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BACKGROUND: Biologic therapies are associated with increased infection risk among elderly patients with inflammatory bowel disease (IBD). However, there are few data on the safety and effectiveness of ustekinumab compared with anti-tumor necrosis factor (anti-TNF) agents in the elderly. METHODS: The study sought to compare the safety and effectiveness of ustekinumab and anti-TNF agents in elderly Crohn's disease (CD) patients. Patients ≥60 years of age who commenced ustekinumab or an anti-TNF agent for CD were included in this retrospective multicenter cohort. The primary outcome was incidence of serious infections requiring hospitalization. Effectiveness was assessed by clinical remission, clinical response, and treatment persistence rates at 6 months. We adjusted for confounders using inverse probability of treatment weighting (IPTW) and performed a logistic regression analysis to assess factors associated with serious infections, clinical remission, and treatment persistence. RESULTS: Eighty-three patients commencing ustekinumab and 124 commencing anti-TNF therapy were included. There was no difference in serious infection rates between anti-TNF agents (2.8%) and ustekinumab (3.1%) (P = .924) after propensity adjustment. Clinical remission rates were comparable at 6 months for ustekinumab (55.9%) and anti-TNF agents (52.4%) (P = .762). There was a significant reduction in HBI at 6 months in both groups. Treatment persistence was comparable between ustekinumab (90.6%) and anti-TNF agents (90.0%) at 6 months. Cox regression analysis did not show differences in treatment persistence (hazard ratio, 1.23; 95% confidence interval, 0.57-2.61; P = .594) and serious infection incidence (hazard ratio, 1.38; 95% confidence interval, 0.25-7.57; P = .709) by 6 months. CONCLUSIONS: We observed comparable safety and effectiveness for ustekinumab and anti-TNF agents in treating elderly CD patients.
In this retrospective multicenter cohort study, we report equal safety and effectiveness for ustekinumab and anti-tumor necrosis factor agents in treating older adults with Crohn's disease over a 6-month period.
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BACKGROUND: Most schwannomas are isolated tumours occurring in otherwise healthy people. However, bilateral vestibular schwannomas (BVS) or multiple non-vestibular schwannomas indicate an underlying genetic predisposition. This is most commonly NF2-related schwannomatosis (SWN), but when BVS are absent, this can also indicate SMARCB1-related or LZTR1-related SWN. METHODS: We assessed the variant detection rates for the three major SWN genes (NF2, LZTR1 and SMARCB1) in 154 people, from 150 families, who had at least one non-vestibular schwannoma, but who did not meet clinical criteria for NF2-related SWN at the time of genetic testing. RESULTS: We found that 17 (11%) people from 13 families had a germline SMARCB1 variant and 19 (12%) unrelated individuals had a germline LZTR1 variant. 19 people had an NF2 variant, but 18 of these were mosaic and 17 were only detected when 2 tumours were available for testing. The overall detection rate was 25% using blood alone, but increased to 36% when tumour analysis was included. Another 12 people had a germline variant of uncertain significance (VUS). CONCLUSIONS: There were similar proportions of LZTR1, SMARCB1 or mosaic NF2. However, since an NF2 variant was detected in tumours from 103 people, it is likely that further cases of mosaicism would be detected if more people had additional tumours available for analysis. In addition, if further evidence becomes available to show that the VUSs are pathogenic, this would significantly increase the proportion of people with a genetic diagnosis. Our results indicate the importance of comprehensive genetic testing and improved variant classification.
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BACKGROUND: South Africa's first SARS-CoV-2 case was identified 5th March 2020 and national lockdown followed March 26th. Households are an important location for secondary SARS-CoV-2 infection. Physical distancing and sanitation - infection mitigation recommended by the World Health Organization (WHO) at the time - are difficult to implement in limited-resource settings because of overcrowded living conditions. METHODS: This study (ClinicalTrials.gov NCT05119348) was conducted from August 2020 to September 2021 in two densely populated, low socioeconomic Cape Town community sub-districts. New COVID-19 index cases (ICs) identified at public clinics were randomised to an infection mitigation intervention (STOPCOV) delivered by lay community health workers (CHWs) or standard of care group. STOPCOV mitigation measures included one initial household assessment conducted by a CHW in which face masks, sanitiser, bleach and written information on managing and preventing spread were provided. This was followed by regular telephonic follow-up from CHWs. SARS-CoV-2 PCR and IgM/IgG serology was performed at baseline, weeks 1, 2, 3 and 4 of follow-up. RESULTS: The study randomised 81 ICs with 245 HHCs. At baseline, no HHCs in the control and 7 (5%) in the intervention group had prevalent SARS-CoV-2. The secondary infection rate (SIR) based on SARS-CoV-2 PCR testing was 1.9% (n = 2) in control and 2.9% (n = 4) in intervention HHCs (p = 0.598). At baseline, SARS-CoV-2 antibodies were present in 15% (16/108) of control and 38% (52/137) of intervention participants. At study end incidence was 8.3% (9/108) and 8.03% (11/137) in the intervention and control groups respectively. Antibodies were present in 23% (25/108) of control HHCs over the course of the study vs. 46% (63/137) in the intervention arm. CHWs made twelve clinic and 47 food parcel referrals for individuals in intervention households in need. DISCUSSION: Participants had significant exposure to SARS-CoV-2 infections prior to the study. In this setting, household transmission mitigation was ineffective. However, CHWs may have facilitated other important healthcare and social referrals.
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COVID-19 , Características da Família , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/transmissão , África do Sul/epidemiologia , Feminino , Masculino , Adulto , Estudos Prospectivos , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Aglomeração , Agentes Comunitários de Saúde , Criança , IdosoRESUMO
Artificial intelligence in the workplace is becoming increasingly common. These tools are sometimes used to aid users in performing their task, for example, when an artificial intelligence tool assists a radiologist in their search for abnormalities in radiographic images. The use of artificial intelligence brings a wealth of benefits, such as increasing the efficiency and efficacy of performance. However, little research has been conducted to determine how the use of artificial intelligence assistants might affect the user's cognitive skills. In this theoretical perspective, we discuss how artificial intelligence assistants might accelerate skill decay among experts and hinder skill acquisition among learners. Further, we discuss how AI assistants might also prevent experts and learners from recognizing these deleterious effects. We then discuss the types of questions: use-inspired basic cognitive researchers, applied researchers, and computer science researchers should seek to answer. We conclude that multidisciplinary research from use-inspired basic cognitive research, domain-specific applied research, and technical research (e.g., human factors research, computer science research) is needed to (a) understand these potential consequences, (b) design artificial intelligence systems to mitigate these impacts, and (c) develop training and use protocols to prevent negative impacts on users' cognitive skills. Only by answering these questions from multidisciplinary perspectives can we harness the benefits of artificial intelligence in the workplace while preventing negative impacts on users' cognitive skills.
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Inteligência Artificial , Humanos , Conscientização/fisiologia , Aprendizagem/fisiologiaRESUMO
To navigate changes within a highly dynamic and complex environment, it is crucial to compare current visual representations of a scene to previously formed representations stored in memory. This process of mental comparison requires integrating information from multiple sources to inform decisions about changes within the environment. In the present article, we combine a novel systems factorial technology change detection task (Blunden et al., 2022) with a set size manipulation. Participants were required to detect 0, 1, or 2 changes of low and high detectability between a memory and probe array of 1-4 spatially separated luminance discs. Analyses using systems factorial technology indicated that the processing architecture was consistent across set sizes but that capacity was always limited and decreased as the number of distractors increased. We developed a novel model of change detection based on the statistical principles of basic sampling theory (Palmer, 1990; Sewell et al., 2014). The sample size model, instantiated parametrically, predicts the architecture and capacity results a priori and quantitatively accounted for several key results observed in the data: (a) increasing set size acted to decrease sensitivity (d') in proportion to the square root of the number of items in the display; (b) the effect of redundancy benefited performance by a factor of the square root of the number of changes; and (c) the effect of change detectability was separable and independent of the sample size costs and redundancy benefits. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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BACKGROUND: Subcutaneous [SC] infliximab may provide multiple benefits over intravenous [IV] formulations. However, studies for efficacy and safety in inflammatory bowel disease [IBD] have been constrained by small sizes that limit the interpretation of outcomes, particularly for subgroups potentially at high risk of disease relapse. METHODS: We conducted a systematic review and random-effects meta-analysis up to January 2023, to evaluate the change in clinical remission after transitioning from IV to SC infliximab in patients with IBD in clinical remission. The primary outcome was measured using the relative risk for meta-analysis. RESULTS: We identified 15 studies of patients establishedâ ≥â 3 months on IV infliximab, consisting of 1371 patients and 840 patient-years of follow-up. There was no loss of clinical remission in the IBD cohort overall, Crohn's disease [CD], or perianal CD [pâ =â 0.55 and pâ =â 0.11 at 9-12 months, and pâ =â 0.50 at 6 months, respectively]. Neither prior IV dose [≤â 10 mg/kg 6-weekly] [pâ =â 0.48] nor IBD disease subtype was associated with an increased clinical relapse rate at 6 months (pâ =â 0.48 and pâ =â 0.45 [UC vs CD], respectively). CONCLUSION: Changing patients established on IV infliximab to an SC formulation is associated with a high ongoing clinical remission and a low adverse event rate. Furthermore, there are no signals for adverse outcomes among different IBD disease subtypes, nor in those on escalated IV infliximab dosing schedules up to 10 mg/kg 6-weekly. These data should provide patients and clinicians alike with confidence in SC infliximab use in IBD.
