Pituitary hypophysitis in granulomatosis with polyangiitis (GPA): a case series.

Granulomatosis with polyangiitis (GPA) rarely involves the pituitary gland. Pituitary involvement has been reported in ~ 1% of all cases of GPA. Most commonly, pituitary swelling and inflammation results in symptoms due to pituitary mass effect and arginine vasopressin deficiency. To date, there are no pituitary-specific treatment guidelines for this rare condition. We present three patients with GPA-related hypophysitis highlighting the spectrum of pituitary involvement. All three patients were successfully treated with immunosuppressive regimens that included rituximab (RTX). Following remission induction with high-dose glucocorticoids, patients received 6 monthly RTX for remission maintenance. RTX was well tolerated without significant side effects.

Adeno-Associated Virus 2 and Human Adenovirus F41 in Wastewater during Outbreak of Severe Acute Hepatitis in Children, Ireland.

During April-July 2022, outbreaks of severe acute hepatitis of unknown etiology (SAHUE) were reported in 35 countries. Five percent of cases required liver transplantation, and 22 patients died. Viral metagenomic studies of clinical samples from SAHUE cases showed a correlation with human adenovirus F type 41 (HAdV-F41) and adeno-associated virus type 2 (AAV2). To explore the association between those DNA viruses and SAHUE in children in Ireland, we quantified HAdV-F41 and AAV2 in samples collected from a wastewater treatment plant serving 40% of Ireland's population. We noted a high correlation between HAdV-F41 and AAV2 circulation in the community and SAHUE clinical cases. Next-generation sequencing of the adenovirus hexon in wastewater demonstrated HAdV-F41 was the predominant HAdV type circulating. Our environmental analysis showed increased HAdV-F41 and AAV2 prevalence in the community during the SAHUE outbreak. Our findings highlight how wastewater sampling could aid in surveillance for respiratory adenovirus species.

Temporal trends in craniopharyngioma management and long-term endocrine outcomes: A multicentre cross-sectional study.

BACKGROUND: The optimal management of craniopharyngiomas remains controversial. OBJECTIVES: To examine temporal trends in the management of craniopharyngioma with a focus on endocrine outcomes. METHODS: This was a cross-sectional, multicentre study. Patients treated between 1951 and 2015 were identified and divided into four quartiles. Demographics, presentation, treatment and outcomes were collected. RESULTS: In total, 142 patients with childhood-onset craniopharyngioma (48/142; 34%) and adult-onset disease (94/142; 66%) were included. The median follow-up was 15 years (IQR 5-23 years). Across quartiles, there was a significant trend towards using transsphenoidal surgery (P < .0001). The overall use of radiotherapy was not different among the four quartiles (P = .33). At the latest clinical review, the incidence of GH, ACTH, gonadotrophin deficiencies and anterior panhypopituitarism fell significantly across the duration of the study. Anterior panhypopituitarism was not affected by treatment modality (surgery vs surgery and radiotherapy) (P = .23). There was no difference in the incidence of high BMI (≥25 kg/m2 ) among the four quartiles (P = .14). BMI was higher in patients who treated with surgery and radiotherapy than those treated with surgery only (P = .006). Tumour regrowth occurred in 51 patients (51/142; 36%) with no difference in regrowth among quartiles over the time course of the study (P = .15). CONCLUSION: We demonstrate a significant reduction in panhypopituitarism in craniopharyngioma patients over time, most likely because of a trend towards more transsphenoidal surgery. However, long-term endocrine sequelae remain common and lifelong follow-up is required.

Initial experience of a large, self-expanding, and fully recapturable transcatheter aortic valve: The UK & Ireland Implanters' registry.

