A European Cost-Utility Analysis of the MiniMed™ 780G Advanced Hybrid Closed-Loop System Versus Intermittently Scanned Continuous Glucose Monitoring with Multiple Daily Insulin Injections in People Living with Type 1 Diabetes.

Background: Advanced hybrid closed-loop (AHCL) automated insulin delivery systems are the most effective therapy in terms of assisting people with type 1 diabetes (T1D) to achieve glycemic targets; however, the cost can represent a barrier to uptake. In this study, a cost-utility analysis of the MiniMed™ 780G AHCL system (MM780G) versus intermittently scanned continuous glucose monitoring (is-CGM) plus multiple daily insulin injections (MDI) in people with T1D not achieving glycemic goals was performed across six European countries. Methods: Clinical input data were sourced from the ADAPT trial. Assuming a baseline HbA1c of 9.04%, HbA1c reductions of 1.54% for AHCL and 0.2% for is-CGM+MDI were modeled. The analyses were performed from a payer perspective over a time horizon of 40 years and an annual discount rate of 3% was applied. Results: Across all countries, the use of AHCL was projected to result in an incremental gain in quality-adjusted life expectancy of >2 quality-adjusted life years (QALYs) versus is-CGM+MDI. Lifetime direct costs were higher with AHCL resulting in incremental cost-utility ratios for AHCL versus is-CGM+MDI ranging from EUR 11,765 per QALY gained in Austria to EUR 43,963 per QALY gained in Italy. Conclusions: For people with T1D managed with is-CGM+MDI not achieving glycemic targets, initiation of the MM780G system was projected to improve long-term clinical outcomes; however, due to differences in health care costs between countries, the health economic outcomes differed. In all included countries, AHCL is likely to be cost-effective relative to is-CGM+MDI for people not achieving glycemic goals with is-CGM+MDI. The ADAPT trial is registered with ClinicalTrials.gov, NCT04235504.

Analysis of Escherichia coli O157 strains in cattle and humans between Scotland and England & Wales: implications for human health.

For the last two decades, the human infection frequency of Escherichia coli O157 (O157) in Scotland has been 2.5-fold higher than in England and Wales. Results from national cattle surveys conducted in Scotland and England and Wales in 2014/2015 were combined with data on reported human clinical cases from the same time frame to determine if strain differences in national populations of O157 in cattle could be associated with higher human infection rates in Scotland. Shiga toxin subtype (Stx) and phage type (PT) were examined within and between host (cattle vs human) and nation (Scotland vs England and Wales). For a subset of the strains, whole genome sequencing (WGS) provided further insights into geographical and host association. All three major O157 lineages (I, II, I/II) and most sub-lineages (Ia, Ib, Ic, IIa, IIb, IIc) were represented in cattle and humans in both nations. While the relative contribution of different reservoir hosts to human infection is unknown, WGS analysis indicated that the majority of O157 diversity in human cases was captured by isolates from cattle. Despite comparable cattle O157 prevalence between nations, strain types were localized. PT21/28 (sub-lineage Ic, Stx2a+) was significantly more prevalent in Scottish cattle [odds ratio (OR) 8.7 (2.3-33.7; P<0.001] and humans [OR 2.2 (1.5-3.2); P<0.001]. In England and Wales, cattle had a significantly higher association with sub-lineage IIa strains [PT54, Stx2c; OR 5.6 (1.27-33.3); P=0.011] while humans were significantly more closely associated with sub-lineage IIb [PT8, Stx1 and Stx2c; OR 29 (4.9-1161); P<0.001]. Therefore, cattle farms in Scotland were more likely to harbour Stx2a+O157 strains compared to farms in E and W (P<0.001). There was evidence of limited cattle strain migration between nations and clinical isolates from one nation were more similar to cattle isolates from the same nation, with sub-lineage Ic (mainly PT21/28) exhibiting clear national association and evidence of local transmission in Scotland. While we propose the higher rate of O157 clinical cases in Scotland, compared to England and Wales, is a consequence of the nationally higher level of Stx2a+O157 strains in Scottish cattle, we discuss the multiple additional factors that may also contribute to the different infection rates between these nations.

Genomic epidemiology of SARS-CoV-2 in a university outbreak setting and implications for public health planning.

Whole genome sequencing of SARS-CoV-2 has occurred at an unprecedented scale, and can be exploited for characterising outbreak risks at the fine-scale needed to inform control strategies. One setting at continued risk of COVID-19 outbreaks are higher education institutions, associated with student movements at the start of term, close living conditions within residential halls, and high social contact rates. Here we analysed SARS-CoV-2 whole genome sequences in combination with epidemiological data to investigate a large cluster of student cases associated with University of Glasgow accommodation in autumn 2020, Scotland. We identified 519 student cases of SARS-CoV-2 infection associated with this large cluster through contact tracing data, with 30% sequencing coverage for further analysis. We estimated at least 11 independent introductions of SARS-CoV-2 into the student population, with four comprising the majority of detected cases and consistent with separate outbreaks. These four outbreaks were curtailed within a week following implementation of control measures. The impact of student infections on the local community was short-term despite an underlying increase in community infections. Our study highlights the need for context-specific information in the formation of public health policy for higher educational settings.