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Fármacos Gastrointestinais , Doenças Inflamatórias Intestinais , Infliximab , Infliximab/administração & dosagem , Infliximab/uso terapêutico , Humanos , Injeções Subcutâneas , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Administração Intravenosa , Doença de Crohn/tratamento farmacológicoRESUMO
The most significant and common cause of anaemia is iron deficiency, which occurs when iron absorption cannot meet the body's demands due to growth, pregnancy, poor nutrition, malabsorption or blood loss. It is estimated that in the UK 11% of the adult population have iron-deficiency anaemia (IDA) and investigation is essential to exclude significant pathology as the underlying cause. It has been shown that IDA is responsible for 57 000 hospital admissions in the UK, and at least 10% of gastroenterology referrals per annum. IDA is a major red flag symptom for gastrointestinal cancer. At the Royal Liverpool University Hospital, a dedicated nurse-led IDA service was developed in 2005 to help alleviate the clinical pressures created by the two week suspected cancer referral pathway. With the success of this service, investigation and management of IDA has been extended to referrals from accident and emergency, with the aim of reducing hospital admissions and to investigating and optimising iron replacement therapy in preoperative patients. Delivering this as a nurse consultant-led service was proposed by the gastroenterology medical team who felt that, as a clinical problem with well established, published investigative algorithms, IDA would be suitable for management in a dedicated nurse-led clinic. This article will focus on the strategies employed to achieve sufficient resources and clinic capacity to run this service effectively, develop strong nurse education and training, and the development of agreed investigation pathways. A robust results review process, with rapid management of abnormal results, was established with timely discharge for those patients with normal results. Optimisation of iron replacement therapy and verification of sustained haematological response was prioritised as this was identified as being poorly managed across all specialties. A process for ongoing audit of results was included to show the success of the service and highlight areas for redesign. Here, we demonstrate the effectiveness of our nurse-led IDA service and suggest it as the basis for other IDA services in the UK and beyond.
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BACKGROUND: While indirect comparison of infliximab (IFX) and vedolizumab (VDZ) in adults with Crohn's disease (CD) or ulcerative colitis (UC) shows that IFX has better effectiveness during induction, and comparable efficacy during maintenance treatment, comparative data specific to subcutaneous (SC) IFX (i.e., CT-P13 SC) versus VDZ are limited. AIM: Pooled analysis of randomised studies to compare efficacy and safety with IFX SC and VDZ in moderate-to-severe inflammatory bowel disease. METHODS: Parallel-group, randomised studies evaluating IFX SC and VDZ in patients with moderate-to-severe CD or UC were identified. Eligible studies reported ≥ 1 prespecified outcome of interest at Week 6 (reflecting treatment during the induction phase) and/or at 1 year (Weeks 50-54; reflecting treatment during the maintenance phase). Prespecified efficacy and safety outcomes considered in this pooled analysis included the proportions of patients achieving disease-specific clinical responses, clinical remission, or discontinuing due to lack of efficacy, and the proportions of patients experiencing adverse events (AEs), serious AEs, infections, serious infections, or discontinuing due to AEs. Data from multiple studies or study arms were extracted and pooled using a random-effect model; comparative analyses were performed separately for patients with CD and UC. RESULTS: We identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ. In patients with CD, intravenous induction therapy with IFX demonstrated better efficacy (non-overlapping 95% confidence intervals [CIs]) compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy (overlapping 95% CIs) than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In patients with UC, efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year. CONCLUSION: IFX SC demonstrated better efficacy than VDZ in patients with CD, and similar efficacy to VDZ in patients with UC; 1-year safety was comparable with IFX SC and VDZ.
