Barriers to the Use of Insulin Therapy and Potential Solutions: A Narrative Review of Perspectives from the Asia-Pacific Region.

The rising prevalence of type 2 diabetes (T2D) is posing major challenges for the healthcare systems of many countries, particularly in the Asia-Pacific Region, in which T2D can present at younger ages and lower body mass index when compared with Western nations. There is an important role for insulin therapy in the management of T2D in these nations, but available evidence suggests that insulin is under-utilized and often delayed, to the detriment of patient prognosis. The authors of this article gathered as an advisory panel (representative of some of the larger Asia-Pacific nations) to identify their local barriers to insulin use in T2D, and to discuss ways in which to address these barriers, with their outputs summarized herein. Many of the key barriers identified are well-documented issues of global significance, including a lack of healthcare resources or of an integrated structure, insufficient patient education, and patient misconceptions about insulin therapy. Barriers identified as more innate to Asian countries included local inabilities of patients to afford or gain access to insulin therapy, a tendency for some patients to be more influenced by social media and local traditions than by the medical profession, and a willingness to switch care providers and seek alternative therapies. Strategies to address some of these barriers are provided, with hypothetical illustrative case histories.

Prevalence of, and factors associated with, diabetes mellitus in people with severe mental illness attending a multidisciplinary, outpatient cardiometabolic health assessment service.

INTRODUCTION: Evaluate the prevalence of, and factors associated with, diabetes in people with severe mental illness (SMI) attending the Collaborative Centre for Cardiometabolic Health in Psychosis (ccCHiP) tertiary referral clinics. RESEARCH DESIGN AND METHODS: Adult patients attending an initial ccCHiP clinic consultation (2014-2019) were studied. Diabetes was defined by an hemoglobin A1c of ≥6.5%, fasting blood glucose of ≥7.0 mmol/L, or a self-reported diagnosis of diabetes and prescription of antihyperglycemic medication. RESULTS: Over 5 years, 1402 individuals attended a baseline consultation. Mean age of 43.9±12.8 years, 63.1% male and 63.5% had a diagnosis of schizophrenia. Prevalence of diabetes was 23.0% (n=322); an additional 19.5% fulfilled criteria for pre-diabetes. Of those with diabetes, 15.8% were newly diagnosed. Of those with pre-existing diabetes, 84.5% were receiving treatment with antihyperglycemic medication. Over 94% of individuals with diabetes had dyslipidemia; half were current smokers; and 46.4% reported sedentary behavior. On multivariate analysis, diabetes was associated with older age, Aboriginal, Indian or Middle Eastern maternal ethnicity, elevated waist-to-height ratio, family history of diabetes and use of antipsychotic medication. CONCLUSION: Prevalence of diabetes mellitus in this multiethnic cohort with SMI is significantly higher than the Australian population. Targeted interventions via an assertive integrated approach are required to optimize cardiometabolic health in this population.

Impact of corticosteroids in hospitalised COVID-19 patients.

BACKGROUND: Corticosteroids are a potential therapeutic agent for patients with COVID-19 pneumonia. The RECOVERY (Randomised Trials in COVID-19 Therapy) trial provided data on the mortality benefits of corticosteroids. The study aimed to determine the association between corticosteroid use on mortality and infection rates and to define subgroups who may benefit from corticosteroids in a real-world setting. METHODS: Clinical data were extracted that included demographic, laboratory data and details of the therapy, including the administration of corticosteroids, azithromycin, hydroxychloroquine, tocilizumab and anticoagulation. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) admission and invasive mechanical ventilation. Outcomes were compared in patients who did and did not receive corticosteroids using the multivariate Cox regression model. RESULTS: 4313 patients were hospitalised with COVID-19 during the study period, of whom 1270 died (29.4%). When administered within the first 7 days after admission, corticosteroids were associated with reduced mortality (OR 0.73, 95% CI 0.55 to 0.97, p=0.03) and decreased transfers to the ICU (OR 0.72, 95% CI 0.47 to 1.11, p=0.02). This mortality benefit was particularly impressive in younger patients (<65 years of age), females and those with elevated inflammatory markers, defined as C reactive protein ≥150 mg/L (p≤0.05), interleukin-6 ≥20 pg/mL (p≤0.05) or D-dimer ≥2.0 µg/L (p≤0.05). Therapy was safe with similar rates of bacteraemia and fungaemia in corticosteroid-treated and non-corticosteroid-treated patients. CONCLUSION: In patients hospitalised with COVID-19 pneumonia, corticosteroid use within the first 7 days of admission decreased mortality and ICU admissions with no associated increase in bacteraemia or fungaemia.

