The new era of immunological treatment, last updated and future consideration of CAR T cell-based drugs.

Cancer treatment is one of the fundamental challenges in clinical setting, especially in relapsed/refractory malignancies. The novel immunotherapy-based treatments bring new hope in cancer therapy and achieve various treatment successes. One of the distinguished ways of cancer immunotherapy is adoptive cell therapy, which utilizes genetically modified immune cells against cancer cells. Between different methods in ACT, the chimeric antigen receptor T cells have more investigation and introduced a promising way to treat cancer patients. This technology progressed until it introduced six US Food and Drug Administration-approved CAR T cell-based drugs. These drugs act against hematological malignancies appropriately and achieve exciting results, so they have been utilized widely in cell therapy clinics. In this review, we introduce all CAR T cells-approved drugs based on their last data and investigate them from all aspects of pharmacology, side effects, and compressional. Also, the efficacy of drugs, pre- and post-treatment steps, and expected side effects are introduced, and the challenges and new solutions in CAR T cell therapy are in the last speech.

Stigmatizing clinical setting erodes physician-patient interaction quality for sexual minority men through perceived HIV stigma and HIV infection concerns in Zambia.

This study investigated whether perceived HIV stigma and HIV infection concerns among healthcare providers (HCPs) mediate the association between stigmatizing clinical setting and their interaction quality with sexual minority men (SMM) patients in Zambia. In 2021, a cross-sectional survey was conducted with 91 HCPs offering HIV-related services to SMM in Zambia. Path analysis was conducted to examine the potential mediation effect of "perceived HIV stigma" and "HIV infection concern" among HCPs in the association between "stigmatizing clinical setting" and their "interaction quality with SMM". Mediators i.e., "perceived HIV stigma" and "HIV infection concern" among HCPs, were associated positively with the stigmatizing clinical setting (ß = 0.329, p < .01, ß = 0.917, p < 0.01), and negatively with physician-patient interaction quality (ß = -0.167, p = 0.051; ß = -0.126, p < 0.05). Stigmatizing clinical setting had a significant and negative indirect effect on HCPs interaction quality with SMM through increased perceived HIV stigma (z = -1.966, p < 0.05) and increased HIV infection concern (z = -1.958, p = 0.050). To improve physician-patient interaction quality, stigma reduction interventions among HCPs, who serve SMM in Zambia, should target development of development of inclusive policies and the cultivation of cultural norms that are supportive and respectful to SMM, and protection of HCPs from enacted stigma due to offering care to SMM.

The Efficacy of Defocus Incorporated Multiple Segments Lenses in Slowing Myopia Progression: Results from Diverse Clinical Circumstances.

PURPOSE: Defocus incorporated multiple segments (DIMS) spectacle lenses were reported to slow myopia progression significantly in a randomized controlled trial (RCT). The study evaluated their effectiveness in clinical settings. DESIGN: Retrospective study. PARTICIPANTS: Patient records involving use of DIMS and single-vision (SV) spectacle lenses were collected from subsidiary hospitals of Aier Eye Hospital Group. METHODS: The spherical equivalent (SE), determined by subjective refraction, was adopted to assess the myopia progression. The strategy of propensity score matching (PSM) was applied to match the confounding baseline characteristics between the 2 groups. The effectiveness was calculated based on the difference of myopia progression of these 2 approaches. MAIN OUTCOME MEASURES: Change in SE. RESULTS: Three thousand six hundred thirty-nine patients with DIMS and 6838 patients with SV spectacles were included. The age of the patients was 6 to 16 years (mean ± standard deviation: 11.02 ± 2.53 years). The baseline SE was between 0.00 and -10.00 diopters (D) (mean ± standard deviation: -2.78 ± 1.74 D). After the PSM, data on 2240 pairs with 1-year follow-up and on 735 pairs with 2-year follow-up were obtained. Significantly slower progression was seen in the DIMS group at both the 1-year (DIMS, -0.50 ± 0.43 D; SV, -0.77 ± 0.58 D; P < 0.001) and 2-year (DIMS, -0.88 ± 0.62 D; SV, -1.23 ± 0.76 D; P < 0.001) subdataset. In the 1-year subdataset, 40% and 19% showed myopia progression of no more than 0.25 D for the DIMS and SV groups, respectively (chi-square, 223.43; P < 0.001), whereas 9% and 22% showed myopia progression of more than 1.00 D for the DIMS and SV groups, respectively (chi-square, 163.38; P < 0.001). In the 2-year subdataset, 33% and 20% showed myopia progression of no more than 0.50 D for the DIMS and SV groups, respectively (chi-square, 31.15; P < 0.001), whereas 12% and 29% showed myopia progression of more than 1.50 D for the DIMS and SV groups (chi-square, 65.60; P < 0.001). CONCLUSIONS: Although the magnitude was lower than that reported in the previous RCT, this large-scale study with diversity of the data sources confirmed the effectiveness of DIMS spectacles to slow myopia progression in clinical practice. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Basic psychological needs satisfaction as a mediator between clinical learning climate, self-regulated learning and perceived learning in the nursing education context.

