graft in the gap between the implant and the socket walls., Materials and Methods: Thirty patients requiring extraction of one anterior tooth (from premolar to premolar) were randomly assigned to one of the two treatment groups (test: IIP + CTG; control: IIP). Cone-beam computed tomography and optically scans were performed before tooth extraction and at 6-month follow-up. Then, DICOM files were superimposed in order to allow the evaluation of osseous ridge and buccal bone changes, while the superimposition of DICOM and Standard Tessellation Language files allowed for evaluating of soft tissue contour. For testing the differences between the two groups, the non-parametric test as Wilcoxon rank-sum test, was used., Results: Twenty-six of the 30 enrolled patients attended the 6-month follow-up visit. The four patients of the control group that were lost to follow-up were analysed under the intention-to-treat principle. No statistically significant differences between the groups were observed for the vertical buccal bone resorption (p = .90), as well as for the horizontal buccal bone resorption at all measured levels. Significant differences were found between the test and control groups in the horizontal dimensional changes of osseous ridge at the most coronal aspect (p = .0003 and p = .02). Changes in tissue contour were between -0.32 and -0.04 mm in the test group and between -1.94 and -1.08 mm in the control group, while changes in soft tissue thickness varied between 1.33 and 2.42 mm in the test group and between -0.16 and 0.88 mm in the control group, with statistically significant differences for both variables at all measured levels. At 6 months, the mean volume increase was 6.76 ± 8.94 mm 3 and 0.16 ± 0.42 mm 3 in the test and control groups, respectively, with a statistically significant difference., Conclusions: The findings of the present study indicate that the adjunct of a CTG at the time of IIP, without bone grafting, does not influence vertical bone resorption. Within the limits of this study, it can be suggested that the adjunct of a CTG at the time of IIP, without bone grafting, reduces the horizontal changes of the alveolar ridge. Moreover, it allows maintenance of the tissue contour due to an increase in soft tissue thickness., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2021. The Author(s).)

Introduction: This analysis assessed the psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), a novel patient-reported outcome (PRO) tool designed to capture patient experiences of the signs, symptoms and impacts of psoriasis., Methods: Blinded data from the BE RADIANT phase 3b trial of bimekizumab were analysed. In BE RADIANT, patients were randomised 1:1 to bimekizumab 320 mg every 4 weeks (Q4W) or secukinumab 300 mg (weekly until Week 4, then Q4W). Three items (itching, skin pain and scaling) of the P-SIM were electronically assessed throughout the trial and were scored from 0 to 10 (none to very severe signs/symptoms/impacts). Test-retest reliability was determined using intraclass correlations. Convergent validity was assessed between P-SIM and other relevant PRO and clinician-reported outcome (ClinRO) scores. Known-groups validity was assessed by comparing mean P-SIM item scores between patient subgroups based on the Psoriasis Area and Severity Index (PASI)/Investigator's Global Assessment (IGA) scores. Responsiveness was assessed via correlations between changes from baseline in P-SIM item scores and other relevant PRO and ClinRO scores. Anchor-based responder analyses and empirical cumulative distribution function (eCDF) curves determined responder thresholds., Results: The three P-SIM items yielded high intraclass coefficients (> 0.70). By Week 48, the three P-SIM items had moderate (> 0.30 and ≤ 0.50) to strong (> 0.50) correlations with other PROs and weaker correlations with ClinROs, demonstrating good convergent validity. For almost all known-group comparisons, statistically significant between-subgroup score differences were seen across all three P-SIM items. Changes from baseline in the P-SIM and other relevant outcomes were above the acceptable threshold of ≤ 0.30, demonstrating sensitivity to change. Anchor-based analyses determined a ≥ four-point reduction from baseline to indicate marked clinically meaningful improvement for the P-SIM., Conclusion: These results support the validity, reliability and sensitivity to change of the P-SIM in assessing key symptoms (itching, skin pain and scaling) in patients with moderate to severe plaque psoriasis., Trial Registration: NCT03536884., (© 2021. The Author(s).)

