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Emerging adults (EAs) with type 1 diabetes (T1D) often experience challenges in diabetes management, in particular transitioning to financial independence. EAs 18-30 years of age with T1D completed online surveys about diabetes distress and an open-ended query about the most important worry among survey questions. Most of the 287 respondents (89.5%) endorsed "Agree" or "Somewhat agree" to the statement "I worry about the cost of diabetes." Responses did not differ by gender, age, diabetes duration, race/ethnicity, diabetes technology use, student status, income, or insurance status. However, a greater proportion of those not endorsing cost as a substantial burden achieved A1c7% (92.9%) versus those who were neutral (46.2%) or who endorsed cost as a burden (50.6%) (

Hypertriglyceridemia is a complication of diabetic ketoacidosis (DKA) secondary to insulin deficiency inhibiting lipoprotein lipase and increasing lipolysis, but it is rare in children. A 7-year-old boy with history of autism spectrum disorder (ASD) presented with abdominal pain, vomiting, and “heavy breathing.” Initial laboratory tests revealed pH 6.87 and glucose 385 mg/dL (21.4 mmol/L), consistent with new-onset diabetes and DKA. His blood appeared lipemic; triglycerides were 17 675 mg/dL (199.6 mmol/L) with normal lipase (10 units/L). He received intravenous insulin and DKA resolved within 24 hours. Insulin infusion continued through day 6 for management of hypertriglyceridemia; triglycerides decreased to 1290 mg/dL (14.6 mmol/L) during this period. He never developed pancreatitis (lipase peaked at 68 units/L) or required plasmapheresis. With his ASD history, he had a restrictive diet high in saturated fat, which included up to 30 breakfast sausages daily. His triglycerides normalized after discharge. Severe hypertriglyceridemia can complicate DKA in newly diagnosed type 1 diabetes (T1D). Hypertriglyceridemia can be safely managed with insulin infusion in the absence of end-organ dysfunction. This complication should be considered in patients with DKA at diagnosis of T1D.

Structures of binary PbO‐SiO2 glasses have been studied in detail over the compositional range 35 to 80 mol% PbO using high‐resolution neutron diffraction, high‐energy X‐ray diffraction, static 207Pb NMR, and structural modeling. The changes in the local environment of Pb(II) are subtle; it has a low coordination to oxygen (∼3 to 4) plus a stereochemically active electron lone pair and, thus, behaves as a glass network forming (or intermediate) cation over the entire composition range. This conclusion contradicts previous reports that Pb(II) is a network modifier at low concentrations, and is supported by an analysis of lead and alkaline earth silicate glass molar volumes. The Pb‐O peak bond length shortens by 0.04 Å with increasing PbO content, indicating stronger, more covalent bonding, and consistent with an increase in the number of short (≤ 2.70 Å) Pb‐O bonds, from 3.3 to 3.6. This is accompanied by increased axial symmetry of the Pb(II) sites, and is interpreted as a gradual transition toward square pyramidal [PbO4] sites such as those found in crystalline PbO polymorphs. An attendant decrease in the periodicity associated with the first sharp diffraction peak (FSDP) toward that of β‐PbO, accompanied by increases in the correlation lengths associated with the plumbite network (FSDP) and silicate anions (neutron prepeak), provides evidence of increased intermediate‐range order and has implications for the glass forming limit imposed by crystallization. Pb(II) electron lone pairs occupy the natural voids within the silicate network at low PbO contents, while at high PbO contents they aggregate to create voids that form part of the plumbite network, analogous to the open channels in Pb11Si3O17 and the layered structures of α‐ and β‐PbO. Si‐O and Pb‐O bond lengths have been correlated with 29Si and 207Pb NMR chemical shifts, respectively. This is the first time that such correlations have been demonstrated for glasses and attests to the accuracy with which pulsed neutron total scattering can measure average bond lengths.

