Background Anastomotic leak is one of the most feared complications of colorectal surgery, and pr... more Background Anastomotic leak is one of the most feared complications of colorectal surgery, and probably linked to poor blood supply to the anastomotic site. Several technologies have been described for intraoperative assessment of bowel perfusion. This systematic review and meta-analysis aimed to evaluate the most frequently used bowel perfusion assessment modalities in elective colorectal procedures, and to assess their associated risk of anastomotic leak. Technologies included indocyanine green fluorescence angiography, diffuse reflectance spectroscopy, laser speckle contrast imaging, and hyperspectral imaging. Methods The review was preregistered with PROSPERO (CRD42021297299). A comprehensive literature search was performed using Embase, MEDLINE, Cochrane Library, Scopus, and Web of Science. The final search was undertaken on 29 July 2022. Data were extracted by two reviewers and the MINORS criteria were applied to assess the risk of bias. Results Some 66 eligible studies involv...
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>BACKGROUND</j... more <jats:title>Abstract</jats:title> <jats:sec> <jats:title>BACKGROUND</jats:title> <jats:p>The aim of the systematic review was to assess recently published studies on diagnostic test accuracy of glioblastoma treatment response monitoring biomarkers in adults, developed through machine learning (ML).</jats:p> </jats:sec> <jats:sec> <jats:title>MATERIAL AND METHODS</jats:title> <jats:p>PRISMA methodology was followed. Articles published 09/2018-01/2021 (since previous reviews) were searched for using MEDLINE, EMBASE, and the Cochrane Register by two reviewers independently. Included study participants were adult patients with high grade glioma who had undergone standard treatment (maximal resection, radiotherapy with concomitant and adjuvant temozolomide) and subsequently underwent follow-up imaging to determine treatment response status (specifically, distinguishing progression/recurrence from progression/recurrence mimics - the target condition). Risk of bias and applicability was assessed with QUADAS 2. A third reviewer arbitrated any discrepancy. Contingency tables were created for hold-out test sets and recall, specificity, precision, F1-score, balanced accuracy calculated. A meta-analysis was performed using a bivariate model for recall, false positive rate and area-under the receiver operator characteristic curve (AUC).</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Eighteen studies were included with 1335 patients in training sets and 384 in test sets. To determine whether there was progression or a mimic, the reference standard combination of follow-up imaging and histopathology at re-operation was applied in 67% (13/18) of studies. The small numbers of patient included in studies, the high risk of bias and concerns of applicability in the study designs (particularly in relation to the reference standard and patient selection due to confounding), and the low level of evidence, suggest that limited conclusions can be drawn from the data. Ten studies (10/18, 56%) had internal or external hold-out test set data that could be included in a meta-analysis of monitoring biomarker studies. The pooled sensitivity was 0.77 (0.65–0.86). The pooled false positive rate (1-specificity) was 0.35 (0.25–0.47). The summary point estimate for the AUC was 0.77.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSION</jats:title> <jats:p>There is likely good diagnostic performance of machine learning models that use MRI features to distinguish between progression and mimics. The diagnostic performance of ML using implicit features did not appear to be superior to ML using explicit features. There are a range of ML-based solutions poised to become treatment response monitoring biomarkers for glioblastoma. To achieve this, the development and validation of ML models require large, well-annotated datasets where the potential for confounding in the study design has been carefully considered. Therefore, multidisciplinary efforts and multicentre collaborations are necessary.</jats:p> </jats:sec>
Background: The Covid-19 pandemic is a healthcare emergency with a significant impact on cancer s... more Background: The Covid-19 pandemic is a healthcare emergency with a significant impact on cancer services provision. In March 2020, our institution adopted the ESMO expert consensus guidelines for radiotherapy management of rectal cancer during the pandemic. Here we present short-term oncological outcomes of this approach compared to the same period in 2018. Methods: Patients who underwent neoadjuvant (chemo) radiotherapy for rectal cancer between 1st March 2020 and 31 May 2020 were identified from a research ethics committee (REC)-approved research database for cancer patients (Guy’s Cancer Cohort). Patient demographics and treatment characteristics were extracted and compared with a control cohort treated in the same period in 2018. The definition of local response was based on identification of downstaging on re-staging Magnetic Resonance Imaging (MRI) post neoadjuvant treatment (mrT3c/d-4 to mrT0-2 and mrT2 to mrT0-1) and classified in a binary format (response vs no response). I...
Background Cataract surgery is the most frequently undertaken NHS surgical procedure. Visual acui... more Background Cataract surgery is the most frequently undertaken NHS surgical procedure. Visual acuity (VA) provides a poor indication of visual difficulty in a complex visual world. In the absence of a suitable outcome metric, recent efforts have been directed towards the development of a cataract patient-reported outcome measure (PROM) of sufficient brevity, precision, and responsiveness to be implementable in routine high volume clinical services. Aim To compare and contrast the two most promising candidate PROMs for routine cataract surgery. Method The psychometric performance and patient acceptability of the recently UK developed five-item Cat-PROM5 questionnaire was compared with the English translation of the Swedish nine-item Catquest-9SF using Rasch-based performance metrics and qualitative semistructured interviews. Results Rasch-based performance was assessed in 822 typical NHS cataract surgery patients across four centres in England. Both questionnaires demonstrated good to excellent performance for all metrics assessed, including Person Reliability Indices of 0.90 (Cat-PROM5) and 0.88 (Catquest-9SF), responsiveness to surgery (Cohen's standardized effect size) of 1.45 SD (Cat-PROM5) and 1.47 SD (Catquest-9SF) and they were highly correlated with each other (R = 0.85). Qualitative assessments confirmed that both questionnaires were acceptable to patients, including in the presence of ocular comorbidities. Preferences were expressed for the shorter Cat-PROM5, which allowed patients to map their own issues to the questions as opposed to the more restrictive specific scenarios of Catquest-9SF. Conclusion The recently UK developed Cat-PROM5 cataract surgery questionnaire is shorter, with performance and patient acceptability at least as good or better than the previous 'best of class' Catquest-9SF instrument.
