Midlands Evidence Repository
Not a member yet
9653 research outputs found
Sort by
Safety, pharmacokinetics, pharmacodynamics, and antitumor activity from a phase I study of simlukafusp alfa (FAP-IL2v) in advanced/metastatic solid tumors
No full textPurpose: Simlukafusp alfa (FAP-IL2v), a tumor-targeted immunocytokine, comprising an interleukin-2 variant moiety with abolished CD25 binding fused to human immunoglobulin G1, is directed against fibroblast activation protein-α. This phase I, open-label, multicenter, dose-escalation and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of FAP-IL2v in patients with advanced/metastatic solid tumors. Methods: Participants received FAP-IL2v intravenously once weekly. Dose escalation started at 5 mg; flat dosing (≤25 mg) and intra-participant up-titration regimens (15/20 mg, 20/25 mg, 20/20/35 mg, 20/35/35 mg) were evaluated. Primary objectives were dose-limiting toxicities (DLT), maximum tolerated dose (MTD), recommended expansion dose, and pharmacokinetics. Results: Sixty-one participants were enrolled. DLTs included fatigue (flat dose 20 mg: n = 1), asthenia (25 mg: n = 1), drug-induced liver injury (up-titration regimen 20/25 mg: n = 1), transaminase increase (20/25 mg: n = 1), and pneumonia (20/35/35 mg: n = 1). Up-titration regimen 15/20 mg was the MTD and was selected as the recommended expansion dose. Increases in peripheral blood absolute immune cell counts were seen for all tested doses (natural killer cells, 13-fold; CD4+ T cells [including Tregs], 2-fold; CD8+ T cells, 3.5-fold), but without any percentage change in Tregs. Clinical activity was observed from 5 mg (objective response rate, 5.1% [n = 3]; disease control rate, 27.1% [n = 16]). Responses were durable (n = 3; 2.8 [censored], 6.3, and 43.4 months). Conclusions: FAP-IL2v had a manageable safety profile and showed initial signs of antitumor activity in advanced/metastatic solid tumors.https://aacrjournals.org/clincancerres/article-abstract/doi/10.1158/1078-0432.CCR-23-3567/743084/Safety-Pharmacokinetics-Pharmacodynamics-and?redirectedFrom=fulltex
Challenges of prenatal diagnosis in obese pregnant women
No full textObesity rates are increasing world-wide with most of the increase in women of the reproductive age group. While recognised as an important contributor to non-communicable diseases, pregnant women with obesity are particularly at risk of not only maternal and pregnant complications but also have an increased risk of congenital malformations. Furthermore, pregnant obese women are more likely to be older and therefore at a greater risk of aneuploidy. Prenatal diagnosis in these women especially those who are morbidly obese is challenging due not only to their weight but the implications of the increase adiposity on biochemical markers of aneuploidy. In this review we discuss the current challenges in providing prenatal diagnosis for these women including those related to the ergonomics of ultrasound and those inherent in them because of their obesity. Appropriate counselling for these women should include the lower sensitivity of the tests, the difficulties in performing some of the procedures (imaging and invasive testing) as well as the increased risk of structural abnormalities related to their obesity.https://www.sciencedirect.com/science/article/abs/pii/S1521693424000166?via%3Dihu
It's only a nasogastric tube, what could go wrong?
No full texthttps://www.magonlinelibrary.com/doi/abs/10.12968/bjon.2024.33.8.S3?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.or
Facilitators and barriers to vaccination uptake in pregnancy: A qualitative systematic review
No full textIntroduction: Vaccination during pregnancy protects both the mother and the foetus from vaccine-preventable diseases. However, uptake of the recommended vaccines (influenza, pertussis, COVID-19) by pregnant women remains low in Europe and the USA. Understanding the reasons for this is crucial to inform strategies to increase vaccination rates in pregnant women. This qualitative systematic review aimed to identify the barriers and facilitators to vaccination against influenza, pertussis/whooping cough and COVID-19 during pregnancy and identify possible strategies to increase vaccination rates. Methods: We conducted a comprehensive search of electronic databases, including Medline, PsycINFO, CINAHL, Web of Science, WHO database, Embase and grey literature to identify qualitative studies that explored barriers and facilitators to vaccine uptake among pregnant women (PROSPERO CRD42023399488). The search was limited to studies published between 2012 and 2022 conducted in high-income countries with established vaccination programmes during pregnancy. Studies were thematically analysed and underwent quality assessment using the Joanna Briggs Institute validated critical appraisal tool for qualitative research. Results: Out of 2681 articles screened, 28 studies (n = 1573 participants) were eligible for inclusion. Five overarching themes emerged relating to personal, provider and systemic factors. Barriers to vaccine uptake included concerns about vaccine safety and efficacy, lack of knowledge about vaccines' benefits and necessity, fear of adverse effects on the foetus or mother and low perception of disease severity. Facilitators included recommendations from trusted healthcare providers, easy access to vaccination, clear communication on the benefits and safety of vaccination, and positive social influences from family and friends. Strategies for increasing vaccination uptake included strong and proactive vaccine recommendations by trusted healthcare professionals, provision of vaccines during routine antenatal care, and clear and consistent communication about vaccines addressing pregnant women's concerns. Conclusion: This review highlights the need for interventions that address the identified barriers to vaccine uptake among pregnant women. Recommendation from a healthcare provider can play a significant role in promoting vaccine uptake, as can clear risk/benefit communication and convenient access to vaccination. Addressing concerns about vaccine safety and providing accurate information about vaccines is also important.https://journals.plos.org/plosone/article?id=10.1371/journal.pone.029840
