Long-term fluctuation in short-wavelength automated perimetry in glaucoma suspects and glaucoma patients

PURPOSE. To determine the magnitude of the homogenous, LF(Ho), and the heterogeneous, LF(He), components of the long-term fluctuation (LF) in glaucoma suspects and in stable primary open angle glaucoma (POAG) patients undergoing short-wavelength automated perimetry (SWAP) and to compare the magnitude of the SWAP LF components with those elicited by standard white-on-white (W-W) perimetry. METHODS. The sample comprised 33 glaucoma suspects and 17 patients with early-to-moderate stable POAG who underwent W-W perimetry and SWAP at each of six visits over a mean period of 12.75 months (SD, 2.29). The LF(Ho), LF(He), and error components of the long-term fluctuation were determined between the third and seventh visual field examinations. The intervening visual field examinations and the optic nerve head parameters, derived both by stereo observation and by the Heidelberg Retinal Tomograph, were used to confirm stability over the follow-up period. RESULTS. The LF(Ho) and LF(He) components were larger in the POAG patients than in the glaucoma suspects for both W-W perimetry and SWAP; the magnitude was independent of the depth of defect and of the short-term fluctuation. All three components of long-term fluctuation were greater for SWAP than for W-W perimetry, both in the glaucoma suspects and in the POAG patients. CONCLUSIONS. SWAP exhibits greater long-term fluctuation than white-on-white perimetry. The usefulness of SWAP will be limited if the extent of this variability is not overcome in future statistical procedures developed to detect progressive visual field loss

CONservative TReatment of Appendicitis in Children – a randomised controlled feasibility Trial (CONTRACT)

Objective To establish the feasibility of a multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy in children with uncomplicated acute appendicitis.Design Feasibility randomised controlled trial with embedded qualitative study to inform recruiter training to optimise recruitment and the design of a future definitive trial.Setting Three specialist paediatric surgery centres in the UK.Patients Children (aged 4–15 years) with a clinical diagnosis of uncomplicated acute appendicitis.Interventions Appendicectomy or a non-operative treatment pathway (comprising broad-spectrum antibiotics and active observation).Main outcome measures Primary outcome measure was the proportion of eligible patients recruited. Secondary outcomes evaluated adherence to interventions, data collection during follow-up, safety of treatment pathways and clinical course.Results Fifty per cent of eligible participants (95% CI 40 to 59) approached about the trial agreed to participate and were randomised. Repeated bespoke recruiter training was associated with an increase in recruitment rate over the course of the trial from 38% to 72%. There was high acceptance of randomisation, good patient and surgeon adherence to trial procedures and satisfactory completion of follow-up. Although more participants had perforated appendicitis than had been anticipated, treatment pathways were found to be safe and adverse event profiles acceptable.Conclusion Recruitment to a randomised controlled trial examining the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy for the treatment of uncomplicated acute appendicitis in children is feasible.Trial registration number ISRCTN15830435

Conservative treatment for uncomplicated appendicitis in children:the CONTRACT feasibility study, including feasibility RCT

