PATIENT SATISFACTION AND DIETARY OUTCOMES FROM ATTENDING A MULTIDISCIPLINARY CYSTINURIA CLINIC

Cystinuria is a genetic disease that leads to frequent cystine stone formation. A reduced methionine (precursor to cystine) diet has been recommended for cystinuria patients, involving maintenance of healthy weight, limiting intake of animal protein and salt whilst increasing vegetable protein, fruit, vegetables and fluid intake. The ability of patients to adhere to these dietary regimes has been questioned. We evaluated the dietetic service and dietary changes within our multidisciplinary cystinuria clinic using food frequency questionnaires (ffqs), dietary change questionnaires (dcqs) and diet histories. Most patients were seen by the dietitian 6–12 monthly.100% of patients felt they benefited from dietetic input. There was a move away from ffqs due to them being difficult and cumbersome to complete. Dcqs and diet histories revealed 23/28 increased fruit and vegetable intake, 20/28 decreased salt intake, 20/28 decreased animal protein intake, 14/28 increased vegetable protein intake and 9/28 increased fluid intake. There were a few discrepancies in reported change between dcqs and diet histories, supporting the use of multi-source feedback for diet analysis.Patients had varying degrees of success with making changes to each dietary parameter. Multi-source diet analysis allowed us to develop tailored consultations. All patients made some positive dietary changes which may help prevent stone formation. The areas of least change were fluid (due to changes made prior to clinic attendance) and vegetable protein. Our results support the need for continued dietetic input. These results should be re-audited to check that patients are maintaining the changes made

Leadership in cardiac surgery

Despite the efficacy of cardiac surgery, less invasive interventions with more uncertain long-term outcomes are increasingly challenging surgery as first-line treatment for several congenital, degenerative and ischemic cardiac diseases. The specialty must evolve if it is to ensure its future relevance. More importantly, it must evolve to ensure that future patients have access to treatments with proven long-term effectiveness. This cannot be achieved without dynamic leadership; however, our contention is that this is not enough. The demands of a modern surgical career and the importance of the task at hand are such that the serendipitous emergence of traditional charismatic leadership cannot be relied upon to deliver necessary change. We advocate systematic analysis and strategic leadership at a local, national and international level in four key areas: Clinical Care, Research, Education and Training, and Stakeholder Engagement. While we anticipate that exceptional individuals will continue to shape the future of our specialty, the creation of robust structures to deliver collective leadership in these key areas is of paramount importanc

COmparing Urolift and Standard Transurethral resection of prostate Ahead of Radiotherapy in men with urinary symptoms secondary to prostate enlargement in Southwest London and North Cumbria (CO-STAR): a study protocol for a randomised feasibility study

Introduction: Patients undergoing prostate radiotherapy with an enlarged prostate can have short-term and long-term urinary complications. Currently, transurethral resection of the prostate (TURP) is the mainstay surgical intervention for men with urinary symptoms due to an enlarged prostate prior to radiotherapy. UroLift (NeoTract, Pleasanton, CA, USA) is a recent minimally invasive alternative, widely used in benign disease but is untested in men with prostate cancer. // Methods and analysis: A multicentre, two-arm study designed in collaboration with a Patient Reference Group to assess the feasibility of randomising men with prostate cancer and coexisting urinary symptoms due to prostate enlargement to TURP or UroLift ahead of radiotherapy. 45 patients will be enrolled and randomised (1:1) using a computer-generated programme to TURP or UroLift. Recruitment and retention will be assessed over a 12 month period. Information on clinical outcomes, adverse events and costs will be collected. Clinical outcomes and patient reported outcome measures will be measured at baseline, 6 weeks postintervention and 3 months following radiotherapy. A further 12 in-depth interviews will be conducted with a subset of patients to assess acceptability using the Theoretical Framework of Acceptability. Descriptive analysis on all outcomes will be performed using Stata (StataCorp V.2021). // Ethics and dissemination: The trial has been approved by the Research Ethics Committee (REC) NHS Health Research Authority (HRA) and Health and Care Research Wales (HCRW). The results will be published in peer-reviewed journals, presented at national meetings and disseminated to patients via social media, charity and hospital websites. // Trial registration number: NCT05840549

Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson's Disease Cohorts

Background: Motor complications are a consequence of the chronic dopaminergic treatment of Parkinson’s disease (PD) and include levodopa-induced dyskinesia (LIDs) and motor fluctuations (MF). Currently, evidence is on lacking whether patients with GBA-associated PD differ in their risk of developing motor complications compared to the general PD population. Objective: To evaluate the association of GBA carrier status with the development of LIDS and MFs from early PD. Methods: Motor complications were recorded prospectively in 884 patients with PD from four longitudinal cohorts using part IV of the UPDRS or MDS-UPDRS. Subjects were followed for up to 11 years and the associations of GBA mutations with the development of motor complications were assessed using parametric accelerated failure time models. Results: In 439 patients from Europe, GBA mutations were detected in 53 (12.1%) patients and a total of 168 cases of LIDs and 258 cases of MF were observed. GBA carrier status was not associated with the time to develop LIDs (HR 0.78, 95%CI 0.47 to 1.26, p = 0.30) or MF (HR 1.19, 95%CI 0.84 to 1.70, p = 0.33). In the American cohorts, GBA mutations were detected in 36 (8.1%) patients and GBA carrier status was also not associated with the progression to LIDs (HR 1.08, 95%CI 0.55 to 2.14, p = 0.82) or MF (HR 1.22, 95%CI 0.74 to 2.04, p = 0.43). Conclusion: This study does not provide evidence that GBA-carrier status is associated with a higher risk of developing motor complications. Publication of studies with null results is vital to develop an accurate summary of the clinical features that impact patients with GBA-associated PD.publishedVersio

Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson's Disease Cohorts

ACKNOWLEDGMENTS The authors would like to thank all of the patients and controls for participation in each of the studies. Equally, we thank all members of each of the study groups and other personnel for their contributions. Funding sources for the respective studies are as follows: The Norwegian ParkWest study has been funded by the Research Council of Norway (177966), the Western Norway Regional Health Authority (911218), the Norwegian Parkinson’s Research Foundation, and Rebergs Legacy. PINE study was supported by Parkinson’s UK (G0502, G0914, G1302), Scottish Government Chief Scientist Office, BMA Doris Hillier Award, the BUPA Foundation, NHS Grampian Endowments, and RS MacDonald Trust. The NYPUM study has been funded by the Swedish Medical Research Council, the Swedish Parkinson’s disease Association, the Swedish Parkinson’s Foundation, Parkinson Research Foundation, Erling Persson Foundation, Kempe Foundation, the Swedish Brain Foundation (Hjarnfonden), and the Vasterbotten County Council. AAS, JMG and GA are supported by the Research Council of Norway (287842). BLF acknowledges support through donations to the UCLA Clinical Neurogenomics Research Center. CK is supported by the NIH grant F32AG063442. The PEG study was supported by NIH/NIEHS grants R01-ES010544 and U54-ES012078. Publication of this manuscript was supported under the The Michael J. Fox Foundation: 2021 RFA: Accelerating Publication of Parkinson’s Disease Replication Data.Peer reviewedPublisher PD

Dermoscopy, with and without visual inspection, for the diagnosis of melanoma in adults

Background: Melanoma has one of the fastest rising incidence rates of any cancer. It accounts for a small percentage of skin cancer cases but is responsible for the majority of skin cancer deaths. Although history-taking and visual inspection of a suspicious lesion by a clinician are usually the first in a series of ‘tests’ to diagnose skin cancer, dermoscopy has become an important tool to assist diagnosis by specialist clinicians and is increasingly used in primary care settings. Dermoscopy is a magnification technique using visible light that allows more detailed examination of the skin compared to examination by the naked eye alone. Establishing the additive value of dermoscopy over and above visual inspection alone across a range of observers and settings is critical to understanding its contribution for the diagnosis of melanoma and to future understanding of the potential role of the growing number of other highresolution image analysis techniques. Objectives: To determine the diagnostic accuracy of dermoscopy for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in adults, and to compare its accuracy with that of visual inspection alone. Studies were separated according to whether the diagnosis was recorded face-to-face (in-person) or based on remote (image-based) assessment. Search methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. Selection criteria: Studies of any design that evaluated dermoscopy in adults with lesions suspicious for melanoma, compared with a reference standard of either histological confirmation or clinical follow-up. Data on the accuracy of visual inspection, to allow comparisons of tests, was included only if reported in the included studies of dermoscopy. Data collection and analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated accuracy using hierarchical summary ROC methods. Analysis of studies allowing direct comparison between tests was undertaken. To facilitate interpretation of results, we computed values of sensitivity at the point on the SROC curve with 80% fixed specificity and values of specificity with 80% fixed sensitivity. We investigated the impact of in-person test interpretation; use of a purposely developed algorithm to assist diagnosis; observer expertise; and dermoscopy training. Main results: A total of 104 study publications reporting on 103 study cohorts with 42,788 lesions (including 5700 cases) were included, providing 354 datasets for dermoscopy. The risk of bias was mainly low for the index test and reference standard domains and mainly high or unclear for participant selection and participant flow. Concerns regarding the applicability of study findings were largely scored as ‘High’ concern in three of four domains assessed. Selective participant recruitment, lack of reproducibility of diagnostic thresholds and lack of detail on observer expertise were particularly problematic. The accuracy of dermoscopy for the detection of invasive melanoma or atypical intraepidermal melanocytic variants was reported in 86 datasets; 26 for evaluations conducted in-person (dermoscopy added to visual inspection) and 60 for image-based evaluations (diagnosis based on interpretation of dermoscopic images). Analyses of studies by prior testing revealed no obvious effect on accuracy; analyses were hampered by the lack of studies in primary care, lack of relevant information and the restricted inclusion of lesions selected for biopsy or excision. Accuracy was higher for in-person diagnosis compared to image-based evaluations (relative diagnostic odds ratio (RDOR) of 4.6; 95% CI 2.4, 9.0, P<0.001). Accuracy was compared for (a) in-person evaluations of dermoscopy (26 evaluations; 23,169 lesions and 1664 melanomas) versus visual inspection alone (13 evaluations; 6740 lesions and 459 melanomas) and for (b) image-based evaluations of dermoscopy (60 evaluations; 13,475 lesions and 2851 melanomas) versus image-based visual inspection (11 evaluations; 1740 lesions and 305 melanomas). For both comparisons, meta-analysis found dermoscopy to be more accurate than visual inspection alone, with RDORs of (a) 4.7 (95% CI: 3.0 to 7.5; P < 0.001) and (b) 5.6 (95% CI: 3.7 to 8.5; P < 0.001). These effects correspond to predicted differences in sensitivity of (a) 16% (95% CI: 8%, 23%) (92% for dermoscopy+visual inspection vs 76% for visual inspection) and (b) 35% (95% CI 24% to 46%) (81% for dermoscopy vs 47% for visual inspection) at a fixed specificity of 80%; and topredicted differences in specificity of (a) 20% (95% CI 7%, 33) (95% for dermoscopy plus visual inspection vs 75% for visual inspection) and (b) 40% (95% CI 27, 57) (82% for dermoscopy vs 42% for visual inspection) at a fixed sensitivity of 80%. Using the median prevalence of disease in each set of studies ((a) 12% for in-person and (b) 24% for image-based) for a hypothetical population of 1000 lesions, an increase in sensitivity of (a) 16% (in-person) and (b) 35% (image-based) from using dermoscopy at a fixed specificity of 80% equates to a reduction in the number of melanomas missed of (a) 19 and (b) 81 with (a) 176 and (b) 152 false positive results. An increase in specificity of (a) 20% (in-person) and (b) 40% (image-based) at a fixed sensitivity of 80% equates to a reduction in the number of unnecessary excisions from using dermoscopy of (a) 176 and (b) 304 with (a) 24 and (b) 48 melanomas missed. The use of a named or published algorithm to assist dermoscopy interpretation (as opposed to no reported algorithm or reported use of pattern analysis) had no significant impact on accuracy either for in-person (RDOR 1.4, 95% CI 0.34, 5.6; P=0.17) or image-based (RDOR 1.4, 95% CI 0.60, 3.3; P=0.22) evaluations. This result was supported by subgroup analysis according to algorithm used. Higher accuracy for observers reported as having high experience and for those classed as ‘expert consultants’ in comparison to those considered to have less experience in dermoscopy was observed, particularly for image-based evaluations. Evidence for the effect of dermoscopy training on test accuracy was very limited but suggested associated improvements in sensitivity. Authors' conclusions: Despite the observed limitations in the evidence base, dermoscopy is a valuable tool to support the visual inspection of a suspicious skin lesion for the detection of melanoma and atypical intraepidermal melanocytic variants, particularly in referred populations and in the hands of experienced users. Data to support its use in primary care is limited however it may assist in triaging suspicious lesions for urgent referral when employed by suitably trained clinicians. Formal algorithms may be of most use for dermoscopy training purposes and for less expert observers, however reliable data comparing approaches using dermoscopy in-person are lacking