PURPOSE: Self-regulated learning (SRL) can enhance students' learning process. Students need support to effectively regulate their learning. However, the effect of learning climate on SRL behavior, its ultimate effect on learning and the underlying mechanisms have not yet been established. We explored these relationships using self-determination theory. MATERIALS AND METHODS: Nursing students (N = 244) filled in questionnaires about SRL behavior, perceived learning, perceived pedagogical atmosphere and Basic Psychological Needs (BPN) satisfaction after their clinical placement. Structural equation modelling was used to test a model in which perceived pedagogical atmosphere affects SRL behavior and subsequent perceived learning through BPN satisfaction. RESULTS: The tested model had an adequate fit (RMSEA = 0.080, SRMR = 0.051; CFI = 0.972; TLI = 0.950). A positively perceived pedagogical atmosphere contributed to SRL behavior, which was fully explained by BPN satisfaction. SRL partially mediated the contribution of pedagogical atmosphere/BPN to perceived learning. CONCLUSIONS: A learning climate that satisfies students' BPN contributes to their SRL behavior. SRL behavior plays a positive but modest role in the relationship between climate and perceived learning. Without a culture that is supportive of learning, implementation of tools to apply SRL behavior may not be effective. Study limitations include reliance on self-report scales and the inclusion of a single discipline.

A Pilot Study to Detect Viable Salmonella spp. in Diarrheal Stool Using Viability Real-Time PCR as a Culture-Independent Diagnostic Tool in a Clinical Setting.

Frontline laboratories are adopting culture-independent diagnostic testing (CIDT) such as nucleic acid amplification tests (NAATs) due to numerous advantages over culture-based testing methods. Paradoxically, the viability of pathogens, a crucial factor determining active infections, cannot be confirmed with current NAATs alone. A recent development of viability PCR (vPCR) was introduced to mitigate this limitation associated with real-time PCR (qPCR) by using a DNA-intercalating dye to remove residual and dead cell DNA. This study assessed the applicability of the vPCR assay on diarrheal stools. Eighty-five diarrheal stools confirmed for Salmonellosis were tested via qPCR and vPCR using in-house primers and probe targeting the invA gene. vPCR-negative stools (Ct cut off > 31) were enriched in mannitol selenite broth (MSB) to verify low bacterial loads. vPCR assay showed ~89% sensitivity (qPCR- and vPCR-positive stools: 76/85). vPCR-negative stools (9/85; qPCR-positive: 5; qPCR-negative: 4) were qPCR- and culture-positive post-MSB-enrichment and confirmed the presence of low viable bacterial loads. Random sampling error, low bacterial loads, and receiving stools in batches could contribute to false negatives. This is a pilot study and further investigations are warranted to explore vPCR to assess pathogen viability in a clinical setting, especially when culture-based testing is unavailable.

Are PROMs passing the message? A reflection with real-life migraine patients.

BACKGROUND: Several patient-reported outcome measures are available to monitor headache impact, but are those reliable in real-life clinical practice? METHODS: Two identical patient-reported outcome measures (HALT-90 and MIDAS) were applied simultaneously in each clinical visit to a series of patients treated with monoclonal antibodies for migraine and intra-individual agreement was evaluated using the intraclass correlation coefficients. RESULTS: Our sample included 92 patients, 92.4% females, 45 years old on average. Moderate (0.50 to 0.75) and even poor (<0.50) ICC were observed in all but the first item of these patient-reported outcome measures in at least one evaluation. Over time, missing data were more frequent and no learning effect was detected. DISCUSSION: We observed intra-personal variation in reliability when answering patient-reported outcome measures, persisting in repeated applications, and a decrease in the motivation to respond, which should alert clinicians for these additional challenges in real-life clinical practice.

Percutaneous Versus Transcutaneous Electrical Nerve Stimulation for the Treatment of Musculoskeletal Pain. A Systematic Review and Meta-Analysis.

BACKGROUND: The justification for this review is the need for high-quality evidence to assist in the decision-making process when applying percutaneous electrical nerve stimulation (PENS) or transcutaneous electrical nerve stimulation (TENS) in a clinical setting. The main aim was to determine if the use of PENS is more effective and should be recommended when compared to TENS for the reduction of musculoskeletal pain intensity. METHODS: A search for randomized controlled trials (RCTs) was performed. Studies published until 31/12/2020, comparing the effectiveness of PENS and TENS, were considered. The main outcome was pain assessed with a visual analog scale or numerical pain rating scale. RESULTS: Nine RCTs were included in the qualitative analysis, with seven of them in the quantitative analysis (n = 527). The overall effect of PENS on pain was statistically but not clinically superior to TENS (mean difference [MD]=-1.0 cm; 95% confidence interval [CI]: -1.5 to -0.4) with a high level of heterogeneity (I2=76%, P > .01). When only studies with a lower risk of bias (n = 3) were analyzed, the heterogeneity decreased to I = 0% (P = .06) and no difference was observed between TENS and PENS (MD=-0.81 cm; 95% CI:-1.6 to 0.02) with a moderate recommendation level according to GRADE. There were no data concerning adverse effects. CONCLUSIONS: There is low-quality of evidence for more pain intensity reduction with PENS, but the difference was not clinically significant. However, when only studies with low risk of bias are meta-analyzed, there is a moderate quality of evidence that there is no difference when TENS or PENS is applied for pain intensity.

A cross-sectional study of participant recruitment rates in published phase III influenza therapeutic randomized controlled trials conducted in the clinical setting.

OBJECTIVE: A recent academic-government partnership demonstrated the feasibility of utilizing Emergency Departments (ED) as a primary site for subject enrollment in clinical trials and achieved high rates of recruitment in two U.S. EDs. Given the ongoing need to test new therapeutics for influenza and other emerging infections, we sought to describe the historical rates of participant recruitment into influenza Phase III therapeutic RCTs in various clinical venues, including EDs. STUDY DESIGN: A cross-sectional study was performed of influenza therapeutic Phase III RCTs published in PubMed, Embase, Scopus, and Clinicaltrials.gov from January 2000 to June 2019. MAIN OUTCOME: To estimate the weighted-average number of influenza-positive participants enrolled per site per season in influenza therapeutic RCT conducted in clinical settings, and to describe basic trial site characteristics. RESULTS: 47 (0.7%) of 7008 articles were included for review of which 43 of 47 (91%) included information regarding enrollment sites; of these, 2 (5%) recruited exclusively from EDs with the remainder recruiting from mixed clinical settings (inpatient, outpatient, and ED). The median enrollment per study was 326 (IQR: 110, 502.5) with a median of 11 sites per study (IQR: 2, 59.5). Included studies reported a median of 201 (IQR: 74, 344.5) confirmed influenza-positive participants per study. The pooled number of participants enrolled per site per season was 11 (95% CI: 10, 12). The pooled enrollment numbers per clinical site after excluding the two 'ED only recruitment' studies were less [10.7 (95% CI: 9.9, 11.6)] than the pooled enrollment numbers per clinical site for the two 'ED only recruitment' studies [89.5 (95% CI 89.2-89.27)]. CONCLUSION AND RELEVANCE: Published RCTs evaluating influenza therapeutics in clinical settings recruit participants from multiple sites but enroll relatively few participants, per site, per season. The few ED-based studies reported recruited more subjects per site per season. Untapped opportunities likely exist for EDs to participate and/or lead therapeutic RCTs for influenza or other emerging respiratory pathogens.

Secukinumab treatment demonstrated high drug survival and sustained effectiveness in patients with severe chronic plaque psoriasis: 21-month analysis in Australian routine clinical practice (SUSTAIN study).

