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Parental experience of neonatal pain research while participating in the Parental touch trial (Petal)
No full textParental involvement in neonatal comfort care is a core component of family-centred care. Yet, parents experience a range of positive and negative feelings when providing pain-relieving interventions for their infants. Parents of infants who participated in the Parental touch trial (Petal), a multicentre randomised controlled trial investigating the impact of gentle parental touch on neonatal pain, were asked to complete an anonymous survey. This survey aimed to (1) explore parent-reported motivations in deciding to participate in the Petal trial; (2) understand parent-reported experiences related to trial participation; (3) understand parents' willingness to participate in future studies; and (4) evaluate parent-reported feelings while they were delivering a gentle touch intervention either before or after a clinically necessary blood test. One hundred six parents (1 parent per infant) took part in the survey. Primary motivators for participation were altruistic. Parents most frequently reported that they wanted their child to take part in the research because it has a potential benefit to babies in the future and because they wanted to improve scientific understanding. Parents reported that providing gentle touch to their children during painful procedures was associated with positive emotions, such as feeling useful" (64%) and "reassured" (53%). Furthermore, nearly all parents (98%) were pleased to have participated in the Petal trial and would consider, or maybe consider, participating in further research studies. These results underscore the importance of structuring trials around parental involvement and providing opportunities for parents to be involved in providing comfort to their infants during necessary painful clinical procedures."Published version, accepted version (12 month embargo), submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Understanding the long-term impact of the COVID-19 pandemic on non-muscle-invasive bladder cancer outcomes: 12-Month follow-up data from the international, prospective COVIDSurg Cancer study
No full textOBJECTIVE: The objective of this study was to report the 12-month oncological outcomes for patients with non-muscle-invasive bladder cancer (NMIBC) within the prospective, international COVIDSurg Cancer study. PATIENTS AND METHODS: Eligible patients were aged ≥18 years and scheduled for elective surgical management of NMIBC with curative intent (transurethral resection of bladder tumour [TURBT] or bladder biopsy) from 21 January to 14 April 2020. The primary outcome was disease recurrence within 12 months of previous elective TURBT/bladder biopsy. Secondary outcomes included disease progression within 12 months of previous elective TURBT/bladder biopsy, site-declared delay to surgery from diagnosis as a consequence of COVID-19 and deviation in standard care due to COVID-19. Comparisons were made to cohorts from the pre-pandemic era. RESULTS: Bladder cancer accounted for 2.2% (n = 446) of patients in the COVIDSurg Cancer study, with data contributed by 27 centres across 12 countries internationally. Within this included cohort, 229 patients had NMIBC and 12-month follow-up data available. On application of National Institute for Health and Care Excellence (NICE) criteria, 47.2% were classified as having high-risk disease. Overall disease recurrence and progression rates were 29.3% and 9.7% at 12 months, respectively. In purely high-risk pre-pandemic cohorts, the International Bladder Cancer Group (IBCG) estimates a recurrence rate of 25% at 12 months, and the European Association of Urology (EAU) NMIBC 2021 scoring model estimates a 12-month progression rate of 3.5%. As a consequence of the COVID-19 pandemic, 10.9% of patients had site-declared delay to TURBT/bladder biopsy; 7.4% did not undergo intravesical therapy or had early discontinuation of this; 9.2% did not undergo early repeat resection for high-risk disease; and 18.3% had a delay to cystoscopic follow-up surveillance. CONCLUSIONS: This prospective study indicates that there were widespread deviations in usual care for NMIBC during the pandemic and that 12-month oncological outcomes appear to be impaired compared to published pre-pandemic outcomes.This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo
Treatment switch from multiple daily insulin injections to sulphonylureas in an African young adult diagnosed with HNF1A MODY: a case report
No full textBACKGROUND: Maturity onset diabetes of the young is one of the commonest causes of monogenic diabetes and can easily be mistaken for type 1 diabetes. A diagnosis of maturity onset diabetes of the young can have direct implications for genetic counseling, family screening, and precision diabetes treatment. However, the cost of genetic testing and identifying individuals to test are the main challenges for diagnosis and management in sub-Saharan Africa. We report the very first documented case of HNF1A maturity onset diabetes of the young in the sub-Saharan African region. CASE PRESENTATION: A 20-year-old female Black African young adult diagnosed with type 1 diabetes aged 14 presented for routine out-patient diabetes consultation. She was on multiple daily insulin injections; total combined dose 0.79 IU/kg/day with an HbA1c of 7.7%. The rest of her laboratory examinations were normal. On extended laboratory analysis, she had good residual insulin secretion with post-meal plasma C-peptide levels at 1150 pmol/L. She tested negative for glutamic acid decarboxylase (GAD65), islet antigen-2 (IA-2), and zinc transporter 8 (ZnT8) islet autoantibodies. Targeted next-generation sequencing (t-NGS) for monogenic diabetes was performed using DNA extracted from a buccal sample. She was diagnosed with HNF1A maturity onset diabetes of the young, with the c.607C > T; p.