Clinician Requests Research Articles

Reanalysis of genomic data in rare disease: current practice and attitudes among Australian clinical and laboratory genetics services.

Reanalyzing stored genomic data over time is highly effective in increasing diagnostic yield in rare disease. Automation holds the promise of delivering the benefits of reanalysis at scale. Our study aimed to understand current reanalysis practices among Australian clinical and laboratory genetics services and explore attitudes towards large-scale automated re-analysis. We collected audit data regarding testing and reanalysis volumes, policies and procedures from all Australian diagnostic laboratories providing rare disease genomic testing. A genetic health professionals' survey explored current practices, barriers to reanalysis, preferences and attitudes towards automation. Between 2018 and 2021, Australian diagnostic laboratories performed over 25,000 new genomic tests and 950 reanalyses, predominantly in response to clinician requests. Laboratory and clinical genetic health professionals (N = 134) identified workforce capacity as the principal barrier to reanalysis. No specific laboratory or clinical guidelines for genomic data reanalysis or policies were identified nationally. Perceptions of acceptability and feasibility of automating reanalysis were positive, with professionals emphasizing clinical and workflow benefits. In conclusion, there is a large and rapidly growing unmet need for reanalysis of existing genomic data. Beyond developing scalable automated reanalysis pipelines, leadership and policy are needed to successfully transform service delivery models and maximize clinical benefit.

Tumor tissue samples collection for scientific research in morphology and molecular oncology

Purpose of the study. Is to describe the experience of creating a collection of biological images of tumor tissues and biomaterials, which are control samples, for scientific research in morphology and molecular oncology.Materials and methods. We studied the molecular markers of cell cycle regulation, apoptosis, oncogenesis and angiogenesis, the expression of proteins that regulate inflammation and tumor infiltrate cells in biocollections of verified tumors of common localizations: e. g. thyroid cancer, colorectal cancer, breast cancer, prostate adenocarcinoma, endometrioid adenocarcinoma. Also, tissue fragments with normal structure or non-tumor pathology (autoimmune thyroiditis, adenomatous and thyrotoxic goiter, benign formations of the colon, fibrocystic disease of the mammary glands, benign prostatic hyperplasia, endometrial hyperplasia) were used as control samples or comparison groups. The total number of tissue samples is n = 7000.Results. It is reasonable to gather the collection in a pathomorphological laboratory according to the profile of the medical institutions, which has a sufficient volume of incoming target material and specialized morphologists to verify tumors of a given localization. It is necessary to consider the regional and ethnic specifics of the population, which determines the sampling and mutational load. The laboratory must initiate an addition to the informed consent of patients about the possibility of conducting morphological and molecular genetic studies for scientific purposes and publishing their results in a depersonalized form for the development of new elaborations, when signing the contracts with legal entities and individuals and when serving patients within an institution. When working with biocollections, it has to consider having registers of tissue biomaterials of target disorder groups of main localizations with downloading by year from an accessible information system, consider external factors affecting the database (changes in clinical recommendations and classifications, the population of patients served, pandemics and other significant events). The standard of the preanalytical stage, data collection, development of protocols for analytical molecular genetic studies and their evaluation, the utilization of the capabilities of working with reagents for scientific tasks and modeling experiments on laboratory animals are crucial.Conclusion. The formed biocollection made it possible to carry out a number of initiative and funded domestic and international scientific projects at the request of clinicians and fundamental researchers, as well as to improve the quality standards of morphological and molecular genetic oncology diagnostics. Biobanking makes the pathological archive more accessible for review and use, significantly expanding its scientific and practical potential. Scientific and medical research do not conflict and can be used within the same laboratory.

Assessment of Scheduling Method,Appointment Delay, and No-show Rate in the Ultrasound Unit of a Nigerian Teaching Hospital

Increasing incidence of no-shows has been identified as a major challenge to planning of appointment schedules which imparts negatively on revenue generation and system efficiency. This cross-sectional study analysed the scheduling method in use, appointment delay time, appointment compliance rate and no-show rate of patients in the ultrasound unit of a Nigerian tertiary hospital, using observation, patient records and questionnaires. Information obtained were: The time interval between clinician request and examination appointment schedule, patient load distribution, scheduling method, number of patients scheduled and number that kept to appointment scheduling, and as well staff opinion on reasons for patients’ length of stay for ultrasound investigations. The results showed that the single-block scheduling method was used and patients’ arrival was highest between 7:12 and 9:00 hours with decreasing rate as the day progresses. The time interval between request and appointment was 12–14 days. Appointment compliance rate was observed to be 5.5, while no show rate was 4.5. Poor state of ultrasound machines was observed to be the highest contributing factor to patient delays with Kendall’s coefficient of concordance 0.466. The findings of this work can be utilized in efficient planning of public hospital ultrasound units to enhance patient access.