OBJECTIVES: The UK & Ireland Implanters' registry is a multicenter registry which reports on real-world experience with novel transcatheter heart valves. BACKGROUND: The 34 mm Evolut R transcatheter aortic valve is a self-expanding and fully recapturable transcatheter aortic valve, designed to treat patients with a large aortic annulus. METHODS: Between January 2017 and April 2018, clinical, procedural and 30-day outcome data were prospectively collected from all patients receiving the 34 mm Evolut R valve across 17 participating centers in the United Kingdom and Ireland. The primary efficacy outcome was the Valve Academic Research Consortium-2(VARC-2)-defined endpoint of device success. The primary safety outcome was the VARC-2-defined composite endpoint of early safety at 30 days. RESULTS: A total of 217 patients underwent attempted implant. Mean age was 79.5 ± 8.8 years and Society of Thoracic Surgeons Predicted Risk of Mortality Score 5.2% ± 3.4%. Iliofemoral access was used in 91.2% of patients. Device success was 79.7%. Mean gradient was 7.0 ± 4.6 mmHg and effective orifice area 2.0 ± 0.6 cm2 . Paravalvular regurgitation was more than mild in 7.2%. A new permanent pacemaker was implanted in 15.7%. Early safety was demonstrated in 91.2%. At 30 days, all-cause mortality was 3.2%, stroke 3.7%, and major vascular complication 2.3%. CONCLUSIONS: Real-world experience of the 34 mm Evolut R transcatheter aortic valve demonstrated acceptable procedural success, safety, valve function, and incidence of new permanent pacemaker implantation.

Interpretation of Serum Gonadotropin Levels in Hyperprolactinaemia.

BACKGROUND/AIMS: Hyperprolactinaemia is a common cause of amenorrhoea due to hypogonadotropic hypogonadism. Prolactin is hypothesised to impede the reproductive axis through an inhibitory action at the hypothalamus. However, limited data exist to aid the interpretation of serum gonadotropins in the context of hyperprolactinaemia. METHODS: Serum gonadotropin values were reviewed in 243 patients with elevated serum monomeric prolactin due to discrete aetiologies at a tertiary reproductive endocrine centre between 2012 and 2015. The cause of hyperprolactinaemia was categorised by an experienced endocrinologist/pituitary multidisciplinary team, unless superseded by histology. The most frequently encountered diagnoses were microprolactinoma (n = 88), macroprolactinoma (n = 46), non-functioning pituitary adenoma (NFPA) (n = 72), drug-induced hyperprolactinaemia (n = 22) and polycystic ovarian syndrome (PCOS) (n = 15). RESULTS: In patients with prolactinoma and modestly raised serum prolactin levels (< 4,000 mU/L), increasingly FSH-predominant gonadotropin values were observed with rising prolactin level, consistent with a progressive reduction in hypothalamic gonadotropin-releasing hormone (GnRH) pulsatility. Patients with prolactinoma and higher prolactin values (> 4,000 mU/L) were more likely to have a reduction in serum levels of both FSH and LH, consistent with direct pituitary gonadotrope dysfunction. Patients with macroadenoma and extremes of serum gonadotropin values (either serum FSH or LH > 8 IU/L) were more likely to have NFPA than prolactinoma. Patients with PCOS and hyperprolactinaemia had LH-predominant secretion in keeping with increased GnRH pulsatility despite a raised prolactin level. CONCLUSION: The pattern of gonadotropin secretion in patients with hyperprolactinaemia reflects the underlying aetiology.

Clinical outcomes in patients with nonfunctioning pituitary adenomas managed conservatively.

CONTEXT: The natural history and the optimum management of patients with nonfunctioning pituitary adenomas (NFPAs) are unclear. OBJECTIVE: Our objective was to characterize the natural history of patients with NFPAs managed conservatively. DESIGN AND PATIENTS: We conducted a retrospective analysis of patients presenting to a tertiary referral centre between 1986 and 2009. Patients with pituitary adenomas and no clinical or biochemical evidence of hormonal hypersecretion were included. Those presenting with apoplexy or a radiological follow-up period of less than 1 year were excluded. The pituitary imaging for all patients was re-examined by two neuroradiologists in consensus. OUTCOME MEASURES: The outcome measures were change in tumour size and pituitary hormone function. RESULTS: Sixty-six patients were managed conservatively for a mean follow-up period of 4·3 years (range: 1-14·7). Forty-seven (71%) had a macroadenoma, and nineteen (29%) had a microadenoma. Tumour size decreased or remained stable in 40% of macroadenomas and 47% of microadenomas. The median annual growth rate of enlarging macroadenomas and microadenomas was 1·0 mm/year and 0·4 mm/year, respectively. The median annual growth rate of macroadenomas was significantly higher than that of microadenomas (P < 0·01). Sixty-eight percentage of patients with a macroadenoma had pituitary hormone deficiency in one or more axes, compared to 42% of those with a microadenoma. CONCLUSION: Patients with NFPAs without optic chiasm compression can be managed conservatively. All patients need pituitary function assessment, irrespective of tumour size. These findings provide clinically relevant data for the management of patients with NFPAs.

