When compared to the general population, people living with Severe Mental Illness are 1.8 times more likely to have obesity while in adult mental health secure units, rates of obesity are 20% higher than the general population. In England there are currently 490,000 people living with SMI. The aim of this systematic review was to collate and synthesise the available quantitative and qualitative evidence on a broad range of weight management interventions for adults living with severe mental illness and overweight or obesity. Primary outcomes were reductions in BMI and body weight. Following sifting, 18 papers were included in the final review, which detailed the results of 19 different interventions, however there was a lack of qualitative evidence. Pooled results for three studies (MD -3.49, 95% CI -6.85, -0.13, p=0.04), indicated a small effect in terms of body weight reduction but no effect on BMI for four studies (MD -0.42, 95% CI -1.27, 0.44, p=0.34). Key recommendations for future research included integration of qualitative methodology into experimental study design, a review of outcome measures and for study authors to follow standardised guidelines for reporting to facilitate complete and transparent reporting.

Prenatal glucocorticoid overexposure causes adult metabolic dysfunction in several species but its effects on adult mitochondrial function remain largely unknown. Using respirometry, this study examined mitochondrial substrate metabolism of fetal and adult ovine biceps femoris (BF) and semitendinosus (ST) muscles after cortisol infusion before birth. Physiological increases in fetal cortisol concentrations pre-term induced muscle- and substrate-specific changes in mitochondrial oxidative phosphorylation capacity in adulthood. These changes were accompanied by muscle-specific alterations in protein content, fibre composition and abundance of the mitochondrial electron transfer system (ETS) complexes. In adult ST, respiration using palmitoyl-carnitine and malate was increased after fetal cortisol treatment but not with other substrate combinations. There were also significant increases in protein content and reductions in the abundance of all four ETS complexes, but not ATP synthase, in the ST of adults receiving cortisol prenatally. In adult BF, intrauterine cortisol treatment had no effect on protein content, respiratory rates, ETS complex abundances or ATP synthase. Activity of citrate synthase, a marker of mitochondrial content, was unaffected by intrauterine treatment in both adult muscles. In the ST but not BF, respiratory rates using all substrate combinations were significantly lower in the adults than fetuses, predominantly in the saline-infused controls. The ontogenic and cortisol-induced changes in mitochondrial function were, therefore, more pronounced in the ST than BF muscle. Collectively, the results show that fetal cortisol overexposure programmes mitochondrial substrate metabolism in specific adult muscles with potential consequences for adult metabolism and energetics.

Prisons are susceptible to outbreaks. Control measures focusing on isolation and cohorting negatively affect wellbeing. We present an outbreak of coronavirus disease 2019 (COVID-19) in a large male prison in Wales, UK, October 2020 to April 2021, and discuss control measures.

We gathered case-information, including demographics, staff-residence postcode, resident cell number, work areas/dates, test results, staff interview dates/notes and resident prison-transfer dates. Epidemiological curves were mapped by prison location. Control measures included isolation (exclusion from work or cell-isolation), cohorting (new admissions and work-area groups), asymptomatic testing (case-finding), removal of communal dining and movement restrictions. Facemask use and enhanced hygiene were already in place. Whole-genome sequencing (WGS) and interviews determined the genetic relationship between cases plausibility of transmission.

Of 453 cases, 53% (n = 242) were staff, most aged 25–34 years (11.5% females, 27.15% males) and symptomatic (64%). Crude attack-rate was higher in staff (29%, 95% CI 26–64%) than in residents (12%, 95% CI 9–15%).

Whole-genome sequencing can help differentiate multiple introductions from person-to-person transmission in prisons. It should be introduced alongside asymptomatic testing as soon as possible to control prison outbreaks. Timely epidemiological investigation, including data visualisation, allowed dynamic risk assessment and proportionate control measures, minimising the reduction in resident welfare.

We assessed the prevalence of antibiotic prescriptions among ambulatory patients tested for coronavirus disease 2019 (COVID-19) in a large public US healthcare system and found a low overall rate of antibiotic prescriptions (6.7%). Only 3.8% of positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) tests were associated with an antibiotic prescription within 7 days.