What Should We Know in Postoperative Surveillance Imaging After Oncoplastic Breast-Conserving Surgery with Pellet-Type Acellular Dermal Matrix?

The aim of this study was to evaluate the usual postoperative imaging findings among patients who underwent oncoplastic breast-conserving surgery (BCS) with acellular dermal matrix (ADM) and to assess the clinical utility of mammography (MG) and ultrasonography (US) in follow-ups. This retrospective review of our prospectively collected database of patients who underwent oncoplastic BCS with ADM was conducted with IRB approval and in HIPPA compliance. A total of 105 patients whose follow-up MG and US studies over 2years after surgery were available were included in this study. Postoperative imaging findings were analyzed based on sequential MG and US follow-ups. The clinical outcomes and pathological data were also reviewed. The diagnostic performance of MG and US for postoperative surveillance was assessed. On MG, ADM presented as an oval (99/105, 94.3%), circumscribed/obscured (65/105, 61.9%), and high-density (56/105, 53.3%) mass with calcifications (54/105, 51.4%). On US, the ADM-filled cavity presented as an oval (93/105, 88.6%), circumscribed (70/105, 66.7%), heterogenous echoic (65/105, 61.9%) mass with marginal/posterior acoustic shadowing (95/105, 90.5%) on US. During the follow-up period (mean, 46.1months; range, 26-58months), four tumor recurrences were diagnosed (4/105, 3.8%). One tumor recurrence detected on MG presented as microcalcifications (1/4, 25%), which were differentiated from benign postoperative calcifications due to their suspicious morphology and location. Two additional recurrences (2/4, 50%), which were MG-negative small masses or intraductal lesions, were detected on US. One tumor recurrence was missed on both MG+US and was detected by magnetic resonance imaging performed at clinician's request. The sensitivity and specificity of MG, US, and MG+US for postoperative surveillance were 25%, 50% and 75% and 100%, 98% and 98%, respectively. Recognition and adequate interpretation of the usual findings after oncoplastic BCS with ADM insertion are important in postoperative imaging surveillance. The sole use of MG is not sufficient for the detection of mass-type tumor recurrence due to the density of inserted ADM fillers. Therefore, the combined use of MG+US could serve as a useful postoperative surveillance tool with increased sensitivity in this population.

Disengagement and loss to follow-up in intravitreal injection clinics for neovascular age-related macular degeneration

Background/ObjectivesTimely assessment and treatment of patients with neovascular AMD (nAMD) are crucial to preservation of vision. Loss to follow up (LTFU) in these patients is a problem but this has not been systematically investigated.Subjects/MethodsA retrospective review of electronic medical records of patients with nAMD first treated with anti-VEGF therapy from 1st Jan 2014 to 31st Dec 2018, was conducted in January 2021. Any patient not seen for more than 12 months was classed as no longer attending.ResultsOf the 1328 patients who attended between 2014 and 2018, 348 had failed to attend and were eligible for inclusion in this study. Reasons noted for discontinuation of care: discharged by clinician (33.3%), died (20.7%), moved to another unit outside of area (17.5%), stopped attending due to ill-health (13.5%), discharged due to failure to attend (5.6%) and patient choice to no longer attend (4.6%). There were 16 (4.6%) who did not receive any further appointments despite clinician request for follow-up. After 5 years, 50.5% of patients were no longer attending for treatment. Age was a factor in failure to attend, with 7 out of 12 patients aged >100 years no longer being followed up, compared to 1 out of 11 of 50–59 year-olds.ConclusionsWhen analysing visual outcomes in an AMD service it is important to characterise the patients who are lost to follow up. The outcomes for this group may be avoidably poor and understanding the factors influencing LTFU rate is crucial to addressing shortcomings in a hospital AMD service.

Human brucellosis in Baringo County, Kenya: Evaluating the diagnostic kits used and identifying infecting Brucella species.