Agricultural and urban practices are correlated to changes in the resistome of riverine systems.

The objective of this study was to comprehensively characterise the resistome, the collective set of antimicrobial resistance genes in a given environment, of two rivers, from their source to discharge into the sea, as these flow through areas of different land use. Our findings reveal significant differences in the riverine resistome composition in areas of different land uses, with increased abundance and diversity of AMR in downstream agricultural and urban locations, with the resistome in urban areas more similar to the resistome in wastewater. The changes in resistome were accompanied by changes in microbial communities, with a reduction in microbial diversity in downstream agricultural and urban affected areas, driven mostly by increased relative abundance in the phyla, Bacteroidetes and Proteobacteria. These results provide insight into how pollution associated with agricultural and urban activities affects microbial communities and influences AMR in aquatic water bodies. These results add valuable insights to form effective strategies for mitigating and preserving aquatic ecosystems. Overall, our study highlights the critical role of the environment in the development and dissemination of AMR and underscores the importance of adopting a One Health approach to address this global public health threat.

Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival.

Objectives: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis. Design and methods: Single-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure. Results: Non-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 - 0.71) or both (HR 0.41, CI 0.25 - 0.64) but not in those who only developed non-endocrine irAEs. Conclusions: Women may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this.

Decay of RNA and infectious SARS-CoV-2 and murine hepatitis virus in wastewater.

Wastewater-based epidemiology (WBE) has been an important tool for population surveillance during the COVID-19 pandemic and continues to play a key role in monitoring SARS-CoV-2 infection levels following reductions in national clinical testing schemes. Studies measuring decay profiles of SARS-CoV-2 in wastewater have underscored the value of WBE, however investigations have been hampered by high biosafety requirements for SARS-CoV-2 infection studies. Therefore, surrogate viruses with lower biosafety standards have been used for SARS-CoV-2 decay studies, such as murine hepatitis virus (MHV), but few studies have directly compared decay rates of both viruses. We compared the persistence of SARS-CoV-2 and MHV in wastewater, using 50 % tissue culture infectious dose (TCID50) and reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays to assess infectious virus titre and viral gene markers, respectively. Infectious SARS-CoV-2 and MHV indicate similar endpoints, however observed early decay characteristics differed, with infectious SARS-CoV-2 decaying more rapidly than MHV. We find that MHV is an appropriate infectious virus surrogate for viable SARS-CoV-2, however inconsistencies exist in viral RNA decay parameters, indicating MHV may not be a suitable nucleic acid surrogate across certain temperature regimes. This study highlights the importance of sample preparation and the potential for decay rate overestimation in wastewater surveillance for SARS-CoV-2 and other pathogens.

Quantitative source apportionment of faecal indicator bacteria from anthropogenic and zoogenic sources of faecal contamination.

Recreational bathing waters are complex systems with diverse inputs from multiple anthropogenic and zoogenic sources of faecal contamination. Faecal contamination is a substantial threat to water quality and public health. Here we present a comprehensive strategy to estimate the contribution of faecal indicator bacteria (FIB) from different biological sources on two at-risk beaches in Dublin, Ireland. The daily FIB loading rate was determined for three sources of contamination: a sewage-impacted urban stream, dog and wild bird fouling. This comparative analysis determined that the stream contributed the highest daily levels of FIB, followed by dog fouling. Dog fouling may be a significant source of FIB, contributing approximately 20 % of E. coli under certain conditions, whereas wild bird fouling contributed a negligible proportion of FIB (<3 %). This study demonstrates that source-specific quantitative microbial source apportionment (QMSA) strategies are vital to identify primary public health risks and target interventions to mitigate faecal contamination.