Background Whilst non-operative treatment is known to be effective for the treatment of uncomplicated acute appendicitis in children, comparative randomised trial data reporting important outcomes compared to appendicectomy are lacking.ObjectivesTo ascertain the feasibility of conducting a multi-centre randomised controlled trial (RCT) testing the effectiveness and cost-effectiveness of a non-operative treatment pathway compared to appendicectomy for the treatment of uncomplicated acute appendicitis in children.•DesignMixed methods study including: a feasibility RCT; embedded and parallel qualitative and survey studies; parallel health economic feasibility study; development of a core outcome set.Setting Three specialist NHS Paediatric Surgical Units in EnglandParticipants Children (aged 4-15 years) clinically diagnosed with uncomplicated acute appendicitis participated in the feasibility RCT. Children, their families, recruiting clinicians and other healthcare professionals involved in caring for children with appendicitis took part in the qualitative study. UK Specialist Paediatric Surgeons took part in the survey. Specialist Paediatric Surgeons, Adult General Surgeons who treat children, and children and young people who previously had appendicitis along with their families took part in the core outcomes set development.Interventions Participants in the feasibility RCT were randomised to a non-operative treatment pathway (broad-spectrum antibiotics and active observation) or appendicectomy.Main outcome measures Primary outcome measure was the proportion of eligible patients recruited to the feasibility trial.Data sourcesNHS casenotes, questionnaire responses, transcribed audio recordings of recruitment discussions and qualitative interviewsResults Overall, 50% (95%CI 40-59) of 115 eligible participants approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow rates of 89%, 85% and 85% at six weeks, three months and six months respectively). More participants had perforated appendicitis than had been anticipated.Qualitative work enabled us to: communicate about the trial effectively with patients and families; design and deliver bespoke training to optimise recruitment; and understand how to optimise design and delivery of a future trial.The health economic study, indicated that the main cost drivers are the ward stay cost and the cost of the operation, and has informed quality of life assessment methods for future work.A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes.There is adequate surgeon interest to justify proceeding to an effectiveness trial with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol.LimitationsSince the feasibility RCT was only performed in three centres we cannot guarantee successful recruitment across a larger number of sites. However, our qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have moved over time.Conclusions A future effectiveness trial is feasible following limited additional preparation to establish appropriate outcome measures and case identification. We recommend a limited package of qualitative work be included to optimise recruitment at new centres in particular.Future work Prior to proceeding to an effectiveness trial we need to: develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis; reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved.Study registration ISRCTN15830435.Funding detailsNIHR HTA programm

CONTRACT Study - CONservative TReatment of Appendicitis in Children (feasibility):study protocol for a randomised controlled Trial

BackgroundCurrently, the routine treatment for acute appendicitis in the United Kingdom is an appendicectomy. However, there is increasing scientific interest and research into non-operative treatment of appendicitis in adults and children. While a number of studies have investigated non-operative treatment of appendicitis in adults, this research cannot be applied to the paediatric population. Ultimately, we aim to perform a UK-based multicentre randomised controlled trial (RCT) to test the clinical and cost effectiveness of non-operative treatment of acute uncomplicated appendicitis in children, as compared with appendicectomy. First, we will undertake a feasibility study to assess the feasibility of performing such a trial.Methods/designThe study involves a feasibility RCT with a nested qualitative research to optimise recruitment as well as a health economic substudy. Children (aged 4–15 years inclusive) diagnosed with acute uncomplicated appendicitis that would normally be treated with an appendicectomy are eligible for the RCT. Exclusion criteria include clinical/radiological suspicion of perforated appendicitis, appendix mass or previous non-operative treatment of appendicitis. Participants will be randomised into one of two arms. Participants in the intervention arm are treated with antibiotics and regular clinical assessment to ensure clinical improvement. Participants in the control arm will receive appendicectomy. Randomisation will be minimised by age, sex, duration of symptoms and centre. Children and families who are approached for the RCT will be invited to participate in the embedded qualitative substudy, which includes recording of recruitment consultants and subsequent interviews with participants and non-participants and their families and recruiters. Analyses of these will inform interventions to optimise recruitment. The main study outcomes include recruitment rate (primary outcome), identification of strategies to optimise recruitment, performance of trial treatment pathways, clinical outcomes and safety of non-operative treatment. We have involved children, young people and parents in study design and delivery.DiscussionIn this study we will explore the feasibility of performing a full efficacy RCT comparing non-operative treatment with appendicectomy in children with acute uncomplicated appendicitis. Factors determining success of the present study include recruitment rate, safety of non-operative treatment and adequate interest in the future RCT. Ultimately this feasibility study will form the foundation of the main RCT and reinforce its design.Trial registrationISRCTN15830435. Registered on 8 February 2017

Effect of a Perioperative, Cardiac Output-Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery A Randomized Clinical Trial and Systematic Review

Importance: small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.Objective: to evaluate the clinical effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm.Design, setting, and participants: OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014.Interventions: patients were randomly assigned to a cardiac output–guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366).Main outcomes and measures: the primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care–free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay.Results: baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, ?0.3% to 13.9%]; P?=?.07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]).Conclusions and relevance: in a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output–guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rate

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant