Ultrasonography led multimodal diagnostic pathway for giant cell arteritis.

OBJECTIVES: To establish the sensitivity and negative predictive value of a multimodal pathway incorporating ultrasonography, 18-fluorodeoxyglucose labelled positron emission tomography computed tomography and temporal artery biopsy for the diagnosis of giant cell arteritis. METHODS: 1000 consecutive referrals for a new diagnosis of giant cell arteritis were analysed. All patients had a protocolized examination. Patients with a negative ultrasonography and a C-reactive protein of ≥ 20 mg/l received an extended ultrasound examination. If that was negative, and there was no other explanation for their presentation, a second test in the form of either a temporal artery biopsy or an 18-fluorodeoxyglucose labelled positron emission tomography computed tomography was offered. We calculated the sensitivity and negative predictive value of the interventions for diagnosing giant cell arteritis. RESULTS: 279/1000 patients had positive ultrasonography for giant cell arteritis. 202 had bilateral superficial temporal arterial involvement. Ultrasonography of the axillary artery and other head/neck arteries increased the yield by 53 and 24 patients respectively. 181 patients were referred for a second test. 24/139 temporal artery biopsies and 7/42 18-fluorodeoxyglucose labelled positron emission tomography computed tomography scans were positive. The sensitivity and negative predictive value rise from 62.3% and 84.7% respectively for imaging superficial temporal arteries alone, to 95.7% and 98.0% respectively for extended ultrasonography plus a second test. CONCLUSIONS: This is the first real world evidence of the utility of ultrasonography for the diagnosis of giant cell arteritis as part of a multimodal diagnostic pathway.

Is diabetic retinopathy screening worthwhile among people first diagnosed with diabetes at older ages? A cohort study of Norfolk diabetic retinopathy screening programme.

AIMS: England's Diabetic Eye Disease Screening Programme offers screening to every resident over age 12 with diabetes, starting as soon as possible after diagnosis and repeated annually. People first diagnosed with diabetes at older ages have shorter life expectancy and therefore may be less likely to benefit from screening and treatment. To inform decisions about whether diabetic eye screening policy should be stratified by age, we investigated the probability of receiving treatment according to age at first screening episode. METHODS: This was a cohort study of participants in the Norfolk Diabetic Retinopathy Screening Programme from 2006 to 2017, with individuals' programme data linked to hospital treatment and death data recorded up to 2021. We estimated and compared the probability, annual incidence and screening costs of receiving retinal laser photocoagulation or intravitreal injection and of death, in age groups defined by age at first screening episode. RESULTS: The probability of death increased with increasing age at diagnosis, while the probability of receiving either treatment decreased with increasing age. The estimated cost of screening per person who received either or both treatments was £18,608 among all participants, increasing with age up to £21,721 in those aged 70-79 and £26,214 in those aged 80-89. CONCLUSIONS: Diabetic retinopathy screening is less effective and less cost-effective with increasing age at diagnosis of diabetes, because of the increasing probability of death before participants develop sight-threatening diabetic retinopathy and can benefit from treatment. Upper age limits on entry into screening programmes or risk stratification in older age groups may, therefore, be justifiable.

Frequency of visual involvement in a 10-year interdisciplinary cohort of patients with giant cell arteritis.

BACKGROUND: We present the largest study of the frequency and nature of visual complications in a cohort of 350 patients consecutively diagnosed with giant cell arteritis (GCA). METHODS: All individuals were assessed using structured forms and diagnosed using imaging or biopsy. A binary logistic regression model was used to analyse data for predicting visual loss. RESULTS: Visual symptoms occurred in 101 (28.9%) patients, with visual loss in one or both eyes in 48 (13.7%) patients. Four patients had binocular visual loss. Anterior ischaemic optic neuropathy (N=31), retinal artery obstruction (N=8) and occipital stroke (N=2) were the main causes of visual loss. Of the 47 individuals who had repeat visual acuity testing at 7 days, three individuals had improvement to 6/9 or better. After introducing the fast-track pathway, the frequency of visual loss decreased from 18.7% to 11.5%. Age at diagnosis (odds ratio (OR) 1.12) and headache (OR 0.22) were significant determinants of visual loss in a multivariate model. Jaw claudication trended to significance (OR 1.96, p=0.054). CONCLUSIONS: We recorded a visual loss frequency of 13.7% in the largest cohort of patients with GCA examined from a single centre. Although improvement in vision was rare, a dedicated fast-track pathway reduced visual loss. Headache could result in earlier diagnosis and protect against visual loss.

Palliative care teaching in the new internal medicine curriculum: Project ECHO-an innovative approach to postgraduate education.

BACKGROUND: The Internal Medicine Training (IMT) Programme is an evolution of Core Medical Training introduced in 2019. The IMT curriculum places an increased emphasis on palliative care; however, access to palliative care training is variable. Project ECHO (Extension of Community Healthcare Outcomes) develops communities of practice and is a valuable tool for medical education. We report on an evaluation of Project ECHO to deliver palliative medicine training across a geographically large deanery in the North of England. METHODS: The Project ECHO training programme involved multipoint video technology, telementoring, expert talks and case-based discussions over six sessions, and was fully mapped to the palliative care component of the IMT curriculum. We collected data particularly around attendance and self-reported confidence and knowledge. RESULTS: By creating a community of practice, we provided virtual placements and over 9 hours of virtual direct contact with palliative medicine consultants; and in total, 921 individual attendances occurred, with 62% attending all six sessions. The course was associated with an increase in self-reported confidence and high satisfaction. DISCUSSION: Project ECHO is an effective method of delivering teaching to trainees across a large geographical area. Course evaluation shows outstanding results in trainee satisfaction, confidence, knowledge, patient care, clinical skills and reduction in fear when managing death and dying.

Quality standards for the care of people with giant cell arteritis in secondary care.

OBJECTIVE: GCA is the commonest primary systemic vasculitis in adults, with significant health economic costs and societal burden. There is wide variation in access to secondary care GCA services, with 34% of hospitals in England not having any formal clinical pathway. Quality standards provide levers for change to improve services. METHODS: The multidisciplinary steering committee were asked to anonymously put forward up to five aspects of service essential for best practice. Responses were qualitatively analysed to identify common themes, subsequently condensed into domain headings, and ranked in order of importance. Quality standards and metrics for each domain were drafted, requiring a minimum 75% agreement. RESULTS: 13 themes were identified from the initial suggestions. Nine quality standards with auditable metrics were developed from the top 10 themes. Patient Access, glucocorticoid use, pathways, ultrasonography, temporal artery biopsy, PET scan access, rheumatology/ophthalmology expertise, education, multidisciplinary working have all been covered in these quality standards. Access to care is a strand that has run through each of the developed standards. An audit tool was developed as part of this exercise. CONCLUSION: These are the first consensus auditable quality standards developed by clinicians from rheumatology and ophthalmology, nursing representatives and involvement of a patient charity. We hope that these standards will be adopted by commissioning bodies to provide levers for change from the improvement of patient care of individuals with GCA.

Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy.

Importance: It is a global challenge to provide regular retinal screening for all people with diabetes to detect sight-threatening diabetic retinopathy (STDR). Objective: To determine if circulating biomarkers could be used to prioritize people with type 2 diabetes for retinal screening to detect STDR. Design, Setting, and Participants: This cross-sectional study collected data from October 22, 2018, to December 31, 2021. All laboratory staff were masked to the clinical diagnosis, assigned a study cohort, and provided with the database containing the clinical data. This was a multicenter study conducted in parallel in 3 outpatient ophthalmology clinics in the UK and 2 centers in India. Adults 40 years and older were categorized into 4 groups: (1) no history of diabetes, (2) type 2 diabetes of at least 5 years' duration with no evidence of DR, (3) nonproliferative DR with diabetic macular edema (DME), or (4) proliferative DR. STDR comprised groups 3 and 4. Exposures: Thirteen previously verified biomarkers were measured using enzyme-linked immunosorbent assay. Main Outcomes and Measures: Severity of DR and presence of DME were diagnosed using fundus photographs and optical coherence tomography. Weighted logistic regression and receiver operating characteristic curve analysis (ROC) were performed to identify biomarkers that discriminate STDR from no DR beyond the standard clinical parameters of age, disease duration, ethnicity (in the UK) and hemoglobin A1c. Results: A total of 538 participants (mean [SD] age, 60.8 [9.8] years; 319 men [59.3%]) were recruited into the study. A total of 264 participants (49.1%) were from India (group 1, 54 [20.5%]; group 2, 53 [20.1%]; group 3, 52 [19.7%]; group 4, 105 [39.8%]), and 274 participants (50.9%) were from the UK (group 1, 50 [18.2%]; group 2, 70 [25.5%]; group 3, 55 [20.1%]; group 4, 99 [36.1%]). ROC analysis (no DR vs STDR) showed that in addition to age, disease duration, ethnicity (in the UK) and hemoglobin A1c, inclusion of cystatin C had near-acceptable discrimination power in both countries (area under the receiver operating characteristic curve [AUC], 0.779; 95% CI, 0.700-0.857 in 215 patients in the UK with complete data; AUC, 0.696; 95% CI, 0.602-0.791 in 208 patients in India with complete data). Conclusions and Relevance: Results of this cross-sectional study suggest that serum cystatin C had good discrimination power in the UK and India. Circulating cystatin-C levels may be considered as a test to identify those who require prioritization for retinal screening for STDR.

Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab.

OBJECTIVES: Secondary inefficacy with infusion reactions and anti-drug antibodies (secondary non-depletion nonresponse, 2NDNR) occurs in 14% of SLE patients receiving repeated rituximab courses. We evaluated baseline clinical characteristics, efficacy and safety of obinutuzumab, a next-generation humanized type-2 anti-CD20 antibody licensed for haematological malignancies in SLE patients with 2NDNR to rituximab. METHODS: We collated data from SLE patients receiving obinutuzumab for secondary non-response to rituximab in BILAG centres. Disease activity was assessed using BILAG-2004, SLEDAI-2K and serology before, and 6 months after, obinutuzumab 2× 1000 mg infusions alongside methylprednisolone 100 mg. RESULTS: All nine patients included in the study received obinutuzumab with concomitant oral immunosuppression. At 6 months post-obinutuzumab, there were significant reductions in median SLEDAI-2K from 12 to 6 (P = 0.014) and total BILAG-2004 score from 21 to 2 (P = 0.009). Complement C3 and dsDNA titres improved significantly (both P = 0.04). Numerical, but not statistically significant improvements were seen in C4 levels. Of 8/9 patients receiving concomitant oral prednisolone at baseline (all >10 mg/day), 5/8 had their dose reduced at 6 months. Four of nine patients were on 5 mg/day and were in Lupus Low Disease Activity State following obinutuzumab. After obinutuzumab, 6/9 patients with peripheral B cell data achieved complete depletion, including 4/4 assessed with highly sensitive assays. Of the nine patients, one obinutuzumab non-responder required CYC therapy. One unvaccinated patient died from COVID-19. CONCLUSIONS: Obinutuzumab appears to be effective and steroid-sparing in renal and non-renal SLE patients with secondary non-response to rituximab. These patients have severe disease with few treatment options but given responsiveness to B cell depletion, switching to humanized type-2 anti-CD20 therapy is a logical approach.

Improving the quality of care for people with giant cell arteritis.

Giant cell arteritis (GCA) is a systemic vasculitis with numerous potential complications and societal costs. After the publication of international guidelines, we found a number of deficiencies in the local care pathway of patients suspected to have GCA. These included poor referral and management pathways, and absence of dedicated monitoring and follow-up. In this paper, we describe a 10-year transformation which led to our service being nominated for a national award.A comprehensive consensus pathway saw referral numbers rise from 19 to 135 from 2012 to 2019. A consensus management pathway has meant that patients are assessed within 2 days of referral and glucocorticoids started at point of referral. All patients with suspected GCA are clerked and managed according to this agreed pathway which is available on the hospital intranet. The introduction of diagnostic ultrasonography has meant that the need for biopsies has dropped by >80% reducing the annual cost of diagnostics by >£140,000. The introduction of a vasculitis specialist nurse has resulted in improving education, contact and speed of access to our service. The improvements in the service resulted in our service becoming a finalist in the Royal College of Physicians Excellence in Patient Care Award in 2020.

The relationship between glycated haemoglobin levels and the risk of giant cell arteritis - a case-control study.

OBJECTIVES: The EULAR core dataset for observational studies in GCA does not include glycated haemoglobin (HbA1c). A multivariable score to stratify the pre-test probability of GCA also does not include HbA1c. There have been contradictory reports about diabetes mellitus being a risk factor for GCA. We report the first study analysing the relationship of pre-diagnosis HbA1c with the risk of GCA. METHODS: This was a single-centre retrospective case-control study conducted in Norfolk, UK. All GCA cases were diagnosed with imaging or biopsy. Each case was assigned two age- and sex-matched controls. The primary outcome measure was the glycaemic status (HbA1c categorized into euglycaemia, pre-diabetes or diabetes mellitus) at diagnosis between cases and controls. The HbA1c was compared between two groups using the Mann-Whitney U test. The glycaemic categorization was compared using the χ2 test. RESULTS: One hundred and twelve cases and 224 controls were included. The median (interquartile range) of HbA1c of cases and controls was 40 (37, 43) and 41 (39, 47) mmol/mol (P < 0.001), respectively. Ten of 112 cases and 52 of 224 controls had diabetes mellitus. The χ2 test demonstrated a significant interaction between glycaemic state and GCA (P = 0.006). Individuals with diabetes mellitus had an odds ratio (95% CI) of 0.32 (0.13, 0.74) (P = 0.008) of having GCA compared with euglycaemic individuals. CONCLUSION: HbA1c in the diabetic range reduces the probability of GCA. HbA1c should be considered in any multivariable score to calculate the risk of GCA, and in future development of diagnostic and classification criteria. There is a need for an epidemiological study looking at the possibility of a protective nature of diabetes mellitus against GCA or whether it is only a mimic.

Validating a diagnostic GCA ultrasonography service against temporal artery biopsy and long-term clinical outcomes.

Currently, there is no mechanism for service validation of diagnostic ultrasonography (US) for giant cell arteritis (GCA). Temporal artery biopsy (TAB) and classification criteria are poor benchmarks. We validated our service against physician-verified diagnosis at 100 weeks (100wD). Twenty-five patients underwent US within 7 days, and TAB within 28 days, of commencing prednisolone. US, TAB and baseline diagnosis (bD) were all compared with 100wD using Cohen's kappa. Fourteen US and 8 TABs were positive. Twenty at baseline and 14 at 100 weeks had diagnosis of GCA. The kappa (95% CI) were 0.4 (0.1, 0.7) for US vs. TAB; 0.5 (0.2, 0.8) for US vs. bD and 0.2 (0.0, 0.4) for TAB vs. bD. Versus 100wD, the kappa (95% CI) were 0.8 (0.6, 1.0) for US; 0.4 (0.1, 0.7) for TAB and 0.6 (0.3, 0.9) for bD. Seven cases were US+/TAB-. Four had alternate confirmation: 18FDG-PET (n = 1), CT Aorta (n = 1) and US at relapse (n = 2). At 100 weeks, 4 cases (all US-/TAB-) with bD of GCA had alternative diagnoses including cancer (n = 2). This is the first study validating US service provision for GCA. Twenty-five US with a robust kappa on comparison with long-term diagnosis validates our service. A diagnosis of GCA should be made with extreme caution for US-/TAB- cases.Key Points• This is the first study offering a way to validate a new diagnostic US service by validation against TAB and long-term physician-verified diagnosis.• US has substantial to near-perfect agreement with long-term physician-verified diagnosis and is more reliable than TAB in our hands.• Alternative diagnoses should be sought in patients with dual negativity for US and TAB.

Anti-VEGF therapies in the treatment of choroidal neovascularisation secondary to non-age-related macular degeneration: a systematic review.

OBJECTIVES: The aim of this study is to systematically review the evidence for anti-vascular endothelial growth factor (VEGF) therapy in choroidal neovascularisation secondary to conditions other than age-related macular degeneration. DATA SOURCES: MEDLINE, MEDLINE in-process, EMBASE and CENTRAL databases and conference abstracts were searched (from inception to Jan 2014). STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Randomised and non-randomised comparative studies with follow-up of at least 6 months were included and were used to assess clinical effectiveness. STUDY APPRAISAL AND SYNTHESIS METHOD: Risk of bias was assessed using the Cochrane risk of bias tool and modified Newcastle-Ottawa Scale. Meta-analysis was not possible due to methodological heterogeneity. RESULTS: 16 studies met the inclusion criteria (1091 eyes; 963 pathological myopia, 74 other conditions). There was large variation in risk of bias across studies. An improvement in best-corrected visual acuity in anti-VEGF arms over comparators was reported in all studies. The proportion of patients improving by at least 15 letters in anti-VEGF arms ranged from 27.3% to 70%. There were no significant differences between bevacizumab and ranibizumab. LIMITATIONS: Owing to the rarity of choroidal neovascularisation secondary to conditions other than age-related macular degeneration or pathological myopia, there are unlikely to ever be sufficiently powered trials in these populations. CONCLUSIONS: Bevacizumab and ranibizumab appear to be effective in improving visual acuity for patients with choroidal neovascularisation secondary to conditions other than age-related macular degeneration. The evidence base is strongest for choroidal neovascularisation secondary to pathological myopia, however, based on current evidence and likely pharmacological pathways, clinicians should consider treatment with either bevacizumab or ranibizumab for rarer causes.

Progression of diabetes retinal status within community screening programs and potential implications for screening intervals.

OBJECTIVE: This study aimed to follow the natural progression of retinal changes in patients with diabetes. Such information should inform decisions with regard to the screening intervals for such patients. RESEARCH DESIGN AND METHODS: An observational study was undertaken linking the data from seven diabetes retinal screening programs across the U.K. for retinal grading results between 2005 and 2012. Patients with absent or background retinopathy were followed up for progression to the end points referable retinopathy and treatable retinopathy (proliferative retinopathy). RESULTS: In total, 354,549 patients were observed for up to 4 years during which 16,196 patients progressed to referable retinopathy. Of patients with no retinopathy in either eye for two successive screening episodes at least 12 months apart, the conditions of between 0.3% (95% CI 0.3-0.8%) and 1.3% (1.0-1.6%) of patients progressed to referable retinopathy, and rates of treatable eye disease were <0.3% at 2 years. The corresponding progression rates for patients with bilateral background retinopathy in successive screening episodes were 13-29% and up to 4%, respectively, in the different programs. CONCLUSIONS: It may be possible to stratify patients for risk, according to baseline retinal criteria, into groups with low and high risk of their conditions progressing to proliferative retinopathy. Screening intervals for such diverse groups of patients could safely be modified according to their risk.

Potential benefits of fast-track concepts in paediatric colorectal surgery.

BACKGROUND: Structured care pathways optimising peri-operative care have been shown to significantly enhance post-operative recovery. We aim to determine if enhanced recovery after surgery (ERAS) principles could provide benefit for paediatric patients undergoing major colorectal resection for inflammatory bowel disease (IBD). METHODS: Children undergoing elective bowel resection for IBD at a regional paediatric unit using standard methods of peri-operative care were matched to adult cases from an associated tertiary referral university hospital already using an ERAS program. Cases were matched for disease type, gender, operative procedure, and ASA grade. RESULTS: Forty-four children undergoing fifty procedures were identified. Thirty-four were matched to adult cases. Total length of stay in the paediatric group was significantly longer than in the adult group (6 vs. 9 days; P=0.001). Paediatric patients were slower to start solid diet (1 vs. 4 days; P<0.0001) and were slower to mobilize post-operatively (1 vs. 4 days; P<0.0001). No difference was seen in time to restoration of bowel function (2 vs. 3 days; P=0.49). Thirty day readmissions and total in-hospital morbidity were not significantly different between the groups. CONCLUSION: Potentially, application of ERAS in paediatric surgery could accelerate recovery and reduce length of post-operative stay thereby improving quality and efficiency of care.