Purpose To develop a short, psychometrically robust and responsive cataract patient reported outc... more Purpose To develop a short, psychometrically robust and responsive cataract patient reported outcome measure suitable for use in high-volume surgical environments. Methods A prospective study in which participants completed development versions of questionnaires exploring the quality of their eyesight using items harvested from two existing United Kingdom developed parent questionnaires. Participants were 822 patients awaiting cataract surgery recruited from 4 cataract surgical centres based in the UK. Exclusion criteria were other visually significant comorbidities and age o50 years. An iterative multi-stage process of evaluation using Rasch and factor analyses with sequential item reduction was undertaken. Results A definitive item set of just five items delivered performance in accordance with the requirements of the Rasch model: no threshold disordering, no misfitting items, Rasch-based reliability 0.90, person separation 2.98, Cronbach's α 0.89, good targeting of questions to patients with cataract with pre-operative item mean − 0.41 logits and absence of significant floor or ceiling effects, minor deviations of item invariance, and confirmed unidimensionality. The test-re-test repeatability intra-class correlation coefficient was 0.89 with excellent responsiveness to surgery, Cohen's d − 1.45 SD. Rasch calibration values are provided for Cat-PROM5 users. Conclusions A psychometrically robust and highly responsive five-item cataract surgery patient reported outcome measure has been developed, which is suitable for use in highvolume cataract surgical services.
Objectives Delayed post-gadolinium magnetic resonance imaging (MRI) detects changes of endolympha... more Objectives Delayed post-gadolinium magnetic resonance imaging (MRI) detects changes of endolymphatic hydrops (EH) within the inner ear in Meniere’s disease (MD). A systematic review with meta-analysis was conducted to summarise the diagnostic performance of MRI descriptors across the range of MD clinical classifications. Materials and methods Case-controlled studies documenting the diagnostic performance of MRI descriptors in distinguishing MD ears from asymptomatic ears or ears with other audio-vestibular conditions were identified (MEDLINE, EMBASE, Web of Science, Scopus databases: updated 17/2/2022). Methodological quality was evaluated with Quality Assessment of Diagnostic Accuracy Studies version 2. Results were pooled using a bivariate random-effects model for evaluation of sensitivity, specificity and diagnostic odds ratio (DOR). Meta-regression evaluated sources of heterogeneity, and subgroup analysis for individual clinical classifications was performed. Results The meta-an...
Aim The aim was to answer the research question: Does a low fibre diet cause constipation in chil... more Aim The aim was to answer the research question: Does a low fibre diet cause constipation in children? Methods Traditional twin study methodology compared monozygous and dizygous twin pairs for concordance for constipation and it’s precursor hard stools from 3 data sources. A UK cohort study had 72 twin pairs with zygosity and data on stool consistency at age 6 months, 2.5 years and 3.5 years. Published data from a US study included 338 twin pairs age 6–19 years and data on parent reported constipation. The UK twin study included 2267 twin pairs with data on self reported constipation and zygosity from 18 to 92 years. These latter data were arbitrarily divided into age groups 10–39 years, 40–59 years and greater than 60 years. A large cohort study of children was examined to ascertain which came first, constipation and its precursor hard stools, or fibre in the diet. Parent questionnaire included stool consistency at 4 weeks (n=6,796–49% of whole cohort), 6 months (n=9,828–70% of cohort), 2.5 years (n=9452%–68%) and parentally reported constipation age 4–10 years (n=8,401–60%). These data were all linked to fibre intake at age 2 years. Results Genetic predisposition explained 100% of hard stools at 6 months and 2.5 years, 66% at 3.5 years, as well as 63% of constipation at 6–19 years, 18% at 18–39 years, 23% age 40–59 years and 6%>60 years. Hard stools, predated fibre in the diet at infant age 4 weeks and at 6 months predicted a lower fibre intake at 2 years (p=0.003). Conclusion For infants and children the major cause of hard stools and constipation appears to be genetic predisposition. A low fibre diet and constipation may be driven by hard stools causing parents to select a low fibre diet that their child will readily eat rather than the traditionally accepted opposite direction for causation. Prolonged effective medical treatment of hard stools in early childhood may increase fibre intake and reduce later chronic idiopathic constipation.