Human brucellosis diagnosis has been a challenge in Brucella-endemic areas. In Kenya, diagnosis is usually carried out using Febrile Brucella Antigen agglutination test (FBAT) whose performance is not well documented. This paper reports on the sensitivity and specificity of the FBAT used for brucellosis diagnosis on blood samples/serum collected in three healthcare facilities in Baringo County, Kenya, and on Brucella species present in the study area. The FBAT test results at the hospitals were used to guide patient management. Patients who visited the hospital's laboratory with a clinician's request for brucellosis testing also filled a questionnaire to assess knowledge and attitudes associated with transmission of the disease in the study area. The remaining serum samples were tested again using FBAT and Rose Bengal Plate Test (RBPT) within a month of blood collection at the University Nairobi Laboratory. The two rapid tests were then compared, with respect to brucellosis diagnostic sensitivity and specificity. To identify infecting Brucella species, a proportion 43% (71/166) of the blood clots were analyzed by multiplex polymerase chain reaction (PCR) using specific primers for B. abortus, B. melitensis, B. ovis and B. suis. Out of 166 serum samples tested, 26.5% (44/166) were positive using FBAT and 10.2% (17/166) positive using RBPT. The sensitivity and specificity of FBAT compared to RBPT was 76.47% and 71.19%, respectively while the positive and negative predictive values were 29.55% and 96.72%, respectively. The FBAT showed higher positivity then RBPT. The difference in sensitivity and specificity of FBAT and RBPTs was relatively low. The high FBAT positivity rate would be indication of misdiagnosis; this would lead to incorrect treatment. Brucella abortus was detected from 9.9% (7/71) of the blood clots tested; no other Brucella species were detected. Thus human brucellosis, in Baringo was mainly caused by B. abortus.

Increasing Quality and Frequency of Goals-of-Care Documentation in the Highest-Risk Surgical Candidates: One-Year Results of the Surgical Pause Program.

We prospectively analyzed a longitudinal cohort of adult patients treated for traumatic orthopaedic injuries that were neither life- nor limb-threatening between January 1, 2020, and July 1, 2021. A rapid multidisciplinary review termed a "surgical pause" (SP) was available to those who were ≥80 years old, were nonambulatory or had minimal ambulation at baseline, and/or resided in a skilled nursing facility, as well as upon clinician request. Metrics analyzed include the proportion and quality of goals-of-care documentation, rate of return to the hospital, complications, length of stay, and mortality. Statistical analysis utilized the Kruskal-Wallis rank and Wilcoxon rank-sum tests for continuous variables and the likelihood-ratio chi-square test for categorical variables. A total of 133 patients were either eligible for the SP or referred by a clinician. Compared with SP-eligible patients who did not undergo an SP, patients who underwent an SP more frequently had goals-of-care notes identified (92.4% versus 75.0%, p = 0.014) and recorded in the appropriate location (71.2% versus 27.5%, p < 0.001), and the notes were more often of high quality (77.3% versus 45.0%, p < 0.001). Mortality rates were nominally higher among SP patients, but these differences were not significant (10.6% versus 5.0%, 5.1% versus 0.0%, and 14.3% versus 7.9% for in-hospital, 30-day, and 90-day mortality, respectively; p > 0.08 for all). The pilot program indicated that an SP is a feasible and effective means of increasing the quality and frequency of goals-of-care documentation in high-risk operative candidates whose traumatic orthopaedic injuries are neither life- nor limb-threatening. This multidisciplinary program aims for goal-concordant treatment plans that minimize modifiable perioperative risks. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Current Laboratory Testing Practices for Assessment of ERBB2/HER2 in Endometrial Serous Carcinoma and Colorectal Carcinoma.

Therapy targeted at human epidermal growth factor receptor 2 (HER2; also known as ERBB2) was used initially for breast and gastroesophageal carcinoma and has more recently been adopted for endometrial serous carcinoma (ESC) and colorectal carcinoma (CRC). There is evidence that predictive biomarker testing algorithms for HER2 must be tumor type specific and that an algorithm validated for one tumor type cannot be applied to another. To describe current laboratory practices for HER2 assessment in ESC and CRC. We surveyed laboratories participating in the 2021 College of American Pathologists (CAP) HER2 immunohistochemistry proficiency testing program. The survey was distributed to 1548 laboratories and returned by 1195, of which 83.5% (998) were in the United States. For ESC, 24.0% (287) of laboratories reported performing in-house testing for HER2 by immunohistochemical staining and/or in situ hybridization; of these, 44.3% (127) performed it reflexively on all cases of ESC. The most common criterion for evaluating HER2 was the American Society of Clinical Oncology/CAP 2018 guideline for breast carcinoma (69.0%; 194 of 281), whereas only 16.0% (45) of laboratories used guidelines specific to ESC. For CRC, 20.2% (239 of 1185) of laboratories performed in-house HER2 testing, and 82.0% of these (196) did the test only at the clinician's request. A plurality (49.4%; 115 of 233) used gastroesophageal cancer guidelines when scoring CRC, 30.0% (70) used the CRC scoring system from the HERACLES trial, and 16.3% (38) used the American Society of Clinical Oncology/CAP 2018 guideline for breast carcinoma. Laboratories vary in their approach to HER2 testing in ESC and CRC. Most laboratories did not report using tumor type-specific recommendations for HER2 interpretation. The lack of standardization could present a challenge to evidence-based practice when considering targeted therapy for these diseases.

1177. Mind the GAPP: Global Arrivals and Pre-treated Patients screening at a children’s cancer center

Abstract Background Clinical and laboratory evaluation for infectious diseases prior to initiation of cancer-directed therapy creates opportunities for risk assessment, infection prevention and targeted treatment. The need may be greater for patients from outside the United States (US) where the epidemiology of infectious diseases may differ. We created the Global Arrivals and Pretreated Patients (GAPP) program to address this need at a referral hospital for children with cancer and blood disorders. Methods Patients accepted for treatment at our hospital are referred to GAPP for the following reasons: 1) residence in the continental US for 1 year or less, 2) travel outside the continental US within 3 months of referral 3) hospitalization outside the continental US, or 4) clinician request. GAPP evaluation includes review of history and laboratory studies, and recommendations for screening tests and management. Results Between March 21, 2019 and May 2, 2022, 35 patients were evaluated; 9 (26%) with solid or CNS tumors, 25 (71%) with hematological malignancies and 1 (3%) with immune thrombocytopenic purpura. Of these, 20/35 (57%) were from Latin America, and 10/35 (29%) from Eastern Europe. Most patients (29/35 [83%]) were seen within 2 weeks of arrival to the institution. Evaluation prompted isolation precautions in 2/35 (6%) for communicable respiratory illness and in 4/35 (11%) for ESBL-producing organism on perianal screen. Additionally, 13 patients were under-immunized (mostly non-immune to hepatitis B [7/35, 20%] or varicella zoster virus [8/35, 22%]), and 9/35 (26%) had an exposure-related risk. Finally, parasitic infection prompted specific management in 4 patients; 3/35 (9%) had positive serology for Toxoplasma gondii requiring appropriate prophylaxis, and 1/35 (3%) was treated for cryptosporidiosis. Conclusion Screening new arrivals to the US prior to administration of immunosuppressive therapy is feasible and may identify risk factors for illness during therapy as well as opportunities for infection prevention, immunization, and treatment or suppression of existing infections. Providers focusing on acute hematologic or oncologic illness may otherwise miss this quality improvement opportunity in a patient group at high risk of poor infectious outcomes. Disclosures Randall Hayden, MD, Inflammatix: Advisor/Consultant|Quidel Corporation: Advisor/Consultant|Roche Diagnostics: Advisor/Consultant|T2 Diagnostics: Advisor/Consultant Gabriela Maron, MD, Astellas Inc,: Grant/Research Support|SymBio Pharmaceuticals: Grant/Research Support Joshua Wolf, MBBS, PhD, Karius: Grant/Research Support|Merck: Participation in industry sponsored research.

Point-of-care ultrasound needs assessment in a paediatric acute care setting in Malawi.