A scoping review of risk factors and transmission routes associated with human giardiasis outbreaks in high-income settings.

The flagellated pathogen Giardia duodenalis is one of the leading causes of parasitic gastrointestinal illness worldwide. In many higher income countries, such as the United Kingdom, the disease is often perceived as being travel-related, likely leading to the under-reporting of sporadic cases and outbreaks. A summary of the literature describing outbreaks and risk factors in higher income countries is necessary to improve our understanding of this pathogen and identify existing knowledge gaps. Initial literature searches were carried out in September 2016 and updated at regular intervals until November 2021, using appropriate search terms in Medline, Embase and PubMed databases. A total of 75 papers met the inclusion criteria, revealing that the consumption of contaminated water and contact with young children of diaper-wearing age were the most common transmission routes leading to outbreaks of giardiasis. Of the ten studies where food was primarily associated with outbreaks, food handlers accounted for eight of these. Another reported transmission route was direct contact with fecal material, which was reported in six studies as the primary transmission route. Travel-associated giardiasis was considered the sole transmission route in two studies, whereas multiple transmission routes contributed to giardiasis outbreaks in eleven studies. The evidence around zoonotic transmission was less clear and hampered by the lack of robust and regularly applied parasite molecular typing techniques. This literature review summarizes the findings of Giardia outbreak investigations and epidemiological studies in high-income countries. Transmission routes are identified and discussed to highlight the associated risk factors. These data also indicate gaps in our current knowledge that include the need for robust, in-depth molecular studies and have underscored the importance of water as a transmission route for Giardia cysts. These future molecular studies will improve our understanding of Giardia epidemiology and transmission pathways in higher income countries to prevent spread of this significantly under-reported pathogen.

Epidemiology and genomic analysis of Shiga toxin-producing Escherichia coli clonal complex 165 in the UK.

Introduction. Shiga toxin-producing Escherichia coli (STEC) is a zoonotic, foodborne gastrointestinal pathogen that has the potential to cause severe clinical outcomes, including haemolytic uraemic syndrome (HUS). STEC-HUS is the leading cause of renal failure in children and can be fatal. Over the last decade, STEC clonal complex 165 (CC165) has emerged as a cause of STEC-HUS.Gap Statement. There is a need to understand the pathogenicity and prevalence of this emerging STEC clonal complex in the UK, to facilitate early diagnosis, improve clinical management, and prevent and control outbreaks.Aim. The aim of this study was to characterize CC165 through identification of virulence factors (VFs) and antimicrobial resistance (AMR) determinants in the genome and to integrate the genome data with the available epidemiological data to better understand the incidence and pathogenicity of this clonal complex in the UK.Methodology. All isolates belonging to CC165 in the archives at the UK public health agencies were sequenced and serotyped, and the virulence gene and AMR profiles were derived from the genome using PHE bioinformatics pipelines and the Centre for Genomic Epidemiology virulence database.Results. There were 48 CC165 isolates, of which 43 were STEC, four were enteropathogenic E. coli (EPEC) and one E. coli. STEC serotypes were predominately O80:H2 (n=28), and other serotypes included O45:H2 (n=9), O55:H9 (n=4), O132:H2 (n=1) and O180:H2 (n=1). All but one STEC isolate had Shiga toxin (stx) subtype stx2a or stx2d and 47/48 isolates had the eae gene encoding intimin involved in the intimate attachment of the bacteria to the human gut mucosa. We detected extra-intestinal virulence genes including those associated with iron acquisition (iro) and serum resistance (iss), indicating that this pathogen has the potential to translocate to extra-intestinal sites. Unlike other STEC clonal complexes, a high proportion of isolates (93%, 40/43) were multidrug-resistant, including resistance to aminoglycosides, beta-lactams, chloramphenicol, sulphonamides, tetracyclines and trimethoprim.Conclusion. The clinical significance of this clonal complex should not be underestimated. Exhibiting high levels of AMR and a combination of STEC and extra-intestinal pathogenic E. coli (ExPEC) virulence profiles, this clonal complex is an emerging threat to public health.

Epidemiological investigations identified an outbreak of Shiga toxin-producing Escherichia coli serotype O26:H11 associated with pre-packed sandwiches.