Comparison of the overnight metyrapone and glucagon stimulation tests in the assessment of secondary hypoadrenalism.

OBJECTIVE: The insulin tolerance test (ITT) is contraindicated in a proportion of patients with suspected ACTH deficiency. The aim of this study was to investigate the diagnostic accuracy of the glucagon stress test (GST) compared with the overnight metyrapone test (OMT) in patients with contraindications to ITT. DESIGN: This was a prospective comparison of the GST to the OMT in patients with suspected ACTH deficiency and contraindications to the ITT. The OMT was used as the standard for comparison. The study was conducted at two tertiary referral centres for pituitary disease. PATIENTS: Seventy-eight patients underwent contemporaneous OMT and GST of whom 61 had sufficient suppression of cortisol during the OMT to be included in the comparison. Forty had suffered traumatic brain injury, 36 had organic pituitary disorders and two were classified as 'other'. MEASUREMENTS: ACTH sufficiency was defined as 0800h 11-deoxycortisol ≥ 200 nmol/l on OMT and peak cortisol ≥ 440 nmol/l on GST, as per local reference ranges. RESULTS: There was significant discrepancy between the proportion of patients diagnosed with ACTH deficiency using the OMT (39%) and GST (89%). From our data, a GST peak cortisol cut-off of ≥350 nm provides the combination of optimal sensitivity (71%) and specificity (57%), compared with a higher sensitivity (88%) but poor specificity (11%) using a cut-off of ≥440 nm. CONCLUSIONS: The GST should be used with caution as a diagnostic test of ACTH reserve. The OMT should be used in preference to the GST to assess the hypothalamic pituitary adrenal axis where ITT is contraindicated.

Drug loaded implantable devices to treat cardiovascular disease.

INTRODUCTION: It is widely acknowledged that cardiovascular diseases (CVDs) continue to be the leading cause of death globally. Furthermore, CVDs are the leading cause of diminished quality of life for patients, frequently as a result of their progressive deterioration. Medical implants that release drugs into the body are active implants that do more than just provide mechanical support; they also have a therapeutic role. Primarily, this is achieved through the controlled release of active pharmaceutical ingredients (API) at the implementation site. AREAS COVERED: In this review, the authors discuss drug-eluting stents, drug-eluting vascular grafts, and drug-eluting cardiac patches with the aim of providing a broad overview of the three most common types of cardiac implant. EXPERT OPINION: Drug eluting implants are an ideal alternative to traditional drug delivery because they allow for accurate drug release, local drug delivery to the target tissue, and minimize the adverse side effects associated with systemic administration. Despite the fact that there are still challenges that need to be addressed, the ever-evolving new technologies are making the fabrication of drug-eluting implants a rewarding therapeutic endeavor with the possibility for even greater advances.

Land use as a critical determinant of faecal and antimicrobial resistance gene pollution in riverine systems.

The WHO recognises antimicrobial resistance (AMR) as a global health threat. The environment can act as a reservoir, facilitating the exchange and the physical movement of resistance. Aquatic environments are at particular risk of pollution, with large rivers subject to pollution from nearby human, industrial or agricultural activities. The land uses associated with these activities can influence the type of pollution. One type of pollution and a likely contributor to AMR pollution that lowers water quality is faecal pollution. Both pose an acute health risk and could have implications for resistance circulating in communities. The effects of land use are typically studied using physiochemical parameters or in isolation of one another. However, this study aimed to investigate the impact of different land uses on riverine systems. We explored whether differences in sources of faecal contamination are reflected in AMR gene concentrations across agricultural and urban areas. Water quality from three rivers impacted by different land uses was assessed over one year by quantifying faecal indicator bacteria (FIB), microbial source tracking markers (MST) and AMR genes. In addition, a multiparametric analysis of AMR gene pollution was carried out to understand whether agricultural and urban areas are similarly impacted. Faecal indicators varied greatly, with the highest levels of FIB and the human MST marker observed in urban regions. In addition, these faecal markers correlated with AMR genes. Similarly, significant correlations between the ruminant MST marker and AMR gene levels in agriculture areas were observed. Overall, applying multiparametric analyses to include AMR gene levels, separation and clustering of sites were seen based on land use characterisation. This study suggests that differences in prescription of antimicrobials used in animal and human healthcare may influence environmental resistomes across agricultural and urban areas. In addition, public health risks due to exposure to faecal contamination and AMR genes are highlighted.