Objective Constipation and soiling are common in childhood. This study examines the comorbidity b... more Objective Constipation and soiling are common in childhood. This study examines the comorbidity between childhood constipation and soiling and early childhood risk factors for these problems. Design The sample comprised 8435 participants from the Avon Longitudinal Study of Parents and Children with maternally reported measures of constipation (six time points between 4 and 10 years) and soiling (five time points between 4 and 9 years). We used latent class analysis to extract longitudinal patterns of constipation and soiling. We examined whether the latent classes are differentially associated with maternally reported risk factors in early childhood (stool consistency, breast feeding, socioeconomic background, gestation, birth weight, developmental level and age at initiation of toilet training) using multinomial logistic regression models. results We extracted four latent classes: 'normative' (74.5%: very low probability of constipation or soiling), 'constipation alone' (13.2%), 'soiling alone' (7.5%) and 'constipation with soiling' (4.8%). Hard stools at 2½ years were associated with increased odds of constipation alone. Developmental delay at 18 months was associated soiling alone and constipation with soiling, but not constipation alone. We found limited evidence of associations with socioeconomic background and no evidence of associations with age at initiation of toilet training, breast feeding, gestational age or birth weight. Conclusion Constipation alone was the most prevalent pattern in this cohort. Treatment for hard stools in early childhood is needed to prevent chronic constipation at school age. Constipation with soiling was less common than soiling alone. Further research is needed into the causes of non-retentive soiling.
European Child & Adolescent Psychiatry, May 10, 2018
To examine prospective associations between psychosocial problems and childhood constipation and ... more To examine prospective associations between psychosocial problems and childhood constipation and soiling. We used latent classes of constipation and soiling ('constipation alone', 'soiling alone', 'constipation with soiling') extracted from longitudinal maternally reported data on constipation (4-10 years) and soiling (4-9 years) from 8435 children (4353 males, 4082 females) from the ALSPAC cohort. We examined the association between maternally reported psychosocial problems at 2-3 years (difficult temperament, behaviour/emotional problems, temper tantrums, behavioural sleep problems and stressful events) and the latent classes using multinomial logistic regression adjusted for a range of confounders relating to the child and family (reference category = normative latent class with very low probability of constipation/soiling). Difficult temperament and emotional/behaviour problems were associated with increased odds of constipation and soiling. Associations were generally strongest for 'constipation with soiling', e.g. difficult mood: 1.42 (1.23-1.64); behaviour problems: 1.48 (1.28-1.71); temper tantrums: 1.89 (1.34-2.65); lack of a regular sleep routine 2.09 (1.35-3.25). Stressful life events were associated with constipation alone [1.23 (1.12-1.36)] and constipation with soiling [1.32 (1.14-1.52)], but not soiling alone. Additional comparisons of the non-normative latent classes provided evidence for differential associations with the risk factors, e.g. frequent temper tantrums were associated with a greater than twofold increase in the odds of constipation with soiling versus constipation alone. Psychosocial problems in early childhood are risk factors for constipation and soiling at school age. An increased understanding of early risk factors for constipation and soiling could aid the identification of children who require treatment.
Programme grants for applied research, Oct 1, 2022
Reports are published in Programme Grants for Applied Research (PGfAR) if (1) they have resulted ... more Reports are published in Programme Grants for Applied Research (PGfAR) if (1) they have resulted from work for the PGfAR programme, and (2) they are of a sufficiently high scientific quality as assessed by the reviewers and editors. Programme Grants for Applied Research programme The Programme Grants for Applied Research (PGfAR) programme, part of the National Institute for Health and Care Research (NIHR), was established in 2006 to fund collaborative, multidisciplinary programmes of applied research to solve health and social care challenges. Findings are expected to provide evidence that lead to clear and identifiable patient benefits, in the relatively near future. PGfAR is researcher led and does not specify topics for research; however, the research must be in an area of priority or need for the NHS and the social care sector of the Department of Health and Social Care, with particular emphasis on health and social care areas that cause significant burden, where other research funders may not be focused, or where insufficient funding is available. The programme is managed by the NIHR Central Commissioning Facility (CCF) with strategic input from the Programme Director. For more information about the PGfAR programme please visit the website: https://www.nihr.ac.uk/explore-nihr/funding-programmes/ programme-grants-for-applied-research.htm
Background Older age is commonly associated with an increased risk of surgical complications and ... more Background Older age is commonly associated with an increased risk of surgical complications and comparatively poor outcomes. Purpose To report cataract surgery outcomes and risk indicators for patients aged 90 years and older. Methods Data collected as part of routine cataract care in 34 centres contributing to the United Kingdom Royal College of Ophthalmologists' National Ophthalmology Database (NOD) were analysed. Very elderly people undergoing cataract surgery were profiled in terms of demographics, pre-and postoperative best-measured visual acuity (VA), ocular co-morbidities, intraoperative posterior capsule rupture (PCR) or vitreous loss or both, and risk indicators for operative PCR and adverse VA outcome. Results 25,856 cataract operations in 19,166 people of 90 years or older between 2000 and 2014 are reported. Preoperative VA was available for 82.4% eyes, being 0.30 LogMAR or better in 21.5%. Postoperative VA was available for 61.8% eyes, being 0.30 LogMAR or better in 74.4%. For those without ocular co-morbidity, postoperative VA was 0.30 LogMAR or better in 84.7%. Various co-morbidities were present in 49% and contributed to an adverse VA outcome. PCR data were available for all operations and occurred in 2.7%. Significant risk indicators for PCR included pseudoexfoliation/phakodonesis, mature cataract, smaller pupil and worse preoperative VA. Conclusions Slightly poorer cataract surgery outcome results were noted in patients of 90 years or older, more so in patients with ocular co-morbidity which was highly prevalent. However, surgeons should not be deterred from offering cataract surgery to the very elderly as successful visual rehabilitation remains achievable.