In October 2019, public health surveillance systems in Scotland identified an increase in the number of reported infections of Shiga toxin-producing Escherichia coli (STEC) O26:H11 involving bloody diarrhoea. Ultimately, across the United Kingdom (UK) 32 cases of STEC O26:H11 stx1a were identified, with the median age of 27 years and 64% were male; six cases were hospitalised. Among food exposures there was an association with consuming pre-packed sandwiches purchased at outlets belonging to a national food chain franchise (food outlet A) [odds ratio (OR) = 183.89, P < 0.001]. The common ingredient identified as a component of the majority of the sandwiches sold at food outlet A was a mixed salad of Apollo and Iceberg lettuce and spinach leaves. Microbiological testing of food and environmental samples were negative for STEC O26:H11, although STEC O36:H19 was isolated from a mixed salad sample taken from premises owned by food outlet A. Contamination of fresh produce is often due to a transient event and detection of the aetiological agent in food that has a short-shelf life is challenging. Robust, statistically significant epidemiological analysis should be sufficient evidence to direct timely and targeted on-farm investigations. A shift in focus from testing the microbiological quality of the produce to investigating the processes and practices through the supply chain and sampling the farm environment is recommended.

Evaluation of the Long-Term Cost-Effectiveness of the Dexcom G6 Continuous Glucose Monitor versus Self-Monitoring of Blood Glucose in People with Type 1 Diabetes in Canada.

BACKGROUND: The Dexcom G6 real-time continuous glucose monitoring (RT-CGM) system is one of the most sophisticated RT-CGM systems developed to date and became available in Canada in 2019. A health economic analysis was performed to determine the long-term cost-effectiveness of the Dexcom G6 RT-CGM system versus SMBG in adults with type 1 diabetes (T1D) in Canada. METHODS: The analysis was performed using the IQVIA Core Diabetes Model. Based on clinical trial data, patients with mean baseline HbA1c of 8.6% were assumed to have a HbA1c reduction of 1.0% with RT-CGM versus 0.4% reduction with SMBG. RT-CGM was also associated with a quality of life (QoL) benefit owing to reduced incidence of hypoglycemia, reduced fear of hypoglycemia (FoH) and elimination of fingerstick testing. Direct medical costs were sourced from published literature, and inflated to 2019 Canadian dollars (CAD). RESULTS: Dexcom G6 RT-CGM was projected to improve mean quality-adjusted life expectancy by 2.09 quality-adjusted life years (QALYs) relative to SMBG (15.52 versus 13.43 QALYs) but mean total lifetime cots were CAD 35,353 higher with RT-CGM (CAD 227,357 versus CAD 192,004) resulting in an incremental cost-effectiveness ratio (ICER) of CAD 16,931 per QALY gained. Sensitivity analyses revealed that assumptions relating to the QoL benefit associated with reduced FoH and the elimination of fingerstick testing with RT-CGM as well as SMBG usage and change in HbA1c were the key drivers of cost-effectiveness. CONCLUSION: For adults with T1D in Canada, RT-CGM is associated with improved glycemic control and QoL benefits owing to a reduced FoH and elimination of the requirement for fingerstick testing and over a lifetime time horizon is cost-effective relative to SMBG.

Influence of socioeconomic deprivation on interventions and outcomes for patients admitted with COVID-19 to critical care units in Scotland: A national cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to significant respiratory failure with between 14% and 18% of hospitalised patients requiring critical care admission. This study describes the impact of socioeconomic deprivation on 30-day survival following critical care admission for COVID-19, and the impact of the COVID-19 pandemic on critical care capacity in Scotland. METHODS: This cohort study used linked national hospital records including ICU, virology testing and national death records to identify and describe patients with COVID-19 admitted to critical care units in Scotland. Multivariable logistic regression was used to assess the impact of deprivation on 30-day mortality. Critical care capacity was described by reporting the percentage of baseline ICU bed utilisation required. FINDINGS: There were 735 patients with COVID-19 admitted to critical care units across Scotland from 1/3/2020 to 20/6/2020. There was a higher proportion of patients from more deprived areas, with 183 admissions (24.9%) from the most deprived quintile and 100 (13.6%) from the least deprived quintile. Overall, 30-day mortality was 34.8%. After adjusting for age, sex and ethnicity, mortality was significantly higher in patients from the most deprived quintile (OR 1.97, 95%CI 1.13, 3.41, p=0.016). ICUs serving populations with higher levels of deprivation spent a greater amount of time over their baseline ICU bed capacity. INTERPRETATION: Patients with COVID-19 living in areas with greatest socioeconomic deprivation had a higher frequency of critical care admission and a higher adjusted 30-day mortality. ICUs in health boards with higher levels of socioeconomic deprivation had both higher peak occupancy and longer duration of occupancy over normal maximum capacity. FUNDING: None.

Evidence of on-going transmission of Shiga toxin-producing Escherichia coli O157:H7 following a foodborne outbreak.

In August 2019, public health surveillance systems in Scotland and England identified seven, geographically dispersed cases infected with the same strain (defined as isolates that fell within the same five single nucleotide polymorphism single linage cluster) of Shiga toxin-producing Escherichia coli O157:H7. Epidemiological analysis of enhanced surveillance questionnaire data identified handling raw beef and shopping from the same national retailer (retailer A) as the common exposure. Concurrently, a microbiological survey of minced beef at retail identified the same strain in a sample of minced beef sold by retailer A, providing microbiological evidence of the link. Between September and November 2019, a further four primary and two secondary cases infected with the same strain were identified; two cases developed haemolytic uraemic syndrome. None of the four primary cases reported consumption of beef from retailer A and the transmission route of these subsequent cases was not identified, although all four primary cases visited the same petting farm. Generally, outbreaks of STEC O157:H7 in the UK appear to be distinct, short-lived events; however, on-going transmission linked to contaminated food, animals or environmental exposures and person-to-person contact do occur. Although outbreaks of STEC caused by contaminated fresh produce are increasingly common, undercooked meat products remain a risk of infection.

Listeria infection in young infants: results from a national surveillance study in the UK and Ireland.

OBJECTIVES: To describe the epidemiology, age at infection, clinical characteristics and outcome of listeria infection in young infants to inform management and empiric antibiotic choice in young infants. DESIGN: Prospective 2-year surveillance of Listeria monocytogenes infection in young infants detected through the British Paediatric Surveillance Unit 'orange card' system and triangulated with the public health laboratories. SETTING: National population study (England, Wales, Scotland and the Ireland) PATIENTS: All infants under 90 days with proven or probable invasive listeriosis MAIN OUTCOME MEASURES: Incidence, mortality, age of infection, clinical characteristics and outcome RESULTS: During a 2-year period (2017-2019), 27 cases of listeriosis in infants <90 days of age were reported. The incidence of listeriosis in this study was 1.8 per 100 000 live births with 7% mortality (2/27). Nearly all cases presented within the first 24 hours of life (26/27). The majority (20/27, 74%) were born preterm and 16/24 (67%) were born to women from ethnic minority backgrounds. CONCLUSIONS: Invasive listeriosis in young infants in the UK and Ireland is rare and presents early in the neonatal period. National guidelines that recommend the use of amoxicillin as part of empiric regimes for sepsis and meningitis in infants over 1 month of age should be modified.

Relation of severe COVID-19 to polypharmacy and prescribing of psychotropic drugs: the REACT-SCOT case-control study.

BACKGROUND: The objective of this study was to investigate the relation of severe COVID-19 to prior drug prescribing. METHODS: Severe cases were defined by entry to critical care or fatal outcome. For this matched case-control study (REACT-SCOT), all 4251 cases of severe COVID-19 in Scotland since the start of the epidemic were matched for age, sex and primary care practice to 36,738 controls from the population register. Records were linked to hospital discharges since June 2015 and dispensed prescriptions issued in primary care during the last 240 days. RESULTS: Severe COVID-19 was strongly associated with the number of non-cardiovascular drug classes dispensed. This association was strongest in those not resident in a care home, in whom the rate ratio (95% CI) associated with dispensing of 12 or more drug classes versus none was 10.8 (8.8, 13.3), and in those without any of the conditions designated as conferring increased risk of COVID-19. Of 17 drug classes postulated at the start of the epidemic to be "medications compromising COVID", all were associated with increased risk of severe COVID-19 and these associations were present in those without any of the designated risk conditions. The fraction of cases in the population attributable to exposure to these drug classes was 38%. The largest effect was for antipsychotic agents: rate ratio 4.18 (3.42, 5.11). Other drug classes with large effects included proton pump inhibitors (rate ratio 2.20 (1.72, 2.83) for = 2 defined daily doses/day), opioids (3.66 (2.68, 5.01) for = 50 mg morphine equivalent/day) and gabapentinoids. These associations persisted after adjusting for covariates and were stronger with recent than with non-recent exposure. CONCLUSIONS: Severe COVID-19 is associated with polypharmacy and with drugs that cause sedation, respiratory depression, or dyskinesia; have anticholinergic effects; or affect the gastrointestinal system. These associations are not easily explained by co-morbidity. Measures to reduce the burden of mortality and morbidity from COVID-19 should include reinforcing existing guidance on reducing overprescribing of these drug classes and limiting inappropriate polypharmacy. REGISTRATION: ENCEPP number EUPAS35558.

Lutetium oxodotreotide (177Lu-Dotatate) for the treatment of unresectable or metastatic progressive gastroenteropancreatic neuroendocrine tumors: a cost-effectiveness analysis for Scotland.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogenous group of tumors. Findings from the phase III NETTER-1 trial showed that treatment of unresectable/metastatic progressive gastrointestinal (GI) NETs with 177Lu-Dotatate resulted in a significant improvement in progression-free survival (PFS) and overall survival (OS) compared with best supportive care (BSC) with high dose octreotide long-acting repeatable (LAR) 60 mg. A health economic analysis was performed using input data from clinical studies and data derived from an indirect comparison to determine the cost-effectiveness of 177Lu-Dotatate in the treatment of GI-NETs and pancreatic NETs (P-NETs) in Scotland. METHODS: Cost-effectiveness analysis was performed from the payer perspective using a three-state partitioned survival model. In the base case 177Lu-Dotatate was compared with BSC in gastrointestinal (GI)-NETs using clinical data from the NETTER-1 trial. A secondary analysis comparing 177Lu-Dotatate with BSC, everolimus or sunitinib in patients with P-NETs was also performed using hazard ratios inferred from indirect comparisons. The base case analysis was performed over a 20-year time horizon with an annual discount rate of 3.5% for both costs and clinical outcomes. RESULTS: For unresectable/metastatic progressive GI-NETs treatment with 177Lu-Dotatate led to a gain in quality-adjusted life expectancy of 1.33 quality-adjusted life years (QALYs) compared with BSC due to extended PFS and OS. Mean total lifetime costs were GBP 35,701 higher with 177Lu-Dotatate, leading to an incremental cost-effectiveness ratio (ICER) of GBP 26,830 per QALY gained. In analyses in patients with P-NETs 177Lu-Dotatate was associated with ICERs below GBP 30,000 per QALY gained in comparisons with BSC, sunitinib and everolimus. CONCLUSIONS: Cost-effectiveness analyses demonstrated that, in Scotland, from the payer perspective, 177Lu-Dotatate at the set acquisition cost is a cost-effective treatment option for patients with unresectable or metastatic progressive GI-NETs or P-NETs.

Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland.

BACKGROUND: We aimed to ascertain the cumulative risk of fatal or critical care unit-treated COVID-19 in people with diabetes and compare it with that of people without diabetes, and to investigate risk factors for and build a cross-validated predictive model of fatal or critical care unit-treated COVID-19 among people with diabetes. METHODS: In this cohort study, we captured the data encompassing the first wave of the pandemic in Scotland, from March 1, 2020, when the first case was identified, to July 31, 2020, when infection rates had dropped sufficiently that shielding measures were officially terminated. The participants were the total population of Scotland, including all people with diabetes who were alive 3 weeks before the start of the pandemic in Scotland (estimated Feb 7, 2020). We ascertained how many people developed fatal or critical care unit-treated COVID-19 in this period from the Electronic Communication of Surveillance in Scotland database (on virology), the RAPID database of daily hospitalisations, the Scottish Morbidity Records-01 of hospital discharges, the National Records of Scotland death registrations data, and the Scottish Intensive Care Society and Audit Group database (on critical care). Among people with fatal or critical care unit-treated COVID-19, diabetes status was ascertained by linkage to the national diabetes register, Scottish Care Information Diabetes. We compared the cumulative incidence of fatal or critical care unit-treated COVID-19 in people with and without diabetes using logistic regression. For people with diabetes, we obtained data on potential risk factors for fatal or critical care unit-treated COVID-19 from the national diabetes register and other linked health administrative databases. We tested the association of these factors with fatal or critical care unit-treated COVID-19 in people with diabetes, and constructed a prediction model using stepwise regression and 20-fold cross-validation. FINDINGS: Of the total Scottish population on March 1, 2020 (n=5 463 300), the population with diabetes was 319 349 (5·8%), 1082 (0·3%) of whom developed fatal or critical care unit-treated COVID-19 by July 31, 2020, of whom 972 (89·8%) were aged 60 years or older. In the population without diabetes, 4081 (0·1%) of 5 143 951 people developed fatal or critical care unit-treated COVID-19. As of July 31, the overall odds ratio (OR) for diabetes, adjusted for age and sex, was 1·395 (95% CI 1·304-1·494; p<0·0001, compared with the risk in those without diabetes. The OR was 2·396 (1·815-3·163; p<0·0001) in type 1 diabetes and 1·369 (1·276-1·468; p<0·0001) in type 2 diabetes. Among people with diabetes, adjusted for age, sex, and diabetes duration and type, those who developed fatal or critical care unit-treated COVID-19 were more likely to be male, live in residential care or a more deprived area, have a COVID-19 risk condition, retinopathy, reduced renal function, or worse glycaemic control, have had a diabetic ketoacidosis or hypoglycaemia hospitalisation in the past 5 years, be on more anti-diabetic and other medication (all p<0·0001), and have been a smoker (p=0·0011). The cross-validated predictive model of fatal or critical care unit-treated COVID-19 in people with diabetes had a C-statistic of 0·85 (0·83-0·86). INTERPRETATION: Overall risks of fatal or critical care unit-treated COVID-19 were substantially elevated in those with type 1 and type 2 diabetes compared with the background population. The risk of fatal or critical care unit-treated COVID-19, and therefore the need for special protective measures, varies widely among those with diabetes but can be predicted reasonably well using previous clinical history. FUNDING: None.