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Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Doença de Crohn , Fármacos Gastrointestinais , Infliximab , Adulto , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/administração & dosagem , Quimioterapia de Indução/métodos , Infliximab/uso terapêutico , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Injeções Subcutâneas , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Resultado do TratamentoRESUMO
OBJECTIVES: Priority Setting Partnerships (PSP's) using the James Lind Alliance (JLA) methodology, bring together health professionals, patients and parents/carers to identify and prioritise unanswered questions that can be addressed by future research projects. To identify and prioritise the top 10 unanswered research priorities in digital technology for adolescents and young people (AYP) with inflammatory bowel disease (IBD). METHODS: A steering group (SG) consisting of AYP with IBD, their parents/carers, representatives from two charities (Crohn's & Colitis UK, Crohn's in Childhood Research Association), patient information forum and paediatric and adult and primary care healthcare professionals was established in 2021. The SG agreed the protocol, and scope of the PSP and oversaw all aspects. SG meetings were chaired by a JLA advisor and followed the established JLA methodology. RESULTS: The initial survey generated 414 in-scope questions from 156 respondents, thematically categorised into 10 themes and consolidated into 92 summary questions by the SG. A comprehensive literature review followed by SG deliberation narrowed the unanswered summary questions to 45, for the interim prioritising survey. One hundred and two respondents ranked their top 10 research questions. Outputs generated top 18 research priorities presented at a final virtual prioritisation workshop, facilitated by JLA advisors and attended by key stakeholders, ranked into top 10 research priorities. DISCUSSION: The top 10 research priorities will encourage researchers to undertake research that addresses these areas of unmet need for AYP living with IBD, their parents/carers and their healthcare professionals, thereby facilitating improved patient care.
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Pesquisa Biomédica , Doenças Inflamatórias Intestinais , Adulto , Humanos , Adolescente , Criança , Tecnologia Digital , Prioridades em Saúde , Comportamento Cooperativo , Inquéritos e Questionários , Pesquisa , Doenças Inflamatórias Intestinais/terapiaRESUMO
BACKGROUND: Over recent years, there has been increasing adoption of minimally invasive surgery (MIS) in the treatment of adrenocortical carcinoma (ACC). However, MIS has been associated with noncurative resection and locoregional recurrence. We aimed to identify risk factors for margin-positivity among patients who undergo MIS resection for ACC. We hypothesized that a simple nomogram can accurately identify patients most suitable for curative MIS resection. METHODS: Curative-intent resections for ACC were identified through the National Cancer Database spanning 2010-2018. Trends in MIS utilization were reported using Pearson correlation coefficients. Factors associated with margin-positive resection were identified among preoperatively available variables using multivariable logistic regression, then incorporated into a predictive model. Model quality was cross validated using an 80% training data set and 20% test data set. RESULTS: Among 1260 ACC cases, 38.6% (486) underwent MIS resection. MIS utilization increased over time at nonacademic centers (R = 0.818, p = 0.007), but not at academic centers (R = 0.009, p = 0.982). Factors associated with margin-positive MIS resection were increasing age, nonacademic center (odds ratio [OR]: 1.8, p = 0.006), cT3 (OR: 4.7, p < 0.001) or cT4 tumors (OR: 14.6, p < 0.001), and right-sided tumors (OR: 2.0, p = 0.006). A predictive model incorporating these four factors produced favorable c-statistics of 0.75 in the training data set and 0.72 in the test data set. A pragmatic nomogram was created to enable bedside risk stratification. CONCLUSIONS: An increasing proportion of ACC are resected via minimally invasive operations, particularly at nonacademic centers. Patient selection based on a few key factors can minimize the risk of noncurative surgery.
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Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Laparoscopia , Humanos , Carcinoma Adrenocortical/cirurgia , Carcinoma Adrenocortical/patologia , Nomogramas , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Neoplasias do Córtex Suprarrenal/cirurgia , Neoplasias do Córtex Suprarrenal/patologia , Estudos RetrospectivosRESUMO
Data quality is often an overlooked feature in the analysis of omics data. This is particularly relevant in studies of chemical and pathogen exposures that can modify an individual's epigenome and transcriptome with persistence over time. Portable, quality control (QC) pipelines for multiple different omics datasets are therefore needed. To meet these goals, portable quality assurance (QA) metrics, metric acceptability criterion, and pipelines to compute these metrics were developed and consolidated into one framework for 12 different omics assays. Performance of these QA metrics and pipelines were evaluated on human data generated by the Defense Advanced Research Projects Agency (DARPA) Epigenetic CHaracterization and Observation (ECHO) program. Twelve analytical pipelines were developed leveraging standard tools when possible. These QC pipelines were containerized using Singularity to ensure portability and scalability. Datasets for these 12 omics assays were analyzed and results were summarized. The quality thresholds and metrics used were described. We found that these pipelines enabled early identification of lower quality datasets, datasets with insufficient reads for additional sequencing, and experimental protocols needing refinements. These omics data analysis and QC pipelines are available as open-source resources as reported and discussed in this article for the omics and life sciences communities.