Identification and quantification of peritoneal metastases in patients with ovarian cancer with multidetector computed tomography: correlation with surgery and surgical outcome.

PURPOSE: The purpose of the study was to determine the performance of a 64-row multidetector computed tomography (MDCT) in identifying peritoneal metastases in ovarian cancer patients undergoing surgical staging or cytoreduction. METHODS: This retrospective study included 76 patients who underwent surgical staging (n = 11) or cytoreduction (n = 65). Patients had MDCT before surgery (mean, 24 [SD, 16.9] days) as well as correlative surgicopathologic data. For the imaging analysis, the peritoneal cavity was divided to 28 segments, which were assessed for absence or presence of disease. Rate of optimal cytoreduction at the time of surgery was recorded. The standard of reference for this study was surgery, unless there was proof of metastasis as assessed by follow-up imaging. Sensitivity and predictive accuracy of CT and surgery compared with the standard of reference were calculated. RESULTS: The overall sensitivity and accuracy were 81.2% and 94.3% for MDCT and 87.4% and 97.2% for surgery (P = 0.14, P = 0.007), respectively. There was no difference in the detection of lesions 1 cm or greater between MDCT and surgery (89.3% and 84.9%, respectively; P = 0.31); however, MDCT was less sensitive than surgery in detecting disease sites of less than 1 cm (65.5% and 92.3%, respectively; P = 0.001). For the subgroup of patients undergoing cytoreduction after neoadjuvant chemotherapy (NAC) (n = 30), sensitivities for MDCT and surgery were similar (80% and 76.9%, respectively [P = 0.71]). Although sensitivity of CT was not altered by NAC (P = 0.92), there was a significant decrease in sensitivity of surgical assessment after NAC (94% vs 76.9%; P = 0.003). CONCLUSIONS: Multidetector computed tomography (MDCT) has similar sensitivity as surgery for peritoneal metastases of 1 cm or greater. The maintained sensitivity of MDCT in detecting peritoneal disease after NAC, which is underestimated at surgery, may help surgical planning and may improve optimal cytoreduction rate in this group of patients.

Getting it right: oncology nurses' understanding of spirituality.

AIM: To explore oncology nurses' understanding of spirituality in order to shed some light on this complex area. METHOD: The study used a qualitative cross-sectional design, inspired by a grounded theory approach. A non-probability sample of seven nurses took part in a focus group and individual semi-structured interviews. Inspired by the framework analysis technique, the data were displayed and reduced to underlying themes. FINDINGS: Five major themes were identified: understanding of spirituality, the nurses' own spirituality, skills required, constraints and barriers to providing spiritual care, and education and support needs. The study found diverse definitions of spirituality, which was viewed as a vague and ambiguous concept, with some participants finding it difficult to differentiate between spirituality and religion. The impact of nurses' own spirituality was also uncovered, with unique findings of guilt, inadequacy, and stress in attempting to address patients' spiritual needs. Lack of time was seen as the main barrier to addressing spiritual needs, along with the emotional demands on the nurse, and a lack of training and education. CONCLUSION: The study finds a need for improved education in spirituality and spiritual care.

Early experience with conversion to sirolimus in a pediatric renal transplant population.

Sirolimus is an immunosuppressive agent that offers potentially significant benefits for young transplant patients facing life-long treatment. Its action of reducing cell proliferation may reduce the risk of chronic allograft nephropathy and posttransplant neoplasia. Twenty-nine children were converted from calcineurin inhibitors to sirolimus after renal transplantation and followed for a minimum of 12 months. Glomerular filtration increased transiently in those converted before 12 months after transplantation but not in those converted later, when chronic histological changes had developed. Mild acute rejection occurred after conversion in 10%, and side effects led to cessation of sirolimus in 31%. Anemia occurred in 55% of patients and responded well to darbepoetin. Most side effects (anemia, hypercholesterolemia, mouth ulcers, and myalgias) became less severe with time. The number of antihypertensive drugs required decreased significantly on sirolimus. Although side effects are frequent on sirolimus, in the majority of children, they are mild enough to allow the patient to continue taking the drug, and for these children the long-term benefits are potentially valuable.