Clinical management and outcome of head and neck paragangliomas (HNPGLs): A single centre retrospective study.

CONTEXT: Head and neck paragangliomas (HNPGLs) are rare, usually benign, slow-growing tumours arising from neural crest-derived tissue. Definitive management pathways for HNPGLs have yet to be clearly defined. OBJECTIVE: To review our experience of the clinical features and management of these tumours and to analyse outcomes of different treatment modalities. METHODS: Demographic and clinical data were obtained from The Northern Ireland Electronic Care Record (NIECR) as well from a prospectively maintained HNPGL database between January 2011 through December 2023. RESULTS: There were 87 patients; 50 females: 37 males with a mean age of 52.3 ± 14.2 years old (range 17-91 years old). 58.6% (n = 51) of patients had carotid body tumours, 25.2% (n = 22) glomus vagal tumours, 6.8% (n = 6) tumours in the middle ear, 2.2% (n = 2) in the parapharyngeal space and 1.1% (n = 1) in the sphenoid sinus. 5.7% (n = 5) of patients had multifocal disease. The mean tumour size at presentation was 3.2 ± 1.4 cm (range 0.5-6.9 cm). Pathogenic SDHD mutations were identified in 41.3% (n = 36), SDHB in 12.6% (n = 11), SDHC in 2.2% (n = 2) and SDHA in 1.1% (n = 1) of the patients. Overall treatment modalities included surgery alone in 51.7% (n = 45) of patients, radiotherapy in 14.9% (n = 13), observation in 28.7% (n = 25), and somatostatin analogue therapy with octreotide in 4.5% (n = 4) of patients. Factors associated with a significantly higher risk of recurrence included age over 60 years (p = .04), tumour size exceeding 2 cm (p = .03), positive SDHx variants (p = .01), and vagal and jugular tumours (p = .04). CONCLUSION: The majority of our patients underwent initial surgical intervention and achieved disease stability. Our results suggest that carefully selected asymptomatic or medically unfit patients can be safely observed provided lifelong surveillance is maintained. We advocate for the establishment of a UK and Ireland national HNPGL registry, to delineate optimal management strategies for these rare tumours and improve long term outcomes.

Whole-Genome sequencing in routine Mycobacterium bovis epidemiology - scoping the potential.

Mycobacterium bovis the main agent of bovine tuberculosis (bTB), presents as a series of spatially-localised micro-epidemics across landscapes. Classical molecular typing methods applied to these micro-epidemics, based on genotyping a few variable loci, have significantly improved our understanding of potential epidemiological links between outbreaks. However, they have limited utility owing to low resolution. Conversely, whole-genome sequencing (WGS) provides the highest resolution data available for molecular epidemiology, producing richer outbreak tracing, insights into phylogeography and epidemic evolutionary history. We illustrate these advantages by focusing on a common single lineage of M. bovis (1.140) from Northern Ireland. Specifically, we investigate the spatial sub-structure of 20 years of herd-level multi locus VNTR analysis (MLVA) surveillance data and WGS data from a down sampled subset of isolates of this MLVA type over the same time frame. We mapped 2108 isolate locations of MLVA type 1.140 over the years 2000-2022. We also mapped the locations of 148 contemporary WGS isolates from this lineage, over a similar geographic range, stratifying by single nucleotide polymorphism (SNP) relatedness cut-offs of 15 SNPs. We determined a putative core range for the 1.140 MLVA type and SNP-defined sequence clusters using a 50 % kernel density estimate, using cattle movement data to inform on likely sources of WGS isolates found outside of core ranges. Finally, we applied Bayesian phylogenetic methods to investigate past population history and reproductive number of the 1.140 M. bovis lineage. We demonstrate that WGS SNP-defined clusters exhibit smaller core ranges than the established MLVA type - facilitating superior disease tracing. We also demonstrate the superior functionality of WGS data in determining how this lineage was disseminated across the landscape, likely via cattle movement and to infer how its effective population size and reproductive number has been in flux since its emergence. These initial findings highlight the potential of WGS data for routine monitoring of bTB outbreaks.

Magnesium implants in orthopaedic surgery create a diagnostic conundrum: A radiology case series and literature review.

During a routine post-operative orthopaedic radiograph reading session, repeated unusual radiographic soft tissue and bone appearances became evident. It was discovered that these patients had received biodegradable magnesium implants which have recently been introduced into orthopaedic clinical practice. To the untrained eye, the combination of peri-metallic bone resorption with associated soft tissue gas, could easily be mistaken for post-operative infection. The aim of this study is to properly characterise the radiographic post-operative appearances of biodegradable magnesium orthopaedic hardware. We retrospectively evaluated radiographs of all patients who underwent magnesium screw implantation for fractures over a 6 month period. Four patients, mean age of 9.75 (range: 6-15) years who underwent magnesium screw fixation following fracture were included in the study. Follow up duration was 100 days (range: 75-122) with a mean of 2.5 postoperative radiographs being performed per patient during this period. All cases demonstrated post-operative peri-metallic radiolucency which developed around the magnesium screws on x-ray, which subsequently resorbed over time. Peri-metallic soft tissue gas was observed in all patients. In two cases, magnesium implants fractured. As the use of biodegradable metal implants becomes more common, it is important for radiologists to be aware of their imaging characteristics. Prior to reporting a case, it would be prudent to know if biodegradable screws have been utilised and whether there exists a clinical concern for post-operative infection in patients with these particular implants, in which case it would be critical not to dismiss peri-prosthetic radiolucencies and soft tissue gas as merely a sequela of the natural metal degradation process.

Follow-Up of Patients After Total Pancreatectomy and Islet Cell Autotransplantation at Off-Site Islet Isolation Facility.

CONTEXT: Total pancreatectomy with islet autotransplantation (TPIAT) is a definitive management for intractable pain in patients with chronic pancreatitis (CP). Islet autotransplantation (IAT) allows for the preservation of beta cells to prevent complications of long-term diabetes. OBJECTIVE: Our study follows TPIAT recipients for up to 12 years to determine the efficacy of the procedure completed with an off-site islet isolation facility. METHODS: Patient demographics, mixed meal tolerance test measures, glycosylated hemoglobin, insulin requirements, and homeostatic model assessment for insulin resistance values were collected prior to surgery and at the most recent follow-up assessment. RESULTS: Forty-four patients (median age, 46.0 years; range, 20-78 years) underwent TPIAT for CP. At an overall median follow-up time of 845.5 days (range, 195-4470 days) 8 patients were insulin independent and 36 patients were insulin dependent. At the most recent follow-up time point, islet yield per kilogram was the strongest indicator of insulin independence. Homeostatic model assessment for insulin resistance values were comparable between insulin independent and dependent cohorts. CONCLUSIONS: Our long-term follow-up data suggest that IAT can effectively reduce insulin requirements and improve postoperative glycemic control.

Ultrasound for the assessment of thyroid nodules: an overview for non-radiologists.

Upon discovery of a thyroid nodule (or nodules), a patient is usually referred for evaluation by ultrasound, which is typically performed by a trained radiologist or sonographer. More recently, this technology has been used intraoperatively by endocrine surgeons and also by endocrinologists, often in the context of 'one-stop shops' or point of care ultrasound in the outpatient setting. Although thyroid nodules are common and most will be benign, the subsequent work up of these can cause anxiety for patients and place a burden on radiologists. In the UK, sonographic features of benign, suspicious or malignant nodules are classified by the British Thyroid Association U1-U5 criteria, which decide whether to biopsy the nodule (typically U3 and above). This article provides an overview of ultrasound in assessing the thyroid nodule in the context of this classification. This can be used as a guide to interpretation of thyroid ultrasonography for non-radiologists.

Pituitary metastasis: a clinical overview.

The pituitary gland is an unusual site for metastatic spread and has been associated with a poor prognosis. Clinical presentation is variable but can include visual field defects, cranial nerve palsies, anterior pituitary dysfunction and/ or diabetes insipidus. Management options include surgery or radiotherapy, chemotherapy/immunotherapy or a conservative approach. The pituitary should not be overlooked as a site for metastasis in patients with known cancer and can be the first presentation of neoplastic disease in some patients. Given that patients are now living longer with cancer, clinicians should be alert to the varied presentation of pituitary metastasis. We provide a clinical overview of pituitary metastasis with the aid of illustrative clinical cases.

Screening attendance, prevalence and severity of diabetic retinopathy (DR) in a cohort of patients with diabetes mellitus secondary to chronic pancreatitis (DMsCP) in Northern Ireland.

INTRODUCTION: This study investigated Northern Ireland Diabetic Eye Screening Programme (NIDESP) attendance and diabetic retinopathy (DR) prevalence/severity in patients with diabetes mellitus secondary to chronic pancreatitis (PwDMsCP). RESEARCH DESIGN AND METHODS: Medical/NIDESP records for all PwDMsCP attending the pancreatic diabetes clinic were analyzed in 2017 (n=78) and 2019 (n=94). RESULTS: Between 2017 and 2019, those without DR decreased (76% to 63%); mild non-proliferative DR (NPDR), severe NPDR and PDR were found in 30%, 2% and 5%, respectively (previously 18%, 4%, 2%); diabetic maculopathy (DMac) was present in 12% (previously 10%). There was no significant difference between worst-eye DR/DMac grade and HbA1c, gender, body mass index, pancreatitis etiology and screening attendance (p>0.05). Patients with proliferative DR had longer diabetes and pancreatitis duration than DR-free patients (both p=0.001). CONCLUSIONS: DR prevalence was similar in PwDMsCP and patients with type 2 diabetes of similar disease duration. This work demonstrates the importance of reaching all patients for establishing DR severity reliably and to provide accessible, equitable care to PwDMsCP.

Pitfalls in Performing and Interpreting Inferior Petrosal Sinus Sampling: Personal Experience and Literature Review.

CONTEXT: Inferior petrosal sinus sampling (IPSS) helps differentiate the source of ACTH-dependent hypercortisolism in patients with inconclusive biochemical testing and imaging, and is considered the gold standard for distinguishing Cushing disease (CD) from ectopic ACTH syndrome. We present a comprehensive approach to interpreting IPSS results by examining several real cases. EVIDENCE ACQUISITION: We performed a comprehensive review of the IPSS literature using PubMed since IPSS was first described in 1977. EVIDENCE SYNTHESIS: IPSS cannot be used to confirm the diagnosis of ACTH-dependent Cushing syndrome (CS). It is essential to establish ACTH-dependent hypercortisolism before the procedure. IPSS must be performed by an experienced interventional or neuroradiologist because successful sinus cannulation relies on operator experience. In patients with suspected cyclical CS, it is important to demonstrate the presence of hypercortisolism before IPSS. Concurrent measurement of IPS prolactin levels is useful to confirm adequate IPS venous efflux. This is essential in patients who lack an IPS-to-peripheral (IPS:P) ACTH gradient, suggesting an ectopic source. The prolactin-adjusted IPS:P ACTH ratio can improve differentiation between CD and ectopic ACTH syndrome when there is a lack of proper IPS venous efflux. In patients who have unilateral successful IPS cannulation, a contralateral source cannot be excluded. The value of the intersinus ACTH ratio to predict tumor lateralization may be improved using a prolactin-adjusted ACTH ratio, but this requires further evaluation. CONCLUSION: A stepwise approach in performing and interpreting IPSS will provide clinicians with the best information from this important but delicate procedure.

Accuracy of a Modified qSOFA Score for Predicting Critical Care Admission in Febrile Children.

BACKGROUND AND OBJECTIVES: The identification of life-threatening infection in febrile children presenting to the emergency department (ED) remains difficult. The quick Sequential Organ Failure Assessment (qSOFA) was only derived for adult populations, implying an urgent need for pediatric scores. We developed and validated a novel, adapted qSOFA score (Liverpool quick Sequential Organ Failure Assessment [LqSOFA]) and compared its performance with qSOFA, Pediatric Early Warning Score (PEWS), and National Institute for Health and Care Excellence (NICE) high-risk criteria in predicting critical care (CC) admission in febrile children presenting to the ED. METHODS: The LqSOFA (range, 0-4) incorporates age-adjusted heart rate, respiratory rate, capillary refill, and consciousness level on the Alert, Voice, Pain, Unresponsive scale. The primary outcome was CC admission within 48 hours of ED presentation, and the secondary outcome was sepsis-related mortality. LqSOFA, qSOFA, PEWS, and NICE high-risk criteria scores were calculated, and performance characteristics, including area under the receiver operating characteristic curve, were calculated for each score. RESULTS: In the initial (n = 1121) cohort, 47 CC admissions (4.2%) occurred, and in the validation (n = 12 241) cohort, 135 CC admissions (1.1%) occurred, and there were 5 sepsis-related deaths. In the validation cohort, LqSOFA predicted CC admission with an area under the receiver operating characteristic curve of 0.81 (95% confidence interval [CI], 0.76 to 0.86), versus qSOFA (0.66; 95% CI, 0.60 to 0.71), PEWS (0.93; 95% CI, 0.90 to 0.95), and NICE high-risk criteria (0.81; 95% CI, 0.78 to 0.85). For predicting CC admission, the LqSOFA outperformed the qSOFA, with a net reclassification index of 10.4% (95% CI, 1.0% to 19.9%). CONCLUSIONS: In this large study, we demonstrate improved performance of the LqSOFA over qSOFA in identifying febrile children at risk for CC admission and sepsis-related mortality. Further validation is required in other settings.

