Midlands Evidence Repository
Not a member yet
9653 research outputs found
Sort by
Primary IgA nephropathy: new insights and emerging therapies
No full textPrimary IgA nephropathy (IgAN) is a common glomerular disorder defined by predominant mesangial IgA deposition. Once thought to follow a progressive course in 10-20% of those diagnosed, emerging evidence now suggests most will progress to kidney failure over their lifetimes. Although the lack of safe and effective treatments to impede disease progression continues to present a challenge, the landscape of IgAN has dramatically evolved over the last 2 years. Driven by fundamental changes to accepted end points for IgAN clinical trials as well as fascinating new insights into the pathophysiology of IgAN, a swathe of novel and repurposed therapies are currently being evaluated. Already, two novel drugs, targeted-release formulation budesonide and sparsentan, have received conditional approvals for the treatment of IgAN, with sodium glucose co-transporter 2 inhibitors establishing themselves as further options. Soon to join this ensemble are likely to be treatments that modulate the complement system and B-cell activity; several are currently undergoing clinical trials in IgAN with promising interim results. In this review, we provide an overview of evolving epidemiological insights, disease mechanisms, emerging therapies, and contemporary challenges surrounding the management of IgAN.https://www.sciencedirect.com/science/article/abs/pii/S2949813924000727?via%3Dihu
Misconducts in research and methods to uphold research integrity
No full textResearch misconduct refers to deliberate or accidental manipulation or misrepresentation of research data, findings, or processes. It can take many forms, such as fabricating data, plagiarism, or failing to disclose conflicts of interest. Data falsification is a serious problem in the field of medical research, as it can lead to the promotion of false or misleading information. Researchers might engage in p-hacking - the practice of using someone else's research results or ideas without giving them proper attribution. Conflict of interest (COI) occurs when an individual's personal, financial, or professional interests could potentially influence their judgment or actions in relation to their research. Nondisclosure of COI can be considered research misconduct and can damage the reputation of the authors and institutions. Hypothesis after results are known can lead to the promotion of false or misleading information. Cherry-picking data is the practice of focusing attention on certain data points or results that support a particular hypothesis, while ignoring or downplaying results that do not. Researchers should be transparent about their methods and report their findings honestly and accurately. Research institutions should have clear and stringent policies in place to address scientific misconduct. This knowledge must become widespread, so that researchers and readers understand what approaches to statistical analysis and reporting amount to scientific misconduct. It is imperative that readers and researchers alike are aware of the methods of statistical analysis and reporting that constitute scientific misconduct.https://journals.lww.com/indianjcancer/abstract/9900/misconducts_in_research_and_methods_to_uphold.81.asp
Royal College of Psychiatrists (RCPsych) Dean's grand rounds - an Innovative medical education tool to bridge the education-practice gap
No full textAims. RCPsych Dean's Grand Rounds focuses on understanding a problem or an opportunity for change in clinical practice using a patient story, academic evidence, and contextual data in this area to bridge the evidence-practice gap using a quality improvement approach. The Dean's Grand Rounds aims to embed the lived experience in clinical practice and use data to drive change. Methods. We held five virtual Dean's Grand Rounds with this format from June 2022 to January 2024. The sessions included a variety ofmedical professionals, carers and expert patients presenting on the chosen theme, followed by a panel discussion. The sessions were thenmade available for on-demand viewing via the RCPsych website for those unable to attend the live session. Qualitative and quantitative feedback helped us improve the sessions iteratively. Results. The sessionshave enabled discussion of broader issues facing staff and patients, facilitating the exchange of ideas between professionals from divisions of the RCPsych from around the world. Participants globally attended these sessions, with over 1,000 registrations for the Grand Rounds on memory clinics and catatonia. The feedback for the sessions was overwhelmingly positive, with many participants praising the involvement of patients and carers and the opportunity to come together at the RCPsych level for learning. Many were attracted