Introduction: Patients with plaque psoriasis experience a variety of signs and symptoms that can impact daily life, which may not be evaluated by clinician-reported outcomes. This study aimed to develop and assess the content validity of a new patient-reported outcome (PRO) measure to capture patient experiences of the signs, symptoms and impacts of psoriasis and aid integration of the patient perspective in treatment benefit-risk decision-making., Methods: The psoriasis symptoms and impacts measure (P-SIM) was developed based on a literature search and interviews with five clinical experts in psoriasis to identify frequent signs, symptoms and impacts of psoriasis. Hybrid concept elicitation, cognitive debriefing and usability testing interviews were conducted with moderate to severe psoriasis patients to evaluate the content validity and patient understanding of the preliminary P-SIM. The preliminary P-SIM was refined using initial quantitative analyses of phase 2b data from psoriasis patients to inform the removal of any items., Results: A preliminary 19-item P-SIM was developed for administration on a hand-held electronic tablet device using a 0-10 numerical response scale over a 24-h recall period. Patient interviews and testing demonstrated most patients interpreted the items and responses as intended, would not re-word any items, felt the responses matched the items and rated the device as easy to use. After quantitative testing, five items were removed from the preliminary 19-item measure because of conceptual overlap, floor effects and/or skewed distributions to generate the final 14-item P-SIM., Conclusions: The P-SIM questionnaire has good content validity; patients reported it was easy to understand and reflective of their experiences. Following psychometric validation, the P-SIM may be a useful PRO measure for capturing the signs, symptoms and impacts of psoriasis and may support clinician-reported outcomes when assessing treatment benefits in clinical trials.

Aim: To compare soft tissue dimensional changes and relative differences in soft and hard tissue volumes 4 months after single-tooth extraction and three different treatment modalities: spontaneous healing (SH) and alveolar ridge preservation by means of a deproteinized bovine bone mineral and a collagen matrix, with (IMPL/DBBM/CM) or without (DBBM/CM) immediate implant placement., Materials and Methods: STL files from study casts obtained at baseline and after 4 months were matched to calculate buccal soft tissue linear and volumetric changes. DICOM files from CBCTs were superimposed to STL files allowing the evaluation of soft tissue thickness at baseline and 4 months., Results: Mean horizontal reduction accounted for 1.46 ± 0.20 (SH), 0.85 ± 0.38 (DBBM-CM) and 0.84 ± 0.30 IMPL/DBBM-CM, with no statistical differences. Soft tissue thickness had a significant mean increase of 0.95 for SH group, compared to a non-significant mean decrease for DBBM-CM (0.20) and IMPL/DBBM-CM groups (0.07)., Conclusion: A preservation technique with DBBM-CM, with or without immediate implant placement, did not reduce the horizontal linear and volumetric changes at the buccal soft tissue profile significantly at 4 months after tooth extraction when compared to spontaneous healing. This is due to a significant increase in soft tissue thickness in spontaneously healing sites., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Patient-reported outcome (PRO) instruments provide robust and effective means of evaluating patients' treatment experience; however, none adequately cover experience using self-injection devices with enhanced features, such as an electromechanical autoinjector (e-Device). The aim of this study was to develop a PRO instrument that accurately assesses patient experience of using an e-Device and to evaluate its psychometric properties., Methods: A mixed-methods approach was taken; two parallel, targeted literature reviews were conducted to identify relevant concepts and existing self-injection PRO instruments that could be adapted. Patient feedback obtained from two focus groups was used to inform initial instrument development. The pilot instrument was then administered in a multicenter, open-label, phase 3 clinical study in which patients self-injected certolizumab pegol using an e-Device, to gather evidence of its psychometric qualities. Exit interviews were conducted with a sub-sample of patients enrolled in the study to confirm the appropriateness and clarity of the items included and cognitively debrief the instrument. Confirmatory factor analysis (CFA) was conducted on all items, and each domain's internal consistency was measured using Cronbach's ɑ., Results: The literature searches identified several e-Device-specific concepts related to device features, device function, side effects/reactions/pain, confidence, and interference/convenience in daily life. Seven existing PRO instruments were identified. The Self-Injection Assessment Questionnaire (SIAQ), containing pre- and post-injection questionnaire modules, was selected as most suitable and adapted using feedback from 19 patients in the two focus groups to form the pilot Assessment of Self-Injection (ASI) questionnaire. CFA resulted in some changes to the grouping of items in the post-injection module domains following psychometric evaluation of the ASI. Internal consistency was satisfactory for all pre- and post-injection domains (ɑ > 0.8). Cognitive debriefing results from 12 patient exit interviews confirmed the ASI's appropriateness and clarity., Conclusions: The ASI was developed iteratively with patient input and was evaluated in its intended clinical context of use. Psychometric analyses indicated promising cross-sectional results; the ASI was well understood and considered relevant by patients self-injecting using the e-Device, suggesting that it could be used in real-world settings to aid with clinical decision making., Trial Registration: NCT03357471.