To describe the use of point-of-care ultrasound (POCUS) in an acute-care paediatric setting in Malawi, including clinical indications, types of examinations and frequency of positive findings. Retrospective, cross-sectional study of a convenience sample of POCUS examinations performed in one tertiary referral hospital in Lilongwe, Malawi over 1 year. POCUS examinations were performed by Paediatric Emergency Medicine physician consultants as part of routine clinical practice and at the request of local clinicians. Images were saved along with the clinical indication and physician interpretation for quality review. Ultrasounds performed by the radiology department and those examinations that were technically faulty, missing clinical application or interpretation were excluded. In total, 225 ultrasounds of 142 patients were analysed. The most common clinical indications for which examinations were completed were respiratory distress (23%), oedema (11.7%) and shock/arrest (6.2%). The most common examinations performed were cardiac (41.8%) and lung (15.1%), focused assessment with sonography in trauma (FAST; 12.9%) and ultrasound-guided procedural examinations (9.8%). Pathology was identified in 68% of non-procedural examinations. Cardiac examinations demonstrated significant pathology, including reduced cardiac function (12.8%), gross cardiac structural abnormality (11.8%) and pericardial effusion (10.3%). POCUS was used for both clinical decision-making and procedural guidance, and a significant number of POCUS examinations yielded positive findings. Thus, we propose that cardiopulmonary, FAST and procedural examinations should be considered in future for the POCUS curriculum in this setting.

Development of an Interoperable and Easily Transferable Clinical Decision Support System Deployment Platform: System Design and Development Study.

BackgroundA clinical decision support system (CDSS) is recognized as a technology that enhances clinical efficacy and safety. However, its full potential has not been realized, mainly due to clinical data standards and noninteroperable platforms.ObjectiveIn this paper, we introduce the common data model–based intelligent algorithm network environment (CANE) platform that supports the implementation and deployment of a CDSS.MethodsCDSS reasoning engines, usually represented as R or Python objects, are deployed into the CANE platform and converted into C# objects. When a clinician requests CANE-based decision support in the electronic health record (EHR) system, patients’ information is transformed into Health Level 7 Fast Healthcare Interoperability Resources (FHIR) format and transmitted to the CANE server inside the hospital firewall. Upon receiving the necessary data, the CANE system’s modules perform the following tasks: (1) the preprocessing module converts the FHIRs into the input data required by the specific reasoning engine, (2) the reasoning engine module operates the target algorithms, (3) the integration module communicates with the other institutions’ CANE systems to request and transmit a summary report to aid in decision support, and (4) creates a user interface by integrating the summary report and the results calculated by the reasoning engine.ResultsWe developed a CANE system such that any algorithm implemented in the system can be directly called through the RESTful application programming interface when it is integrated with an EHR system. Eight algorithms were developed and deployed in the CANE system. Using a knowledge-based algorithm, physicians can screen patients who are prone to sepsis and obtain treatment guides for patients with sepsis with the CANE system. Further, using a nonknowledge-based algorithm, the CANE system supports emergency physicians’ clinical decisions about optimum resource allocation by predicting a patient’s acuity and prognosis during triage.ConclusionsWe successfully developed a common data model–based platform that adheres to medical informatics standards and could aid artificial intelligence model deployment using R or Python.

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies: incidence using different testing criteria, and case series.

To estimate the incidence of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies utilising different testing criteria, and review the clinical details of a series of patients with associated autoimmune myopathy. The incidence of anti-HMGCR antibodies in 2019 from 3 groups, South West London, Berkshire/Surrey and Southampton, were compared in the adult population. Anti-HMGCR antibodies were measured by commercial chemiluminescent and immunodot assays. The case notes of patients with anti-HMGCR antibodies were reviewed for the case series. The estimated incidence of anti-HMGCR antibodies in the first 2 groups was 1.94 per million adults per year, and in the third group 10.3 per million adults per year. In the first 2 groups the test criteria restricted analysis to specific clinician request for anti-HMGCR. In the third group test criteria included cases with less specific clinical features or a cytoplasmic indirect immunofluorescence anti-nuclear antibody pattern. The latter strategy had a positive predictive value of 66.1% for anti-HMGCR associated myopathy. A case series of 27 patients with anti-HMGCR antibodies revealed 19 with myopathy, oesophageal involvement in 26% and median peak CK 8000 IU/L. Response to treatment, including intravenous immunoglobulin, was good with CK normalising after median 5.5 months. In 8 cases there was no evidence of autoimmune muscle disease, 7 not statin exposed. Varying criteria result in a 5-fold difference in estimated incidence of anti-HMGCR antibodies, revealing positive cases without evidence of myopathy. Patients with anti-HMGCR myopathy respond well to immune suppression, supporting wider testing for these antibodies amongst patients with myopathy.

Measurement of histological clearance margins in basal cell carcinoma.