BackgroundSubarachnoid hemorrhage from cerebral aneurysm rupture is a major cause of morbidity an... more BackgroundSubarachnoid hemorrhage from cerebral aneurysm rupture is a major cause of morbidity and mortality. Early aneurysm identification, aided by automated systems, may improve patient outcomes. Therefore, a systematic review and meta-analysis of the diagnostic accuracy of artificial intelligence (AI) algorithms in detecting cerebral aneurysms using CT, MRI or DSA was performed.MethodsMEDLINE, Embase, Cochrane Library and Web of Science were searched until August 2021. Eligibility criteria included studies using fully automated algorithms to detect cerebral aneurysms using MRI, CT or DSA. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis: Diagnostic Test Accuracy (PRISMA-DTA), articles were assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Meta-analysis included a bivariate random-effect model to determine pooled sensitivity, specificity, and area under the receiver operator characteristic curve (ROC-AUC). PROSPERO: CRD4202...
Background Surgery for established cataract is highly cost-effective and uncontroversial, yet unc... more Background Surgery for established cataract is highly cost-effective and uncontroversial, yet uncertainty remains for individuals about when to proceed and when to delay surgery during the earlier stages of cataract. Objective We aimed to improve decision-making for cataract surgery through the development of evidence-based clinical tools that provide general information and personalised risk/benefit information. Design We used a mixed methodology consisting of four work packages. Work package 1 involved the development and psychometric validation of a brief, patient self-reported measure of visual difficulty from cataract and its relief from surgery, named Cataract Patient-Reported Outcome Measure, five items (Cat-PROM5). Work package 2 involved the review and refinement of risk models for adverse surgical events (posterior capsule rupture and visual acuity loss related to cataract surgery). Work package 3 involved the development of prediction models for the Cat-PROM5-based self-r...
Association of General Paediatrics and Society of Paediatric Gastroenterology, Hepatology and Nutrition, 2019
Aim The aim was to answer the research question: Does a low fibre diet cause constipation in chil... more Aim The aim was to answer the research question: Does a low fibre diet cause constipation in children? Methods Traditional twin study methodology compared monozygous and dizygous twin pairs for concordance for constipation and it’s precursor hard stools from 3 data sources. A UK cohort study had 72 twin pairs with zygosity and data on stool consistency at age 6 months, 2.5 years and 3.5 years. Published data from a US study included 338 twin pairs age 6–19 years and data on parent reported constipation. The UK twin study included 2267 twin pairs with data on self reported constipation and zygosity from 18 to 92 years. These latter data were arbitrarily divided into age groups 10–39 years, 40–59 years and greater than 60 years. A large cohort study of children was examined to ascertain which came first, constipation and its precursor hard stools, or fibre in the diet. Parent questionnaire included stool consistency at 4 weeks (n=6,796–49% of whole cohort), 6 months (n=9,828–70% of cohort), 2.5 years (n=9452%–68%) and parentally reported constipation age 4–10 years (n=8,401–60%). These data were all linked to fibre intake at age 2 years. Results Genetic predisposition explained 100% of hard stools at 6 months and 2.5 years, 66% at 3.5 years, as well as 63% of constipation at 6–19 years, 18% at 18–39 years, 23% age 40–59 years and 6%>60 years. Hard stools, predated fibre in the diet at infant age 4 weeks and at 6 months predicted a lower fibre intake at 2 years (p=0.003). Conclusion For infants and children the major cause of hard stools and constipation appears to be genetic predisposition. A low fibre diet and constipation may be driven by hard stools causing parents to select a low fibre diet that their child will readily eat rather than the traditionally accepted opposite direction for causation. Prolonged effective medical treatment of hard stools in early childhood may increase fibre intake and reduce later chronic idiopathic constipation.
induced wheeze and community acquired pneumonia. The current usage of CXR's needs to be explored ... more induced wheeze and community acquired pneumonia. The current usage of CXR's needs to be explored and appropriateness evaluated. Aims To audit appropriateness of CXR requests in children presenting with bronchiolitis, community acquired pneumonia or viral induced wheeze, against national guidelines. Methods Prospective observational study performed from 13 th October to 13 th November 2014, across general paediatric departments in Wales. Structured questionnaires completed, with questions based upon: CXR request reasons, clinical diagnosis pre CXR and management plan pre and post CXR. Results 9 hospitals participated. A total of 183 cases received, 76 of these were omitted as request reasons were outside the project remit, leaving a total of 107 cases. Table 2 illustrates the reasons for CXR requests. 16% of chest radiographs performed were indicated as per national guidance. Chest radiographs did not alter clinical management in 98% nor alter clinical diagnosis in 100%. Conclusions A unique study involving CXR requests in doctors practising across Wales. This study highlights the overuse of chest radiographs as when used inappropriately do not alter clinical diagnosis or management. This has cost and radiation implications for the paediatric population. We recommend a quality improvement project aiming to decrease numbers of unnecessary CXR's requested in general paediatric departments across Wales.