Inclusion of hydrodynamic properties of bathing waters is critical in selecting faecal indicators to assess public health impacts of faecal contamination.

The EU Bathing Water Directive (BWD) requires member states to assess bathing water quality according to the levels of faecal indicator bacteria (FIB) in designated bathing areas. However, this criterion has two significant limitations given that the BWD does not; (i) account for differences in hydrodynamic properties of bathing waters and, (ii) assumes that all faecal pathogens decay equally in aquatic environments. This study simulated sewage discharge events in three hypothetical aquatic environments characterised by different advection and dispersion parameters in the solute transport equation. Temporal changes in the downstream concentration of six faecal indicators were determined in simulations that utilised measured decay rates of each faecal indicator from a programme of controlled microcosm experiments in fresh and seawater environments. The results showed that the decay rates of faecal indicators are not a critical parameter in advection dominant water bodies, such as in fast-flowing rivers. Therefore, faecal indicator selection is less important in such systems and for these, FIB remains the most cost-effective faecal indicator to monitor the public health impacts of faecal contamination. In contrast, consideration of faecal indicator decay is important when assessing dispersion and advection/dispersion dominant systems, which would pertain to transitional (estuarine) and coastal waterbodies. Results suggest that the inclusion of viral indicators, such as crAssphage and PMMoV, could improve the reliability of water quality modelling and minimise the risk of waterborne illnesses from faecal contamination.

Bacteriophages from faecal contamination are an important reservoir for AMR in aquatic environments.

Bacteriophages have been shown to play an important role in harbouring and propagating antibiotic resistance genes (ARGs). Faecal matter contains high levels of phages, suggesting that faecal contamination of water bodies may lead to increased antimicrobial resistance (AMR) levels due to increased phage loading in aquatic environments. In this study, we assessed whether faecal pollution of three rivers (Rivers Liffey, Tolka, and Dodder) was responsible for increased levels of ARGs in phage particles using established phage-faecal markers, focusing on four ARGs (blaTEM, tet(O), qnrS, and sul1). We observed all four ARGs in phage fractions in all three rivers, with ARGs more frequently observed in agricultural and urban sampling sites compared to their source. These findings highlight the role of faecal pollution in environmental AMR and the impact of agricultural and urban activities on water quality. Furthermore, our results suggest the importance of including phages as indicators when assessing environmental AMR, as they serve as significant reservoirs of resistance genes in aquatic environments. This study provides important insights into the role of faecal pollution and phages in the prevalence of AMR in the environment and the need for their inclusion in future studies to provide a comprehensive understanding of environmental AMR.

Natural history of non-functioning pituitary microadenomas: results from the UK non-functioning pituitary adenoma consortium.