BACKGROUND: Drug survival measures the rate and duration of adherence to a given therapeutic agent and evaluates its long-term effectiveness, safety, and real-world utility. The SUSTAIN study sought to establish the drug survival and effectiveness of secukinumab for patients with severe chronic plaque psoriasis (CPP) in the Australian clinical setting. METHODS: Data of all patients (aged ≥18 years) from Australasian Psoriasis Registry (APR) treated with secukinumab were analysed. The primary objective was to describe the drug survival of secukinumab at 9 months. Key secondary objectives included drug survival of secukinumab at 3, 6, 15, and 21 months, stratified by biologic-naïve vs biologic-experienced patients; proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75/90/100 responses; and changes in health-related quality of life over time utilising the Dermatology Life Quality Index (DLQI). RESULTS: Of 294 patients included in this analysis, 110 (37.4%) were biologic-naïve and 184 (62.6%) biologic-experienced. Kaplan-Meїer drug survival rates in biologic-naïve vs biologic-experienced patients were 0.92 vs. 0.86 (9 months) and 0.82 vs. 0.68 (21 months), respectively. The proportion of patients with PASI 75/90/100 responses for biologic-naïve vs. biologic-experienced was 100/87.7/38.4 vs 98.5/61.5/27.2 (9 months) and 100/81.0/41.7 vs. 98.4/62.0/24.2 (21 months), respectively. The mean (standard deviation [SD]) DLQI in biologic-naïve vs. experienced patients was 2.2 (4.1) vs. 3.1 (5.2) (9 months) and 1.4 (2.5) vs. 3.1 (5.3) (21 months). No new safety signals were observed. CONCLUSIONS: Secukinumab demonstrated high drug survival and sustained effectiveness in Australian real-world setting, in biologic-naïve and biologic-experienced patients with severe CPP.

Dichotomous effects of autophagy on infarct volume in experimental permanent/transient ischemic stroke model: a systematic review and meta-analysis.

According to the recent findings, autophagy modulation is being a potential therapeutic target in the management of ischemic stroke in a pre-clinical setting. However, the pros and cons of autophagic response strongly depend on the activation time of autophagy after injury. In this systematic review, we aimed to explore the impacts of pharmacological modulation of autophagy on infarct size in experimental ischemic stroke models. Based on our preliminary search, 3551 publications were identified. Of twenty-nine publications that met the inclusion criteria, twenty studies reported infarct volume reduction by percentage (%) with no evidence of any publication bias while nine studies reported by mm3, which had publication bias (39.25 units, standardized mean differences (SMD) = 41.92, 95% confidence interval (CI): 30.33 to 53.51). Based on a meta-analysis, the point estimate (pooled mean difference) for improvement of infarct volume during autophagy modulation according to the mm3 and percentage were 35.64 (mean differences (MD) = 35.64, 95% CI: 26.43 to 44.85, z-value = 7.58, p-value < 0.001) and 14.38 (MD = 14.38, 95% CI = 10.50 to 18.26, z-value = 7.26, p < 0.001) units, respectively. Despite the undeniable role of autophagy in ischemic stroke, the dichotomous effects of autophagy regarding infarct volume reduction should be taken into account. Based on our findings, the studies included in this meta-analysis mostly reported a negative relation between autophagy induction and stroke volume development due to over-activity of autophagy upon the severe ischemic stroke; therefore, further pre-clinical studies are also recommended to establish adjusted autophagy with considering a time-dependent effect as a promising therapeutic target.

A process to gain access for research in the clinical setting.

Researchers and clinical nurses need to collaborate to develop the clinical setting. Negotiating access to do research in the clinical setting can be challenging. The task of gaining access is often omitted and scarcely described in the literature. The aim of this article is to describe a process to gain access based on the authors' individual and collective experience through reflective conversations. The process consists of four key components: researcher, review board, gatekeepers and participants. Each component is linked and a crucial step to gain access to the clinical setting and ultimately to the participants. The gaining access process may prepare novice researchers for the specific considerations, time and effort required to initiate research in the clinical setting.

Instrumental and sensory techniques to characterize the texture of foods suitable for dysphagic people: A systematic review.

The interest to characterize texture-modified foods (TMFs) intended for people with oropharyngeal dysphagia (OD) has grown significantly since 2011. Several instrumental and sensory techniques have been applied in the analysis of these foods. The objective of the present systematic review was to identify the most appropriate techniques, especially for the food industry and clinical setting. The search was carried out in three online databases according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA). Across the multiple trials reviewed, Texture Profile Analysis and the Uniaxial Compression Test were most used as the instrumental technique for solid foods, and the Back Extrusion Test for fluid and semisolid foods. All trials used descriptive analysis as the sensory technique. However, the experimental conditions of the trials lacked standardization. Consequently, the results of the trials were not comparable. To properly characterize the texture of TMFs intended for OD by each technique, an international consensus is needed to establish standardized experimental conditions. Methods based on these techniques should also be validated by collaborative studies to verify repeatability, replicability, and reproducibility.

