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A face-to-face survey on the practice of ophthalmic clinicians in the management of dry eye disease in patients undergoing cataract surgery
No full textINTRODUCTION: Dry eye disease (DED) can impact the accuracy of biometry measurements prior to cataract surgery (CS), influence visual performance post-CS, and can be exacerbated by CS. We performed a survey to evaluate the DED practice of clinicians directly caring for CS patients. DESIGN: Prospective face-to-face survey. METHOD: Face-to-face survey consisting of 12 questions relating to CS clinicians' estimations of DED pre- and post-CS, dry eye tests performed, and the management of DED. RESULT: There were one hundred and twenty-seven responders (39% consultants, 37% trainees/fellows, 8% associate specialists, 6% specialty doctors, 8% optometrists, 2% nurse specialists), with a 100% response rate. Sixty-seven percent routinely assessed for DED pre-CS, with 81% anticipating mild to moderative negative effects of CS on DED. Approximately 75% estimated that over 10% of pre-operative patients had asymptomatic DED, with another 10% or more suffering symptomatic DED. Almost 80% estimated that 10% or more of patients suffered DED post-CS. More DED tests were performed pre- compared to post-operatively (p = 0.02). More consultants performed dry eye tests post-operatively compared to non-consultants (p = 0.02). Most common treatment options included lubricating drops (95%), lid hygiene (75%) and night ointment/gels (54%). Seventy-six percent of surgeons performing CS stated they coated the ocular surface with an ophthalmic visco-surgical device and 34% limited intra-operative light exposure peri-operatively to limit DED. DISCUSSION: Despite the anticipated negative effects of CS on DED, 1 in 3 clinicians in our survey were not assessing routinely for DED prior to CS, and fewer dry eye tests were performed post-operatively compared to pre-surgery.This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).Journal 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
High-Risk Outcomes in In Vitro Fertilization Pregnancies for Women of a Very Advanced Maternal Age: Insights from a Multi-Hospital Study in Greece
No full textBackground: In vitro fertilization (IVF) has transformed infertility treatment, yet it is associated with increased risks of adverse perinatal outcomes, particularly in women of advanced maternal age. This study aimed to investigate the prevalence of complications such as preeclampsia (PE), gestational diabetes mellitus (GDM), preterm labor (PTL), low birth weight (LBW), and placental abnormalities (PA) among women over 50 undergoing assisted reproductive technology (ART) in Greece, where the eligibility age limit has been recently raised to 54 years. Methods: We conducted a retrospective analysis of pregnancy outcomes in women over 50 compared to those under 50, utilizing medical records mainly from University Hospital of Ioannina but also from other public hospitals and private clinics in Greece. Results: Our findings indicate that women over 50 face an increased risk of developing preeclampsia (PE) by 4.61 times, GDM by 1.69 times, PTL by 1.82 times, LBW by 1.67 times, and PA by 3.92 times. Conclusions: These results underscore the need for heightened awareness and the monitoring of pregnancy complications in this demographic, informing clinical strategies to improve maternal and neonatal outcomes.This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Journal 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
Disparity in endoscopic localisation of early distal colorectal cancers: a retrospective cohort analysis from a single institution
No full textBACKGROUND: Accurate staging of distal colorectal cancers is paramount in guiding neoadjuvant therapy, peri-operative, and ostomy planning. Early colonic lesions can be difficult to visualise on computed tomography (CT) scans, with tumour location solely deduced via endoscopy with the potential for introducing error. We aimed to address the paucity in literature in this area and assessed the accuracy of radiological and endoscopic localisation of distal colorectal cancers. METHODS: Retrospective analysis of an electronic database of patients at a large District General Hospital (DGH) diagnosed with distal colorectal cancer between January 2014 to January 2023 was performed. Patient demographics, investigations, endoscopic, and operative findings were analysed. Outcomes were assessed to determine disparities between pre-operative endoscopy and final tumour location. RESULTS: A total of 212 patients were endoscopically diagnosed with distal sigmoid tumour. Of these, 207 (97.6%) had a CT scan performed with 25.1% (52/207) lesions not being identified on this imaging modality with the remainder (74.9%; 155/207) being reported as visible. 