to the sessions because of the themes discussed, with 68.5% having excellent overall experience.Over 92% of the feedback participants thought the Grand Rounds had improved their professional practice. The majority of the feedback participants strongly agreed that lived experience is an important element in understanding the evidence-practice gap (4.4 on a Likert scale of 1, strongly disagree; 5, strongly agree) and that the Grand Rounds had enhanced their understanding of academic evidence and contextual data in the area (4.4, 4.39 respectively on a Likert scale of 1, strongly disagree; 5, strongly agree). The themes that stood out in the feedback were that participants liked the Grand Rounds format and were grateful to hear from patients, with suggestions to allocate more time for questions and answers. Learning from the feedback, we set up a resources page for each Grand Rounds to enable further learning. Conclusion. In their revitalised format, these sessions are proving highly effective in bringing the worldwide RCPsych community together to improve patient care and deliver educational and informative interactive content available on demand.https://www.cambridge.org/core/journals/bjpsych-open/article/royal-college-of-psychiatrists-rcpsych-deans-grand-rounds-an-innovative-medical-education-tool-to-bridge-the-educationpractice-gap/2B02C076567BEC809AF7D8ED50FB1E9
Effective induction programme for higher specialist trainees : a quality improvement project
No full textAims. To create a safe and effective induction programme for Higher Specialist Trainees (HST) at Nottinghamshire Healthcare NHS Foundation Trust. An effective induction improves trainees' satisfaction, they feel welcomed and valued. It improves patient safety, retention, and recruitment (GMC Report 2020). Methods. Based on GMC report, published in 2020, a survey was developed locally and data for 2021 HST induction was collected using digital platform. Initial stakeholder analysis completed, and relevant parties were invited to share the results. Two key deliverables were identified after consultation, one was a dedicated induction programme for HST which was co-produced along with trainees and stakeholders. The other deliverable was updating the induction booklet. The proposed induction plan was implemented in August 2023, the survey was repeated to the new HST cohort following induction via digital platform. Results of the survey were analysed via mixed methods (qualitative & quantitative). Results. The surveys conducted in 2021 and 2023 were compared and there was an increase in response rate from 50% to 64%. The domains were devised from GMC standards and assessed by if staff had received everything in the domain within a week of starting their placement and results evaluated using a t-test. Domain A is gaining access to places and system (keys, fobs, security passes, computers, ID badges, mobile phones, IT system). This significantly improved from 27% to 88% with a p-value of < 0.001. Domain B is physical orientation of the setting (staff facilities such as lockers, parking, library, and site layout). This significantly improved from 45% to 88% with a p-value of < 0.018. Domain C is gaining day to day knowledge (HR, rota, annual leave, study leave, pay-roll, mandatory training, e-expenses, and guardian of safe working). There was no significant change between 9% and 19% with a p-value of < 0.48. Domain D is an understanding of expectations (duties and responsibility during working hours, on-call, team introduction). This significantly improved from 9% to 69% with a p-value of < 0.002. HSTs were given the chance to add comments and the responses in 2023 were more positive "excellent induction compared to previous years" compared with 2021 when HSTs felt isolated and devalued "worst ever induction in whole career in NHS". Conclusion. Overall, the results of the 2023 survey showed considerable improvement in all the key areas of induction within one week of starting the placement. Domain C demonstrates a challenge still and needs further work
Invasive group A streptococcal disease
No full textWe report on two children who had presented in a poor clinical state after an initial bout of cough, sore throat and fever for a few days. Both of them had multisystemic involvement with fluid-refractory septic shock requiring ionotropic support, intubation and care in the paediatric intensive care unit. Recent significant rise in scarlet fever has led to a significant increase in the number of invasive group A streptococcal infections with increased mortality in paediatric patients. Both of them had co-infection with influenza, which could have led to an increased risk of invasive group A streptococcal (iGAS) infection. After prompt treatment, including early initiation of antibiotics, they both recovered well. To our knowledge, there are no reported cases of iGAS infection from the UK in any medical journal though the fatal cases have been reported to the health statistics department by various National Health Service trusts individually.https://casereports.bmj.com/content/17/1/e254646.lon
Exploring the perspectives of underrepresented voices: Perceptions and experiences of uterine cancer for black African, Caribbean, black British, and mixed-black women in the UK to develop strategies for early symptom presentation
No full textObjectives: The uterine cancer (UC) mortality rate in the UK is significantly higher for women who belong to a Black ethnic group compared to those from other ethnic groups. This study aimed to understand the views and experiences of UC amongst Black ethnic minority women in the UK, with a focus on awareness and presentation of red-flag symptoms. Methods: Women of Black African, Caribbean, Black British and Mixed-Black ethnicity were purposefully recruited to participate in focus groups and individual semi-structured interviews. Results: Twenty women from different regions in England participated in the study. Reflexive thematic analysis of the data led to the identification of three main themes: 1) Healthcare inequities; 2) Support and sense making with other Black women; and 3) Knowledge dissemination, mobilisation, and empowerment. Perceptions of inequitable healthcare provision and distrust influenced how participants, and their peer networks, approached seeking assistance from healthcare professionals. Concerns were also raised about culturally insensitive information resources, including issues of language, literacy, and representation, all of which served as potential barriers for women within Black ethnic minority groups. Conclusions: The deficiency of targeted knowledge mobilisation and specific UC information aimed at Black ethnicity women living in the UK, reportedly contributes to the dissemination of misconceptions and an atmosphere of apprehension around a UC diagnosis. The insights from this study highlight the significance of designing culturally sensitive strategies to promote informed decision-making and empower the dissemination of accurate health knowledge amongst Black women.https://www.gynecologiconcology-online.net/article/S0090-8258(23)01574-3/abstrac
The transformative potential of citizen science for mental health
No full textCitizen science is an approach to knowledge production through public engagement in scientific research activities, whereby citizens actively contribute to science either with their intellectual effort, surrounding knowledge, or their tools and resources. The European Citizen Science Association identified ten defining principles, including having a genuine scientific outcome and citizens participating in multiple stages of the scientific process. Citizen science is well established in fields such as ecology, where it has enabled large-scale, continent-wide studies. Citizen science improves public understanding of science, and hence increases public engagement in the scientific process.https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(24)00008-7/abstrac
Circulating sphingolipids and relationship to cardiac remodelling before and following a low-energy diet in asymptomatic Type 2 Diabetes
No full textBackground: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous multi-system syndrome with limited efficacious treatment options. The prevalence of Type 2 diabetes (T2D) continues to rise and predisposes patients to HFpEF, and HFpEF remains one of the biggest challenges in cardiovascular medicine today. Novel therapeutic targets are required to meet this important clinical need. Deep phenotyping studies including -OMIC analyses can provide important pathogenic information to aid the identification of such targets. The aims of this study were to determine; 1) the impact of a low-energy diet on plasma sphingolipid/ceramide profiles in people with T2D compared to healthy controls and, 2) if the change in sphingolipid/ceramide profile is associated with reverse cardiovascular remodelling. Methods: Post-hoc analysis of a randomised controlled trial (NCT02590822) including adults with T2D with no cardiovascular disease who completed a 12-week low-energy (∼810 kcal/day) meal-replacement plan (MRP) and matched healthy controls (HC). Echocardiography, cardiac MRI and a fasting blood for lipidomics were undertaken pre/post-intervention. Candidate biomarkers were identified from case-control comparison (fold change > 1.5 and statistical significance p < 0.05) and their response to the MRP reported. Association between change in biomarkers and change indices of cardiac remodelling were explored. Results: Twenty-four people with T2D (15 males, age 51.1 ± 5.7 years), and 25 HC (15 male, 48.3 ± 6.6 years) were included. Subjects with T2D had increased left ventricular (LV) mass:volume ratio (0.84 ± 0.13 