Helping parents know when to seek help for an acutely ill child: Evidence based co-development of a mobile phone app using complex intervention methodology
No full textBackground: Acute illness accounts for the majority of episodes of illness in children under five years of age and is the age group with the highest consultation rate in general practice in the UK. The number of children presenting to emergency care is also steadily increasing, having risen beyond pre-pandemic numbers. Such high, and increasing, rates of consultation have prompted concerns about parents' level of knowledge and confidence in caring for their children when they are ill, and particularly when and how to seek help appropriately. Aim: The ASK SNIFF collaboration research programme identified parents' need for accurate and accessible information to help them know when to seek help for a sick child in 2010. This paper presents the resulting programme of research which aimed to co-develop an evidence-based safety netting intervention (mobile app) to help parents know when to seek help for an acutely ill child under the age of five years in the UK. Methods: Our programme used a collaborative six step process with 147 parent and 324 health professional participants over a period of six years including: scoping existing interventions, systematic review, qualitative research, video capture, content identification and development, consensus methodology, parent and expert clinical review. Results: Our programme has produced evidence-based content for an app supported by video clips. Our collaborative approach has supported every stage of our work, ensuring that the end result reflects the experiences, perspectives and expressed needs of parents and the clinicians they consult. Conclusion: We have not found any other resource which has used this type of approach, which may explain why there is no published evaluation data demonstrating the impact of existing UK resources. Future mobile apps should be designed and developed with the service users for whom they are intended.https://www.sciencedirect.com/science/article/pii/S1386505624001229?via%3Dihu
Typology of employers offering line manager training for mental health
Get PDF© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Occupational Medicine.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits
unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.BACKGROUND: Mental ill health has a high economic impact on society and employers. National and international policy advocates line manager (LM) training in mental health as a key intervention, but little is known about employer training provisions. AIMS: To explore the prevalence and characteristics of organizations that offer LM training in mental health. METHODS: Secondary analysis of existing longitudinal anonymised organizational-level survey data derived from computer-assisted telephone interview surveys collected in four waves (2020:1900 firms, 2021:1551, 2022:1904, 2023:1902) in England, before, during and after a global pandemic. RESULTS: The proportion of organizations offering LM training in mental health increased pre- to post-pandemic (2020:50%, 2023:59%) but 41% do not currently provide it. Logistic regression confirmed that LM training is more likely to be offered by large-sized enterprises, organizations with a larger proportion of employees who are younger (aged 25-49), female, disabled and from ethnic minority communities. Sector patterns were inconsistent, but in 2023, organizations from the 'Hospitality' and 'Business Services' sectors were more likely to provide LM training than other sectors. CONCLUSIONS: Continued efforts are needed to increase the proportion of employers offering LM training in mental health, particularly small- to medium-sized enterprises, and organizations with predominantly male, White and/or older workforces.https://academic.oup.com/occmed/article/74/3/242/7667610?login=tru
Prospective evaluation of the impact of multi-channel studies on treatment outcomes in children with sleep disordered breathing
Get PDFThere are significant variations in practice regarding the use of sleep studies in children with symptoms of sleep disordered breathing (SDB) prior to adenotonsillectomy. Current UK guidance recommends the selective use of sleep studies to confirm a diagnosis of obstructive sleep apnoea (OSA) when there is diagnostic uncertainty, in children with comorbidities, or to assess perioperative risk when severe OSA is suspected. We have developed a novel paediatric sleep service over the past decade based on the routine use of multi-channel sleep studies (MCSS) before adenotonsillectomy. We present the results of a prospective evaluation assessing the impact of our service on treatment outcomes. We conducted a prospective service evaluation of 49 children with SDB seen between July 2021 and August 2022. We used medical records and a sleep study database to determine treatment outcomes. Otolaryngologists completed a questionnaire before each multi-channel sleep study to help evaluate the impact of sleep study findings on surgical decision making. Questionnaire responses before MCSS showed that clinicians thought 66 % of children were ‘likely’, ‘very likely’ or ‘definitely’ would require surgery but only 54 % of children underwent surgery following their sleep study. We estimate that the use of MCSS was associated with a 21 % reduction in children undergoing surgery in this small sample. We conclude that our use of MCSS facilitates conservative management, allowing a significant reduction in the number of children with SDB undergoing surgery, but further validation of MCSS against polysomnography is required.https://www.sciencedirect.com/science/article/pii/S259014272400009
Usability of web-based tools designed for communication and decision-making in dementia: Systematic review and design brief
No full textINTRODUCTION: There is an increased number of web-based tools designed for people with dementia and their family caregivers and addressing communication and decision-making. The loss of cognitive functions associated with dementia can impact individuals' experiences and use of web-based tools. There is a need for high quality and user-friendly web-based tools that support communication and decision-making for people with dementia and their family caregivers. OBJECTIVE: To identify usability requirements, usability testing methods, and design suggestions from studies focusing on web-based tools for communication and decision-making support in dementia care. METHODS: We conducted a systematic review with narrative synthesis. Five databases were systematically searched in February 2023. The quality of the included studies was assessed using the Mixed Methods Appraisal Tool. RESULTS: A total of 1,032 articles were identified and 7 fulfilled inclusion criteria. Web-based tools addressed technology usage, health promotion, home modification information, shared decision-making facilitation, information needs and social isolation. Methods to test usability included surveys, interviews, focus groups, cognitive walkthroughs and think-aloud procedures. Findings suggested reducing cognitive load, enhancing readability, providing clear language, and emphasising the need for additional support for people with dementia. Design recommendations include optimising information delivery and presentation, enhancing visual elements, streamlining navigation, providing concrete examples, using clear language, and offering training and tailored support. CONCLUSION: Usability requirements ranged from visual appearance and navigation to delivery of content and support needed. This review contributes to efforts to improve design and development of web-based tools targeting communication and decision-making in dementia care. Further research should address tailored support to enhance usability for people with dementia.https://www.sciencedirect.com/science/article/abs/pii/S138650562400147
Achievement of LDL-C goal following acute coronary syndrome: are targets being met?
Get PDFIntroduction Reduction of low-density lipoprotein C (LDL-C) slows progression of atherosclerosis and decreases risk of future cardiovascular events following acute coronary syndrome (ACS). However, notable differences exist between European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines on lipid lowering goals. For patients diagnosed with ACS, NICE 2023 guidance recommends a target LDL-C level of 2.0 mmol/l or less, or non-HDL cholesterol level of 2.6 mmol/l or less. NICE also recommend full lipid profile evaluation on admission and 2–3 months after starting or changing treatment. ESC 2019 dyslipidaemia guidelines recommend high intensity statin therapy for a 50% reduction in LDL-C or LDL-C levels of <1.4 mmol/l in very high-risk patients. Failure to reach lipid targets should warrant consideration of novel lipid lowering therapies. We sought to determine the proportion of patients with ACS who achieved LDL-C goals by 3 months and to assess adherence to lipid profile monitoring recommendations. Methods In this retrospective cohort analysis, patients with confirmed ACS from 1st June 2022 to 31st May 2023 were identified from our local Myocardial Ischaemia National Audit Project (MINAP) dataset. Lipid profile, baseline demographic and medical therapy data were collected from our Trust online laboratory reporting system, healthcare summary records and correspondence. Data was analysed using GraphPad Prism and Microsoft Excel. Results Of the 343 patients included in the study, mean age was 67.9 years, 67.7% were male and 12.2% had previously diagnosed dyslipdiaemia (table 1). 72.9% met the NICE target, and 34.6% met the ESC target. During admission for ACS 12.0% of patients had a lipid profile taken and 31.2% had a lipid profile <3 months following discharge (table 2). 2.9% of patients had a lipid profile both during admission and <3 months of discharge. 88.8% of patients were discharged on a statin, 3.8% on combination or newer lipid lowering therapies, and 7.4% on no lipid lowering therapy at all. Of the 301 patients discharged on a statin, 18.6% reported an intolerance or side effect. 64.3% reduced their statin dose or were prescribed an alternative statin, 5.4% were started on Ezetimibe. 23.2% received no alternative lipid lowering therapy agent. Conclusion This data demonstrates that NICE and ESC 3 month lipid targets are not being met in post ACS patients at our institution. Given the availability of new lipid lowering therapies, this study highlights that improvements in both serial lipid profile monitoring and prescription of novel therapies can be made to reduce risk of future cardiovascular events.https://heart.bmj.com/content/110/Suppl_3/23