Effects of intense pulsed light and gamma irradiation on Bacillus cereus spores in mesquite pod flour.

This study was conducted to evaluate the inactivation of Bacillus cereus spore in mesquite flour with intense pulsed light (IPL) and gamma radiation. The physical, chemical, and toxicity of treated mesquite flour were also investigated. The results showed that up to 3.51 log10CFU/g B. cereus spore inactivation was achieved with 8 kGy of gamma radiation, and up to 1.69 log10CFU/g reductions could be achieved after 28s of catalytic IPL exposure. Although chemometric analysis showed 9-hydroxy-10,12-octadecadienoic acid was slightly increased after a 28s-catalytic IPL treatment, the concentration is within the acceptable range. No significant increase in acetic or propionic acids (typical off-flavor volatile compounds) was observed after either treatment. For cytotoxicity, the Caco-2 cell viability analysis revealed that these two technologies did not induce significant cytotoxicity to the treated mesquite flour. Overall, these two technologies exhibit strong potential for the decontamination of B. cereus in mesquite flour.

Practical use of insulin degludec/insulin aspart in a multinational setting: beyond the guidelines.

Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec, which provides long-lasting basal insulin coverage, and insulin aspart, which targets postprandial glycaemia. This review provides expert opinion on the practical clinical use of IDegAsp, including: dose timings relative to meals, when and how to intensify treatment from once-daily (OD) to twice-daily (BID) dose adjustments, and use in special populations (including hospitalized patients). IDegAsp could be considered as one among the choices for initiating insulin treatment, preferential to starting on basal insulin alone, particularly for people with severe hyperglycaemia and/or when postprandial hyperglycaemia is a major concern. The recommended starting dose of IDegAsp is 10 units with the most carbohydrate-rich meal(s), followed by individualized dose adjustments. Insulin doses should be titrated once weekly in two-unit steps, guided by individualized fasting plasma glucose targets and based on patient goals, preferences and hypoglycaemia risk. Options for intensification from IDegAsp OD are discussed, which should be guided by HbA1c, prandial glucose levels, meal patterns and patient preferences. Recommendations for switching to IDegAsp from basal insulin, premixed insulins OD/BID, and basal-plus/basal-bolus regimens are discussed. IDegAsp can be co-administered with other antihyperglycaemic drugs; however, sulphonylureas frequently need to be discontinued or the dose reduced, and the IDegAsp dose may need to be decreased when sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists are added. Considerations around the initiation or continuation of IDegAsp in hospitalized individuals are discussed, as well as in those undergoing medical procedures.

Heterogeneity in Economic and Carbon Benefits of Electric Technology Vehicles in the US.

To broadly contribute to sustainable mobility, electric technology vehicles (hybrid, electric, and plug-in-hybrid) must become more price competitive with internal combustion vehicles. This study assesses the economic and carbon benefits of electric technology vehicles in the U.S., accounting for household-by-household behavioral variability and geographical differences in fuel and electricity prices. This finer resolution provides insight into subsets of the population for whom adoption is economically or environmentally favorable, allowing us to construct marginal abatement cost curves for CO2 that account for geographic, behavioral, and stock heterogeneities. Currently, low gasoline prices and high initial expense means that, without subsidies, few consumers benefit financially from electric technology vehicles (1.7% of drivers). However, improved technology dramatically and nonlinearly increases both the number of consumers that benefit and corresponding carbon emissions that could be abated without government subsidy. Our results clarify cost targets that electric vehicle technology must achieve in order to deliver net financial and subsidy-free environmental benefits.

Routine glucose assessment in the emergency department for detecting unrecognised diabetes: a cluster randomised trial.