vs. 0.70 ± 0.08, p < 0.001), increased systolic function but impaired diastolic function compared to HC. Twelve long-chain polyunsaturated sphingolipids, including four ceramides, were downregulated in subjects with T2D at baseline. Three sphingomyelin species and all ceramides were inversely associated with LV mass:volume. There was a significant increase in all species and shift towards HC following the MRP, however, none of these changes were associated with reverse cardiac remodelling. Conclusion: The lack of association between change in sphingolipids/ceramides and reverse cardiac remodelling following the MRP casts doubt on a causative role of sphingolipids/ceramides in the progression of heart failure in T2D.https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-023-03623-
A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3
No full textPPFIA3 encodes the protein-tyrosine phosphatase, receptor-type, F-polypeptide-interacting-protein-alpha-3 (PPFIA3), which is a member of the LAR-protein-tyrosine phosphatase-interacting-protein (liprin) family involved in synapse formation and function, synaptic vesicle transport, and presynaptic active zone assembly. The protein structure and function are evolutionarily well conserved, but human diseases related to PPFIA3 dysfunction are not yet reported in OMIM. Here, we report 20 individuals with rare PPFIA3 variants (19 heterozygous and 1 compound heterozygous) presenting with developmental delay, intellectual disability, hypotonia, dysmorphisms, microcephaly or macrocephaly, autistic features, and epilepsy with reduced penetrance. Seventeen unique PPFIA3 variants were detected in 18 families. To determine the pathogenicity of PPFIA3 variants in vivo, we generated transgenic fruit flies producing either human wild-type (WT) PPFIA3 or five missense variants using GAL4-UAS targeted gene expression systems. In the fly overexpression assays, we found that the PPFIA3 variants in the region encoding the N-terminal coiled-coil domain exhibited stronger phenotypes compared to those affecting the C-terminal region. In the loss-of-function fly assay, we show that the homozygous loss of fly Liprin-α leads to embryonic lethality. This lethality is partially rescued by the expression of human PPFIA3 WT, suggesting human PPFIA3 function is partially conserved in the fly. However, two of the tested variants failed to rescue the lethality at the larval stage and one variant failed to rescue lethality at the adult stage. Altogether, the human and fruit fly data reveal that the rare PPFIA3 variants are dominant-negative loss-of-function alleles that perturb multiple developmental processes and synapse formation.https://www.cell.com/ajhg/fulltext/S0002-9297(23)00436-
The development and internal pilot trial of a digital physical activity and emotional well-being intervention (Kidney BEAM) for people with chronic kidney disease
No full textThis trial assessed the feasibility and acceptability of Kidney BEAM, a physical activity and emotional well-being self-management digital health intervention (DHI) for people with chronic kidney disease (CKD), which offers live and on-demand physical activity sessions, educational blogs and videos, and peer support. In this mixed-methods, multicentre randomised waitlist-controlled internal pilot, adults with established CKD were recruited from five NHS hospitals and randomised 1:1 to Kidney BEAM or waitlist control. Feasibility outcomes were based upon a priori progression criteria. Acceptability was primarily explored via individual semi-structured interviews (n = 15). Of 763 individuals screened, n = 519 (68%, 95% CI 65 to 71%) were eligible. Of those eligible, n = 303 (58%, 95% CI 54-63%) did not respond to an invitation to participate by the end of the pilot period. Of the 216 responders, 50 (23%, 95% CI 18-29%) consented. Of the 42 randomised, n = 22 (10 (45%) male; 49 ± 16 years; 14 (64%) White British) were allocated to Kidney BEAM and n = 20 (12 (55%) male; 56 ± 11 years; 15 (68%) White British) to the waitlist control group. Overall, n = 15 (30%, 95% CI 18-45%) withdrew during the pilot phase. Participants completed a median of 14 (IQR 5-21) sessions. At baseline, 90-100% of outcome data (patient reported outcome measures and a remotely conducted physical function test) were completed and 62-83% completed at 12 weeks follow-up. Interview data revealed that remote trial procedures were acceptable. Participants' reported that Kidney BEAM increased their opportunity and motivation to be physically active, however, lack of time remained an ongoing barrier to engagement with the DHI. An randomised controlled trial of Kidney BEAM is feasible and acceptable, with adaptations to increase recruitment, retention and engagement.Trial registration NCT04872933. Date of first registration 05/05/2021.https://www.nature.com/articles/s41598-023-50507-