Background Anastomotic leak is one of the most feared complications of colorectal surgery, and pr... more Background Anastomotic leak is one of the most feared complications of colorectal surgery, and probably linked to poor blood supply to the anastomotic site. Several technologies have been described for intraoperative assessment of bowel perfusion. This systematic review and meta-analysis aimed to evaluate the most frequently used bowel perfusion assessment modalities in elective colorectal procedures, and to assess their associated risk of anastomotic leak. Technologies included indocyanine green fluorescence angiography, diffuse reflectance spectroscopy, laser speckle contrast imaging, and hyperspectral imaging. Methods The review was preregistered with PROSPERO (CRD42021297299). A comprehensive literature search was performed using Embase, MEDLINE, Cochrane Library, Scopus, and Web of Science. The final search was undertaken on 29 July 2022. Data were extracted by two reviewers and the MINORS criteria were applied to assess the risk of bias. Results Some 66 eligible studies involv...
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>BACKGROUND</j... more <jats:title>Abstract</jats:title> <jats:sec> <jats:title>BACKGROUND</jats:title> <jats:p>The aim of the systematic review was to assess recently published studies on diagnostic test accuracy of glioblastoma treatment response monitoring biomarkers in adults, developed through machine learning (ML).</jats:p> </jats:sec> <jats:sec> <jats:title>MATERIAL AND METHODS</jats:title> <jats:p>PRISMA methodology was followed. Articles published 09/2018-01/2021 (since previous reviews) were searched for using MEDLINE, EMBASE, and the Cochrane Register by two reviewers independently. Included study participants were adult patients with high grade glioma who had undergone standard treatment (maximal resection, radiotherapy with concomitant and adjuvant temozolomide) and subsequently underwent follow-up imaging to determine treatment response status (specifically, distinguishing progression/recurrence from progression/recurrence mimics - the target condition). Risk of bias and applicability was assessed with QUADAS 2. A third reviewer arbitrated any discrepancy. Contingency tables were created for hold-out test sets and recall, specificity, precision, F1-score, balanced accuracy calculated. A meta-analysis was performed using a bivariate model for recall, false positive rate and area-under the receiver operator characteristic curve (AUC).</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Eighteen studies were included with 1335 patients in training sets and 384 in test sets. To determine whether there was progression or a mimic, the reference standard combination of follow-up imaging and histopathology at re-operation was applied in 67% (13/18) of studies. The small numbers of patient included in studies, the high risk of bias and concerns of applicability in the study designs (particularly in relation to the reference standard and patient selection due to confounding), and the low level of evidence, suggest that limited conclusions can be drawn from the data. Ten studies (10/18, 56%) had internal or external hold-out test set data that could be included in a meta-analysis of monitoring biomarker studies. The pooled sensitivity was 0.77 (0.65–0.86). The pooled false positive rate (1-specificity) was 0.35 (0.25–0.47). The summary point estimate for the AUC was 0.77.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSION</jats:title> <jats:p>There is likely good diagnostic performance of machine learning models that use MRI features to distinguish between progression and mimics. The diagnostic performance of ML using implicit features did not appear to be superior to ML using explicit features. There are a range of ML-based solutions poised to become treatment response monitoring biomarkers for glioblastoma. To achieve this, the development and validation of ML models require large, well-annotated datasets where the potential for confounding in the study design has been carefully considered. Therefore, multidisciplinary efforts and multicentre collaborations are necessary.</jats:p> </jats:sec>
Background: The Covid-19 pandemic is a healthcare emergency with a significant impact on cancer s... more Background: The Covid-19 pandemic is a healthcare emergency with a significant impact on cancer services provision. In March 2020, our institution adopted the ESMO expert consensus guidelines for radiotherapy management of rectal cancer during the pandemic. Here we present short-term oncological outcomes of this approach compared to the same period in 2018. Methods: Patients who underwent neoadjuvant (chemo) radiotherapy for rectal cancer between 1st March 2020 and 31 May 2020 were identified from a research ethics committee (REC)-approved research database for cancer patients (Guy’s Cancer Cohort). Patient demographics and treatment characteristics were extracted and compared with a control cohort treated in the same period in 2018. The definition of local response was based on identification of downstaging on re-staging Magnetic Resonance Imaging (MRI) post neoadjuvant treatment (mrT3c/d-4 to mrT0-2 and mrT2 to mrT0-1) and classified in a binary format (response vs no response). I...
Background Cataract surgery is the most frequently undertaken NHS surgical procedure. Visual acui... more Background Cataract surgery is the most frequently undertaken NHS surgical procedure. Visual acuity (VA) provides a poor indication of visual difficulty in a complex visual world. In the absence of a suitable outcome metric, recent efforts have been directed towards the development of a cataract patient-reported outcome measure (PROM) of sufficient brevity, precision, and responsiveness to be implementable in routine high volume clinical services. Aim To compare and contrast the two most promising candidate PROMs for routine cataract surgery. Method The psychometric performance and patient acceptability of the recently UK developed five-item Cat-PROM5 questionnaire was compared with the English translation of the Swedish nine-item Catquest-9SF using Rasch-based performance metrics and qualitative semistructured interviews. Results Rasch-based performance was assessed in 822 typical NHS cataract surgery patients across four centres in England. Both questionnaires demonstrated good to excellent performance for all metrics assessed, including Person Reliability Indices of 0.90 (Cat-PROM5) and 0.88 (Catquest-9SF), responsiveness to surgery (Cohen's standardized effect size) of 1.45 SD (Cat-PROM5) and 1.47 SD (Catquest-9SF) and they were highly correlated with each other (R = 0.85). Qualitative assessments confirmed that both questionnaires were acceptable to patients, including in the presence of ocular comorbidities. Preferences were expressed for the shorter Cat-PROM5, which allowed patients to map their own issues to the questions as opposed to the more restrictive specific scenarios of Catquest-9SF. Conclusion The recently UK developed Cat-PROM5 cataract surgery questionnaire is shorter, with performance and patient acceptability at least as good or better than the previous 'best of class' Catquest-9SF instrument.