(Arg203Cys) pathogenic variant, which has never been reported in sub-Saharan Africa. Her clinical practitioners provided genetic and therapeutic counseling. Within 10 months following the diagnosis of maturity onset diabetes of the young, she was successfully switched from multiple daily insulin injections to oral antidiabetic tablets (sulphonylurea) while maintaining stable glycemic control (HBA1c of 7.0%) and reducing hypoglycemia. She expressed a huge relief from the daily finger pricks for blood glucose monitoring. CONCLUSION: This case reveals that HNF1A maturity onset diabetes of the young (and probably other causes of monogenic diabetes) can present in sub-Saharan Africa. A diagnosis of maturity onset diabetes of the young can have significant life-changing therapeutic implications.Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo
Hiding in plain sight: a partial deletion of BRCA1 exon 7 undetectable by MLPA is a Nepali founder variant
No full textThis is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Expanding the genetic and phenotypic landscape of replication factor C complex-related disorders: RFC4 deficiency is linked to a multisystemic disorder
No full textThe precise regulation of DNA replication is vital for cellular division and genomic integrity. Central to this process is the replication factor C (RFC) complex, encompassing five subunits, which loads proliferating cell nuclear antigen onto DNA to facilitate the recruitment of replication and repair proteins and enhance DNA polymerase processivity. While RFC1's role in cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is known, the contributions of RFC2-5 subunits on human Mendelian disorders is largely unexplored. Our research links bi-allelic variants in RFC4, encoding a core RFC complex subunit, to an undiagnosed disorder characterized by incoordination and muscle weakness, hearing impairment, and decreased body weight. We discovered across nine affected individuals rare, conserved, predicted pathogenic variants in RFC4, all likely to disrupt the C-terminal domain indispensable for RFC complex formation. Analysis of a previously determined cryo-EM structure of RFC bound to proliferating cell nuclear antigen suggested that the variants disrupt interactions within RFC4 and/or destabilize the RFC complex. Cellular studies using RFC4-deficient HeLa cells and primary fibroblasts demonstrated decreased RFC4 protein, compromised stability of the other RFC complex subunits, and perturbed RFC complex formation. Additionally, functional studies of the RFC4 variants affirmed diminished RFC complex formation, and cell cycle studies suggested perturbation of DNA replication and cell cycle progression. Our integrated approach of combining in silico, structural, cellular, and functional analyses establishes compelling evidence that bi-allelic loss-of-function RFC4 variants contribute to the pathogenesis of this multisystemic disorder. These insights broaden our understanding of the RFC complex and its role in human health and disease.Published version, accepted version (6 month embargo), submitted versionJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
Editor's choice - June 2024
No full textAccepted version (12 month embargo)RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Dyspnea (breathlessness) in amyotrophic lateral sclerosis/motor neuron disease: prevalence, progression, severity, and correlates
No full textObjective: Dyspnea, or breathlessness, is an important symptom in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). We examined the measurement properties of the Dyspnea-12. Methods: Rasch analysis enabled conversion of raw Dyspnea-12 scores to interval level metric equivalents. Converted data were used to perform trajectory modeling; those following different trajectories were compared for demographic, clinical, symptom, and functioning characteristics. Logistic regression examined differences between distinct trajectories. Results: In 1022 people, at baseline, mean metric Dyspnea-12 was 7.6 (SD 9.3). 49.8% had dyspnea, severe in 12.6%. Trajectory analysis over 28 months revealed three breathlessness trajectories: group 1 reported none at baseline/follow-up (42.7%); group 2 significantly increased over time (9.4%); group 3 had a much higher level at baseline which rose over follow-up (47.9%). Group 3 had worse outcomes on all symptoms, functioning and quality of life; compared to group 1, their odds of: respiratory onset sixfold greater; King's stage =3 2.9 greater; increased odds of being bothered by choking, head drop, fasciculations, and muscle cramps; fatigue and anxiety also elevated (p < .01). Conclusion: Dyspnea is a cardinal symptom in ALS/MND and can be quickly measured using the Dyspnea-12. Raw scores can easily be converted to interval level measurement, for valid change scores and trajectory modeling. Dyspnea trajectories reveal different patterns, showing that clinical services must provide monitoring which is customized to individual patient need. Almost half of this large population had worsening dyspnea, confirming the importance of respiratory monitoring and interventions being integrated into routine ALS care.published versionNot hel
The predictive role of symptoms in COVID-19 diagnostic models: A longitudinal insight