Long-Term Cost-Effectiveness the Dexcom G6 Real-Time Continuous Glucose Monitoring System Compared with Self-Monitoring of Blood Glucose in People with Type 1 Diabetes in France.

INTRODUCTION: The aim was to determine the long-term cost-effectiveness of the Dexcom G6 real-time continuous glucose monitoring (RT-CGM) system versus self-monitoring of blood glucose (SMBG) in adults with type 1 diabetes (T1D) in France. METHODS: The analysis was performed using the IQVIA Core Diabetes Model and utilized clinical input data from the DIAMOND clinical trial in adults with T1D. Simulated patients were assumed to have a mean baseline HbA1c of 8.6%, and those in the RT-CGM arm were assumed to have a HbA1c reduction of 1.0% compared with 0.4% in the SMBG arm. A quality of life (QoL) benefit associated with a reduced fear of hypoglycemia (FoH) and elimination of the requirement for fingerstick testing in the RT-CGM arm was also applied. RESULTS: The G6 RT-CGM system was associated with an incremental gain in quality-adjusted life expectancy of 1.38 quality-adjusted life years (QALYs) compared with SMBG (10.64 QALYs versus 9.23 QALYs). Total mean lifetime costs were 21,087 euros higher with RT-CGM (148,077 euros versus 126,990 euros), resulting in an incremental cost-effectiveness ratio of 15,285 euros per QALY gained. CONCLUSIONS: In France, based on a willingness-to-pay threshold of 50,000 euros per QALY gained, the use of the G6 RT-CGM system is cost-effective relative to SMBG for adults with long-standing T1D, driven primarily by improved glycemic control and the QoL benefit associated with reduced FoH and elimination of the requirement for fingerstick testing.

Rapid Epidemiological Analysis of Comorbidities and Treatments as risk factors for COVID-19 in Scotland (REACT-SCOT): A population-based case-control study.

BACKGROUND: The objectives of this study were to identify risk factors for severe coronavirus disease 2019 (COVID-19) and to lay the basis for risk stratification based on demographic data and health records. METHODS AND FINDINGS: The design was a matched case-control study. Severe COVID-19 was defined as either a positive nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the national database followed by entry to a critical care unit or death within 28 days or a death certificate with COVID-19 as underlying cause. Up to 10 controls per case matched for sex, age, and primary care practice were selected from the national population register. For this analysis-based on ascertainment of positive test results up to 6 June 2020, entry to critical care up to 14 June 2020, and deaths registered up to 14 June 2020-there were 36,948 controls and 4,272 cases, of which 1,894 (44%) were care home residents. All diagnostic codes from the past 5 years of hospitalisation records and all drug codes from prescriptions dispensed during the past 240 days were extracted. Rate ratios for severe COVID-19 were estimated by conditional logistic regression. In a logistic regression using the age-sex distribution of the national population, the odds ratios for severe disease were 2.87 for a 10-year increase in age and 1.63 for male sex. In the case-control analysis, the strongest risk factor was residence in a care home, with rate ratio 21.4 (95% CI 19.1-23.9, p = 8 × 10-644). Univariate rate ratios for conditions listed by public health agencies as conferring high risk were 2.75 (95% CI 1.96-3.88, p = 6 × 10-9) for type 1 diabetes, 1.60 (95% CI 1.48-1.74, p = 8 × 10-30) for type 2 diabetes, 1.49 (95% CI 1.37-1.61, p = 3 × 10-21) for ischemic heart disease, 2.23 (95% CI 2.08-2.39, p = 4 × 10-109) for other heart disease, 1.96 (95% CI 1.83-2.10, p = 2 × 10-78) for chronic lower respiratory tract disease, 4.06 (95% CI 3.15-5.23, p = 3 × 10-27) for chronic kidney disease, 5.4 (95% CI 4.9-5.8, p = 1 × 10-354) for neurological disease, 3.61 (95% CI 2.60-5.00, p = 2 × 10-14) for chronic liver disease, and 2.66 (95% CI 1.86-3.79, p = 7 × 10-8) for immune deficiency or suppression. Seventy-eight percent of cases and 52% of controls had at least one listed condition (51% of cases and 11% of controls under age 40). Severe disease was associated with encashment of at least one prescription in the past 9 months and with at least one hospital admission in the past 5 years (rate ratios 3.10 [95% CI 2.59-3.71] and 2.75 [95% CI 2.53-2.99], respectively) even after adjusting for the listed conditions. In those without listed conditions, significant associations with severe disease were seen across many hospital diagnoses and drug categories. Age and sex provided 2.58 bits of information for discrimination. A model based on demographic variables, listed conditions, hospital diagnoses, and prescriptions provided an additional 1.07 bits (C-statistic 0.804). A limitation of this study is that records from primary care were not available. CONCLUSIONS: We have shown that, along with older age and male sex, severe COVID-19 is strongly associated with past medical history across all age groups. Many comorbidities beyond the risk conditions designated by public health agencies contribute to this. A risk classifier that uses all the information available in health records, rather than only a limited set of conditions, will more accurately discriminate between low-risk and high-risk individuals who may require shielding until the epidemic is over.

Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study.

OBJECTIVE: To assess the risk of hospital admission for coronavirus disease 2019 (covid-19) among patient facing and non-patient facing healthcare workers and their household members. DESIGN: Nationwide linkage cohort study. SETTING: Scotland, UK, 1 March to 6 June 2020. PARTICIPANTS: Healthcare workers aged 18-65 years, their households, and other members of the general population. MAIN OUTCOME MEASURE: Admission to hospital with covid-19. RESULTS: The cohort comprised 158 445 healthcare workers, most of them (90 733; 57.3%) being patient facing, and 229 905 household members. Of all hospital admissions for covid-19 in the working age population (18-65 year olds), 17.2% (360/2097) were in healthcare workers or their households. After adjustment for age, sex, ethnicity, socioeconomic deprivation, and comorbidity, the risk of admission due to covid-19 in non-patient facing healthcare workers and their households was similar to the risk in the general population (hazard ratio 0.81 (95% confidence interval 0.52 to 1.26) and 0.86 (0.49 to 1.51), respectively). In models adjusting for the same covariates, however, patient facing healthcare workers, compared with non-patient facing healthcare workers, were at higher risk (hazard ratio 3.30, 2.13 to 5.13), as were household members of patient facing healthcare workers (1.79, 1.10 to 2.91). After sub-division of patient facing healthcare workers into those who worked in "front door," intensive care, and non-intensive care aerosol generating settings and other, those in front door roles were at higher risk (hazard ratio 2.09, 1.49 to 2.94). For most patient facing healthcare workers and their households, the estimated absolute risk of hospital admission with covid-19 was less than 0.5%, but it was 1% and above in older men with comorbidity. CONCLUSIONS: Healthcare workers and their households contributed a sixth of covid-19 cases admitted to hospital. Although the absolute risk of admission was low overall, patient facing healthcare workers and their household members had threefold and twofold increased risks of admission with covid-19.

Cost-effectiveness of Lutetium [177Lu] oxodotreotide versus best supportive care with octreotide in patients with midgut neuroendocrine tumors in France.

BACKGROUND AND AIMS: In France, there are approximately 2,400 new cases of neuroendocrine tumors (NETs) annually. Peptide receptor radionuclide therapy with 177Lu-Dotatate plus long-acting repeatable [LAR] octreotide 30 mg has been shown to significantly improve progression-free survival and overall survival relative to high-dose octreotide LAR 60 mg in patients with unresectable or metastatic progressive midgut NETs. A long-term cost-effectiveness analysis was performed to assess whether 177Lu-Dotatate is a cost-effective option versus octreotide 60 mg for patients with unresectable/metastatic progressive midgut NETs from the perspective of French healthcare payer. METHODS: The analysis was performed using a three-state partitioned survival model. In the base case analysis 177Lu-Dotatate plus octreotide LAR 30 mg was compared with high-dose octreotide LAR 60 mg in patients with midgut NETs. Survival data were obtained from the phase III NETTER-1 trial in patients with metastatic midgut NETs. Future costs and clinical outcomes were discounted at 4% per annum. One-way deterministic and probabilistic sensitivity analyses were performed. RESULTS: In the base case analysis, for patients with midgut NETs, 177Lu-Dotatate treatment improved quality-adjusted life expectancy by 1.21 quality-adjusted life years (QALYs) relative to octreotide LAR 60 mg and the lifetime treatment costs were EUR 50,784 higher with 177Lu-Dotatate resulting in an incremental cost-effectiveness ratio (ICER) of EUR 42,106 per QALY gained versus octreotide LAR 60 mg. When compared with everolimus, 177Lu-Dotatate was associated with an ICER of EUR 59,769 per QALY gained. Sensitivity analyses showed that the results were sensitive to methods used to extrapolate survival data. CONCLUSIONS: For patients with advanced progressive midgut NETs 177Lu-Dotatate is likely to be considered a cost-effective option versus octreotide 60 mg from the perspective of the French healthcare payer.

Dysregulation of protein degradation in the hippocampus is associated with impaired spatial memory during the development of obesity.