Emerging adults (EA) with type 1 diabetes (T1D) have multiple developmental stage-specific challenges in diabetes management, including the transition to financial independence. The recently validated Problem Areas in Diabetes-EA (PAID-EA) survey is the first measure of diabetes distress (DD) in EA to include financial concerns. A sample of 287 participants with T1D ages 18-30 years completed an online survey including the 25-item PAID-EA, measures of DD and depressive symptomology, and clinical and demographic questions. To evaluate content validity, 2 open-ended questions asked for the most important worry mentioned and what worries were missed in the questions. Responses were analyzed using directed qualitative content analysis. As cost emerged as a major contributor to DD, responses to the PAID-EA item 21 (“I worry about the cost of diabetes”) were analyzed using Chi-square or Fisher’s exact test to assess participant factors associated with cost-related DD. Most participants (89%) provided open-ended responses (78% female, mean age 24 years) . Cost was the most frequent code in the qualitative analysis: 15% reported DD related to cost and 6% to insurance. Responses included worries about aging out of parents’ insurance and limitations on career choices to ensure payment for diabetes supplies. In all survey respondents, 90% replied “Agree” or “Somewhat agree” to PAID-EA item 21. Responses to this item did not differ by gender, age (< vs. >=25) , continuous glucose monitor use (Y/N) , insulin pump use (Y/N) , student status (full time vs. part time vs. no) , income (< vs ≥$75k) , or insurance status (parent vs. own vs. uninsured) . A greater proportion of those with HbA1c ≥ 7% endorsed worry about cost than with HbA1c < 7% (94% vs. 87%, p = 0.008) . Diabetes cost was a major contributor to DD in this sample of EA with T1D. Worry about diabetes costs was endorsed by nearly all participants, especially those not meeting glycemic targets. Managing the cost of diabetes care for EA may be an avenue to reduce DD. Disclosure R.J.Vitale: None. K.Wentzell: None. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. Funding NIH T32DK007260NIH T32DK007529NIH P30DK036836

The developmental stage of emerging adulthood covers a wide age span (ages 18-30 years) with potential for differing emotional burdens for those living with type 1 diabetes (T1D) . To further confirm the content validity of the PAID-EA and to investigate differences between younger and older emerging adults, item responses on the newly developed, previously validated PAID-EA survey were examined by age group. Emerging adults (N=287) with T1D completed online measures of diabetes distress, depressive symptomology, and the PAID-EA. The PAID-EA has 25 items and uses a 5 point Likert-type response scale with options ranging from agree to disagree. The sample was split into 2 age groups: younger emerging adults (ages 18-24, N=143) and older emerging adults (ages 25-30, N=122) . Self-reported HbA1c was significantly worse in younger vs. older emerging adults (7.4% vs. 6.8%, p Disclosure K.Wentzell: None. R.J.Vitale: None. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. Funding Joslin DRC: P30DK036836 NIH: T32DK007260, T32DK007529

Aim: Management of type 1 diabetes (T1D) is a complex multi-step process in which executive function (EF) skills (planning, organization, problem solving) are critical for optimal control. In teens with T1D, EF may be important in transitioning from parent-supervised care to self-care. Methods: In an 18-month study, teens aged 13-17 years with T1D and parents completed the Diabetes Family Responsibility Questionnaire (DFR) and Readiness for Independent Self-Care Questionnaire (RISQ) every 6 months. Teen EF was assessed by parent proxy-report using Behavior Rating Inventory of Executive Function (BRIEF) . T-score ≥60 defined risk of executive dysfunction for the Global EF Composite (GEC) , Behavioral Regulation Index (BRI) and Metacognition Index (MI) . EF, demographic, and T1D treatment variables were used to predict change in RISQ over time using longitudinal mixed models with false discovery rate adjustment. Results: 169 teens (54% male) participated with baseline age 15.9±1.3 years, T1D duration 8.4±3.7 years, HbA1c 8.6±1.2%, 74.6% insulin pump use, and 21.3% continuous glucose monitor (CGM) use. 31.4% of teens had a parent-reported GEC score ≥60. After adjusting for age, gender, and parent-reported DFR (pDFR) , those with GEC ≥60 had parent-reported RISQ (pRISQ) 4.1 points lower than those with GEC Conclusion: EF, especially metacognition, appears important for acquisition of self-care behaviors for teens with T1D. Evaluating EF during adolescence may identify teens with executive dysfunction who may need extra support during the transition process. Disclosure R.J.Vitale: None. L.J.Tinsley: None. L.K.Volkening: None. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. Funding NIH T32DK007529NIH P30DK036836NIH R01DK095273JDRF 2-SRA-2014-253-M-B

Objective Accurate and robust quality measurement is critical to the future of value-based care. Having incomplete information when calculating quality measures can cause inaccuracies in reported patient outcomes. This research examines how quality calculations vary when using data from an individual electronic health record (EHR) and longitudinal data from a health information exchange (HIE) operating as a multisource registry for quality measurement. Materials and Methods Data were sampled from 53 healthcare organizations in 2018. Organizations represented both ambulatory care practices and health systems participating in the state of Kansas HIE. Fourteen ambulatory quality measures for 5300 patients were calculated using the data from an individual EHR source and contrasted to calculations when HIE data were added to locally recorded data. Results A total of 79% of patients received care at more than 1 facility during the 2018 calendar year. A total of 12 994 applicable quality measure calculations were compared using data from the originating organization vs longitudinal data from the HIE. A total of 15% of all quality measure calculations changed (P Discussion These results demonstrate that quality measures calculated using single-site EHR data may be limited by incomplete information. Effective data sharing significantly changes quality calculations, which affect healthcare payments, patient safety, and care quality. Conclusions Federal, state, and commercial programs that use quality measurement as part of reimbursement could promote more accurate and representative quality measurement through methods that increase clinical data sharing.

Objective: Diabetes mellitus is associated with poor outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Diabetic ketoacidosis (DKA) has also been reported to occur with this virus. A cluster of cases of euglycemic DKA (euDKA) was identified in patients with type 2 diabetes mellitus using sodium-glucose cotransporter-2 inhibitors (SGLT2is) who developed SARS-CoV-2 infection. Methods: The cases were identified by the authors while providing clinical care, and details were collected. Results: Five cases of euDKA, presenting with glucose levels

Primary hyperparathyroidism has been reported in pediatric patients presenting with slipped capital femoral epiphysis (SCFE), but never in patients with ectopic parathyroid adenoma. A 12-year-old boy with obesity and autism spectrum disorder presented with a limp and was found to have bilateral SCFE. Calcium was elevated to 12.3 mg/dL with parathyroid hormone (PTH) of 1191 pg/mL. Neck ultrasound revealed no parathyroid adenoma. He was discharged following bilateral surgical pinning with plans for outpatient workup. Repeat labs 5 days later demonstrated calcium had risen to 16.7 mg/dL. Technetium-99m sestamibi scintigraphy and a computed tomography scan revealed a 2.7 × 1.6 × 1.9 cm intrathymic mediastinal lesion. He underwent a thoracoscopic resection of the mass, and intraoperative PTH levels fell appropriately. Pathology revealed a parathyroid adenoma. Postoperatively, the patient developed hungry bone syndrome followed by normocalcemic secondary hyperparathyroidism which resolved with high-dose vitamin D supplementation. Primary hyperparathyroidism presenting as SCFE in a pediatric patient has been reported in 13 previous cases. This is the first reported case of bilateral SCFE arising from an ectopic parathyroid adenoma. Thoracoscopic resection is a relatively new approach in pediatrics. Primary hyperparathyroidism can be associated with SCFE, especially bilateral, and should be considered in patients with traditional risk factors for SCFE. Pediatric patients with primary hyperparathyroidism and negative neck imaging should be further evaluated for ectopic parathyroid adenomas with nuclear medicine or cross-sectional imaging that includes the head, neck, and mediastinum. Thoracoscopic resection can be considered in pediatric patients with mediastinal ectopic parathyroid adenoma.

SummaryThe integral membrane protein Apq12 is an important nuclear envelope (NE)/ER modulator that cooperates with the nuclear pore complex (NPC) biogenesis factors Brl1 and Brr6. How Apq12 executes these functions is unknown. Here we identified a short amphipathic α-helix (AαH) in Apq12 that links the two transmembrane domains in the perinuclear space and has liposome-binding properties. Cells expressing an APQ12 (apq12-ah) version in which AαH is disrupted show NPC biogenesis and NE integrity defects, without impacting upon Apq12-ah topology or NE/ER localization. Overexpression of APQ12 but not apq12-ah triggers striking over-proliferation of the outer nuclear membrane (ONM)/ER and promotes accumulation of phosphatidic acid (PA) at the NE. Apq12 and Apq12-ah both associate with NPC biogenesis intermediates and removal of AαH increases both Brl1 levels and the interaction between Brl1 and Brr6. We conclude that the short amphipathic α-helix of Apq12 regulates the function of Brl1 and Brr6 and promotes PA accumulation at the NE during NPC biogenesis.

Background: Although the prevalence of overweight and obesity (OW/OB) has increased in the last three decades, studies show that these conditions are sub-optimally documented by physicians. Health information technology tools have varying effects on improving documentation of OW/OB but often have to be complemented with other interventions to be effective. Objective: Upon identifying low rates of documentation of diagnoses of overweight and obesity by resident and attending physicians, despite the use of an electronic health record (EHR) with automated BMI calculations, we performed a quality improvement (QI) project to improve documentation of these diagnoses for patients in our community hospital primary care clinic. Methods: The EHR was reviewed to determine documentation rates by resident and attending physicians between 1 March 2018 and 31 September 2018. We collected pre-intervention data, developed interventions, and implemented tests of change using Plan-Do-Study-Act (PDSA) cycles to improve documentation of OW/OB. Results: Documentation of overweight and obesity diagnoses increased from a baseline of 46% to 79% over a 20-week period after initiation of our project. Conclusion: We demonstrate the successful implementation of resident-led, multi-faceted interventions in a team-based QI project to optimize documentation of OW/OB in the EHR.

Adjunctive therapies to insulin in the treatment of type 1 diabetes mellitus (T1D) have gained popularity in efforts to achieve glycemic targets, and sodium-glucose transporter inhibitors (SGLT inhibitors) are an appealing option due to associated weight loss, low risk of hypoglycemia, and significant improvements in cardiorenal outcomes seen in persons with type 2 diabetes mellitus (T2D). The increased risk of diabetic ketoacidosis (DKA), including euglycemic DKA, has led many to be wary of their use in T1D, especially given limited data regarding cardiorenal protection in this population and limited pediatric data overall. The phase 3 trials of these agents in T1D have yielded lower HbA1c, decreased total daily insulin dose, and small but significant weight loss with no increase in hypoglycemia. These trials also reported increased risks of genital mycotic infection and DKA. SGLT inhibitors have been approved as adjunctive therapy to insulin in adults with T1D in Europe and Japan, but the United States Food and Drug Administration has rejected similar applications. While several approaches to mitigate the risk of DKA have been developed, no randomized trials using such tools have been conducted. More research is needed to minimize risk of DKA and to better evaluate the cardiorenal impact of these agents in persons with T1D.

Nutrient discharge into rivers and estuaries and the factors that control it need to be further understood to decrease the risk of harmful algae blooms on these ecosystems. Preliminary seasonal physicochemical parameters at six stations along the Negro River Estuary (Argentina) were studied during 2019 (Austral summer, winter, and spring) with high- and low-frequency data. Three of the stations were mainly estuarine-influenced and three were marine-influenced ones. The concentration of phosphate (P), river discharge, meteorological conditions, seasonality, and physicochemical variables were analyzed. Total phosphorus (TP) showed seasonal variations and was higher than previously reported for the upper watershed in all stations in the warmer months, except for the marine control one. Orthophosphate values were also high compared to previous watershed data and changed independently of TP fluctuations. Changing turbidity, water temperature, pH, and conductivity did not appear to have an essential role in phosphorus variations. An unexplained high TP spike in the late spring sample shows the need for further research in the area, while the seawater mixing with P-rich river water could be acting as a dilution agent at the mouth of the river.

Primary care panel size plays an increasing role in measuring primary care provider (ie, physicians and advanced practice providers, which include nurse practitioners and physician assistants) workload, setting practice capacity, and determining pay and can influence quality of care, access, and burnout. However, reported panel sizes vary widely.To identify how panels are defined, the degree of variation in these definitions, the consequences of different definitions of panel size, and research on strengths of different approaches.Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, MEDLINE, Web of Science, Embase, and Dissertations and Theses Global databases were searched from inception to April 28, 2021, for subject headings and text words to capture concepts of primary care panel size. Article review and data abstraction were performed independently by 2 reviewers. Main outcomes reported included rules for adding or removing patients from panels, rules for measuring primary care provider resources, consequences of different rules on reported panel size, and research on advantages and disadvantages of different rules.The literature search yielded 1687 articles, with 294 potentially relevant articles and 74 containing relevant data. Specific practices were identified from 29 health care systems and 5 empanelment implementation guides. Patients were most commonly empaneled after 1 primary care visit (24 of 34 [70.6%]), but some were empaneled only after several visits (5 [14.8%]), enrollment in a health plan (4 [11.8%]) or any visit to the health care system (1 [3.0%]). Patients were removed when no visit had occurred in a specified look-back period, which varied from 12 to 42 months. Regarding primary care provider resources, half of organizations assigned advanced practice providers independent panels and half had them share panels with a physician, increasing the physician's panel by 50% to 100%. Analyses demonstrated that changes in individual rules for adding patients, removing patients, or estimating primary care provider resources could increase reported panel size from 20% to 100%, without change in actual primary care provider workload. No research was found investigating advantages of different definitions.Much variation exists in how panels are defined, and this variation can have substantial consequences on reported panel size. Research is needed on how to define primary care panels to best identify active patients, which could contribute to a widely accepted standard approach to panel definition.

Background: Primary hyperparathyroidism has been reported in 13 pediatric patients presenting with slipped capital femoral epiphysis (SCFE), but never in patients with ectopic parathyroid adenoma [1]. Case report: A 12-year-old boy with obesity (BMI 99th percentile) and autism spectrum disorder presented with a limp and was found to have bilateral SCFE. Calcium was elevated to 12.3 mg/dL (reference range 8.0–10.5) with phosphorus of 3.2 mg/dL (3.0–5.7), alkaline phosphatase 775 units/L (40–360), tubular reabsorption of phosphorus 89% (&gt 95%), 25OH-vitamin D 12.1 ng/mL (30–80), 1,25OH-vitamin D 246.6 pg/mL (19.9–79.3), and PTH 1191 pg/mL (10–65). He had significant neuropsychiatric agitation but denied constipation, polyuria, and other symptoms of hypercalcemia. He had in situ pinning of the SCFE bilaterally and was hyperhydrated with minimal improvement in his calcium level. Neck ultrasound revealed no parathyroid adenoma. He was discharged on cholecalciferol 1000 IU daily with plans for outpatient Tc-99m Sestamibi scintigraphy. Following discharge, he developed significant nausea, did not tolerate the cholecalciferol, and was non-weight bearing. Repeat labs and imaging 5 days later demonstrated calcium had risen to 16.7 mg/dL with phosphorus of 2.2 mg/dL. He was admitted and calcium improved transiently to less than 12 mg/dL with intranasal calcitonin therapy. Sestamibi and subsequent CT scan revealed a 2.7x1.6x1.9 cm ectopic parathyroid adenoma in the upper anterior mediastinum. He had thoracoscopic resection of the mass, which was revealed to be intrathymic, and PTH levels fell from 1613 pg/mL pre-operatively to 76 pg/mL 30 minutes post-resection. Post-operatively, he developed hungry bone syndrome with a calcium nadir of 7.6 mg/dL and phosphorus nadir of 1.6 mg/dL, which required oral calcium and calcitriol for 10 days. With normalization of his calcium, his neuropsychiatric symptoms improved. Pathology revealed a parathyroid adenoma. Conclusion: Primary hyperparathyroidism can be associated with SCFE and should be considered even in patients with traditional risk factors for SCFE, especially with bilateral disease. Pediatric patients with primary hyperparathyroidism and negative neck imaging should be further evaluated for ectopic parathyroid adenomas. References: 1. George, G.S., Raizada, N., Jabbar, P.K., Chellamma, J., Nair, A. Slipped Capital Femoral Epiphysis in Primary Hyperparathyroidism - Case Report with Literature Review. Indian J Endocrinol Metab. 2019 Jul-Aug;23(4):491–494.

Introduction Pancreatic cancer is a leading cause of death in North America and Western Europe with rising rates in the developing world. Endoscopic ultrasound (EUS) with FNA (fine needle aspiration) is a critical component in the evaluation and diagnosis of pancreatic lesions with a high sensitivity and specificity. In this paper, we report patients at our center who eventually developed pancreatic cancer despite an early negative EUS, and identifying factors that may result in a missed diagnosis. Methods The University of Louisville database was queried for patients who had a Whipple procedure for presumed benign disease and had a pre-operative EUS between 2008 and 2018. Patients who had pancreatic adenocarcinoma on final pathology were identified. Demographic, clinical, EUS, operative, and pathologic details were reviewed for each case in efforts to identify factors associated with failure to diagnose a pancreatic malignancy on EUS. Results Five patients who had pancreatic adenocarcinoma on final pathology were reviewed in detail and their cases are presented in the paper. Four of the patients had dilation of the common bile duct, three had chronic pancreatitis. Two of them had previous surgery on the pancreas or bile ducts. Conclusions All of the patients presented in the paper had variables that made their EUS evaluation challenging. A high index of suspicion must be maintained in patients that do not improve after appropriate treatment of their strictures or pancreatic lesions. In the future, new techniques, such as fine needle biopsy and biomarker assays, may improve diagnosis accuracy.

Aim Amidst COVID-19 pandemic, the health care delivery in India faces major challenges owing to the overwhelming hospitals, exhausted healthcare workers, and shortage of crucial medical supplies such as ventilators and oxygen. The study aims to propose a novel successful interventional home care model, the Virtual COVID In-Patient (VCIP) care for effective COVID management. Methods The Covid-19 positive patients enrolled in VCIP were chosen for the study. A 24/7 active multidisciplinary WhatsApp group was created for each patient, for remote monitoring of temperature, blood pressure, blood glucose, respiratory and pulse rate along with the symptoms. Advice on sleep and exercises were given along with the medication via video-audio consultations. Lab facility was provided at the doorstep. Training on various devices, medications including steroids, delivering subcutaneous injections etc were given via video platforms. Results Among the 220 patients who availed the VCIP facility, only two were hospitalized, yielding a 99.5 % success rate in preventing hospitalizations and patients enrolled have been immensely satisfied with their experience. Conclusions With similar pandemics anticipated in near future, VCIP model may be considered for successful domiciliary treatment and overcoming the challenges.

Kenya has increasingly relied on modern agricultural technology to increase productivity since land extensification is no longer a feasible option to satisfy national food demands. Hybrid maize varieties have been one of the more successful technologies developed, responsible for dramatic yield increases in the developed world since World War II and more recently as an integral part of the Green Revolution. The purpose of this paper is to investigate the factors that affect the adoption of hybrid maize varieties in Kenya. A household survey was conducted to collect data on demographic and socioeconomic factors, as well as to elicit farmers’ perceptions of the agronomic and consumption benefits of hybrid maize compared to open pollinated varieties. Using econometric (discrete choice) models, results showed that farmers’ perceive that hybrid maize provides significant benefits in obtaining higher yields, but are less effective protecting against drought. Several other demographic and socioeconomic variables also had positive effects on hybrid maize adoption including access to modern farm equipment, distance to market, age, gender, education level and occupation of the household head. As Kenya and other African countries look to biotechnology as a means to increase productivity, the seed industry will need to continue finding ways to develop genetically modified maize to improve drought protection. Key words: Hybrid maize, adoption, open pollinated variety, farmer’s preference, Kenya.

The US Environmental Protection Agency (USEPA) and several states are considering regulatory limits for hexavalent chromium (Cr(VI))

India has over 70 million citizens with diabetes, the second-most of any country worldwide. Disparities in learning skills, resources, education, and physician practices make it difficult to practically implement the diabetes management guidelines recommended by international scientific organizations. In its guidelines, the International Diabetes Federation advocates for three different levels of care based on availability of resources. This study investigates the differences in intermediate health outcomes between two diabetes care programs: one a comprehensive diabetes centre, the other a limited care setting. The comprehensive centre offers telemedicine and periodic diabetes education, empowering patients and providing 24-hour advice on lifestyle modifications, diet, and exercise. All patients of this centre practice self-monitoring of blood glucose. The subjects in the limited care setting receive minimal investigations and periodic physical follow-ups, and few patients have access to home glucose monitoring. The results showed that HbA1c (7.62 vs. 8.58, p=0.003), cholesterol (134.4 vs. 173.4, p

ObjectiveThe objective of this study was to improve the telephone communication experience for patients in a primary care practice.DesignAn exploratory survey was conducted that revealed suboptimal patient satisfaction with clinic access due to the telephone triage system. Several interventions were designed: a monthly quality meeting was established among clinic staff, all phone interactions were recorded in the electronic medical record (EMR) and clinic appointments were made available several months in advance. A follow-up survey was conducted to evaluate these interventions.SettingThe study was conducted in a multispecialty, urban-based, resident-faculty practice from November 2016 to November 2017.ParticipantsSubjects were recruited in a convenience sample from the waiting room. 200 subjects participated in the initial survey and 215 in the second survey.ResultsAfter the interventions, patients felt that their questions were answered more frequently than before (pConclusionImproving telephone triage through implementing a monthly quality improvement meeting, optimising use of the EMR and opening schedules several months in advance resulted in several improvements in the patient experience, but did not change use of emergency services. Further interventions, including increased resource allocation, are needed to optimise patient experience.

In theory, the logic of decision rules should be atomic. In practice, this is not always possible; initially simple logic statements tend to be overloaded with additional conditions restricting the scope of such rules. By doing so, the original logic soon becomes encumbered with contextual knowledge. Contextual knowledge is re-usable on its own and could be modeled separately from the logic of a rule without losing the intended functionality. We model constraints to explicitly define the context where knowledge of decision rules is actionable. We borrowed concepts from Semantic Web, Complex Adaptive Systems, and Contextual Reasoning. The proposed approach provides the means for identifying and modeling contextual knowledge in a simple, sound manner. The methodology presented herein facilitates rule authoring, fosters consistency in rules implementation and maintenance; facilitates developing authoritative knowledge repositories to promote quality, safety and efficacy of healthcare; and paves the road for future work in knowledge discovery.

The androgen receptor is a major driver of prostate cancer and inhibition of its transcriptional activity using competitive antagonists, such as enzalutamide remains a frontline therapy for prostate cancer management. However, the majority of patients eventually develop drug resistance. We propose that targeting the androgen receptor for degradation via Proteolysis Targeting Chimeras (PROTACs) will be a better therapeutic strategy for targeting androgen receptor signaling in prostate cancer cells. Here we perform a head-to-head comparison between a currently approved androgen receptor antagonist enzalutamide, and its PROTAC derivative, ARCC-4, across different cellular models of prostate cancer drug resistance. ARCC-4 is a low-nanomolar androgen receptor degrader able to degrade about 95% of cellular androgen receptors. ARCC-4 inhibits prostate tumor cell proliferation, degrades clinically relevant androgen receptor point mutants and unlike enzalutamide, retains antiproliferative effect in a high androgen environment. Thus, ARCC-4 exemplifies how protein degradation can address the drug resistance hurdles of enzalutamide.

Current drinking water standards for chromium are for the combined total of both hexavalent and trivalent chromium (Cr(VI) and Cr(III)). However, recent studies have shown that Cr(III) is not carcinogenic to rodents, whereas mice chronically exposed to high levels of Cr(VI) developed duodenal tumors. These findings may suggest the need for environmental standards specific for Cr(VI). Whether the intestinal tumors arose through a mutagenic or non-mutagenic mode of action (MOA) greatly impacts how drinking water standards for Cr(VI) are derived. Herein, X-ray fluorescence (spectro)microscopy (m-XRF) was used to image the Cr content in the villus and crypt regions of duodena from B6C3F1 mice exposed to 180 mg/l Cr(VI) in drinking water for 13 weeks. DNA damage was also assessed by c-H2AX immunostaining. Exposure to Cr(VI) induced villus blunting and crypt hyperplasia in the duodenum—the latter evidenced by lengthening of the crypt compartment by � 2-fold with a concomitant 1.5-fold increase in the number of crypt enterocytes. c-H2AX immunostaining was elevated in villi, but not in the crypt compartment. m-XRF maps revealed mean Cr levels >30 times higher in duodenal villi than crypt regions; mean Cr levels in crypt regions were only slightly above background signal. Despite the presence of Cr and elevated c-H2AX immunoreactivity in villi, no aberrant foci indicative of transformation were evident. These findings do not support a MOA for intestinal carcinogenesis involving direct Cr-DNA interaction in intestinal stem cells, but rather support a non-mutagenic MOA involving chronic wounding of intestinal villi and crypt cell hyperplasia.