OBJECTIVE: The optimal approach to the surveillance of non-functioning pituitary microadenomas (micro-NFPAs) is not clearly established. Our aim was to generate evidence on the natural history of micro-NFPAs to support patient care. DESIGN: Multi-centre, retrospective, cohort study involving 23 endocrine departments (UK NFPA consortium). METHODS: Clinical, imaging, and hormonal data of micro-NFPA cases between January, 1, 2008 and December, 21, 2021 were analysed. RESULTS: Data for 459 patients were retrieved [median age at detection 44 years (IQR 31-57)-152 males/307 females]. Four hundred and nineteen patients had more than two magnetic resonance imagings (MRIs) [median imaging monitoring 3.5 years (IQR 1.71-6.1)]. One case developed apoplexy. Cumulative probability of micro-NFPA growth was 7.8% (95% CI, 4.9%-8.1%) and 14.5% (95% CI, 10.2%-18.8%) at 3 and 5 years, respectively, and of reduction 14.1% (95% CI, 10.4%-17.8%) and 21.3% (95% CI, 16.4%-26.2%) at 3 and 5 years, respectively. Median tumour enlargement was 2 mm (IQR 1-3) and 49% of micro-NFPAs that grew became macroadenomas (nearly all >5 mm at detection). Eight (1.9%) patients received surgery (only one had visual compromise with surgery required >3 years after micro-NFPA detection). Sex, age, and size at baseline were not predictors of enlargement/reduction. At the time of detection, 7.2%, 1.7%, and 1.5% patients had secondary hypogonadism, hypothyroidism, and hypoadrenalism, respectively. Two (0.6%) developed hypopituitarism during follow-up (after progression to macroadenoma). CONCLUSIONS: Probability of micro-NFPA growth is low, and the development of new hypopituitarism is rare. Delaying the first follow-up MRI to 3 years and avoiding hormonal re-evaluation in the absence of tumour growth or clinical manifestations is a safe approach for micro-NFPA surveillance.

Adjuvant lithium improves the efficacy of radioactive iodine treatment in Graves' and toxic nodular disease.

CONTEXT: Lithium increases iodine retention in the thyroid gland and inhibits thyroid hormone release. Although lithium has been reported to improve the efficacy of radioactive iodine (RAI) treatment in Graves' disease, its role as an adjunct to RAI treatment of hyperthyroidism, particularly in toxic nodular disease, remains contentious. OBJECTIVE: To assess whether adjuvant lithium increases the efficacy of a fixed dose RAI regimen in Graves' and toxic nodular hyperthyroid patients. DESIGN AND SETTING: Retrospective cohort study in a tertiary referral centre. Two hundred and four hyperthyroid patients (163 Graves' disease, 26 toxic multinodular goitre and 15 solitary toxic thyroid adenoma). INTERVENTION: One hundred and three patients received RAI alone (median dose 558 MBq). One hundred and one patients received RAI (median dose 571 MBq) with adjuvant lithium (800 mg/day for 10 days). MAIN OUTCOME MEASURE: Proportion of patients cured at any time over a 1-year period following RAI treatment. Cure was defined as sustained (two or more sequential time points) biochemical euthyroidism or hypothyroidism during the follow-up period. RESULTS: The likelihood of cure at any time was 60% greater in all hyperthyroid patients (Graves' plus toxic nodular disease) receiving adjuvant lithium (n = 204, P = 0·003). In patients with Graves' disease receiving RAI + lithium, there was a similar occurrence in cure (n = 163, P = 0·006). Cure was twice as likely in patients with toxic nodular (non-Graves') disease receiving RAI + lithium compared with RAI alone (n = 41, P = 0·01). CONCLUSIONS: This study supports the use of adjuvant lithium to improve the efficacy of RAI in the treatment of Grave's disease and suggests a novel role in the management of toxic nodular (non-Graves') disease.

Improved diagnostic accuracy for neuroendocrine neoplasms using two chromogranin A assays.

CONTEXT: Chromogranin A (Cg A) is the best available diagnostic marker for neuroendocrine neoplasms (NENs). However, clinical interpretation of Cg A results may be limited by considerable heterogeneity between commonly available Cg A assays. Variation in diagnostic accuracy of these assays largely reflects differences in antibody specificities. We compared the diagnostic utility of four Cg A assays [Imperial Supra-regional Assay Service radioimmunoassay (SAS) and three commercial assays, Cisbio, DAKO and Eurodiagnostica]. METHOD: Plasma Cg A was measured using these four assays in 125 patients with NENs, 41 patients with cancers other than NENs and 108 healthy controls. RESULT: There was no significant difference in diagnostic accuracy between any of the four assays alone and no single assay positively identified all patients with NEN. However, concordance between assays was variable. Cisbio and SAS assays were least concordant. We, therefore, hypothesized that using a combination of the least concordant Cg A assays will improve NEN diagnosis by detecting a larger number of Cg A epitopes and hence patients with NEN. Consistent with our hypothesis, multiple logistic regression analysis showed that the combination of Cisbio and SAS assays was more useful than any other combinations or any assay alone in predicting a NEN diagnosis. CONCLUSION: Although individually, all four Cg A assays are similarly useful for the measurement of Cg A in the diagnosis of a NEN, in patients with a suspected NEN, negative results by one assay should prompt analysis by a second assay. The combination of Cisbio and SAS assays may have greatest diagnostic utility.