Dermoscopy, with and without visual inspection, for the diagnosis of melanoma in adults

Background: Melanoma has one of the fastest rising incidence rates of any cancer. It accounts for a small percentage of skin cancer cases but is responsible for the majority of skin cancer deaths. Although history-taking and visual inspection of a suspicious lesion by a clinician are usually the first in a series of ‘tests’ to diagnose skin cancer, dermoscopy has become an important tool to assist diagnosis by specialist clinicians and is increasingly used in primary care settings. Dermoscopy is a magnification technique using visible light that allows more detailed examination of the skin compared to examination by the naked eye alone. Establishing the additive value of dermoscopy over and above visual inspection alone across a range of observers and settings is critical to understanding its contribution for the diagnosis of melanoma and to future understanding of the potential role of the growing number of other highresolution image analysis techniques. Objectives: To determine the diagnostic accuracy of dermoscopy for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in adults, and to compare its accuracy with that of visual inspection alone. Studies were separated according to whether the diagnosis was recorded face-to-face (in-person) or based on remote (image-based) assessment. Search methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. Selection criteria: Studies of any design that evaluated dermoscopy in adults with lesions suspicious for melanoma, compared with a reference standard of either histological confirmation or clinical follow-up. Data on the accuracy of visual inspection, to allow comparisons of tests, was included only if reported in the included studies of dermoscopy. Data collection and analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated accuracy using hierarchical summary ROC methods. Analysis of studies allowing direct comparison between tests was undertaken. To facilitate interpretation of results, we computed values of sensitivity at the point on the SROC curve with 80% fixed specificity and values of specificity with 80% fixed sensitivity. We investigated the impact of in-person test interpretation; use of a purposely developed algorithm to assist diagnosis; observer expertise; and dermoscopy training. Main results: A total of 104 study publications reporting on 103 study cohorts with 42,788 lesions (including 5700 cases) were included, providing 354 datasets for dermoscopy. The risk of bias was mainly low for the index test and reference standard domains and mainly high or unclear for participant selection and participant flow. Concerns regarding the applicability of study findings were largely scored as ‘High’ concern in three of four domains assessed. Selective participant recruitment, lack of reproducibility of diagnostic thresholds and lack of detail on observer expertise were particularly problematic. The accuracy of dermoscopy for the detection of invasive melanoma or atypical intraepidermal melanocytic variants was reported in 86 datasets; 26 for evaluations conducted in-person (dermoscopy added to visual inspection) and 60 for image-based evaluations (diagnosis based on interpretation of dermoscopic images). Analyses of studies by prior testing revealed no obvious effect on accuracy; analyses were hampered by the lack of studies in primary care, lack of relevant