Point of Care Thyroid Ultrasound (POCUS) in Endocrine Outpatients: A Pilot Study.

BACKGROUND: Thyroid ultrasound is used for the assessment and characterisation of thyroid nodules/goitres and to guide diagnostic biopsy, it is normally performed by radiologists. Point of care ultrasound (POCUS) by trained non-radiologists, has the potential to reduce cost, expedite diagnosis and enhance patient satisfaction if embedded in an outpatient clinic setting. AIM: To perform a pilot of the use of point of care thyroid ultrasound in an endocrine outpatient setting for the assessment of thyroid nodules and goitres. METHODS: Thyroid ultrasound was undertaken with consultant radiologist supervision, over a period of 16 months between January 2017 to April 2018. Using a GE Logic e7 portable thyroid ultrasound machine with 12 MHz linear probe. All scans were performed on patients attending for assessment of thyroid disorders at the Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast. RESULTS: Thyroid ultrasound was performed on 40 patients (M:10,F30), mean age 52 years, range 23-77 years, median follow up 14 months, range 6-18 months. Twenty scans were performed to assess thyroid nodules, 13 for investigation of a goitre and the remaining 7 were for patient preference. 39 patients had benign thyroid disease, 1 patient had a confirmed newly diagnosed papillary thyroid carcinoma (PTC). The ultrasound 'U' classification was U1 and U2 (n=37), U3 and above (n=3). Fine needle biopsy (FNA) was performed on 9 patients with one confirmed as a thyroid carcinoma (Thy1;n=2, Thy2;n=6 and Thy 5;n=1). Thyroid ultrasound reporting was broadly similar between radiologist and non-radiologist (p< 0.01). Time to scan was reduced during the pilot from the existing model (n=40) of a mean of 52 days (range 7-95 days) to 1 day (p<0.01). CONCLUSION: With appropriate training and radiology supervision, point of care thyroid ultrasound can be performed accurately and safely in outpatients by an endocrinologist. There are potential benefits in terms of cost savings, time to scan, reduction in clinic visits, and in expediting diagnosis.

Time to Diagnosis in Cushing's Syndrome: A Meta-Analysis Based on 5367 Patients.

CONTEXT: Signs and symptoms of Cushing's syndrome (CS) overlap with common diseases, such as the metabolic syndrome, obesity, osteoporosis, and depression. Therefore, it can take years to finally diagnose CS, although early diagnosis is important for prevention of complications. OBJECTIVE: The aim of this study was to assess the time span between first symptoms and diagnosis of CS in different populations to identify factors associated with an early diagnosis. DATA SOURCES: A systematic literature search via PubMed was performed to identify studies reporting on time to diagnosis in CS. In addition, unpublished data from patients of our tertiary care center and 4 other centers were included. STUDY SELECTION: Clinical studies reporting on the time to diagnosis of CS were eligible. Corresponding authors were contacted to obtain additional information relevant to the research question. DATA EXTRACTION: Data were extracted from the text of the retrieved articles and from additional information provided by authors contacted successfully. From initially 3326 screened studies 44 were included. DATA SYNTHESIS: Mean time to diagnosis for patients with CS was 34 months (ectopic CS: 14 months; adrenal CS: 30 months; and pituitary CS: 38 months; P < .001). No difference was found for gender, age (<18 and ≥18 years), and year of diagnosis (before and after 2000). Patients with pituitary CS had a longer time to diagnosis in Germany than elsewhere. CONCLUSIONS: Time to diagnosis differs for subtypes of CS but not for gender and age. Time to diagnosis remains to be long and requires to be improved.

Diabetes and Chronic Pancreatitis: Considerations in the Holistic Management of an Often Neglected Disease.

Diabetes secondary to chronic pancreatitis (CP) or type 3cDM refers to a brittle form of diabetes and is often characterised by hypoglycaemic episodes, erratic glycaemic control, and impaired quality of life. It differs from other forms of diabetes and is typically characterised by concurrent pancreatic endocrine and exocrine insufficiency which can present as malabsorption and nutritional deficiencies. In this review, we discuss the pathogenesis, epidemiology, and the practicalities of diagnosis, screening, and management of this condition.