Antibiotic Abuse and Antimicrobial Resistance in Hospital Environment: A Retrospective Observational Comparative Study.

Background and Objectives: Antimicrobial resistance represents a serious problem, and it may be life-threatening in the case of severe hospital-acquired infections (HAI). Antibiotic abuse and multidrug resistance (MDR) have significantly increased this burden in the last decades. The aim of this study was to investigate the distribution and susceptibility rates of five selected bacterial species (E. coli, K. pneumoniae, P. aeruginosa, S. aureus and E. faecium) in two healthcare settings located in the Apulia region (Italy). Materials and Methods: Setting n.1 was a university hospital and setting n.2 was a research institute working on oncological patients. All the enrolled patients were diagnosed for bacterial HAI. The observation period was between August and September 2021. Clinical samples were obtained from several biological sources, in different hospital wards. Bacterial identification and susceptibility were tested by using the software VITEC 2 Single system. Results: In this study, a higher incidence of multi-drug-resistant K. pneumoniae was reported (42,2% in setting n.1 and 50% in setting n.2), with respect to the Italian 2019 statistics report (30.3%). All the isolates of E. faecium and S. aureus were susceptible to linezolid. All the bacterial isolates of P. aeruginosa and most of K. pneumoniae were susceptible to ceftazidime-avibactam. Amikacin and nitrofurantoin represented a good option for treating E. coli infections. Multidrug-resistant (MDR) P. aeruginosa, methicillin-resistant S. aureus (MRSA) and vancomycin-resistantE. faecium (VRE) had a lower incidence in the clinical setting, with respect to E. coli and K. pneumoniae. Conclusions: The data obtained in this study can support clinicians towards a rational and safe use of antibiotics for treating the infections caused by these resistant strains, to enhance the overall efficacy of the current antibiotic protocols used in the main healthcare environments.

Quality of life and its association with psychiatric disorders in outpatients with trauma history in a tertiary hospital in Kathmandu, Nepal: a cross-sectional study.

BACKGROUND: Quality of life is an important indicator of health and has multiple dimensions. It is adversely affected in patients with trauma history, and psychiatric disorders play an important role therein. Studies in trauma-affected populations focus mainly on the development of psychiatric disorders. Our study explored various aspects of quality of life in trauma patients in a clinical setting, mainly focusing on the association of psychiatric disorders on various domains of quality of life. METHODS: One hundred patients seeking help at the psychiatry outpatient of a tertiary hospital in Kathmandu, Nepal, and with history of trauma were interviewed using the World Health Organization Composite International Diagnostic Interview version 2.1 for trauma categorization. Post-traumatic stress disorder symptoms were assessed using the Post-Traumatic Stress Disorder Checklist-Civilian Version; while the level of anxiety and depression symptoms was assessed using the 25-item Hopkins Symptom Checklist-25. Quality of life was assessed using the World Health Organization Quality Of Life-Brief Version measure. Information on sociodemographic and trauma-related variables was collected using a semi-structured interview schedule. The associations between psychiatric disorders and quality of life domains were explored using bivariate analyses followed by multiple regressions. RESULTS: The mean scores (standard deviations) for overall quality of life and health status perception were 2.79 (.87) and 2.35 (1.11), respectively. The mean scores for the physical, psychological, social and environmental domains were 12.31 (2.96), 11.46 (2.84), 12.79 (2.89), and 13.36 (1.79), respectively. Natural disaster was the only trauma variable significantly associated with overall quality of life, but not with other domains. Anxiety, depression and post-traumatic stress disorder were all significantly associated with various quality of life domains, where anxiety had the greatest number of associations. CONCLUSION: Quality of life, overall and across domains, was affected in various ways based on the presence of psychiatric disorders such as anxiety, depression and post-traumatic stress disorder in patients with trauma. Our findings therefore emphasize the need to address these disorders in a systematic way to improve the patients' quality of life.

A story half told: a qualitative study of medical students' self-directed learning in the clinical setting.