Food manufacturers are under increasing pressure to limit the amount of free sugars in their products. Many have reformulated products to replace sucrose, glucose and fructose with alternative sweeteners, but some of these have been associated with additional health concerns. Rare sugars are ‘monosaccharides and their derivatives that hardly exist in nature’, and there is increasing evidence that they could have health benefits. This review aimed to scope the existing literature in order to identify the most commonly researched rare sugars, to ascertain their proposed health benefits, mechanisms of action and potential uses and to highlight knowledge gaps. A process of iterative database searching identified fifty-five relevant articles. The reported effects of rare sugars were noted, along with details of the research methodologies conducted. Our results indicated that the most common rare sugars investigated are d-psicose and d-tagatose, with the potential health benefits divided into three topics: glycaemic control, body composition and CVD. All the rare sugars investigated have the potential to suppress postprandial elevation of blood glucose and improve glycaemic control in both human and animal models. Some animal studies have suggested that certain rare sugars may also improve lipid profiles, alter the gut microbiome and reduce pro-inflammatory cytokine expression. The present review demonstrates that rare sugars could play a role in reducing the development of obesity, type 2 diabetes and/or CVD. However, understanding of the mechanisms by which rare sugars may exert their effects is limited, and their effectiveness when used in reformulated products is unknown.

The impact of change in socio-economic status (SES) from childhood to adulthood (SES mobility) on adult diet is not well understood. This study examined associations between three SES mobility variables (area disadvantage, education, occupation) and adult diet quality. 1482 Australian participants reported childhood area-level SES in 1985 (aged 10–15 years) and retrospectively reported highest parental education and main occupation (until participant age 12) and own area-level SES, education, occupation and dietary intake in 2004–2006 (aged 26–36 years). A Dietary Guidelines Index (DGI) was calculated from food frequency and habit questionnaires. A higher score (range 0–100) indicated better diet quality. Sex-stratified linear regression models adjusted for confounders. Area-level SES mobility was not associated with diet quality. Compared with stable high (university) education, stable low (school only) was associated with lower DGI scores (males: β = –5·5, 95 % CI: −8·9, –2·1; females: β = –6·3, 95 % CI: −9·3, –3·4), as was downward educational mobility (participant’s education lower than their parents) (males: β = –5·3, 95 % CI: −8·5, –2·0; females: β = –4·5, 95 % CI: −7·2, –1·7) and stable intermediate (vocational) education among males (β = –3·9, 95 % CI: −7·0, −0·7). Compared with stable high (professional/managerial) occupation, stable low (manual/out of workforce) males (β = –4·9, 95 % CI: −7·6, –2·2), and participants with downward occupation mobility (males: β = –3·2, 95 % CI: −5·3, –1·1; females: β = –2·8, 95 % CI: −4·8, –0·8) had lower DGI scores. In this cohort, intergenerational low education and occupation, and downward educational and occupational mobility, were associated with poor adult diet quality.

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.

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.

Target Product Profiles (TPPs) outline the characteristics that new health technologies require to address an unmet clinical need. To date, published TPPs for medical tests have focused on infectious diseases, mostly in the context of low- and middle-income countries. Recently, there have been calls for a broader use of TPPs as a mechanism to ensure that diagnostic innovation is aligned with clinical needs, yet the methodology underpinning TPP development remains suboptimal. Here, we propose that early economic evaluation (EEE) should be integrated within the TPP methodology to create a more rigorous framework for the development of “fit-for-purpose” tests. We discuss the potential benefits that EEE could bring to the core activities underpinning TPP development—scoping, drafting, consensus building, and updating—and argue that using EEE to help inform TPPs provides a more objective, evidence-based, and transparent approach to defining test specifications.