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Sequenciamento de Nucleotídeos em Larga Escala , Software , Humanos , Análise de Sequência de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Controle de Qualidade , TranscriptomaRESUMO
Aldehyde oxidase (AOX) is a cytosolic drug-metabolizing enzyme which has attracted increasing attention in drug development due to its high hepatic expression, broad substrate profile and species differences. In contrast, there is limited information on the presence and activity of AOX in extrahepatic tissues including ocular tissues. Because several ocular drugs are potential substrates for AOX, we performed a comprehensive analysis of the AOX1 expression and activity profile in seven ocular tissues from humans, rabbits, and pigs. AOX activities were determined using optimized assays for the established human AOX1 probe substrates 4-dimethylamino-cinnamaldehyde (DMAC) and phthalazine. Inhibition studies were undertaken in conjunctival and retinal homogenates using well-established human AOX1 inhibitors menadione and chlorpromazine. AOX1 protein contents were quantitated with targeted proteomics and confirmed by immunoblotting. Overall, DMAC oxidation rates varied over 10-fold between species (human ËË rabbit Ë pig) and showed 2- to 6-fold differences between tissues from the same species. Menadione seemed a more potent inhibitor of DMAC oxidation across species than chlorpromazine. Human AOX1 protein levels were highest in the conjunctiva, followed by most posterior tissues, whereas anterior tissues showed low levels. The rabbit AOX1 expression was high in the conjunctiva, retinal pigment epithelial (RPE), and choroid while lower in the anterior tissues. Quantification of pig AOX1 was not successful but immunoblotting confirmed the presence of AOX1 in all species. DMAC oxidation rates and AOX1 contents correlated quite well in humans and rabbits. This study provides, for the first time, insights into the ocular expression and activity of AOX1 among multiple species.
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Aldeído Oxidase , Vitamina K 3 , Humanos , Coelhos , Animais , Suínos , Aldeído Oxidase/química , Aldeído Oxidase/metabolismo , Vitamina K 3/metabolismo , Clorpromazina , Oxirredução , Fígado/metabolismoRESUMO
BACKGROUND: Tobacco-related disparities are a leading contributor to health inequities among marginalized communities. Lack of support from health professionals is one of the most cited barriers to tobacco cessation reported by these communities. Improving the proficiencies with which health professionals incorporate social and cultural influences into therapeutic interactions has the potential to address this critical barrier. In general, training to improve these proficiencies has shown promise, but the specific proficiencies required for treating tobacco use among marginalized communities are unknown. This project aimed to develop a competency-based curriculum to improve these proficiencies among health professionals with experience and training in the evidence-based treatment of tobacco use, and then pilot test the content delivered via an expert review of a virtual, self-paced workshop. METHODS: We used the Delphi Technique to systematically identify the specific competencies and corresponding knowledge and skill sets required to achieve these proficiencies. Educational content was developed to teach these competencies in a virtual workshop. The workshop was evaluated by 11 experts in the field by examining pre- and post-training changes in perceived knowledge, skill, and confidence levels and other quantitative and qualitative feedback. Repeated measures analysis of variance and paired sample t-tests were used to examine pre-post training differences. RESULTS: Six competencies and corresponding skill sets were identified. After exposure to the virtual workshop, the experts reported significant increases in the overall proficiency for each competency as well as increases in nearly all levels of knowledge, skill, and confidence within the competency skill sets. Qualitative and quantitative findings indicate that content was relevant to practice. CONCLUSIONS: These findings provide preliminary support for 6 competencies and skills sets needed to improve therapeutic interpersonal interactions that recognize the importance of social and cultural influences in the treatment of tobacco use.