Purpose To develop a short, psychometrically robust and responsive cataract patient reported outc... more Purpose To develop a short, psychometrically robust and responsive cataract patient reported outcome measure suitable for use in high-volume surgical environments. Methods A prospective study in which participants completed development versions of questionnaires exploring the quality of their eyesight using items harvested from two existing United Kingdom developed parent questionnaires. Participants were 822 patients awaiting cataract surgery recruited from 4 cataract surgical centres based in the UK. Exclusion criteria were other visually significant comorbidities and age o50 years. An iterative multi-stage process of evaluation using Rasch and factor analyses with sequential item reduction was undertaken. Results A definitive item set of just five items delivered performance in accordance with the requirements of the Rasch model: no threshold disordering, no misfitting items, Rasch-based reliability 0.90, person separation 2.98, Cronbach's α 0.89, good targeting of questions to patients with cataract with pre-operative item mean − 0.41 logits and absence of significant floor or ceiling effects, minor deviations of item invariance, and confirmed unidimensionality. The test-re-test repeatability intra-class correlation coefficient was 0.89 with excellent responsiveness to surgery, Cohen's d − 1.45 SD. Rasch calibration values are provided for Cat-PROM5 users. Conclusions A psychometrically robust and highly responsive five-item cataract surgery patient reported outcome measure has been developed, which is suitable for use in highvolume cataract surgical services.
Objectives Delayed post-gadolinium magnetic resonance imaging (MRI) detects changes of endolympha... more Objectives Delayed post-gadolinium magnetic resonance imaging (MRI) detects changes of endolymphatic hydrops (EH) within the inner ear in Meniere’s disease (MD). A systematic review with meta-analysis was conducted to summarise the diagnostic performance of MRI descriptors across the range of MD clinical classifications. Materials and methods Case-controlled studies documenting the diagnostic performance of MRI descriptors in distinguishing MD ears from asymptomatic ears or ears with other audio-vestibular conditions were identified (MEDLINE, EMBASE, Web of Science, Scopus databases: updated 17/2/2022). Methodological quality was evaluated with Quality Assessment of Diagnostic Accuracy Studies version 2. Results were pooled using a bivariate random-effects model for evaluation of sensitivity, specificity and diagnostic odds ratio (DOR). Meta-regression evaluated sources of heterogeneity, and subgroup analysis for individual clinical classifications was performed. Results The meta-an...
Aim The aim was to answer the research question: Does a low fibre diet cause constipation in chil... more Aim The aim was to answer the research question: Does a low fibre diet cause constipation in children? Methods Traditional twin study methodology compared monozygous and dizygous twin pairs for concordance for constipation and it’s precursor hard stools from 3 data sources. A UK cohort study had 72 twin pairs with zygosity and data on stool consistency at age 6 months, 2.5 years and 3.5 years. Published data from a US study included 338 twin pairs age 6–19 years and data on parent reported constipation. The UK twin study included 2267 twin pairs with data on self reported constipation and zygosity from 18 to 92 years. These latter data were arbitrarily divided into age groups 10–39 years, 40–59 years and greater than 60 years. A large cohort study of children was examined to ascertain which came first, constipation and its precursor hard stools, or fibre in the diet. Parent questionnaire included stool consistency at 4 weeks (n=6,796–49% of whole cohort), 6 months (n=9,828–70% of cohort), 2.5 years (n=9452%–68%) and parentally reported constipation age 4–10 years (n=8,401–60%). These data were all linked to fibre intake at age 2 years. Results Genetic predisposition explained 100% of hard stools at 6 months and 2.5 years, 66% at 3.5 years, as well as 63% of constipation at 6–19 years, 18% at 18–39 years, 23% age 40–59 years and 6%>60 years. Hard stools, predated fibre in the diet at infant age 4 weeks and at 6 months predicted a lower fibre intake at 2 years (p=0.003). Conclusion For infants and children the major cause of hard stools and constipation appears to be genetic predisposition. A low fibre diet and constipation may be driven by hard stools causing parents to select a low fibre diet that their child will readily eat rather than the traditionally accepted opposite direction for causation. Prolonged effective medical treatment of hard stools in early childhood may increase fibre intake and reduce later chronic idiopathic constipation.