ABSTRACT IMPACT: This work examines the association between diabetes mellitus and latent tuberculosis infection among a cohort of household contacts exposed to active tuberculosis in Ethiopia, focusing attention on the need for further translational research to determine the mechanisms of susceptibility to Mycobacterium tuberculosis infection among individuals with diabetes and pre-diabetes. OBJECTIVES/GOALS: Diabetes mellitus (DM) is an established risk factor for active TB disease, but there is limited understanding of the relationship of DM and latent tuberculosis (LTBI). We sought to determine the relationship between DM or pre-DM with LTBI among household or close contacts (HHCs) of active TB cases in Ethiopia. METHODS/STUDY POPULATION: We conducted a cross-sectional study of the HHCs of index active TB cases enrolled in an ongoing TB Research Unit (TBRU) study in Addis Ababa, Ethiopia. HHCs of individuals with laboratory-confirmed TB had QuantiFERON ®-TB Gold Plus (QFT) and glycated hemoglobin (HbA1c) tests performed. LTBI was defined as a positive QFT and lack of symptoms. HbA1C results were used to define no DM (HbA1c <5.7), pre-DM (HbA1c 5.7-6.5%), and DM (HbA1c >6.5% or prior history of diabetes). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) after adjustment for age, sex and HIV status as potential confounders. RESULTS/ANTICIPATED RESULTS: Among 466 HHCs, the median age was 29 years (IQR 23-38), 58.8% were female, 3.4% were HIV-positive, and median BMI was 20.9 kg/m^2 (IQR 18.9-23.8). Overall, 329 HHCs (70.6%) had LTBI, 26 (5.6%) had DM and 73 (15.7%) had pre-DM. Compared to HHC without DM, the prevalence of LTBI was higher in those with pre-DM (68.9% vs. 72.6%; OR 1.19, 95% CI 0.69-2.13) and those with DM (88.5%; OR 3.45, 95% CI 1.17-14.77). In multivariable analysis, there was a trend towards increased LTBI risk among HHCs with DM vs. without DM (OR 2.16, 95% CI 0.67-9.70) but the difference was not statistically significant. Among HHCs with LTBI, the median IFN-? response to TB1 antigen was modestly greater in those with DM (5.3 IU/mL; IQR 3.0-7.8) and pre-DM (5.4 IU/mL; IQR 2.0-8.4) compared to HHCs without DM (4.3 IU/mL; IQR 1.4-7.7). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results suggest that DM may increase the risk of LTBI among HHCs recently exposed to active TB. Among those with LTBI, increased IFN-? antigen response in the presence of DM and pre-DM may indicate an exaggerated but ineffectual response to TB. Further investigation is needed to assess how dysglycemia impacts susceptibility to M. tuberculosis.

A multiproxy record from Twin Ponds, VT, is used to reconstruct climatic variability during the late Pleistocene to early Holocene transition. Pollen, ostracodes, δ18O, and lithologic records from 13.5 to 9.0 cal ka BP are presented. Pollen- and ostracode-inferred climatic reconstructions are based on individual species’ environmental preferences and the modern analog technique. Principal components analysis of all proxies highlights the overall warming trend and centennial-scale climatic variability. During the Younger Dryas cooling event (YD), multiple proxies show evidence for cold winter conditions and increasing seasonality after 12.5 cal ka BP. The early Holocene shows an initial phase of rapid warming with a brief cold interval at 11.5 cal ka BP, followed by a more gradual warming; a cool, wet period from 11.2 to 10.8 cal ka BP; and cool, dry conditions from 10.8 to 10.2 cal ka BP. The record ends with steady warming and increasing moisture. Post-YD climatic variability has been observed at other sites in the northeastern United States and points to continued instability in the North Atlantic during the final phases of deglaciation.

A set of durum wheat genotypes from New South Wales (NSW, Durum Breeding Australia (DBA) Northern Program), South Australia (SA, DBA Southern Program and Australian Grain Technology), ICARDA and CIMMYT (International Centre for Research in Dryland Agriculture and International Centre for Maize and Wheat Improvement) was evaluated over 3 years (2012–2014) in field trials containing rainfed and watered blocks in Narrabri, NSW, Australia. Data on yield and other agronomic traits were analysed using a multi-environment trial approach that accommodated the factorial treatment structure (genotype by irrigation regime) within individual trials. Considerable variation was observed in the durum germplasm for productivity and grain quality traits. DBA Bindaroi (NSW) and 101042 (ICARDA) were the top yielders in watered and rainfed blocks, respectively. The yield was positively and strongly related to both harvest index and grains/m2, but grains/m2 was negatively related to thousand grain weight (TGW) and positively related to screenings. TGW and screenings were strongly negatively related and TGW and grains/m2 showed a weak positive relationship. Promising genotypes were identified, with superior traits to both the bread wheat check, EGA Gregory and the durum check, Caparoi. Overall, lines from SA and ICARDA were superior for yield but those from NSW were superior for quality parameters including TGW and screenings. These results suggested the possibility of developing high yielding high-quality durum varieties by crossing NSW lines with SA, CIMMYT and ICARDA lines through simultaneous selection for yield, TGW and low screenings. The results also suggested that productivity in rainfed conditions was positively related to productivity under watering, but further research is required to establish this.