Basal cell carcinoma (BCC) is a common cancer, with a high risk of local recurrence. A quantifiable measurement of the histological margins of BCC in excisions is a recurrent demand of clinicians; however, there are currently no international guidelines indicating its value. A questionnaire validated by four experts in dermatopathology and formatted under a 'Google Forms'-type interface was sent by e-mail to physicians specializing in surgical pathology or dermatopathology and practising in France from 20 March 2018 to 20 May 2018. The results were compared between subgroups according to age and subspecialisation, especially dermatopathology. The questionnaire was completed by 225 practitioners. Microscopic margins were systematically measured in 77.3% of cases, sometimes in 19.6% and never in 3.1%. The main reason was to report factually insufficient margins (66.5%), followed by laboratory routine (45%) or clinician requests (43.1%). For 72% of respondents, the clinical or histopathological criteria did not influence their practice. The most used tool was a graduated ruler placed under a microscope (44.3% of cases). Compared to other groups, dermatopathologists measured BCC margins less systematically [only in certain situations (33.3 versus 14.9%) or never (10.5 versus 0.6%) (P < 0.001)] and used an eyepiece reticle more extensively (53.1 versus 29.8%; P = 0.0029). The measurement of histological margins in BCC is common practice in France, although there are no recommendations. Our survey suggests that it represents a way for pathologists to specify an insufficient margin and therefore the need for scar revision.

Expanding the Molecular Genetic Spectrum of Bone and Soft Tissue Fibrosarcomas: An Institutional Experience.

Introduction. Fibrosarcomas, once comprising the majority of unclassifiable spindle-cell sarcomas, are now regarded as a diagnosis of exclusion. Objectives. Prompted by an index report of neurotrophic receptor tyrosine kinase (NTRK)3 fusion in fibrosarcomas by Yamazaki et al bone/soft tissue tumors diagnosed as fibrosarcoma at our institution were evaluated in an attempt to expand the genetic spectrum of fibrosarcomas and identify therapeutically targetable cases. Methods. Institutional archives were searched for cases diagnosed as "fibrosarcoma" involving bone/soft tissue from 2000 to present. Twenty-one cases meeting inclusion criteria were identified, 10 of which had formalin-fixed paraffin-embedded tissue available for molecular testing. One case, at the submitting clinician's request, underwent outside deoxyribonucleic acid/ribonucleic acid (DNA/RNA) sequencing while the 9 remaining cases underwent in-house next-generation sequencing RNA fusion analysis. Results. At the time of diagnosis the mean age was 54.5 (range 14-88) with a male to female ratio of 1.5:1. Locations included soft tissue of the lower extremity (3), trunk (2), pelvis (2), head (1), upper extremity (1), and bone (1). Of the 10 cases, 1 demonstrated an FNDC3B-PIK3CA gene fusion and 1 demonstrated a BRAF (p.G469A) mutation and CDKN2A/B loss. Conclusion. In conclusion, our study demonstrated gene fusions in 1 (10%) of 10 fibrosarcomas diagnosed at our institution in the past 20 years, including FNDC3B-PIK3CA gene fusion. Additionally, 1 case harbored BRAF (p.G469A) mutation and CDKN2A/B loss with no evidence of gene fusion. NTRK rearrangements were not detected. The significance of these molecular aberrations is presently unclear and future studies are needed to establish whether these findings carry any clinicopathologic significance.