Objective Constipation and soiling are common in childhood. This study examines the comorbidity b... more Objective Constipation and soiling are common in childhood. This study examines the comorbidity between childhood constipation and soiling and early childhood risk factors for these problems. Design The sample comprised 8435 participants from the Avon Longitudinal Study of Parents and Children with maternally reported measures of constipation (six time points between 4 and 10 years) and soiling (five time points between 4 and 9 years). We used latent class analysis to extract longitudinal patterns of constipation and soiling. We examined whether the latent classes are differentially associated with maternally reported risk factors in early childhood (stool consistency, breast feeding, socioeconomic background, gestation, birth weight, developmental level and age at initiation of toilet training) using multinomial logistic regression models. results We extracted four latent classes: 'normative' (74.5%: very low probability of constipation or soiling), 'constipation alone' (13.2%), 'soiling alone' (7.5%) and 'constipation with soiling' (4.8%). Hard stools at 2½ years were associated with increased odds of constipation alone. Developmental delay at 18 months was associated soiling alone and constipation with soiling, but not constipation alone. We found limited evidence of associations with socioeconomic background and no evidence of associations with age at initiation of toilet training, breast feeding, gestational age or birth weight. Conclusion Constipation alone was the most prevalent pattern in this cohort. Treatment for hard stools in early childhood is needed to prevent chronic constipation at school age. Constipation with soiling was less common than soiling alone. Further research is needed into the causes of non-retentive soiling.
European Child & Adolescent Psychiatry, May 10, 2018
To examine prospective associations between psychosocial problems and childhood constipation and ... more To examine prospective associations between psychosocial problems and childhood constipation and soiling. We used latent classes of constipation and soiling ('constipation alone', 'soiling alone', 'constipation with soiling') extracted from longitudinal maternally reported data on constipation (4-10 years) and soiling (4-9 years) from 8435 children (4353 males, 4082 females) from the ALSPAC cohort. We examined the association between maternally reported psychosocial problems at 2-3 years (difficult temperament, behaviour/emotional problems, temper tantrums, behavioural sleep problems and stressful events) and the latent classes using multinomial logistic regression adjusted for a range of confounders relating to the child and family (reference category = normative latent class with very low probability of constipation/soiling). Difficult temperament and emotional/behaviour problems were associated with increased odds of constipation and soiling. Associations were generally strongest for 'constipation with soiling', e.g. difficult mood: 1.42 (1.23-1.64); behaviour problems: 1.48 (1.28-1.71); temper tantrums: 1.89 (1.34-2.65); lack of a regular sleep routine 2.09 (1.35-3.25). Stressful life events were associated with constipation alone [1.23 (1.12-1.36)] and constipation with soiling [1.32 (1.14-1.52)], but not soiling alone. Additional comparisons of the non-normative latent classes provided evidence for differential associations with the risk factors, e.g. frequent temper tantrums were associated with a greater than twofold increase in the odds of constipation with soiling versus constipation alone. Psychosocial problems in early childhood are risk factors for constipation and soiling at school age. An increased understanding of early risk factors for constipation and soiling could aid the identification of children who require treatment.
Programme grants for applied research, Oct 1, 2022
Reports are published in Programme Grants for Applied Research (PGfAR) if (1) they have resulted ... more Reports are published in Programme Grants for Applied Research (PGfAR) if (1) they have resulted from work for the PGfAR programme, and (2) they are of a sufficiently high scientific quality as assessed by the reviewers and editors. Programme Grants for Applied Research programme The Programme Grants for Applied Research (PGfAR) programme, part of the National Institute for Health and Care Research (NIHR), was established in 2006 to fund collaborative, multidisciplinary programmes of applied research to solve health and social care challenges. Findings are expected to provide evidence that lead to clear and identifiable patient benefits, in the relatively near future. PGfAR is researcher led and does not specify topics for research; however, the research must be in an area of priority or need for the NHS and the social care sector of the Department of Health and Social Care, with particular emphasis on health and social care areas that cause significant burden, where other research funders may not be focused, or where insufficient funding is available. The programme is managed by the NIHR Central Commissioning Facility (CCF) with strategic input from the Programme Director. For more information about the PGfAR programme please visit the website: https://www.nihr.ac.uk/explore-nihr/funding-programmes/ programme-grants-for-applied-research.htm
Background Older age is commonly associated with an increased risk of surgical complications and ... more Background Older age is commonly associated with an increased risk of surgical complications and comparatively poor outcomes. Purpose To report cataract surgery outcomes and risk indicators for patients aged 90 years and older. Methods Data collected as part of routine cataract care in 34 centres contributing to the United Kingdom Royal College of Ophthalmologists' National Ophthalmology Database (NOD) were analysed. Very elderly people undergoing cataract surgery were profiled in terms of demographics, pre-and postoperative best-measured visual acuity (VA), ocular co-morbidities, intraoperative posterior capsule rupture (PCR) or vitreous loss or both, and risk indicators for operative PCR and adverse VA outcome. Results 25,856 cataract operations in 19,166 people of 90 years or older between 2000 and 2014 are reported. Preoperative VA was available for 82.4% eyes, being 0.30 LogMAR or better in 21.5%. Postoperative VA was available for 61.8% eyes, being 0.30 LogMAR or better in 74.4%. For those without ocular co-morbidity, postoperative VA was 0.30 LogMAR or better in 84.7%. Various co-morbidities were present in 49% and contributed to an adverse VA outcome. PCR data were available for all operations and occurred in 2.7%. Significant risk indicators for PCR included pseudoexfoliation/phakodonesis, mature cataract, smaller pupil and worse preoperative VA. Conclusions Slightly poorer cataract surgery outcome results were noted in patients of 90 years or older, more so in patients with ocular co-morbidity which was highly prevalent. However, surgeons should not be deterred from offering cataract surgery to the very elderly as successful visual rehabilitation remains achievable.
