What are the perspectives of adults aged 18-40 living with type 2 diabetes in urban settings towards barriers and opportunities for better health and well-being: a mixed-methods study.

OBJECTIVES: Delivered as part of the global assessment of diabetes in urban settings, this study explores different aspects of living with type 2 diabetes, for adults aged 18-40. Primary questions were as follows: (1) can we identify subgroups of adults under 40 years old sharing specific perspectives towards health, well-being and living with type 2 diabetes and (2) do these perspectives reveal specific barriers to and opportunities for better type 2 diabetes prevention and management and improved well-being? DESIGN: The study employed a mixed-method design with data collected through demographic questionnaires, Q-sort statement sorting exercises, focus groups discussions and individual interviews. SETTING: Primary care across Greater Manchester, UK. PARTICIPANTS: Those aged between 18 and 40, with a confirmed type 2 diabetes diagnosis, and living in Greater Manchester were eligible to participate. A total of 46 people completed the Q-sort exercise and 43 were included in the final analysis. Of those, 29 (67%) identified as female and 32 (75%) as white. Most common time since diagnosis was between 5 and 10 years. RESULTS: The Q-sort analysis categorised 35 of the 43 participants (81%) into five subgroups. Based on average statement sorts for each subgroup, perspectives were characterised as: (1) stressed and calamity coping (n=13), (2) financially disadvantaged and poorly supported (n=12), (3) well-intentioned but not succeeding (n=5), (4) withdrawn and worried (n=2) and (5) young and stigmatised (n=3). Holistic analysis of our qualitative data also identified some common issues across these subgroups. CONCLUSIONS: Adults under 40 with type 2 diabetes are not a homogeneous group, but fall into five identifiable subgroups. They also experience issues specific to this age group that make it particularly difficult for them to focus on their own health. More tailored support could help them to make the necessary lifestyle changes and manage their type 2 diabetes better.

High-field magnetic resonance microscopy of aortic plaques in a mouse model of atherosclerosis.

OBJECTIVES: Pre-clinical models of human atherosclerosis are extensively used; however, traditional histological methods do not allow for a holistic view of vascular lesions. We describe an ex-vivo, high-resolution MRI method that allows the 3 dimensional imaging of the vessel for aortic plaque visualization and quantification. MATERIALS AND METHODS: Aortas from apolipoprotein-E-deficient (apoE-/-) mice fed an atherogenic diet (group 1) or a control diet (group 2) were subjected to 14 T MR imaging using a 3D gradient echo sequence. The obtained data sets were reconstructed (Matlab), segmented, and analyzed (Avizo). The aortas were further sectioned and subjected to traditional histological analysis (Oil-Red O and hematoxylin staining) for comparison. RESULTS: A resolution up to 15 × 10x10 µm3 revealed that plaque burden (mm3) was significantly (p < 0.05) higher in group 1 (0.41 ± 0.25, n = 4) than in group 2 (0.01 ± 0.01, n = 3). The achieved resolution provided similar detail on the plaque and the vessel wall morphology compared with histology. Digital image segmentation of the aorta's lumen, plaque, and wall offered three-dimensional visualizations of the entire, intact aortas. DISCUSSION: 14 T MR microscopy provided histology-like details of pathologically relevant vascular lesions. This work may provide the path research needs to take to enable plaque characterization in clinical applications.

Quantitative genetic analysis reveals potential to breed for improved white clover growth in symbiosis with nitrogen-fixing Rhizobium bacteria.

White clover (Trifolium repens) is integral to mixed pastures in New Zealand and temperate agriculture globally. It provides quality feed and a sustainable source of plant-available nitrogen (N) via N-fixation through symbiosis with soil-dwelling Rhizobium bacteria. Improvement of N-fixation in white clover is a route to enhancing sustainability of temperate pasture production. Focussing on seedling growth critical for crop establishment and performance, a population of 120 half-sibling white clover families was assessed with either N-supplementation or N-fixation via inoculation with a commercial Rhizobium strain (TA1). Quantitative genetic analysis identified significant (p < 0.05) family additive genetic variance for Shoot and Root Dry Matter (DM) and Symbiotic Potential (SP), and Root to Shoot ratio. Estimated narrow-sense heritabilities for above-ground symbiotic traits were moderate (0.24-0.33), and the strong (r ≥ 0.97) genetic correlation between Shoot and Root DM indicated strong pleiotropy or close linkage. The moderate (r = 0.47) phenotypic correlation between Shoot DM under symbiosis vs. under N-supplementation suggested plant growth with mineral-N was not a strong predictor of symbiotic performance. At 5% among-family selection pressure, predicted genetic gains per selection cycle of 19 and 17% for symbiotic traits Shoot DM and Shoot SP, respectively, highlighted opportunities for improved early seedling establishment and growth under symbiosis. Single and multi-trait selection methods, including a Smith-Hazel index focussing on an ideotype of high Shoot DM and Shoot SP, showed commonality of top-ranked families among traits. This study provides a platform for proof-of-concept crosses to breed for enhanced seedling growth under Rhizobium symbiosis and is informative for other legume crops.

Treatment Patterns in Patients with Locally Advanced or Metastatic Non-Small-Cell Lung Cancer Treated with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: Analysis of US Insurance Claims Databases.

BACKGROUND: Most patients with epidermal growth factor receptor mutation-positive (EGFRm) non-small-cell lung cancer (NSCLC) acquire resistance to first-line (1L) first- or second-generation (1G/2G) EGFR-TKIs; therefore, it is important to optimize 1L treatment to improve patient outcomes. OBJECTIVE: To retrospectively examine treatment patterns in locally advanced/metastatic NSCLC using MarketScan® Commercial and Medicare Supplemental Databases (all US census regions). PATIENTS AND METHODS: Adults with a lung cancer diagnosis code between 1 January 2015-31 March 2018 were analyzed from diagnosis (index) through a variable-length follow-up. Patients had ≥ 1 pharmacy claim for 1G/2G EGFR-TKIs on or within 60 days post-index. Data were stratified by presence or absence of central nervous system (CNS) metastases (30 days pre-index through study end). RESULTS: 578 patients were included (median age 63 years, 64% female). Median follow-up was 13.5 months. The most frequently prescribed 1L EGFR-TKI was erlotinib (414/578, 72%). Median time to 1L treatment discontinuation was 8.2 (95% confidence interval (CI) 6.9, 9.0) months in patients diagnosed with CNS metastases at any time, and 7.7 (95% CI 6.9, 8.9) months in patients without CNS metastases. 270/578 patients (47%) discontinued 1L EGFR-TKIs; 209/270 (77%) initiated second-line (2L) therapy, most frequently osimertinib (96/209, 46%). CONCLUSIONS: In an analysis of US claims data, nearly half of patients discontinued 1L EGFR-TKIs, and 46% who initiated 2L received osimertinib. As nearly a quarter of patients who discontinued 1L EGFR-TKIs did not receive 2L treatment, this study highlights the need for optimal 1L treatment in EGFRm locally advanced/metastatic NSCLC.

Lumbar instability as an etiology of low back pain and its treatment by prolotherapy: A review.

BACKGROUND: Low back pain is a significant spinal disorder that affects much of the population at some point during their lives. OBJECTIVE: While proper diagnosis is key, diagnosing the underlying cause of low back pain may often be unclear. METHOD: In this review article, we discuss lumbar instability as an etiology of low back pain and its treatment by prolotherapy. RESULTS: Spinal ligaments may be an underlying culprit in the development of lumbar instability with resultant low back pain and associated disorders. CONCLUSION: In these cases, adequate treatment consisting of non-biologic prolotherapy or cellular prolotherapy, including platelet rich plasma (PRP), can be beneficial in restoring spinal stability and resolving chronic low back pain.

Priming with Retinoic Acid, an Active Metabolite of Vitamin A, Increases Vitamin A Uptake in the Small Intestine of Neonatal Rats.

Given that combined vitamin A (VA) and retinoic acid (RA) supplementation stimulated the intestinal uptake of plasma retinyl esters in neonatal rats, we administrated an RA dose as a pretreatment before VA supplementation to investigate the distinct effect of RA on intestinal VA kinetics. On postnatal days (P) 2 and 3, half of the pups received an oral dose of RA (RA group), while the remaining received canola oil as the control (CN). On P4, after receiving an oral dose of 3H-labeled VA, pups were euthanized at selected times (n = 4-6/treatment/time) and intestine was collected. In both CN and RA groups, intestinal VA mass increased dramatically after VA supplementation; however, RA-pretreated pups had relatively higher VA levels from 10 h and accumulated 30% more VA over the 30-h study. Labeled VA rapidly peaked in the intestine of CN pups and then declined from 13 h, while a continuous increase was observed in the RA group, with a second peak at 10 h and nearly twice the accumulation of 3H-labeled VA compared to CN. Our findings indicate that RA pretreatment may stimulate the influx of supplemental VA into the intestine, and the increased VA accumulation suggests a potential VA storage capacity in neonatal intestine.

A Yoga Intervention for Young Children: Self-Regulation and Emotion Regulation.

Yoga-based interventions have been implemented in schools and demonstrated promising results on students' self-regulation outcomes. Nevertheless, there is limited literature on the effects that yoga may have for children in the early primary grades, despite the evidence demonstrating that this is an opportune period in development for early self-regulation. Few studies have focused on young children living in the context of economic difficulty, which can hinder children's development of self-regulatory skills and educational trajectories. The effects of an eight-week yoga intervention on economically disadvantaged pre-kindergarten and kindergarten children's self-regulation and emotion regulation were examined via a paired within-subjects comparison study. Nine classrooms were assigned to the yoga intervention (Treatment First, TxFirst; n = 90) or a wait-list control group (Treatment Second, TxSecond; n = 64). All children were assessed at pre-intervention (Time 1), post-intervention assessment for TxFirst (Time 2), and post-intervention assessment for TxSecond (Time 3). Children demonstrated significant predicted gains on a behavioral task of self-regulation and declines in teacher-rated submissive venting and total behavior problems. Implications for future research are discussed, with a focus on including follow-up assessments and multiple dimensions of fidelity of implementation.

Effect of an Integrated Clinical Pharmacist on the Drivers of Provider Burnout in the Primary Care Setting.

PURPOSE: As the prevalence of provider burnout continues to increase, it is critical to identify interventions that may impact provider satisfaction, such as an integrated clinical pharmacist. This study aimed to assess the perceived effect of pharmacist integration on primary care provider satisfaction and drivers of provider burnout in the primary care setting. METHODS: A cross-sectional survey with 11 questions across 4 domains was distributed to primary care providers in a large integrated health system. RESULTS: Of 295 providers invited to take the survey, 119 responded (40% response rate). Most providers had worked with a pharmacist for at least 2 years and utilized them weekly or daily. At least 87% of provider respondents strongly agreed or somewhat agreed that the integrated clinical pharmacist reduced their workload by working directly with patients and non-provider staff, improved overall medication use, helped patients meet health goals and quality measures, and overall helped them to effectively manage their panel of patients. Providers found greater meaning in work through the presence of the clinical pharmacist, which allowed them more time to focus on professionally fulfilling aspects of their work and helped them feel less emotional exhaustion. Overall, 91% of providers were extremely satisfied with the clinical pharmacy service. CONCLUSIONS: These findings may be used to justify the expansion of clinical pharmacy services in primary care to practice areas experiencing problems with 4 specific drivers of provider burnout: workload and job demands, efficiency and resources, meaning in work, and social support and community at work.

Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study.

BACKGROUND: Patients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to first define the changes in potential biomarkers following cytotoxic chemotherapy alone. This study reports the impact of standard cytotoxic chemotherapy across a range of circulating and imaging biomarkers. METHODS: A single-centre, prospective, biomarker-driven study. Eligible patients included those diagnosed with colorectal cancer with liver metastases that were planned to receive first line oxaliplatin plus 5-fluorouracil or capecitabine. Patients underwent paired blood sampling and magnetic resonance imaging (MRI), and biomarkers were associated with progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty patients were recruited to the study. Data showed that chemotherapy significantly reduced the number of circulating tumour cells as well as the circulating concentrations of Ang1, Ang2, VEGF-A, VEGF-C and VEGF-D from pre-treatment to cycle 2 day 2. The changes in circulating concentrations were not associated with PFS or OS. On average, the MRI perfusion/permeability parameter, Ktrans, increased in response to cytotoxic chemotherapy from pre-treatment to cycle 2 day 2 and this increase was associated with worse OS (HR 1.099, 95%CI 1.01-1.20, p = 0.025). CONCLUSIONS: In patients diagnosed with colorectal cancer with liver metastases, treatment with standard chemotherapy changes cell- and protein-based biomarkers, although these changes are not associated with survival outcomes. In contrast, the imaging biomarker, Ktrans, offers promise to direct molecularly targeted therapies such as anti-angiogenic agents.

Early, empiric high-dose leucovorin rescue in lymphoma patients treated with sequential doses of high-dose methotrexate.

BACKGROUND: In patients exposed to high-dose methotrexate (HDMTX; >1g/m2) with a history of elevated methotrexate (MTX) concentrations during previous doses, it is unclear whether prescribing high-dose leucovorin (HDLV) rescue limits future high levels or reduces the likelihood of acute kidney injury (AKI). METHODS: This retrospective, single-center study longitudinally followed adult lymphoma patients treated with HDMTX between 1/1/2011 and 10/31/2017 from diagnosis until 30 days after the last HDMTX dose. Endpoints included elevated MTX concentrations at 48 h (>1.0 µmol/L) and incident AKI after each HDMTX dose. RESULTS: The 321 included patients had a median (IQR) age of 65 (57, 72) years, 190 (59%) were male, and 293 (91%) were Caucasian. There were 1558 HDMTX doses [median (IQR) 3 (2, 6) doses per patient] prescribed with 265 (83%) patients receiving more than one MTX dose. Those receiving HDLV rescue were more likely to have an elevated MTX concentration after that dose (OR = 2.69, 95% CI: 1.75-4.11, p < 0.001). Receiving HDLV rescue was associated with a greater likelihood of AKI after MTX (OR = 2.18, 95% CI: 1.38-3.43, p < 0.001). Hospital LOS was longer in those prescribed empiric HDLV rescue after MTX than those prescribed standard leucovorin with an estimated difference of 1.1 days, (95% CI: 0.5-1.7, p < 0.001). CONCLUSION: Sequential HDMTX doses are associated with a significant incidence of elevated MTX levels and AKI during lymphoma management. HDLV rescue prescribed during subsequent MTX doses in patients with a previously elevated level was not associated with improved safety outcomes. The optimal supportive care strategy following HDMTX administration requires further investigation.

Digital bathroom scales with open source software provide valid dynamic ground reaction force data for assessment and biofeedback.

BACKGROUND: Measuring dynamic vertical ground reaction force allows for assessment of important clinical and physical capacity factors such as weight bearing asymmetry, force distribution, and rate of force development. However, current technologies for accurately assessing ground reaction force are typically expensive. RESEARCH QUESTION: The aim of this study was to examine the validity and reliability of obtaining static and dynamic ground reaction force data from low-cost modified digital bathroom scales. METHODS: Four modified bathroom scales, two units each of two different brands, were examined. Repeated mechanical loading trials were performed with known loads ranging from 0.01 to 65 kg, with acquired data compared against the known loading to calculate accuracy, hysteresis, and non-linearity. Dynamic trials consisting of 5 times sit-to-stand and weight-shifting were performed by 32 adults. Absolute and relative agreement intraclass correlation coefficient, and Pearson's and Spearman's correlations were performed to determine validity and reliability for the mechanical tests. Bland-Altmann plots were created for each comparison. Mean absolute error (MAE) and unbiased cross-correlation were performed on the dynamic data, comparing the calibrated data to the known values from a Bertec force platform. RESULTS: Hysteresis and non-linearity were excellent (<0.2 % full-scale), and mechanical test results showed excellent reliability and validity. Cross-correlation results for the dynamic data were excellent, however MAE for the more rapid sit-to-stand task was higher than the slower weight-shifting test. This may have been due to the low default sampling rate for the lowest noise setting of the HX711 amplifier (10 Hz). SIGNIFICANCE: In summary, our results suggest that digital bathroom scales can be easily and inexpensively modified to obtain accurate vertical ground reaction force data, with sensitivity to detect changes of as little as 0.01 kg.

Vitamin A Corrects Tissue Deficits in Diet-Induced Obese Mice and Reduces Influenza Infection After Vaccination and Challenge.

OBJECTIVE: Individuals with obesity suffer from an increased susceptibility to severe respiratory viral infections and respond poorly to vaccinations, making it imperative to identify interventions. Recent evidence suggesting that obesity leads to tissue-specific vitamin A deficiency led to an investigation of whether high-dose oral vitamin A, a treatment used for remediating vitamin A deficiency in developing countries, could correct obesity-associated tissue deficits. METHODS: Adult C57BL/6 diet-induced obese mice were supplemented with vitamin A for 4 weeks. A subset of mice were then vaccinated with inactivated influenza virus and challenged. Following supplementation, tissue vitamin A levels, lung immune cell composition, blood inflammatory cytokines, antibody responses, and viral clearance were evaluated. RESULTS: Supplementation significantly improved vitamin A levels in lung and adipose tissues in diet-induced obese mice. Additionally, supplementation decreased inflammatory cytokines in the blood and altered the lung immune environment. Importantly, vaccinated, vitamin A-treated diet-induced obese mice exhibited improved antibody responses and significantly reduced viral loads post challenge compared with PBS-treated mice. CONCLUSIONS: Results demonstrate a low-cost intervention that may correct vitamin A tissue deficits and help control respiratory viral infections in individuals with obesity.

Occupational Contamination with a Highly Enriched Uranium Solution.

This medical case report describes the first reported instance of occupational skin contamination with a uranyl nitrate solution containing highly enriched uranium. The report provides an overview of the unique medical treatment and management considerations in such a case. Internal dose assessment is covered in detail. The discussion covers key points regarding uranium characteristics, chemical and radiological damage to body tissues from HEU exposure, and resources available for assistance with a case of radiological contamination. This information adds to the limited medical literature on this topic and provides a valuable reference for medical personnel when dealing with this uncommon problem.

Maintaining Iron Homeostasis Is the Key Role of Lysosomal Acidity for Cell Proliferation.

The lysosome is an acidic multi-functional organelle with roles in macromolecular digestion, nutrient sensing, and signaling. However, why cells require acidic lysosomes to proliferate and which nutrients become limiting under lysosomal dysfunction are unclear. To address this, we performed CRISPR-Cas9-based genetic screens and identified cholesterol biosynthesis and iron uptake as essential metabolic pathways when lysosomal pH is altered. While cholesterol synthesis is only necessary, iron is both necessary and sufficient for cell proliferation under lysosomal dysfunction. Remarkably, iron supplementation restores cell proliferation under both pharmacologic and genetic-mediated lysosomal dysfunction. The rescue was independent of metabolic or signaling changes classically associated with increased lysosomal pH, uncoupling lysosomal function from cell proliferation. Finally, our experiments revealed that lysosomal dysfunction dramatically alters mitochondrial metabolism and hypoxia inducible factor (HIF) signaling due to iron depletion. Altogether, these findings identify iron homeostasis as the key function of lysosomal acidity for cell proliferation.

Optogenetic stimulation of kisspeptin neurones within the posterodorsal medial amygdala increases luteinising hormone pulse frequency in female mice.

Kisspeptin within the arcuate nucleus of the hypothalamus is a critical neuropeptide in the regulation of reproduction. Together with neurokinin B and dynorphin A, arcuate kisspeptin provides the oscillatory activity that drives the pulsatile secretion of gonadotrophin-releasing hormone (GnRH), and therefore luteinising hormone (LH) pulses, and is considered to be a central component of the GnRH pulse generator. It is well established that the amygdala also exerts an influence over gonadotrophic hormone secretion and reproductive physiology. The discovery of kisspeptin and its receptor within the posterodorsal medial amygdala (MePD) and our recent finding showing that intra-MePD administration of kisspeptin or a kisspeptin receptor antagonist results in increased LH secretion and decreased LH pulse frequency, respectively, suggests an important role for amygdala kisspeptin signalling in the regulation of the GnRH pulse generator. To further investigate the function of amygdala kisspeptin, the present study used an optogenetic approach to selectively stimulate MePD kisspeptin neurones and examine the effect on pulsatile LH secretion. MePD kisspeptin neurones in conscious Kiss1-Cre mice were virally infected to express the channelrhodopsin 2 protein and selectively stimulated by light via a chronically implanted fibre optic cannula. Continuous stimulation using 5 Hz resulted in an increased LH pulse frequency, which was not observed at the lower stimulation frequencies of 0.5 and 2 Hz. In wild-type animals, continuous stimulation at 5 Hz did not affect LH pulse frequency. These results demonstrate that selective activation of MePD Kiss1 neurones can modulate hypothalamic GnRH pulse generator frequency.

Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&D Supplements to Humoral Immune Responses Following Pediatric Influenza Vaccination.

Maximizing vaccine efficacy is critical, but previous research has failed to provide a one-size-fits-all solution. Although vitamin A and vitamin D supplementation studies have been designed to improve vaccine efficacy, experimental results have been inconclusive. Information is urgently needed to explain study discrepancies and to provide guidance for the future use of vitamin supplements at the time of vaccination. We conducted a randomized, blinded, placebo-controlled study of influenza virus vaccination and vitamin supplementation among 2 to 8 (inclusive) year old children over three seasons, including 2015-2016 (n = 9), 2016-2017 (n = 44), and 2017-2018 (n = 26). Baseline measurements of vitamins A and D were obtained from all participants. Measurements were of serum retinol, retinol-binding protein (RBP, a surrogate for retinol), and 25-hydroxyvitamin D (25(OH)D). Participants were stratified into two groups based on high and low incoming levels of RBP. Children received two doses of the seasonal influenza virus vaccine on days 0 and 28, either with an oral vitamin supplement (termed A&D; 20,000 IU retinyl palmitate and 2000 IU cholecalciferol) or a matched placebo. Hemagglutination inhibition (HAI) antibody responses were evaluated toward all four components of the influenza virus vaccines on days 0, 28, and 56. Our primary data were from season 2016-2017, as enrollment was highest in this season and all children exhibited homogeneous and negative HAI responses toward the Phuket vaccine at study entry. Responses among children who entered the study with insufficient or deficient levels of RBP and 25(OH)D benefited from the A&D supplement (p < 0.001 for the day 28 Phuket response), whereas responses among children with replete levels of RBP and 25(OH)D at baseline were unaffected or weakened (p = 0.02 for the day 28 Phuket response). High baseline RBP levels associated with high HAI titers, particularly for children in the placebo group (baseline RBP correlated positively with Phuket HAI titers on day 28, r = 0.6, p = 0.003). In contrast, high baseline 25(OH)D levels associated with weak HAI titers, particularly for children in the A&D group (baseline 25(OH)D correlated negatively with Phuket HAI titers on day 28, r = -0.5, p = 0.02). Overall, our study demonstrates that vitamin A&D supplementation can improve immune responses to vaccines when children are vitamin A and D-insufficient at baseline. Results provide guidance for the appropriate use of vitamins A and D in future clinical vaccine studies.

Intestinal permeability and inflammation mediate the association between nutrient density of complementary foods and biochemical measures of micronutrient status in young children: results from the MAL-ED study.

BACKGROUND: Environmental enteric dysfunction (EED) is thought to increase the risk of micronutrient deficiencies, but few studies adjust for dietary intakes and systemic inflammation. OBJECTIVE: We tested whether EED is associated with micronutrient deficiency risk independent of diet and systemic inflammation, and whether it mediates the relation between intake and micronutrient status. METHODS: Using data from 1283 children in the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health) birth cohort we evaluated the risk of anemia, low retinol, zinc, and ferritin, and high transferrin receptor (TfR) at 15 mo. We characterized gut inflammation and permeability by myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT) concentrations from asymptomatic fecal samples averaged from 9 to 15 mo, and averaged the lactulose:mannitol ratio z-score (LMZ) at 9 and 15 mo. Nutrient intakes from complementary foods were quantified monthly from 9 to 15 mo and densities were averaged for analyses. α-1-Acid glycoprotein at 15 mo characterized systemic inflammation. Relations between variables were modeled using a Bayesian network. RESULTS: A greater risk of anemia was associated with LMZ [1.15 (95% CI: 1.01, 1.31)] and MPO [1.16 (1.01, 1.34)]. A greater risk of low ferritin was associated with AAT [1.19 (1.03, 1.37)] and NEO [1.22 (1.04, 1.44)]. A greater risk of low retinol was associated with LMZ [1.24 (1.08, 1.45)]. However, MPO was associated with a lower risk of high transferrin receptor [0.86 (0.74, 0.98)], NEO with a lower risk of low retinol [0.75 (0.62, 0.89)], and AAT with a lower risk of low plasma zinc [0.83 (0.70, 0.99)]. Greater nutrient intake densities (vitamins A and B6, calcium, protein, and zinc) were negatively associated with EED. Inverse associations between nutrient densities and micronutrient deficiency largely disappeared after adjustment for EED, suggesting that EED mediates these associations. CONCLUSIONS: EED is independently associated with an increased risk of low ferritin, low retinol, and anemia. Greater nutrient density from complementary foods may reduce EED, and the control of micronutrient deficiencies may require control of EED.

Design and methods of Shape Up Under 5: Integration of systems science and community-engaged research to prevent early childhood obesity.

Shape Up Under 5 (SUU5) was a two-year early childhood obesity prevention pilot study in Somerville, Massachusetts (2015-2017) designed to test a novel conceptual framework called Stakeholder-driven Community Diffusion. For whole-of-community interventions, this framework posits that diffusion of stakeholders' knowledge about and engagement with childhood obesity prevention efforts through their social networks will improve the implementation of health-promoting policy and practice changes intended to reduce obesity risk. SUU5 used systems science methods (agent-based modeling, group model building, social network analysis) to design, facilitate, and evaluate the work of 16 multisector stakeholders ('the Committee'). In this paper, we describe the design and methods of SUU5 using the conceptual framework: the approach to data collection, and methods and rationale for study inputs, activities and evaluation, which together may further our understanding of the hypothesized processes within Stakeholder-driven Community Diffusion. We also present a generalizable conceptual framework for addressing childhood obesity and similar complex public health issues through whole-of-community interventions.

Iron deficiency anemia associated with extracorporeal photopheresis: A retrospective analysis.

BACKGROUND: Extracorporeal photopheresis (ECP) is associated with few adverse effects. We have anecdotally noted patients treated with long-term ECP develop iron deficiency anemia (IDA). METHODS: We performed a retrospective chart review of adult patients who received ECP for any indication at Mayo Clinic Rochester and Mayo Clinic Arizona. The primary objective was to describe the cumulative incidence of IDA at 1 year of ECP therapy. RESULTS: A total of 123 patients were eligible for analysis. Graft-vs-host disease was the most common indication for ECP (n = 76, 61.8%). At 1 year of ECP therapy, the cumulative incidence of IDA was 24.1% (95% CI, 14.2%-32.9%). At 5 years, the cumulative incidence of IDA was 68.3% (95% CI, 38%-83.8%). Risk factors for the development of IDA included: cumulative number of ECP sessions (HR 1.34, 95% CI, 1.05-1.73 per 10 additional sessions, P = .022), an indication for ECP of solid organ transplant rejection (compared to cutaneous T-cell lymphoma, HR 5.46, 95% CI, 2.06-14.49, P < .001), and proton pump inhibitor use at baseline (HR 2.15, 95% CI, 1.1-4.21, P = .03). Iron supplementation was initiated in 29 of 37 evaluable patients who developed IDA, with a cumulative incidence of supplementation in 77.2% patients within 3 months of recognition of IDA (95% CI, 55.8%-88.3%). Hemoglobin normalized in 50.1% of patients started on iron supplementation for IDA within 7 months (95% CI, 25.2%-66.7%). CONCLUSIONS: Iron deficiency anemia is common in patients receiving long-term ECP and occurs throughout ECP therapy. IDA resolved with iron supplementation in half of patients.

Comparison of intravenous and oral definitive antibiotic regimens in hospitalised patients with Gram-negative bacteraemia from a urinary tract infection.

OBJECTIVES: Transitioning patients from intravenous (IV) to oral antibiotic therapy has been shown to be a successful approach for several infections. However, minimal data exist evaluating outcomes following transition from to oral antibiotics for patients with bacteraemia secondary to a urinary tract infection (UTI). This study compared treatment failures between patients treated exclusively with IV antibiotics and those transitioned from IV to oral antibiotics for bacteraemia secondary to UTI. METHODS: This single-centre, retrospective cohort study included hospitalised, non-critically ill adult patients treated with culture-susceptible antibiotic therapy for 7-21 days. Patients were divided into two cohorts based on the route of definitive antibiotic administration. Treatment failure was a composite outcome of death and recurrence of the index micro-organism within 21 days following negative blood cultures. RESULTS AND DISCUSSION: Among the 346 patients enrolled, 82 (23.7%) were in the IV cohort and 264 (76.3%) were in the IV-to-oral cohort. A total of six treatment failures occurred; 2 (2.4%) in the IV cohort and 4 (1.5%) in the oral transition cohort (hazard ratio=0.62, 95% confidence interval 0.11-3.39; P=0.58). All failures were due to recurrence of the index organism. Secondary outcomes demonstrated a significantly higher rate of IV line-associated complications in the IV cohort (P=0.03) and a favourable hospital length of stay in the oral cohort (P<0.001). Patients transitioned from IV to oral antibiotics based on culture-susceptibility data experienced similarly low rates of treatment failure as those who received exclusive IV therapy.