No full textTo investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%-22.7%) in participants reporting loss of appetite and 31.9% (27.1%-36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms' dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.Published versionRD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
The burden of periprosthetic femoral fractures in England and Wales: Insights from the first two years of data collection in the National Hip Fracture Database and regional variation in care
No full textINTRODUCTION: Periprosthetic femoral fractures (PPFFs) represent an important healthcare problem, with a rising incidence noted due to an increase in the number of arthroplasty surgeries being performed. There is a current lack of national consensus as to how these complex, often frail patients are managed. AIMS: Our primary aim was to present the epidemiology of PPFFs in England and Wales over the first two years of data collection by the National Hip Fracture Database (NHFD). Secondary aims included how well the NHFD Key Performance Indicators (KPIs) are met for PPFF patients, whether centres reporting a higher burden of PPFF patients are more likely to meet KPIs compared to lower volume centres, and to also identify if regional variation in care for these patients exist. METHODS: Patients aged 60 years or over, admitted to any acute hospital in England or Wales with a PPFF within the period 1st January 2020 to 31st December 2021 were included. Fractures were classified using the Vancouver system. The primary outcome of interest was the incidence of PPFF in England and Wales. Secondary outcomes included i) geographical distribution, ii) pattern of injury, iii) treatment received, iv) KPI performance nationally, v) KPI performance by top 5 highest volume hospitals vs the rest, vi) KPI performance by region and vii) KPI performance compared with native hip fracture patients. RESULTS: A total of 5,566 PPFFs were reported during our study period. A 31 % increase in cases was seen between 2020 and 2021 (2,405 to 3,161). The South-West of England reported the highest burden of PPFFs (14 % of all cases reported in 2021). Vancouver B subtypes were most common around hip replacements (62 %) and C subtype around knee replacements (55 %). A total of 4,598 patients (82.6 %) underwent operative management. There was regional variation in KPI attainment. When compared to KPI attainment for native hip fractures PPFF care under performed in most regions and domains. High volume PPFF centres were not associated with improved attainment of KPIs. CONCLUSION: We have described the incidence, nature, and management of PPFF at national and regional levels using routinely collected NHFD data. Both numerically and due to case complexity, PPFF are a considerable challenge to patients and health services alike. This epidemiology is not captured by other existing datasets and increased case contribution to the NHFD is encouraged to improve understanding and enable prioritisation and delivery of further care and research.Published version, accepted version (12 month embargo), submitted versionJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
Update Systematic Review, Meta-Analysis and GRADE Assessment of the Evidence on Parastomal Hernia Prevention-A EHS, ESCP and EAES Collaborative Project
No full textObjective: To perform a systematic review and meta-analysis on the effectiveness of prophylactic mesh for the prevention of parastomal hernia in end colostomy, with the ultimate objective to summarize the evidence for an interdisciplinary, European rapid guideline. Methods: We updated a previous systematic review with de novo evidence search of PubMed from inception up to June 2022. Primary outcome was quality of life (QoL). Secondary outcomes were clinical diagnosis of parastomal hernia, surgery for parastomal hernia, and 30 day or in-hospital complications Clavien-Dindo =3. We utilised the revised Cochrane Tool for randomised trials (RoB 2 tool) for risk of bias assessment in the included studies. Minimally important differences were set a priori through voting of the panel members. We appraised the evidence using GRADE and we developed GRADE evidence tables. Results: We included 12 randomized trials. Meta-analysis suggested no difference in QoL between prophylactic mesh and no mesh for primary stoma construction (SMD = 0.03, 95% CI [-0.14 to 0.2], I(2) = 0%, low certainty of evidence). With regard to parastomal hernia, the use of prophylactic synthetic mesh resulted in a significant risk reduction of the incidence of the event, according to data from all available randomized trials, irrespective of the follow-up period (OR = 0.33, 95% CI [0.18-0.62], I(2) = 74%, moderate certainty of evidence). Sensitivity analyses according to follow-up period were in line with the primary analysis. Little to no difference in surgery for parastomal hernia was encountered after pooled analysis of 10 randomised trials (OR = 0.52, 95% CI [0.25-1.09], I(2) = 14%). Finally, no significant difference was found in Clavien-Dindo grade 3 and 4 adverse events after surgery with or without the use of a prophylactic mesh (OR = 0.77, 95% CI [0.45-1.30], I(2) = 0%, low certainty of evidence). Conclusion: Prophylactic synthetic mesh placement at the time of permanent end colostomy construction is likely associated with a reduced risk for parastomal hernia and may confer similar risk of peri-operative major morbidity compared to no mesh placement. There may be no difference in quality of life and surgical repair of parastomal hernia with the use of either approach.Published version, accepted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text