38.2% (79/207) of tumours were in the sigmoid colon, 17.4% (36/207) rectosigmoid, and 19.3% (40/207) in the rectum. Pre-operative magnetic resonance imaging (MRI) was performed in 42.5% (90/212) of cases showing 84 tumours: 6.0% (5/84) sigmoid colon, 9.5% (8/84) rectosigmoid and 83.3% (70/84) rectal cancers (upper: 34, mid-rectum: 26, low: 10), with one anal cancer. 42.3% (22/52) of patients with non-visible lesions on CT had MRI scans: 68.2% (15/22) had rectal cancer (upper: 10, mid-rectum: 4, low: 1). Of the 30 where MRI was not performed, 46.7% (14) had sigmoid cancer, 16.7% (5) rectosigmoid, and 33.3% (10) rectal intraoperatively. Overall, 30.7% (65/212) of patients reported as having a distal sigmoid lesion endoscopically in fact had rectal cancer intra-operatively (rectosigmoid lesions excluded). CONCLUSION: Endoscopic localisation of distal colorectal tumours can be unreliable for accurate staging and operative planning. A pre-operative MRI scan should be considered in such instances, and particularly for non-visible lesions on CT scan. This may improve peri-operative planning, staging accuracy and patient outcomes.Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.Not hel
Treatment options to support the elimination of hepatitis C: an open-label, factorial, randomised controlled non-inferiority trial
No full textBACKGROUND: WHO recommends treating hepatitis C infection with one of three antiviral combinations for 8-12 weeks. No randomised trials have compared these regimens, and high cure rates might be achievable with shorter durations of therapy. We aimed to compare sofosbuvir-daclatasvir with sofosbuvir-velpatasvir, and to evaluate potential novel treatment strategies. METHODS: We conducted a multi-arm, open-label, randomised controlled non-inferiority trial in two public hospitals in Viet Nam. Adults (aged ≥18 years) with chronic hepatitis C infection and mild-to-moderate liver fibrosis were eligible. Recruitment was stratified by centre and viral genotype (1-5 vs 6) with 1:1 random allocation to an oral fixed-dose combination of sofosbuvir 400 mg plus daclatasvir 60 mg (sofosbuvir-daclatasvir) or sofosbuvir 400 mg plus velpatasvir 100 mg (sofosbuvir-velpatasvir). Participants were simultaneously factorially randomly assigned to one of four treatment strategies: 12 weeks' standard of care (SOC); 4 weeks' therapy with four weekly PEGylated interferon alfa-2a subcutaneous injections; induction and maintenance therapy with 2 weeks' standard therapy followed by 10 weeks' therapy 5 days a week; and response-guided therapy (RGT) for 4, 8, or 12 weeks determined by viral load on day 7. The primary outcome was sustained virological response (SVR) 12 weeks after treatment completion, analysed in all evaluable participants regardless of actual treatment received. We chose a 5% non-inferiority margin for the drug comparison, and a 10% non-inferiority margin for the treatment strategy comparisons. Safety was assessed in all randomised participants. This trial is registered with ISRCTN, 61522291, and is completed. FINDINGS: Between June 19, 2020, and May 10, 2023, 624 participants were randomised (470 [75%] were male and 154 [25%] were female). 296 (47%) had genotype 6 and 328 (53%) had genotypes 1-5. The primary outcome was assessable in 609 (98%) participants. SVR occurred in 294 (97%) of 302 participants in the sofosbuvir-daclatasvir group and 292 (95%) of 307 participants in the sofosbuvir-velpatasvir group (risk difference 2·2%, 90% credible interval [CrI] -0·2 to 4·8, within the 5% non-inferiority margin; 93% probability that sofosbuvir-daclatasvir is superior to sofosbuvir-velpatasvir). SVR occurred in 148 (99%) of 150 in the SOC group, 143 (94%) of 152 in the 4-week antiviral plus interferon group (-4·5%, 90% CrI -8·3 to -1·3), 151 (99%) of 152 in the induction-maintenance group (0·6%, -1·1 to 2·7), and 144 (93%) of 155 in the RGT group (-5·7%, -9·6 to -2·3); all risk differences were within the 10% non-inferiority margin. Serious adverse events were rare (11 [4%] of 313 participants in the sofosbuvir-velpatasvir group vs six [2%] of 311 in the sofosbuvir-daclatasvir group; risk difference -1·6% [95% CrI -4·2 to 0·8]) with no evidence of differences between regimens or strategies, but adverse reactions were very common in the 4-week antiviral plus interferon group compared with the other treatment strategies (risk difference vs SOC group, 66·8% [59·2 to 74·0]; p<0·0001). INTERPRETATION: Sofosbuvir-daclatasvir was non-inferior to sofosbuvir-velpatasvir. High efficacy was seen with novel strategies, which might help to inform approaches to treatment for harder-to-reach populations. FUNDING: Wellcome Trust.CC BY 4.0 (Creative Commons Attribution
Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal (UNIVERSAL) study: a prospective observational cohort study protocol
No full textBACKGROUND: Respiratory viral infections (RVIs) are a significant cause of morbidity and hospital admission worldwide. However, the management of most viral infection-associated diseases remains primarily supportive. The recent COVID-19 pandemic has underscored the urgent need for a deeper understanding of RVIs to improve patient outcomes and develop effective treatment strategies. The Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal Study is an observational study which addresses this need by investigating the heterogeneity of RVIs in hospitalised adults, aiming to identify clinical and biological predictors of adverse outcomes. This study aims to bridge critical knowledge gaps in the clinical course and the economic impact of RVIs by characterising the phenotypic diversity of these infections and their recovery patterns following hospital admission and thus assisting with the optimal design of future interventional studies. METHODS AND ANALYSIS: This prospective longitudinal observational study (V.6, 20 September 2023) will be conducted across multiple UK secondary care sites from August 2022 onwards, with an aim to enrol 1000 participants testing positive for RVI. Adults admitted with respiratory symptoms who test positive for RVIs via the BioFire® FilmArray® System or other validated diagnostic PCR tests will be enrolled. The data collected include patient demographics, clinical history, comorbidities and symptoms experienced prior to, during and after hospitalisation with follow-up after discharge at weeks 1, 2, 4, 8, 12 and 26. In addition, biological samples are collected at multiple time points during the hospital stay. The primary endpoints are to study the impact of different RVIs and identify predictors of disease progression and length of stay. Secondary endpoints include time to recovery and healthcare cost. Exploratory endpoints focus on biomarker profiles associated with virus type and clinical outcomes. ETHICS AND DISSEMINATION: The study protocol received ethical approval from the relevant committees (English Ethics Reference Number: 22/WM/0119; Scottish Ethics Reference Number: 22-SS-0101, 20/09/2023). For patients who lack the capacity to consent, the study complies with the Mental Capacity Act 2005, using a consultee process where a family member, carer or an independent clinician may provide assent on behalf of the patient. Data from all the study centres will be analysed together and disseminated through peer-reviewed journals, conference presentations and workshops. The study group will ensure that participants and their families are informed of the study findings promptly and in an accessible format. TRIAL REGISTRATION NUMBER: ISRCTN49183956.CC BY 4.0 (Creative Commons Attribution
The effect of minimum volume recommendations on surgeon activity for first revision total knee replacement: an analysis of 2009-2019 United Kingdom National Joint Registry data
No full textAIMS: The aim of this study was to investigate changes in first time revision knee replacement (RevKR) volumes following the publication of a report identifying low surgeon volumes in England. As a secondary aim we sought to investigate the rate of accrual of volumes for early career surgeons. METHODS: This population-based cohort study used data from the United Kingdom National Joint Registry. Patients undergoing first time RevKR between 1st January 2009 and 31 December 2019. Annual revision volumes for each surgeon were calculated and trends in surgeon volumes plotted as medians and bootstrapped 95% confidence intervals. Data before and after the report was compared. The rate of accrual of experience for new surgeons inclusive of both first-time revisions and re-revisions was calculated and adjusted for unit volume. RESULTS: A total of 21,067 patients were included. Over the whole study period, 123/1433 (8.58%) of surgeons achieved a mean annual volume of 15 or more revisions. Temporal trends in surgeon revision volumes observed an increase for non-acute indications. New surgeons in lower volume units have 42% lower chance of reaching 15 operations per year compared to those in the highest volume units (HR 0.52; 95% CI 0.33 to 0.83). CONCLUSIONS: We observed an increase in surgeon volumes following the report in first time non acute RevKRs. New RevKR surgeons were more likely to achieve and maintain revision volume targets in higher volume centres, this supports the drive for dual consultant operating and prospective revision knee consultants being appointed to highest volume units.CC BY 4.0 Internationa
