UNASSIGNED: the advent of biological therapies has already revolutionized treatment strategies and disease course of several rheumatologic conditions, and monoclonal antibodies (mAbs) targeting cytokines and interleukins represent a considerable portion of this family of drugs. In Systemic Lupus Erythematosus (SLE) dysregulation of different cytokine and interleukin-related pathways have been linked to disease development and perpetration, offering palatable therapeutic targets addressable via such mAbs.
UNASSIGNED: In this review, we provide an overview of the different biological therapies under development targeting cytokines and interleukins, with a focus on mAbs, while providing the rationale behind their choice as therapeutic targets and analyzing the scientific evidence linking them to SLE pathogenesis.
UNASSIGNED: an unprecedented number of clinical trials on biological drugs targeting different immunological pathways are ongoing in SLE. Their success might allow us to tackle present challenges of SLE management, including the overuse of glucocorticoids in daily clinical practice, as well as SLE heterogenicity in treatment response among different individuals, hopefully paving the way toward precision medicine.

UNASSIGNED: The study was designed to develop and validate a new drug clinical trial participation feelings questionnaire (DCTPFQ) for cancer patients.
UNASSIGNED: Data collection and analysis involved a combination of qualitative and quantitative methods. There were two phases to this study. Phase Ⅰ involved developing a questionnaire to establish a list of items to be included in the pool: A theoretical framework was constructed based on the transitions theory and the Roper-Logan-Tierney theory. After incorporating a theoretical framework, interviewing participants, and reviewing the literature, 44 items were generated. After a Delphi consultation and a pilot test, 36 items proceeded to item analysis and exploratory factor analysis (EFA), and a four-factor structure with 21 items was formed. Confirmatory factor analysis (CFA), test-retest reliability, criteria-related validity, and internal consistency tests were conducted in phase II to examine the psychometric properties.
UNASSIGNED: There were 21 items on the DCTPFQ, ranging from 1 (fully disagree) through 5 (fully agree). As a result of EFA and CFA, the four factors of DCTPFQ could be verified, including cognitive engagement, subjective experience, medical resources, and relatives and friends\' support. Test-retest reliability of the DCTPFQ was 0.840, and Cronbach\'s alpha was 0.934. DCTPFQ is significantly correlated with the Fear of Progression Questionnaire-short form (r = 0.731, p < 0.05) and the Mishel\'s Uncertainty in Illness Scale (r = 0.714, p < 0.05).
UNASSIGNED: The DCTPFQ is a useful tool for measuring the drug clinical trial participation feelings among cancer patients.

Background: Natural products are widely used for primary insomnia (PI). This systematic review with trial sequential analysis (TSA) aimed to summarize evidence pertaining to the effectiveness and safety of Zao Ren An Shen (ZRAS) prescription, a commercial Chinese polyherbal preparation, for treating PI. Methods: Controlled clinical trials appraising ZRAS compared to controls or as an add-on treatment were systematically searched across seven databases until January 2024. Cochrane ROB 2.0 and ROBINS-I tools were adopted to determine risk of bias. Quality of evidence was assessed using the GRADE framework. Results: We analyzed 22 studies, involving 2,142 participants. The effect of ZRAS in reducing Pittsburgh Sleep Quality Index scores was found to be comparable to benzodiazepines [MD = 0.39, 95%CI (-0.12, 0.91), p = 0.13] and superior to Z-drugs [MD = -1.31, 95%CI (-2.37, -0.24), p = 0.02]. The addition of ZRAS to hypnotics more significantly reduced polysomnographically-recorded sleep onset latency [MD = -4.44 min, 95%CI (-7.98, -0.91), p = 0.01] and number of awakenings [MD = -0.89 times, 95%CI (-1.67, -0.10), p = 0.03], and increased total sleep time [MD = 40.72 min, 95%CI (25.14, 56.30), p < 0.01], with fewer adverse events than hypnotics alone. TSA validated the robustness of these quantitative synthesis results. However, the quality of evidence ranged from very low to low. The limited data available for follow-up did not support meta-synthesis. Conclusion: While ZRAS prescription shows promising effectiveness in treating PI, the overall quality of evidence is limited. Rigorously-designed randomized control trials are warranted to confirm the short-term efficacy of ZRAS and explore its medium-to-long-term efficacy. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=471497), identifier (CRD42023471497).

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BACKGROUND: Radiotherapy (RT) clinical trials allow patients to access cutting-edge innovative cancer treatments. Clinical Research Therapy Radiographers (CRRs) play an important role in the management and care of RT trial patients. The COVID-19 pandemic caused major disruption to RT trial delivery. Measures to mitigate COVID-19 risk continue to have an effect on patient contact and communication within cancer centres in the United Kingdom (UK). This study aimed to explore patient perspectives regarding their recent RT trial experience in Northern Ireland (NI), UK.
METHODS: A single centre service evaluation was conducted in NI. Patients who were recruited into a RT clinical trial from January 2020 to January 2023 were invited to participate. Surveys were posted to 50 participants in April 2023. Quantitative and qualitative data was captured and analysed using descriptive statistics and Braun and Clarke\'s six-step thematic analysis framework respectively. Ethical approval was obtained through Ulster University and the NHS Trust.
RESULTS: Forty-three of the 50 invited participants responded (86%). Forty-two respondents (79%) had a prostate cancer diagnosis. Forty-one (98%) participants indicated that CRRs were always approachable, polite and courteous and would recommend taking part in a RT trial to friends and family. Identified areas for improvement included aspects regarding consent and participant decision-making.
CONCLUSIONS: This study suggests that despite the implemented measures to suspend research and mitigate COVID-19 risk, patients remained highly satisfied with the quality of care that they received through their participation in RT trials.
CONCLUSIONS: The results of this service evaluation will facilitate maintenance and improvement of patient focused delivery of cancer trials within the host centre. This study builds on evidence highlighting the importance of the CRR role and role development for radiographers.

Globally, Alzheimer\'s disease (AD) is the most widespread chronic neurodegenerative disorder, leading to cognitive impairment, such as aphasia and agnosia, as well as mental symptoms, like behavioral abnormalities, that place a heavy psychological and financial burden on the families of the afflicted. Unfortunately, no particular medications exist to treat AD, as the current treatments only impede its progression.The link between AD and type 2 diabetes (T2D) has been increasingly revealed by research; the danger of developing both AD and T2D rises exponentially with age, with T2D being especially prone to AD. This has propelled researchers to investigate the mechanism(s) underlying this connection.A critical review of the relationship between insulin resistance, Aβ, oxidative stress, mitochondrial hypothesis, abnormal phosphorylation of Tau protein, inflammatory response, high blood glucose levels, neurotransmitters and signaling pathways, vascular issues in AD and diabetes, and the similarities between the two diseases, is presented in this review. Grasping the essential mechanisms behind this detrimental interaction may offer chances to devise successful therapeutic strategies.

Nintedanib, a primary treatment for lung fibrosis, has gathered substantial attention due to its multifaceted potential. A tyrosine kinase inhibitor, nintedanib, inhibits multiple signalling receptors, including endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR) and ultimately inhibits fibroblast proliferation and differentiation. Therefore, nintedanib has been studied widely for other ailments like cancers and hepatic fibrosis, apart from lung disorders. Commercially, nintedanib is available as soft gelatin capsules for treatment against idiopathic pulmonary fibrosis. Since it has very low oral bioavailability (4.7%), high doses of a drug, such as 100-150 mg, are administered, which can cause problems of gastrointestinal irritation and hepatotoxicity. The article begins with exploring the mechanism of action of nintedanib, elucidating its complex interactions within cellular pathways that govern fibrotic processes. It also emphasizes the pharmacokinetics of nintedanib, clinical trial insights, and the limitations of conventional formulations. The article mainly focuses on the emerging landscape of nanoparticle-based carriers such as hybrid liposome-exosome, nano liquid crystals, discoidal polymeric, and magnetic systems, offering promising avenues to optimize drug targeting, address its efficacy issues and minimise adverse effects. However, none of these delivery systems are commercialised, and further research is required to ensure safety and effectiveness in clinical settings. Yet, as research progresses, these advanced delivery systems promise to revolutionise the treatment landscape for various fibrotic disorders and cancers, potentially improving patient outcomes and quality of life.