An ultrasound (US) study is often the first imaging approach in patients with abdominal symptoms or signs related to abdominal diseases, and it is often part of the routine workup. The pancreatic gland, despite its retroperitoneal site, can be efficiently examined with US thanks to advances in US technologies. Nowadays, a pancreatic US study could be considered complete if multiparametric, including the use of Doppler imaging, US elastography, and contrast-enhanced imaging for the study of a pancreatic mass. A complete US examination could contribute to a faster diagnosis, especially if the pancreatic lesion is incidentally detected, addressing second-step imaging modalities correctly., (© 2019 by the American Institute of Ultrasound in Medicine.)

To evaluate pancreatic neuroendocrine neoplasms (panNENs) grade prediction by means of qualitative and quantitative CT evaluation, and 3D CT-texture analysis. Patients with histopathologically-proven panNEN, availability of Ki67% values and pre-treatment CT were included. CT images were retrospectively reviewed, and qualitative and quantitative images analysis were done; for quantitative analysis four enhancement-ratios and three permeability-ratios were created. 3D CT-texture imaging analysis was done (Mean Value; Variance; Skewness; Kurtosis; Entropy). Subsequently, these features were compared among the three grading (G) groups. 304 patients affected by panNENs were considered, and 100 patients were included. At qualitative evaluation, frequency of irregular margins was significantly different between tumor G groups. At quantitative evaluation, for all ratios, comparisons resulted statistical significant different between G1 and G3 groups and between G2 and G3 groups. At 3D CT-texture analysis, Kurtosis resulted statistical significant different among three G groups and Entropy resulted statistical significant different between G1 and G3 and between G2 and G3 groups. Quantitative CT evaluation of panNENs can predict tumor grade, discerning G1 from G3 and G2 from G3 tumors. CT-texture analysis can predict panNENs tumor grade, distinguishing G1 from G3 and G2 from G3, and G1 from G2 tumors.

Pancreatic neuroendocrine neoplasms (P-NENs) are the second most common solid pancreatic neoplasms. P-NENs have a wide range of imaging features presentations and they can be detected with typical and atypical imaging presentations. Typical and atypical appearances can be explained by pathologic correlations. P-NENs are generally hypervascular lesions, showing a typical enhancement behavior after contrast media injection during imaging methods, but they could also have different imaging features, creating some difficulty in differential diagnosis. For this reason, radiologists should be aware of different imaging presentations of these neoplasms. Radiological evaluation has a critical role in P-NENs identification, characterization, and staging of these neoplasms, especially in those cases in which surgery is the treatment of choice. The present paper shows, indicating the underlying pathologic correlations, typical and atypical presentations of NENs. KEY POINTS: • P-NENs have a wide range of imaging features presentations, typical and atypical. • Pathology could help in better understanding the typical P-NENs appearance at imaging. • P-NENs are generally hypervascular lesions. • Radiological evaluation has a critical role in P-NENs identification and management. • Radiologists should know every type of different imaging presentation of P-NENs to better diagnose these kinds of lesions.