Neoadjuvant PARP inhibitor scheduling in BRCA1 and BRCA2 related breast cancer: PARTNER, a randomized phase II/III trial
No full textPoly (ADP-ribose) polymerase inhibitors (PARPi) exploit DNA repair deficiency in germline BRCA1 and BRCA2 pathogenic variant (gBRCAm) cancers. Haematological toxicity limits chemotherapy-PARPi treatment combinations. In preclinical models we identified a schedule combining olaparib and carboplatin that avoids enhanced toxicity but maintains anti-tumour activity. We investigated this schedule in a neoadjuvant, phase II-III, randomised controlled trial for gBRCAm breast cancers (ClinicalTrials.gov ID:NCT03150576; PARTNER). The research arm included carboplatin (Area Under the Curve 5, 3-weekly); paclitaxel (80 mg/m(2), weekly) day 1, plus olaparib (150 mg twice daily) day 3-14 (4 cycles), followed by anthracycline-containing chemotherapy (3 cycles); control arm gave chemotherapy alone. The primary endpoint, pathological complete response rate, showed no statistical difference between research 64.1% (25/39); control 69.8% (30/43) (p = 0.59). However, estimated survival outcomes at 36-months demonstrated improved event-free survival: research 96.4%, control 80.1% (p = 0.04); overall survival: research 100%, control 88.2% (p = 0.04) and breast cancer specific survival: research 100%, control 88.2% (p = 0.04). There were no statistical differences in relapse-free survival and distant disease-free survival, both were: research 96.4%, control 87.9% (p = 0.20). Similarly, local recurrence-free survival and time to second cancer were both: research 96.4%, control 87.8% (p = 0.20). The PARTNER trial identified a safe, tolerable schedule combining neoadjuvant chemotherapy with olaparib. This combination demonstrated schedule-dependent overall survival benefit in early-stage gBRCAm breast cancer. This result needs confirmation in larger trials.CC BY 4.0 (Creative Commons Attribution
MIKROBE: a feasibility study for a randomised controlled trial of one-stage or two-stage surgery for prosthetic knee infection
No full textBACKGROUND: Total knee replacement surgery is common, with over 107,000 operations performed in the UK in 2019. After surgery, about 1% of patients develop a deep infection, known as a prosthetic joint infection. Two types of operations, one- or two-stage revision surgery, are routinely performed to treat the infection. Re-infection rates are similar, but there is uncertainty regarding longer-term outcomes for patients. The aim of this study was to establish the feasibility of conducting a future randomised controlled trial that will compare clinical and cost-effectiveness of one-stage versus two-stage revision knee surgery for prosthetic joint infection. METHODS: Following eligibility screening, consenting patients took part in an audio-recorded consultation with their surgeon and were then randomised on a 1:1 allocation to one-stage or two-stage revision surgery. Patient-reported outcome measures were administered at baseline and 3 and 6 months postoperatively. Embedded qualitative work with patient participants and nonparticipants and with surgeons to understand the acceptability of trial processes and involvement was undertaken. Patient and public involvement and engagement activities were conducted throughout the study. RESULTS: Of 136 patients screened, only 3 were randomised and had surgery as part of the study. Qualitative data were collected from the three participants, as well as from two eligible patients who declined participation and two who withdrew from participation after the initial patient-surgeon consultation. Five surgeons took part in qualitative interviews prior to study end. CONCLUSION: This study indicated that a larger randomised controlled trial evaluating one-stage versus two-stage revision knee surgery for prosthetic joint infection is not feasible with the current straightforward randomised controlled trial design. Future research needs to consider the most appropriate study design and methodology to address this important research question. TRIAL REGISTRATION: No.: NCT04458961.CC BY 4.0 Internationa