B-PO01-002 REMOTE MONITORING OF LOW VOLTAGE CARDIAC IMPLANTABLE DEVICES - A HIGH VOLUME CENTRE EXPERIENCE

Unlike patients implanted with high voltage devices who are routinely enrolled in Remote monitoring (RM) programmes, standard practice for low voltage devices is routine in-person (IP) clinic follow up. In response to the COVID-19 pandemic all patients, post implant or under routine follow up in our institution, with low voltage devices were enrolled onto RM to reduce IP clinic visits. There are limited data investigating the real-world efficacy of RM in this population. To assess the feasibility of RM in patients with low voltage devices. All patients with a pacemaker (PPM) or cardiac resynchronisation therapy pacemaker (CRTP) that underwent remote review between 24th June and 31st October 2020 were prospectively assessed. Both de-novo implants and routine follow ups were included. Transmissions that were scheduled, triggered by automated alerts or were as a result of clinician or patient request were reviewed. Time taken to report, and actions taken were assessed. A total of 294 patients were reviewed; 57.5% males, mean age 76 (SD 14) years. This included 228 PPMs and 66 CRTPs (67% de-novo implants and 33% routine follow up); 51% Boston Scientific, 31% Abbott, 18% Medtronic and 1% Biotronik. Overall transmissions; 78% scheduled, 20% alerts, 2% patient request and 0.3% clinician request. Overall mean reporting time was 19 (SD 11) minutes. The mean time was longer for scheduled compared to non-scheduled follow up (19 (SD 10) vs 16 (SD 12) minutes, p=0.0005). There was no difference in the time taken to review PPM and CRTPs (p=0.43). Those patients requiring action following review were significantly longer (21 (SD 12) vs 16 (SD 9) minutes, p=0.002). Of the 52% requiring additional review; 64% were for programming issues, 33% required clinical review (arrhythmia/wound/heart failure), 2% were booked as back-up prior to procedure and a further 1% at patient request. Optimising baseline programming for de-novo implants would have reduced additional review for changes by 29%. RM is feasible in this population and may be used to reduce the number of IP visits. Clinic review may be further reduced by optimising programmed parameters at implant and enhancing patient pathways, specifically with regards to Heart Failure assessment.

Combining multi-antigenic immunodot with indirect immunofluorescence on HEp-2 cells improves the diagnosis of systemic sclerosis

Systemic sclerosis (SSc) is associated, in nearly all patients, with autoantibodies (Ab). Accordingly, and in order to identify major (anti-CEN A/B and anti-Topo I) but also minor Abs, the usefulness of combining indirect immunofluorescence (IIF) on HEp-2 cells with an 11 multi-antigenic SSc immunodot was explored. 1689 samples tested at the request of clinicians, were evaluated retrospectively. The positivity rate was 28.8% and the diagnosis of SSc was supported for 232 samples. Two groups of Abs were considered: group 1, Abs (anti-CENP A/B, anti-Topo I) present at elevated levels in SSc patients; group 2, Abs for which the Ab specificity (odds ratio and/or positive predictive value) was improved by using IIF on HEp-2 cells (RNA-Polymerase III, fibrillarin, Th/T0, PM-Scl). Altogether, this study highlights the utility of combining IIF on HEp-2 cells with the SSc immunodot as the first line of an SSc Abs detection/SSc diagnostic strategy.

Helicopter emergency medical service dispatch in older trauma: time to reconsider the trigger?

BackgroundHelicopter Emergency Medical Services (HEMS) respond to serious trauma and medical emergencies. Geographical disparity and the regionalisation of trauma systems can complicate accurate HEMS dispatch. We sought to evaluate HEMS dispatch sensitivity in older trauma patients by analysing critical care interventions and conveyance in a well-established trauma system.MethodsAll trauma patients aged ≥65 years that were attended by the Air Ambulance Kent Surrey Sussex over a 6-year period from 1 July 2013 to 30 June 2019 were included. Patient characteristics, critical care interventions and hospital disposition were stratified by dispatch type (immediate, interrogate and crew request).Results1321 trauma patients aged ≥65 were included. Median age was 75 years [IQR 69–89]. HEMS dispatch was by immediate (32.0%), interrogation (43.5%) and at the request of ambulance clinicians (24.5%). Older age was associated with a longer dispatch interval and was significantly longer in the crew request category (37 min [34–39]) compared to immediate dispatch (6 min [5–6] (p = .001). Dispatch by crew request was common in patients with falls < 2 m, whereas pedestrian road traffic collisions and falls > 2 m more often resulted in immediate dispatch (p = .001). Immediate dispatch to isolated head injured patients often resulted in pre-hospital emergency anaesthesia (PHEA) (39%). However, over a third of head injured patients attended after dispatch by crew request received PHEA (36%) and a large proportion were triaged to major trauma centres (69%).ConclusionsMany patients who do not fulfil the criteria for immediate HEMS dispatch need advanced clinical interventions and subsequent tertiary level care at a major trauma centre. Further studies should evaluate if HEMS activation criteria, nuanced by age-dependant triggers for mechanism and physiological parameters, optimise dispatch sensitivity and HEMS utilisation.

Does the law require reinterpretation and return of revised genomic results?

Does the law require reinterpretation and return of revised genomic results?