BACKGROUND: Medical educators have promoted self-directed learning (SDL) as an important means of enabling students to take responsibility for their own learning throughout their training and practice. While SDL has been well-studied in classroom settings, it remains a story half told: barriers to and facilitators of SDL in the clinical setting are not yet well described. The goals of this study were to explicate student experiences of SDL in their clinical training and to identify the roles that local social and cultural contexts play in shaping their experiences of SDL. METHODS: To understand students' conceptualization and experiences of SDL in the clinical setting, we carried out a qualitative study with 15 medical students at Harvard Medical School. The semi-structured interviews were recorded and transcribed. Using an interpretivist approach, data were analyzed both deductively and inductively using the Framework method of content analysis. RESULTS: Participants described patient care activities as primary motivators for engagement in SDL in the clinical setting. Participants' descriptions of SDL aligned with Knowles' steps in SDL, with an additional step of consolidation of learning related to their patients' diagnosis and management. Participants described using a range of cognitive, social-emotional, and peer learning strategies to enhance their SDL. Participants who described a growth mindset appeared to engage in SDL more easily. Learning environments that fostered SDL were those in which faculty and residents demonstrated an educational orientation, promoted psychological safety, and invited student engagement. Teams with perceived excessive work demands were perceived to be less supportive of SDL. CONCLUSIONS: Our study enhances previous classroom-based models of SDL by providing specific, practical implications for both students and faculty in the clinical training setting. Participants described SDL in the clinical setting as patient-centered, and when effectively implemented, SDL appears to support a mastery rather than performance orientation. Our study paves the way for improving medical students' clinical SDL and helping them become lifelong learners in the field of medicine.

An Inertial Measurement Unit-Based Wireless System for Shoulder Motion Assessment in Patients with Cervical Spinal Cord Injury: A Validation Pilot Study in a Clinical Setting.

Residual motion of upper limbs in individuals who experienced cervical spinal cord injury (CSCI) is vital to achieve functional independence. Several interventions were developed to restore shoulder range of motion (ROM) in CSCI patients. However, shoulder ROM assessment in clinical practice is commonly limited to use of a simple goniometer. Conventional goniometric measurements are operator-dependent and require significant time and effort. Therefore, innovative technology for supporting medical personnel in objectively and reliably measuring the efficacy of treatments for shoulder ROM in CSCI patients would be extremely desirable. This study evaluated the validity of a customized wireless wearable sensors (Inertial Measurement Units-IMUs) system for shoulder ROM assessment in CSCI patients in clinical setting. Eight CSCI patients and eight healthy controls performed four shoulder movements (forward flexion, abduction, and internal and external rotation) with dominant arm. Every movement was evaluated with a goniometer by different testers and with the IMU system at the same time. Validity was evaluated by comparing IMUs and goniometer measurements using Intraclass Correlation Coefficient (ICC) and Limits of Agreement (LOA). inter-tester reliability of IMUs and goniometer measurements was also investigated. Preliminary results provide essential information on the accuracy of the proposed wireless wearable sensors system in acquiring objective measurements of the shoulder movements in CSCI patients.

Direct prospective comparison of 18F-FDG PET and arterial spin labelling MR using simultaneous PET/MR in patients referred for diagnosis of dementia.

PURPOSE: 18F-FDG PET is routinely used as an imaging marker in the early and differential diagnosis of dementing disorders and has incremental value over the clinical neurological and neuropsychological evaluation. Perfusion MR imaging by means of arterial spin labelling (ASL) is an alternative modality to indirectly measure neuronal functioning and could be used as complement measurement in a single MR session in the workup of dementia. Using simultaneous PET-MR, we performed a direct head-to-head comparison between enhanced multiplane tagging ASL (eASL) and 18F-FDG PET in a true clinical context of subjects referred for suspicion of neurodegenerative dementia. METHODS: Twenty-seven patients underwent a 20-min 18F-FDG PET/MR and simultaneously acquired eASL on a GE Signa PET/MR. Data were compared with 30 screened age- and gender-matched healthy controls. Both integral eASL and 18F-FDG datasets were analysed visually by two readers unaware of the final clinical diagnosis, either in normal/abnormal classes, or full differential diagnosis (normal, Alzheimer type dementia [AD], dementia with Lewy Bodies [LBD], frontotemporal dementia [FTD] or other). Reader confidence was assessed with a rating scale (range 1-4). Data were also analysed semiquantitatively by VOI and voxel-based analyses. RESULTS: The ground truth diagnosis for the patient group resulted in 14 patients with a neurodegenerative cognitive disorder (AD, FTD, LBD) and 13 patients with no arguments for an underlying neurodegenerative cause. Visual analysis resulted in equal specificity (0.70) for differentiating normal and abnormal cases between the two modalities, but in a higher sensitivity (0.93), confidence rating (0.64) and interobserver agreement for 18F-FDG PET compared with eASL. The same was true for assigning a specific differential diagnosis (sensitivity: and 0.39 for 18F-FDG PET and eASL, respectively). Semiquantitative analyses revealed prototypical patterns for AD and FTD, with both higher volumes of abnormality and intensity differences on 18F-FDG PET. CONCLUSION: In a direct head-to-head comparison on a simultaneous GE Signa PET/MR, 18F-FDG PET performed better compared with ASL in terms of sensitivity and reader confidence, as well as volume and intensity of abnormalities. However, using pure semiquantitative analysis, similar diagnostic accuracy between the two modalities was obtained. Therefore, ASL may still serve as complement to neuroreceptor or protein deposition PET studies when a single simultaneous investigation is warranted.