A Survey of Patient's Perceptions and Proposed Provision of a 'Patient Portal' in Endocrine Outpatients.

INTRODUCTION: Patient portals are online electronic medical record applications that allow patients greater control of their own health and encourage meaningful interaction with their healthcare providers. The uptake of this technology is commonplace throughout developed healthcare economies and is on the Northern Ireland Electronic Healthcare Record (NIECR) roadmap. AIM: To assess patients' perceptions and proposed provision of a patient portal in endocrinology outpatients. METHODS: Patients (n=75) attending three endocrinology outpatient clinics were eligible to participate. After discussion at clinic, invited patients were contacted via e-mail to complete a confidential and anonymised online survey. There were a total of 23 questions in the survey which included a mix of free text and categorical responses. The survey duration was conducted over a 6-month period. RESULTS: The survey response rate was 51/75 (68%), M33:F18. 46/51 (90%) had access to smart phones, 45/51 (88%) used the internet daily. 31/51 (60%) of respondents were aged between 18-45, 20/51 (40%) were aged ≥ 45 years. 50/51 (98%) reported they would use the technology if available. 47/51 (92%) felt engaging with a patient portal would enhance communication with their doctor and improve understanding of their medical issues. Reported perceived applications of use included; remote access and advice for test results and medical questions, arranging appointments, requesting prescriptions and health promotion. 90% of respondents said they would be content to access results even if abnormal. Possible barriers to adoption of this technology included data protection and understanding medical terminology. CONCLUSIONS: The overall response to the provision of this technology was positive, although concerns regarding data protection remain prevalent. Perceived benefits included enhanced doctor-patient communication, optimizing workflow and improving patient engagement.

Variability of Late-Night Salivary Cortisol in Cushing Disease: A Prospective Study.

Background: The frequency of variable hormonogenesis in patients with Cushing disease (CD) but without cyclical symptoms is unclear. Aim: To assess the frequency of variable hormonogenesis in patients presenting with CD. Methods: Over a 6-month period, patients with confirmed or suspected CD provided late-night salivary samples for up to 42 consecutive nights. Results: Of 19 patients confirmed to have CD, 16 provided at least 7 consecutive salivary samples, and 13 provided at least 21; these 16 patients are the subjects of this report. Twelve patients had at least three peak and two trough levels of late-night salivary cortisol (LNSC) but in only two patients were strict criteria for cyclical hormonogenesis fulfilled; variation was assessed as random in the others. Eight patients had de novo CD, and eight had recurrent/persistent disease. All patients with recurrent/persistent CD had two or more normal results, and in four of these patients, >50% of LNSC were normal. In six patients with de novo disease with at least one normal LNSC level, the maximum levels ranged from 1.55 to 15.5 times the upper limit of normal. Conclusions: Extreme fluctuations of cortisol production, measured by sequential LNSC, are common in CD. In newly diagnosed disease, this may only occasionally impair diagnostic ability, whereas in most patients with recurrent/persistent disease after pituitary surgery, LNSC is frequently within the reference range, with potential to cause diagnostic problems.

Surgical outcomes in patients with Cushing's disease: the Cleveland clinic experience.

CONTEXT: Transsphenoidal surgery (TSS) to resect a pituitary adenoma is considered first-line treatment for patients with Cushing's disease (CD). Early, post-operative remission rates >80% are expected for patients with a microadenoma (≤ 10 mm) visible on magnetic resonance (MR) imaging. OBJECTIVE: To report surgical outcomes and predictors of remission in a specialist center for patients with CD. PATIENTS AND METHODS: Clinical data was obtained from a prospective CD database in addition to review of all electronic medical, laboratory and surgical patient records. Patients who underwent their first TSS by one neurosurgeon between 2004 and 2013, and had a minimum 1 year follow up, were evaluated. RESULTS: One hundred and one consecutive patients with CD (73F, 28M) underwent TSS. Median (range) age and follow-up were 47 (15-87) and 4.33 (1-9.8) years, respectively. At surgery, 74 (73.2%) patients had a microadenoma, 27 a macroadenoma; six of the latter patients had a planned, subtotal resection to control neurological signs due to mass effect. Initial remission rates were: microadenoma, 89% (66/74); macroadenoma, 63% (17/27); and 81% (17/21) in those macroadenomas where complete surgical removal was anticipated. Initial non-remission occurred in 18 patients, ten macro- and eight microadenoma; six of 18 had residual disease on most recent follow up. Six (2 macro, 4 micro) of the 83 patients with initial remission have had late (>12 months) recurrence of hypercortisolism that required either repeat TSS or adjunctive therapy, three of whom have persistent hypercortisolism. Macroadenoma (p = 0.003) and tumor invasion beyond the pituitary and sella (p < 0.001) were associated with failure to obtain remission with the initial TSS and greater likelihood of late recurrence. Patients in whom no lesion was seen on neuroimaging had rates of initial remission (21/25 or 84%) and a similar late recurrence rate of 4% (1/25) in comparison with those with MR-visible microadenomas (3/49, or 6%). CONCLUSIONS: A team-based approach, in a specialized pituitary center, can lead to initial and durable, long-term remission in patients with CD. The presence of a macroadenoma and tumor extension beyond the pituitary and sella were predictive of initial non-remission as well as risk of late recurrence.