Assessing Sarcopenia, Frailty, and Malnutrition in Community-Dwelling Dependant Older Adults-An Exploratory Home-Based Study of an Underserved Group in Research.

BACKGROUND: Adults of advanced age, with functional dependency, socioeconomic disadvantage, or a need for home care, are expected to be at high risk of sarcopenia, frailty and malnutrition, yet are likely to be underrepresented in research. We aimed to explore the assessment of sarcopenia, frailty, and malnutrition in-home, and to describe the practicality of performing these assessments. METHODS: Home-based health assessments and post-study feedback surveys were conducted among community-dwelling older adults ≥65 years in receipt of state-funded home care (n = 31). Assessments included probable sarcopenia [hand-grip strength (HGS), chair rise-test, and SARC-F case-finding tool], the Mini Nutritional Assessment (MNA), and the Clinical Frailty Scale (CFS). RESULTS: The study group was of mean age 83.2 ± 8.2 years, 74% were female and 23% lived in socioeconomically disadvantaged areas. Almost all met the criteria for probable sarcopenia (94%, n = 29/31), were frail or vulnerable by the CFS (97%, n = 30/31), and over a quarter were at risk of malnutrition (26%, n = 8). Participants had low physical activity (71.0%, n = 22/31), with a mean daytime average of 11.4 ± 1.6 h spent sitting. It was possible to assess probable sarcopenia (by HGS and SARC-F, but not the chair rise test), malnutrition (MNA), and frailty (CFS). Home-based research was a complex environment, and unearthed significant unmet need, prompting referrals to health services (36%, n = 11), in addition to technology assistance. The majority of participants (93%) reported a willingness to partake in future research. CONCLUSIONS: Most community-dwelling older people in receipt of home support, assessed in this exploratory study, were at risk of probable sarcopenia, frailty, and low physical activity, with over a quarter were at risk of malnutrition. Our initial findings provide practical data for large scale studies and may inform the development of intervention studies aiming to support ageing in place.

Effectiveness of short, personalised student assistantships: an evaluative study across eight London hospitals.

OBJECTIVES: Student assistantships are recommended to prepare medical graduates for clinical practice. Traditionally, assistantships have consisted of longer placements, often up to 15 weeks. However, within the constraints of the final year, medical schools need to carefully balance the time required for specialty placements, assessments and the risk of student burnout. We set out to evaluate the effectiveness of shorter, personalised student assistantships. DESIGN: An evaluative study on the changes in final year student confidence in preparedness for practice after a 3-week assistantship with defined learning objectives and learning needs assessment. SETTING: Eight hospitals affiliated with Imperial College School of Medicine. OUTCOMES: Student confidence in 10 learning outcomes including organising ward rounds, documentation, communication with colleagues, communication with patients and relatives, patient handover, practical procedures, patient management, acute care, prioritisation and out-of-hours clinical work. RESULTS: Two hundred and twenty final year medical students took part in the student assistantship, of whom 208 completed both the pre-assistantship and post-assistantship confidence rating questionnaires (95% completion rate). After the assistantship, 169 (81%) students expressed increased confidence levels in one or more learning objectives. For each individual learning objective, there was a significant change in the proportion of students who agreed or strongly agreed after the assistantship (p<0.0001). CONCLUSION: Overall, the focused 3-week, personalised student assistantships led to significant improvement across all learning objectives related to preparedness for practice. The use of the pre-assistantship confidence rating questionnaire allowed students to identify and target areas of learning needs during their assistantship.