Beyond the dermis-high-risk invasive squamous cell carcinoma: a retrospective review.

OBJECTIVE: Most cutaneous squamous cell carcinomas (cSCC) are low risk and can be treated with simple excision or ablation. High-risk cSCC require invasive treatment, including radical surgery. We present our experience in treating invasive cSCC of the pelvis and extremities. METHOD: A retrospective review of the data of patients with invasive cSCC, indicated for surgery between 2014 and 2018, from a single institution was carried out. RESULTS: A total of 19 patients (nine men, 10 women) were included in the study. Mean age was 62 years; mean tumour size was 8.6cm). Of the 19 patients, five patients with paraplegia with cSCC arising from hard-to-heal ulcers died of infection or bleeding after surgery or systemic therapy. Also, nine patients with localised cSCC underwent margin-negative resection with or without radiation; one patient experienced disease relapse. Of the participants, two patients with previous transplants and multifocal aggressive cSCC underwent numerous resections but succumbed to disease, and two patients who presented with locally recurrent disease after previous positive margin resection and radiation underwent re-resection but developed recurrent disease. CONCLUSIONS: Prognosis for invasive cSCC largely depends on clinical setting. Tumours arising from ulcers in patients with paraplegia have a poor prognosis regardless of treatment. Invasive cSCC in transplant patients are often multifocal and often recur. Debulking procedures are associated with local recurrence despite radiation. Patients presenting with localised disease have a favourable prognosis with wide resection, flap coverage and adjuvant therapy.

Internet-based cognitive behavioral therapy for anxiety in an outpatient specialized care setting: A qualitative study of the patients' experience of the therapy.

Knowledge about user experiences of internet-based cognitive behavioral therapy (iCBT) has mostly been drawn from non-clinical groups or with iCBT offered via self-referral. The present study therefore focused on patients who had undergone iCBT with minimal support while actively awaiting outpatient psychological treatment in the form of face-to-face CBT. To seek out barriers to adherence the study also included patients who had withdrawn from the iCBT treatment before completion. The study was performed in an outpatient clinic for anxiety disorders where twelve participants with a primary diagnosis of either social anxiety disorder or panic disorder were recruited from an ongoing randomized control trial for semi-structured interviews. Statements from the interviews showed that the iCBT treatment was unfavorably compared to the usual face-to-face treatment at the clinic. Despite this, a majority of the interview participants still expressed to have experienced various benefits from the treatment. Some participants did however, experience difficulties putting the materials to practical use. Furthermore, a large majority of the participants expressed a need for additional support, with a strong tendency for non-completers specifically expressing a need for face-to-face contact with a clinician. Implications for future research and implementation of iCBT in clinical practice are discussed.

Personal and social influences on the use of humour in the interactions of student nurses in UK clinical settings.

Humour is a centuries-old phenomenon studied by many disciplines. Social and personal identity play a role in the creation, recognition, understanding, appreciation and use of humour. This study, which used interpretative phenomenological analysis to explore preregistration nursing students' experiences of the use of humour in the UK clinical setting, highlights what affects the students' use of humour. The influence of sex, age, and culture and ethnicity on the participants' use of humour with patients and healthcare staff is evidenced and explored; the influence of sex did not strictly follow traditional expectations.