Spontaneous Hypoglycemia After Islet Autotransplantation for Chronic Pancreatitis.

CONTEXT: Spontaneous hypoglycemia has been reported in patients after total pancreatectomy (TP) and islet autotransplantation (IAT) with maintained insulin independence. Details surrounding these events have not been well described. OBJECTIVE: The objective of the study was to determine the frequency and characteristics of spontaneous hypoglycemia in patients undergoing TP-IAT and/or to ascertain predictive or protective factors of its development. DESIGN: This was an observational cohort study in 40 patients who underwent TP-IAT from August 2008 to May 2014, with a median follow-up of 34 months. SETTING: The study was conducted at a single institution (Cleveland Clinic). PATIENTS: Patients included recipients of TP-IAT. INTERVENTION: The intervention included small, frequent meals in those patients who developed spontaneous hypoglycemia. MAIN OUTCOME MEASURES: Incidence of spontaneous hypoglycemia development, characteristics of the patients developing hypoglycemia, and their response to small, frequent meals were measured. RESULTS: Six of 12 patients, who maintained insulin independence, developed spontaneous hypoglycemia. The episodes could be fasting, postprandial, and/or exercise associated, with the frequency ranging from two to three times daily to once every 1-2 weeks. All patients experienced at least one episode that required external assistance, glucagon administration, and/or emergent medical attention. Patients who developed hypoglycemia had a lower median age and tended to have a lower median islet equivalent/kg body weight but a higher median total islet equivalent, body mass index, and homeostatic model assessment for insulin resistance score. All patients who received small, frequent meal intervention had improvement in severity and/or frequency of the hypoglycemic episodes. CONCLUSIONS: Spontaneous hypoglycemia is prevalent after TP-IAT. Although the underlying pathophysiology responsible for these hypoglycemia events remains to be elucidated, small, frequent meal intervention is helpful in ameliorating this condition.

Identifying risk factors for progression to critical care admission and death among individuals with acute pancreatitis: a record linkage analysis of Scottish healthcare databases.

OBJECTIVES: Acute pancreatitis (AP) can initiate systemic complications that require support in critical care (CC). Our objective was to use the unified national health record to define the epidemiology of AP in Scotland, with a specific focus on deterministic and prognostic factors for CC admission in AP. SETTING: Health boards in Scotland (n=4). PARTICIPANTS: We included all individuals in a retrospective observational cohort with at least one episode of AP (ICD10 code K85) occurring in Scotland from 1 April 2009 to 31 March 2012. 3340 individuals were coded as AP. METHODS: Data from 16 sources, spanning general practice, community prescribing, Accident and Emergency attendances, hospital in-patient, CC and mortality registries, were linked by a unique patient identifier in a national safe haven. Logistic regression and gamma models were used to define independent predictive factors for severe AP (sAP) requiring CC admission or leading to death. RESULTS: 2053 individuals (61.5% (95% CI 59.8% to 63.2%)) met the definition for true AP (tAP). 368 patients (17.9% of tAP (95% CI 16.2% to 19.6%)) were admitted to CC. Predictors of sAP were pre-existing angina or hypertension, hypocalcaemia and age 30-39 years, if type 2 diabetes mellitus was present. The risk of sAP was lower in patients with multiple previous episodes of AP. In-hospital mortality in tAP was 5.0% (95% CI 4.1% to 5.9%) overall and 21.7% (95% CI 19.9% to 23.5%) in those with tAP necessitating CC admission. CONCLUSIONS: National record-linkage analysis of routinely collected data constitutes a powerful resource to model CC admission and prognosticate death during AP. Mortality in patients with AP who require CC admission remains high.