Background: Due to limited therapeutic options and potential for spread, carbapenem-resistant Enterobacteriaceae (CRE)-producing New Delhi metallo-β-lactamases (NDMs) are a public health priority. We investigated the epidemiology of NDM-producing CRE reported to the CDC to clarify its distribution and relative prevalence. Methods: The CDC’s Antibiotic Resistance Laboratory Network supports molecular testing of CRE for 5 carbapenemases nationally. Although KPC is the most common carbapenemase in the United States, non-KPC carbapenemases are a growing concern. We analyzed CRE with any of 4 non-KPC plasmid-mediated carbapenemases (NDM, VIM, IMP, or OXA-48 type) isolated from specimens collected from January 1, 2017, through June 30, 2019; only a patient’s first isolate per organism–carbapenemase combination was included. We excluded isolates from specimen sources associated with colonization screening (eg, perirectal). We compared the proportion of NDM-producing CRE to all non-KPC–producing CP-CRE between period A (January to June 2018) and period B (January to June 2019). Health departments and the CDC collected additional exposure and molecular information in selected states to better describe current NDM-producing CRE epidemiology. Results: Overall, 47 states reported 1,013 non–KPC-producing CP-CRE (range/state, 1–109 isolates; median, 11 isolates); 46 states reported 631 NDM-producing CRE (range/state, 1–84; median, 6). NDM-producing CRE increased quarterly from the third quarter of 2018 through the second quarter of 2019; CP-CRE isolates with other non-KPC carbapenemases remained stable (Fig. 1). In period A, 124 of 216 emerging CP-CRE had NDM (57.1%), compared with 255 of 359 emerging CP-CRE (71.0%) during period B (P = .1179). Among NDM-producing CRE, the proportion of Enterobacter spp increased from 10.5% in 2018 to 18.4% in 2019 (P = .0467) (Fig. 2). In total, 18 states reported more NDM-producing CRE in the first 6 months of 2019 than in all of 2018. Connecticut, Ohio, and Oregon were among states that conducted detailed investigations; these 3 states identified 24 NDM-producing CRE isolates from 23 patients in period B. Overall, 5 (21.7%) of 22 patients with history available traveled internationally ≤12 months prior to culture; 17 (73.9%) acquired NDM-producing CRE domestically. Among 15 isolates sequenced, 8 (53.3%) carried NDM-5 (6 E. coli, 1 Enterobacter spp and 1 Klebsiella spp) and 7 (46.7%) carried NDM-1 (6 Enterobacter spp and 1 Klebsiella spp). Species were diverse; no single strain type was shared by >2 isolates. Conclusions: Detection of NDM-producing CRE has increased across the AR Lab Network. Among states with detailed information available, domestic acquisition was common, and no single variant or strain predominated. Aggressive public health response and further understanding of current US NDM-CRE epidemiology are needed to prevent further spread.