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Currículo , Uso de Tabaco , Humanos , Escolaridade , Processos MentaisRESUMO
High-grade serous ovarian carcinoma (HGSOC) is characterised by poor outcome and extreme chromosome instability (CIN). Therapies targeting centrosome amplification (CA), a key mediator of chromosome missegregation, may have significant clinical utility in HGSOC. However, the prevalence of CA in HGSOC, its relationship to genomic biomarkers of CIN and its potential impact on therapeutic response have not been defined. Using high-throughput multi-regional microscopy on 287 clinical HGSOC tissues and 73 cell lines models, here we show that CA through centriole overduplication is a highly recurrent and heterogeneous feature of HGSOC and strongly associated with CIN and genome subclonality. Cell-based studies showed that high-prevalence CA is phenocopied in ovarian cancer cell lines, and that high CA is associated with increased multi-treatment resistance; most notably to paclitaxel, the commonest treatment used in HGSOC. CA in HGSOC may therefore present a potential driver of tumour evolution and a powerful biomarker for response to standard-of-care treatment.
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Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Centrossomo/metabolismo , Cistadenocarcinoma Seroso/genéticaRESUMO
Objective: To explore Young Persons (YP) and healthcare professionals (HCP) experiences of virtual consultations (VC) and establish whether developmentally appropriate healthcare can be delivered virtually. Method: YP and HCP questionnaire surveys were designed and piloted. Electronic questionnaire links were sent by post, email or text message January-April 2021 to YP aged 13-25 years old, with predefined chronic gastrointestinal conditions, attending a gastroenterology/hepatology VC. HCP undertaking VC were invited to complete staff questionnaire. Results were anonymous and collated using Excel version 2302. Results: Five UK hospital trusts participated, with 35 HCP responses. Of the 100 YP completing the survey 66% were female and 34% male aged between 13 years and 25 years (median: 18 years). 13% were new appointments and 87% follow ups, 29% were by video, 69% by phone and 2% gave no response. 80% of HCP spoke to YP directly but not privately (69%). 87% of YP and 88% HCP found VC useful. 83% of YP want VC again, although 20% preferred face to face. 43% of HCP required improved phone/internet connection. 77% of YP required hospital appointments for tests following VC. Conclusions: Overall respondents were satisfied with VC, finding them useful, convenient and time saving. Successful VC rely on appropriate patient selection and availability of reliable technology. Patient preference is key which may alter with time.
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Gold catalysis is an important method for alkyne functionalization. Here we report the gold-catalyzed formal [3+2] aminative cyclization of yndiamides and isoxazoles in a direct synthesis of polysubstituted diaminopyrroles, which are important motifs in drug discovery. Key to this process is the formation, and subsequent cyclization, of an α-imino gold Fischer carbene, which represents a new type of gold carbene intermediate. The reaction proceeds rapidly under mild conditions, with high regioselectivity being achieved by introducing a subtle steric bias between the nitrogen substituents on the yndiamide. DFT calculations revealed that the key to this regioselectivity was the interconversion of isomeric gold keteniminiun ions via a low-barrier π-complex transition state, which establishes a Curtin-Hammett scenario for isoxazole addition. By using benzisoxazoles as substrates, the reaction outcome could be switched to a formal [5+2] cyclization, leading to 1,4-oxazepines.
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Wild and managed bees are critical for the stability of trophic webs, angiosperm reproduction, and agricultural productivity. Unfortunately, as many as 40% of crop pollinators are in a steep decline due to habitat loss and exposure to agrochemicals. Pyrethroids, neonicotinoids, and macrocyclic lactones are among the many agrochemicals toxic to pollinating insects that are used extensively in industrial beef cattle feeding operations throughout the world. Fugitive feedyard particulate matter (PM) transports agrochemicals into the surrounding environs. To determine the impact of agrochemical-laden feedyard particulate matter on bee pollinators, we conducted in situ experiments wherein honeybees and mason bees were placed downwind and upwind of feedyards (N = 40). Concurrent, colocated total suspended particulate matter samples contained multiple insecticides and parasiticides including pyrethroids, neonicotinoids, and macrocyclic lactones, in significantly higher concentrations downwind of feedyards (bifenthrin, 8.45 ± 4.92; permethrin, 1032.34 ± 740.76; clothianidin, 3.61 ± 1.48; imidacloprid, 73.32 ± 47.52; thiamethoxam, 5.81 ± 3.16; abamectin, 0.45 ± 0.29; ivermectin, 8.88 ± 5.06 ng/g). Honeybees and mason bees sited downwind of feedyards always experienced higher mortality than those correspondingly sited upwind, and male mason bees experienced significantly higher mortality compared to females when both were sited downwind. Bees occurring downwind of beef cattle feedyards for 1 h are 232-260% more likely to die than those occurring upwind. Thus, agrochemicals used on and emitted from beef cattle feedyards are significant threats to bee pollinators.