information and the restricted inclusion of lesions selected for biopsy or excision. Accuracy was higher for in-person diagnosis compared to image-based evaluations (relative diagnostic odds ratio (RDOR) of 4.6; 95% CI 2.4, 9.0, P<0.001). Accuracy was compared for (a) in-person evaluations of dermoscopy (26 evaluations; 23,169 lesions and 1664 melanomas) versus visual inspection alone (13 evaluations; 6740 lesions and 459 melanomas) and for (b) image-based evaluations of dermoscopy (60 evaluations; 13,475 lesions and 2851 melanomas) versus image-based visual inspection (11 evaluations; 1740 lesions and 305 melanomas). For both comparisons, meta-analysis found dermoscopy to be more accurate than visual inspection alone, with RDORs of (a) 4.7 (95% CI: 3.0 to 7.5; P < 0.001) and (b) 5.6 (95% CI: 3.7 to 8.5; P < 0.001). These effects correspond to predicted differences in sensitivity of (a) 16% (95% CI: 8%, 23%) (92% for dermoscopy+visual inspection vs 76% for visual inspection) and (b) 35% (95% CI 24% to 46%) (81% for dermoscopy vs 47% for visual inspection) at a fixed specificity of 80%; and topredicted differences in specificity of (a) 20% (95% CI 7%, 33) (95% for dermoscopy plus visual inspection vs 75% for visual inspection) and (b) 40% (95% CI 27, 57) (82% for dermoscopy vs 42% for visual inspection) at a fixed sensitivity of 80%. Using the median prevalence of disease in each set of studies ((a) 12% for in-person and (b) 24% for image-based) for a hypothetical population of 1000 lesions, an increase in sensitivity of (a) 16% (in-person) and (b) 35% (image-based) from using dermoscopy at a fixed specificity of 80% equates to a reduction in the number of melanomas missed of (a) 19 and (b) 81 with (a) 176 and (b) 152 false positive results. An increase in specificity of (a) 20% (in-person) and (b) 40% (image-based) at a fixed sensitivity of 80% equates to a reduction in the number of unnecessary excisions from using dermoscopy of (a) 176 and (b) 304 with (a) 24 and (b) 48 melanomas missed. The use of a named or published algorithm to assist dermoscopy interpretation (as opposed to no reported algorithm or reported use of pattern analysis) had no significant impact on accuracy either for in-person (RDOR 1.4, 95% CI 0.34, 5.6; P=0.17) or image-based (RDOR 1.4, 95% CI 0.60, 3.3; P=0.22) evaluations. This result was supported by subgroup analysis according to algorithm used. Higher accuracy for observers reported as having high experience and for those classed as ‘expert consultants’ in comparison to those considered to have less experience in dermoscopy was observed, particularly for image-based evaluations. Evidence for the effect of dermoscopy training on test accuracy was very limited but suggested associated improvements in sensitivity. Authors' conclusions: Despite the observed limitations in the evidence base, dermoscopy is a valuable tool to support the visual inspection of a suspicious skin lesion for the detection of melanoma and atypical intraepidermal melanocytic variants, particularly in referred populations and in the hands of experienced users. Data to support its use in primary care is limited however it may assist in triaging suspicious lesions for urgent referral when employed by suitably trained clinicians. Formal algorithms may be of most use for dermoscopy training purposes and for less expert observers, however reliable data comparing approaches using dermoscopy in-person are lacking