Disclosures: None

Funding: None

Background: In April 2019, the Georgia Department of Public Health (DPH) initiated whole-genome sequencing (WGS) on NDM-producing Enterobacteriaceae identified since January 2018. The WGS data analyzed at CDC identified related Klebsiella pneumoniae isolates with hypervirulence markers from 2 patients. Carbapenemase-producing hypervirulent K. pneumoniae (CP-hvKP) are rarely reported in the United States, but they can to cause serious, highly resistant, invasive infections. We conducted an investigation to identify cases and prevent spread. Methods: We defined a case as NDM-producing K. pneumoniae with ≥4 hypervirulence markers identified by WGS, isolated from any specimen source from a Georgia patient. We reviewed the case patient’s medical history to identify potentially affected facilities. We also performed PCR-based colonization screening and retrospective and prospective laboratory-based surveillance. Finally, we assessed facility infection control practices. Results: Overall, 7 cases from 3 case patients (A, B, and C) were identified (Fig. 1). The index case specimen was collected from case-patient A at ventilator-capable skilled nursing facility 1 (vSNF1) in May 2018. Case-patient A had been hospitalized for 1 month in India before transfer to the United States. Case-patient B’s initial isolate was collected in January 2019 on admission to vSNF2 from a critical access hospital (CAH). The CAH laboratory retrospectively identified case-patient C, who overlapped with case-patient B at the CAH in October 2018. The CAH and the vSNF2 are geographically distant from vSNF1. Case-patients B and C had no known epidemiologic links to case-patient A. Colonization screening occurred at vSNF1 in May 2018, following detection of NDM-producing K. pneumoniae from case-patient A ∼1 year before determining that the isolate carried hypervirulence markers. Among 30 residents screened, 1 had NDM and several had other carbapenemases. Subsequent screening did not identify additional NDM. Colonization screening of 112 vSNF2 residents and 13 CAH patients in 2019 did not reveal additional case patients; case-patient B resided at vSNF2 at the time of screening and remained colonized. At all 3 facilities, the DPH assessed infection control practices, issued recommendations to resolve lapses, and monitored implementation. The DPH sequenced all 27 Georgia NDM–K. pneumoniae isolates identified since January 2018; all were different multilocus sequence types from the CP-hvKP isolates, and none possessed hypervirulence markers. Conclusions: We hypothesize that CP-hvKP was imported by a patient hospitalized in India and spread to 3 Georgia facilities in 2 distinct geographic regions through indirect patient transfers. Although a response to contain NDM at vSNF1 in 2018 likely limited CP-hvKP transmission, WGS identified hvKP and established the relatedness of isolates from distinct regions, thereby directing the DPH’s additional containment activities to halt transmission.

Funding: None

Disclosures: None

Background: Carbapenem-resistant Enterobacteriaceae (CRE) represent a significant antibiotic resistance threat, in part because carbapenemase genes can spread on mobile genetic elements. Here, we describe the molecular epidemiology and outcomes of patients with CRE bacteriuria from the same city in a nonoutbreak setting. Methods: The Georgia Emerging Infections Program performs active, population-based CRE surveillance in Atlanta. We studied a cohort of patients with CRE (resistant to all tested third-generation cephalosporins and ≥1 carbapenem, excluding ertapenem) first identified in urine, and not in a prior or simultaneous sterile site, between 2012 and 2015. Whole-genome sequencing (WGS) was performed on a convenience sample. We obtained epidemiologic and outcome data through chart review and Georgia Vital Statistics records (90-day mortality). Using WGS, we created a core-genome alignment-based phylogenetic tree of the Klebsiella pneumoniae isolates and calculated the SNP difference between each sample. Using SAS version 9.4 software, we performed the Fisher exact test and univariable odds ratios (OR) with 95% CI to compare patient isolates with and without a carbapenemase gene. Results: Among 81 patients included, the median age was 68 (IQR, 57–74) years, and most were female (58%), black (60%), and resided in a long-term care facility 4 days prior to culture isolation (53%). Organisms isolated were K. pneumoniae (84%), Escherichia coli (7%), Enterobacter cloacae (7%), and Klebsiella oxytoca (1%). WGS identified at least 1 β-lactamase gene in 91% of the isolates; 85% contained a carbapenemase gene, the most frequent of which was blaKPC-3 (94%). Patients with CRE containing a carbapenemase gene were more likely to be black (OR, 3.7; 95% CI, 1.0–13.8) and to have K. pneumoniae (OR, 8.9; 95% CI, 2.2–35.0). Using a core-genome alignment of 3,708 genes (~63% of the complete genome), we identified a median of 67 (IQR, 23–3,881) SNP differences between each K. pneumoniae isolate. A phylogenetic tree identified clustering around carbapenemase gene and multilocus sequence type (84% were ST 258) but not based on referring laboratory or county of residence (Fig. 1). Although 7% of patients developed an invasive CRE infection within 1 year and 21% died within 90 days, having a carbapenemase gene was not associated with these outcomes. Conclusions: Molecular sequencing of a convenience sample of CRE bacteriuria support K. pneumoniae ST258 harboring blaKPC-3 being distributed throughout the Atlanta area, across the healthcare continuum. Overall mortality was high in this population, but the presence of carbapenemase genes was not associated with worse outcomes.

Funding: None

Disclosures: None

Disclosures: None

Funding: None