Studies have shown that long-term exposure to high fat and other obesogenic diets results in insulin resistance and altered blood brain barrier permeability, dysregulation of intracellular signaling mechanisms, changes in DNA methylation levels and gene expression, and increased oxidative stress and neuroinflammation in the hippocampus, all of which are associated with impaired spatial memory. The ubiquitin-proteasome system controls the majority of protein degradation in cells and is a critical regulator of synaptic plasticity and memory formation. Yet, whether protein degradation in the hippocampus becomes dysregulated following weight gain and is associated with obesity-induced memory impairments is unknown. Here, we used a high fat diet procedure in combination with behavioral and subcellular fractionation protocols and a variety of biochemical assays to determine if ubiquitin-proteasome activity becomes altered in the hippocampus during obesity development and whether this is associated with impaired spatial memory. We found that only 6 weeks of exposure to a high fat diet was sufficient to impair performance on an object location task in rats and resulted in dynamic dysregulation of ubiquitin-proteasome activity in the nucleus and cytoplasm of cells in the hippocampus. Furthermore, these changes in the protein degradation process extended into cortical regions also involved in spatial memory formation. Collectively, these results indicate that weight gain-induced memory impairments may be due to altered ubiquitin-proteasome signaling that occurs during the early stages of obesity development.

Long-term Cost-Effectiveness of Dexcom G6 Real-time Continuous Glucose Monitoring Versus Self-Monitoring of Blood Glucose in Patients With Type 1 Diabetes in the U.K.

OBJECTIVE: A long-term health economic analysis was performed to establish the cost-effectiveness of real-time continuous glucose monitoring (RT-CGM) (Dexcom G6) versus self-monitoring of blood glucose (SMBG) alone in U.K.-based patients with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: The analysis used the IQVIA CORE Diabetes Model. Clinical input data were sourced from the DIAMOND trial in adults with T1D. Simulations were performed separately in the overall population of patients with baseline HbA1c ≥7.5% (58 mmol/mol), and a secondary analysis was performed in patients with baseline HbA1c ≥8.5% (69 mmol/mol). The analysis was performed from the National Health Service health care payer perspective over a lifetime time horizon. RESULTS: In the overall population, G6 RT-CGM was associated with a mean incremental gain in quality-adjusted life expectancy of 1.49 quality-adjusted life years (QALYs) versus SMBG (mean [SD] 11.47 [2.04] QALYs versus 9.99 [1.84] QALYs). Total mean (SD) lifetime costs were also pounds sterling (GBP) 14,234 higher with RT-CGM (GBP 102,468 [35,681] versus GBP 88,234 [39,027]) resulting in an incremental cost-effectiveness ratio of GBP 9,558 per QALY gained. Sensitivity analyses revealed that the findings were sensitive to changes in the quality-of-life benefit associated with reduced fear of hypoglycemia and avoidance of fingerstick testing as well as the HbA1c benefit associated with RT-CGM use. CONCLUSIONS: For U.K.-based T1D patients, the G6 RT-CGM device is associated with significant improvements in clinical outcomes and, over patient lifetimes, is a cost-effective disease management option relative to SMBG on the basis of a willingness-to-pay threshold of GBP 20,000 per QALY gained.

An update on the incidence of human giardiasis in Scotland, 2011-2018.

BACKGROUND: Giardia duodenalis is one of the most common parasites in the UK to cause diarrhoeal illness. Giardiasis is likely to be significantly under-reported in the UK as laboratory testing is largely based on examining stool samples from individuals with a recent travel history. This results in the majority of locally-acquired cases going undetected. To increase awareness of giardiasis, we describe data gathered from cases reported within Scotland during 2011-2018. METHODS: All of the 21 Scottish National Health Service (NHS) diagnostic microbiology laboratories performed microscopy examination to detect Giardia cysts in stools, from mostly travel-related cases. The exception was one laboratory that implemented an antigen-based enzyme immunoassay in 2015. This resulted in every submitted stool being tested for Giardia. Laboratory-confirmed cases of giardiasis were reported to Health Protection Scotland (HPS) via the Electronic Communication of Surveillance in Scotland (ECOSS) during the eight-year period. Data for calculating the incidence per 100,000 of the population were obtained from the National Records of Scotland mid-2018 population estimates in Scotland. RESULTS: A total of 1631 Scottish cases were reported during 2011-2018 (8-year mean: 204; range: 166-269). National Health Service Grampian, Borders and Lothian reported the highest incidence of Giardia (9.8, 7.5 and 6.7 per 100,000, respectively), all of which were above the Scottish mean incidence (3.8 per 100,000). Following the implementation of antigen testing in NHS Grampian during 2015, reports significantly increased 3.6-fold (P = 0.005). The highest incidence of giardiasis occurred in the 20-49 years age group (mean 5.4 per 100,000). Of interest, the mean incidence of giardiasis was significantly higher in males than in females (4.8 versus 3.1 per 100,000, respectively; P < 0.0001). CONCLUSIONS: This report highlights the need to capture enhanced information on every laboratory-confirmed case of giardiasis to gain a better understanding of the local sources and transmission pathways occurring in Scotland. In addition, implementing sensitive, automated technologies across UK NHS diagnostic microbiology laboratories to permit the efficient, routine testing of every submitted stool for Giardia, should be encouraged to ensure all cases are identified and treated appropriately.