P152 The incidence of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies may be higher than we think

Abstract Background/Aims Statins are associated with muscle symptoms, from myalgia with normal CK, to rhabdomyolysis. A sub-group have an autoimmune necrotising myopathy with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies. This can present variably, from mild self-limiting illness to severe myopathy unresponsive to statin withdrawal, requiring long-term immunosuppression. A study from New Zealand estimated the incidence of anti-HMGCR-associated myositis to be 1 in 90,000 statin users, and an incidence of 1 in 500,000 has been estimated in a US population. Anti-HMGCR antibodies were first reported in 2010. As they are new, and testing is not widely available, they may be under-recognised in the routine assessment of patients with myopathies. However, detection is important as prompt immunosuppression may be needed. Methods We compared the 2019 incidence of anti-HMGCR antibodies in Southern England from two different laboratory groups, utilising different testing criteria. The St George’s and Berkshire Surrey Pathology Services (StG/BSPS) laboratories serve a population of 3.25 million and test anti-HMGCR antibodies solely on clinician request. The Southampton laboratory serves a population of 2.33 million and tests anti-HMGCR as part of the immunoblot for all myositis-associated antibodies and where clinical details suggest myositis or ILD. Results In 2019, 14 tests were performed by StG/BSPS and 662 by Southampton, with anti-HMGCR positives of 5 (36%) and 28 (4.2%) respectively. Adjusted to include only the adult population, the incidence of anti-HMGCR antibodies is 1 in 514,000 in the StG/BSPS area versus 1 in 66,000 in the Southampton area. We estimate statins to be used in 308,000 adults in the StG/BSPS and in 220,000 in the Southampton areas, assuming treatment in 12% of adults and age demographics representative of the national population. This suggests an incidence of anti-HMGCR antibodies of approximately 1 in 62,000 statin users in the StG/BSPS area and 1 in 8,000 statin users in the Southampton area, though statin exposure was not confirmed in all positive cases. Preliminary data from 17 anti-HMGCR positive cases shows that 76% had taken statins, for an average duration of 5.84 years (range 0.75-16 years). Median peak CK was 6489 (range 241-27555). 76% required immunosuppression, of which 70% required two or more different treatments. Conclusion The 7.7-fold higher incidence from the Southampton laboratory reflects a proactive approach, selecting far more samples for anti-HMGCR assessment than specifically requested by clinicians. This demonstrates under-awareness of this antibody in routine care. We propose adoption of an algorithm to trigger more widespread testing for anti-HMGCR antibodies, to identify cases amongst those with statin-associated myalgia or myositis, and in others without statin exposure. This will lead to better understanding of the spectrum of clinical disease associated with anti-HMGCR antibodies, as well as early detection and treatment of those who develop a necrotising myopathy. Disclosure V.M.K. Joseph: None. E.C. Rose: None. M. Lloyd: None. C.J. Edwards: None. S.K. Amar: None. T. Forster: None. K.A. Smith: None. R.D. Wheeler: None. P.D.W. Kiely: None.

Convalescent COVID-19 plasma

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease. December 31, 2019 marked the day the World Health Organization (WHO) first became aware of an infectious outbreak in the Hubei province in China. Until January 2021, more than two million people died from COVID-19. The use of convalescent plasma (CP) has been widely used in different outbreaks as the first therapeutic option given the lack of effective medications or vaccines, and often as a last chance or experimental treatment. CP is a strategy of passive immunisation. Possible mechanisms of CP-COVID-19 action are antiviral and immunomodulatory. The established protocol for CP-COVID-19 collection defines activities and criteria related to recruiting and informing potential CP donors, clinical and laboratory examination, plasma collection, labelling and storage. Plasma is collected by apheresis/plasmapheresis. Administration of plasma is performed at the request of clinicians, according to the strict indications based on the severity of clinical picture, expressed by precisely determined "scoring" of symptoms. The risks transfusion recipients are likely to be exposed to do not differ from those of standard plasma recipients. At the Blood Transfusion Institute of Serbia, the first plasmapheresis from the recovered patient-donor was performed on 11 April 2020 and so far, collection and distribution of CP-COVID-19 have been performed continuously. During the observation period, preliminary results of the effect of CP transfusion, along with other applied therapy, indicate its favourable effect, both worldwide and in Serbia. CP-COVID-19 should be used as early as possible in the course of infection in order to achieve the best outcomes.