UNASSIGNED: This is a summary of two studies that looked at the safety and effectiveness of a potential new treatment, N-803 (Anktiva), in combination with a standard treatment bacillus Calmette-Guerin (BCG) for people with non-muscle invasive bladder cancer (NMIBC).One study was a Phase 1b study that tested increasing doses of N-803 in combination with the same dose of BCG in people with NMIBC who had never received BCG previously (BCG-naive). The other study is a Phase 2/3 study of N-803 and BCG in people with NMIBC whose cancer wasn\'t eliminated by BCG alone (BCGunresponsive).
UNASSIGNED: In the Phase 1b study, the nine participants were split into three groups of 3 participants who received a dose of 100, 200, or 400 μg N-803 along with a standard 50 mg dose of BCG. In the Phase 2/3 study, one group (cohort A) of participants with carcinoma in situ (CIS) disease and another group (cohort B) with papillary disease were treated with 400 μg N-803 plus 50 mg BCG. There was also a cohort C that received only 400 μg N-803. Treatments were delivered directly into the bladder once a week for 6 weeks in a row.
UNASSIGNED: N-803 plus BCG eliminated NMIBC in all nine BCG-naive participants and the effects were long-lasting, with participants remaining NMIBC-free for a range of 8.3 to 9.2 years.As reported in 2022, cancer was eliminated in 58 of 82 (71%) participants with BCG-unresponsive CIS disease and the effect was also long-lasting. Importantly, approximately 90% of the successfully treated participants avoided surgical removal of the bladder. In cohort B participants with papillary disease, 40 of 72 (55.4%) were cancer-free 12 months after treatment. N-803 used alone was only effective in 2 of 10 participants. In both studies, the combination of N-803 and BCG was found to be associated with very few adverse events.Based on results from the Phase 2/3 study, the U.S. Food and Drug Association (FDA) approved the use of N-803 plus BCG for the treatment of BCG-unresponsive bladder CIS with or without Ta/T1 papillary disease.Clinical Trial Registration: NCT02138734 (Phase 1b study), NCT03022825 (Phase 2/3 study).
Addition of the IL-15 superagonist N-803 to BCG therapy produces a high rate of success in eliminating non-muscle invasive bladder cancer in both BCG-naive and BCG-unresponsive patients, with long-lasting effects that allow patients to avoid surgical removal of the bladder.

Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented populations. The eligibility criteria for 196 Alzheimer\'s Disease and Related Dementias (AD/ADRD) trials funded by the National Institute on Aging were analyzed to identify common criteria and their potential to disproportionately exclude participants by race/ethnicity. The trials were categorized by type (48 Phase I/II pharmacological, 7 Phase III/IV pharmacological, 128 non-pharmacological, 7 diagnostic, and 6 neuropsychiatric) and target population (51 AD/ADRD, 58 Mild Cognitive Impairment, 25 at-risk, and 62 cognitively normal). Eligibility criteria were coded into the following categories: Medical, Neurologic, Psychiatric, and Procedural. A literature search was conducted to describe the prevalence of disparities for eligibility criteria for African Americans/Black (AA/B), Hispanic/Latino (H/L), American Indian/Alaska Native (AI/AN) and Native Hawaiian/Pacific Islander (NH/PI) populations. The trials had a median of 15 criteria. The most frequent criterion were age cutoffs (87% of trials), specified neurologic (65%), and psychiatric disorders (61%). Underrepresented groups could be disproportionately excluded by 16 eligibility categories; 42% of trials specified English-speakers only in their criteria. Most trials (82%) contain poorly operationalized criteria (i.e., criteria not well defined that can have multiple interpretations/means of implementation) and criteria that may reduce racial/ethnic enrollment diversity.

BACKGROUND: Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its application remains unclear. While several predictors of upper limb PSS are known, their utility in clinical practice in relation to BoNT-A treatment has yet to be fully elucidated. The COLOSSEO-BoNT study aims to investigate predictors of PSS and the effects of BoNT-A timing on spasticity-related metrics in a real-world setting.
METHODS: The recruitment will involve approximately 960 patients who have recently experienced an ischaemic stroke (within 10 days, V0) and will follow them up for 24 months. Parameters will be gathered at specific intervals: (V1) 4, (V2) 8, (V3) 12, (V4) 18 months and (V5) 24 months following enrolment. Patients will be monitored throughout their rehabilitation and outpatient clinic journeys and will be compared based on their BoNT-A treatment status-distinguishing between patients receiving treatment at different timings and those who undergo rehabilitation without treatment. Potential predictors will encompass the Fugl-Meyer assessment, the National Institute of Health Stroke Scale (NIHSS), stroke radiological characteristics, performance status, therapies and access to patient care pathways. Outcomes will evaluate muscle stiffness using the modified Ashworth scale and passive range of motion, along with measures of quality of life, pain, and functionality.
BACKGROUND: This study underwent review and approval by the Ethics Committee of the Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy. Regardless of the outcome, the findings will be disseminated through publication in peer-reviewed journals and presentations at national and international conferences.
BACKGROUND: NCT05379413.