BackgroundSubarachnoid hemorrhage from cerebral aneurysm rupture is a major cause of morbidity an... more BackgroundSubarachnoid hemorrhage from cerebral aneurysm rupture is a major cause of morbidity and mortality. Early aneurysm identification, aided by automated systems, may improve patient outcomes. Therefore, a systematic review and meta-analysis of the diagnostic accuracy of artificial intelligence (AI) algorithms in detecting cerebral aneurysms using CT, MRI or DSA was performed.MethodsMEDLINE, Embase, Cochrane Library and Web of Science were searched until August 2021. Eligibility criteria included studies using fully automated algorithms to detect cerebral aneurysms using MRI, CT or DSA. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis: Diagnostic Test Accuracy (PRISMA-DTA), articles were assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Meta-analysis included a bivariate random-effect model to determine pooled sensitivity, specificity, and area under the receiver operator characteristic curve (ROC-AUC). PROSPERO: CRD4202...
Background Surgery for established cataract is highly cost-effective and uncontroversial, yet unc... more Background Surgery for established cataract is highly cost-effective and uncontroversial, yet uncertainty remains for individuals about when to proceed and when to delay surgery during the earlier stages of cataract. Objective We aimed to improve decision-making for cataract surgery through the development of evidence-based clinical tools that provide general information and personalised risk/benefit information. Design We used a mixed methodology consisting of four work packages. Work package 1 involved the development and psychometric validation of a brief, patient self-reported measure of visual difficulty from cataract and its relief from surgery, named Cataract Patient-Reported Outcome Measure, five items (Cat-PROM5). Work package 2 involved the review and refinement of risk models for adverse surgical events (posterior capsule rupture and visual acuity loss related to cataract surgery). Work package 3 involved the development of prediction models for the Cat-PROM5-based self-r...
Association of General Paediatrics and Society of Paediatric Gastroenterology, Hepatology and Nutrition, 2019
Aim The aim was to answer the research question: Does a low fibre diet cause constipation in chil... more Aim The aim was to answer the research question: Does a low fibre diet cause constipation in children? Methods Traditional twin study methodology compared monozygous and dizygous twin pairs for concordance for constipation and it’s precursor hard stools from 3 data sources. A UK cohort study had 72 twin pairs with zygosity and data on stool consistency at age 6 months, 2.5 years and 3.5 years. Published data from a US study included 338 twin pairs age 6–19 years and data on parent reported constipation. The UK twin study included 2267 twin pairs with data on self reported constipation and zygosity from 18 to 92 years. These latter data were arbitrarily divided into age groups 10–39 years, 40–59 years and greater than 60 years. A large cohort study of children was examined to ascertain which came first, constipation and its precursor hard stools, or fibre in the diet. Parent questionnaire included stool consistency at 4 weeks (n=6,796–49% of whole cohort), 6 months (n=9,828–70% of cohort), 2.5 years (n=9452%–68%) and parentally reported constipation age 4–10 years (n=8,401–60%). These data were all linked to fibre intake at age 2 years. Results Genetic predisposition explained 100% of hard stools at 6 months and 2.5 years, 66% at 3.5 years, as well as 63% of constipation at 6–19 years, 18% at 18–39 years, 23% age 40–59 years and 6%>60 years. Hard stools, predated fibre in the diet at infant age 4 weeks and at 6 months predicted a lower fibre intake at 2 years (p=0.003). Conclusion For infants and children the major cause of hard stools and constipation appears to be genetic predisposition. A low fibre diet and constipation may be driven by hard stools causing parents to select a low fibre diet that their child will readily eat rather than the traditionally accepted opposite direction for causation. Prolonged effective medical treatment of hard stools in early childhood may increase fibre intake and reduce later chronic idiopathic constipation.
induced wheeze and community acquired pneumonia. The current usage of CXR's needs to be explored ... more induced wheeze and community acquired pneumonia. The current usage of CXR's needs to be explored and appropriateness evaluated. Aims To audit appropriateness of CXR requests in children presenting with bronchiolitis, community acquired pneumonia or viral induced wheeze, against national guidelines. Methods Prospective observational study performed from 13 th October to 13 th November 2014, across general paediatric departments in Wales. Structured questionnaires completed, with questions based upon: CXR request reasons, clinical diagnosis pre CXR and management plan pre and post CXR. Results 9 hospitals participated. A total of 183 cases received, 76 of these were omitted as request reasons were outside the project remit, leaving a total of 107 cases. Table 2 illustrates the reasons for CXR requests. 16% of chest radiographs performed were indicated as per national guidance. Chest radiographs did not alter clinical management in 98% nor alter clinical diagnosis in 100%. Conclusions A unique study involving CXR requests in doctors practising across Wales. This study highlights the overuse of chest radiographs as when used inappropriately do not alter clinical diagnosis or management. This has cost and radiation implications for the paediatric population. We recommend a quality improvement project aiming to decrease numbers of unnecessary CXR's requested in general paediatric departments across Wales.
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Papers by Mariusz Grzeda