Time Below Range and Its Influence on Hypoglycemia Awareness and Severe Hypoglycemia: Insights From the Association of British Clinical Diabetologists Study
No full textOBJECTIVE: This study aimed to explore the relationship between time below range (TBR), impaired awareness of hypoglycemia (IAH), and severe hypoglycemia (SH). RESEARCH DESIGN AND METHODS: This cross-sectional study analyzed data from individuals with diabetes using continuous glucose monitors (CGMs) in the Association of British Clinical Diabetologists audit. Hypoglycemia awareness was assessed via the Gold score (≥4 denoting IAH), and SH was defined as hypoglycemia requiring third-party assistance. Logistic regression was used to determine the association between TBR percentage (<70 mg/dL; 3.9 mmol/L) at first follow-up and follow-up Gold score and SH incidence. The Youden J index identified optimal TBR percentage cutoffs for detecting IAH and SH. RESULTS: The study included 15,777 participants, with follow-up TBR and SH data available for 5,029. The median TBR percentage was 4% (interquartile range 2-6.6%), with 42% meeting the recommended TBR of ≤4%. Adjusted for age, sex, and BMI, TBR was significantly associated with SH (P < 0.001) and IAH (P = 0.005). Optimal TBR cutoffs for identifying IAH and SH were 3.35% and 3.95%, yielding negative predictive value (NPV) values of 85% and 97%, respectively. CONCLUSIONS: Our findings support the international consensus recommending a TBR of <4% in type 1 diabetes, with high NPV values suggesting the utility of TBR in screening for SH.Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.Journal 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
A systematic analysis of the contribution of genetics to multimorbidity and comparisons with primary care data
No full textBACKGROUND: Multimorbidity, the presence of two or more conditions in one person, is common but studies are often limited to observational data and single datasets. We address this gap by integrating large-scale primary-care and genetic data from multiple studies to interrogate multimorbidity patterns and producing digital resources to support future research. METHODS: We defined chronic, common, and heritable conditions in individuals aged ≥65 years, using two large primary-care databases [CPRD (UK) N = 2,425,014 and SIDIAP (Spain) N = 1,053,640], and estimated heritability using the same definitions in UK Biobank (N = 451,197). We used logistic regression to estimate the co-occurrence of pairs of conditions in the primary care data. Linkage disequilibrium score regression was used to estimate genetic similarity between pairs of conditions. Meta-analyses were conducted across databases, and up to three sources of genetic data, for each pair of conditions. We classified pairs of conditions as across or within-domain based on the international classification of disease. FINDINGS: We identified 72 chronic conditions, with 43.6% of 2546 pairs showing higher co-occurrence than chance in primary care and evidence of shared genetics. Many across-domain pairs exhibited substantial shared genetics (e.g., iron deficiency anaemia and peripheral arterial disease: genetic correlation R(g) = 0.45 [95% Confidence Intervals 0.27:0.64]). 33 pairs displayed negative genetic correlations, such as skin cancer and rheumatoid arthritis (R(g) = -0.14 [-0.21:-0.06]), due to potential adverse drug effects. Discordance between genetic and primary care data was also observed, e.g., abdominal aortic aneurysm and bladder cancer co-occurred in primary care but were not genetically correlated (Odds-Ratio = 2.23 [2.09:2.37], R(g) = 0.04 [-0.20:0.28]) and schizophrenia and fibromyalgia were less likely to co-occur together in primary care but were positively genetically correlated (OR = 0.84 [0.75:0.94], R(g) = 0.20 [0.11:0.29]). INTERPRETATION: Most pairs of chronic conditions show evidence of shared genetics, and co-occurrence in primary care, suggesting shared mechanisms. The identified patterns of shared genetics, negative correlations and discordance between genetic and observational data provide a foundation for future multimorbidity research. FUNDING: UK Medical Research Council [MR/W014548/1].This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Journal 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