OBJECTIVE: To determine whether routine blood glucose assessment of patients admitted to hospital from emergency departments (EDs) results in higher rates of new diagnoses of diabetes and documentation of follow-up plans. DESIGN, SETTING: Cluster randomised trial in 18 New South Wales public district and tertiary hospitals, 31 May 2011 - 31 December 2012; outcomes follow-up to 31 March 2016. PARTICIPANTS: Patients aged 18 years or more admitted to hospital from EDs. INTERVENTION: Routine blood glucose assessment at control and intervention hospitals; automatic requests for glycated haemoglobin (HbA1c ) assessment and notification of diabetes services about patients at intervention hospitals with blood glucose levels of 14 mmol/L or more. MAIN OUTCOME MEASURE: New diagnoses of diabetes and documented follow-up plans for patients with admission blood glucose levels of 14 mmol/L or more. RESULTS: Blood glucose was measured in 133 837 patients admitted to hospital from an ED. The numbers of new diabetes diagnoses with documented follow-up plans for patients with blood glucose levels of 14 mmol/L or more were similar in intervention (83/506 patients, 16%) and control hospitals (73/278, 26%; adjusted odds ratio [aOR], 0.83; 95% CI 0.42-1.7; P = 0.61), as were new diabetes diagnoses with or without plans (intervention, 157/506, 31%; control, 86/278, 31%; aOR, 1.51; 95% CI, 0.83-2.80; P = 0.18). 30-day re-admission (31% v 22%; aOR, 1.34; 95% CI, 0.86-2.09; P = 0.21) and post-hospital mortality rates (24% v 22%; aOR, 1.07; 95% CI, 0.74-1.55; P = 0.72) were also similar for patients in intervention and control hospitals. CONCLUSION: Glucose and HbA1c screening of patients admitted to hospital from EDs does not alone increase detection of previously unidentified diabetes. Adequate resourcing and effective management pathways for patients with newly detected hyperglycaemia and diabetes are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12611001007921.

Household food waste collection: Building service networks through neighborhood expansion.

In this paper we develop a residential food waste collection analysis and modeling framework that captures transportation costs faced by service providers in their initial stages of service provision. With this framework and model, we gain insights into network transportation costs and investigate possible service expansion scenarios faced by these organizations. We solve a vehicle routing problem (VRP) formulated for the residential neighborhood context using a heuristic approach developed. The scenarios considered follow a narrative where service providers start with an initial neighborhood or community and expands to incorporate other communities and their households. The results indicate that increasing household participation, decreases the travel time and cost per household, up to a critical threshold, beyond which we see marginal time and cost improvements. Additionally, the results indicate different outcomes in expansion scenarios depending on the household density of incorporated neighborhoods. As household participation and density increases, the travel time per household in the network decreases. However, at approximately 10-20 households per km2, the decrease in travel time per household is marginal, suggesting a lowerbound household density threshold. Finally, we show in food waste collection, networks share common scaling effects with respect to travel time and costs, regardless of the number of nodes and links.

Rates of hypoglycaemia are lower in patients treated with insulin degludec/liraglutide (IDegLira) than with IDeg or insulin glargine, regardless of the hypoglycaemia definition used.

AIMS: To re-analyse, using a series of alternative hypoglycaemia definitions, the data from 2 trials, DUAL I and V, in which the once-daily, fixed ratio combination of insulin degludec/liraglutide (IDegLira) was compared with basal insulin therapy. MATERIAL AND METHODS: Post hoc analyses of the DUAL I (patients uncontrolled on oral antidiabetic drugs) and DUAL V (patients uncontrolled on insulin glargine (IGlar) U100) trials were carried out using different definitions of hypoglycaemia and according to whether treatments were administered in the morning or afternoon. Rates of hypoglycaemia for the definitions of confirmed and American Diabetes Association (ADA)-documented symptomatic hypoglycaemia were compared according to age, gender and body mass index (BMI). RESULTS: Although hypoglycaemia rates differed according to the alternative hypoglycaemia definitions, rates were consistently lower with IDegLira vs insulin degludec (IDeg) and IGlar U100. Despite glycated haemoglobin concentrations being lower with IDegLira at end of treatment, confirmed and nocturnal-confirmed hypoglycaemia rates were lower for IDegLira vs IDeg and IGlar U100, irrespective of dosing time. The definitions of confirmed and ADA-documented symptomatic hypoglycaemia did not have a significant effect on the treatment difference between IDegLira and IDeg, liraglutide or IGlar U100 when further assessed by baseline age, gender and BMI. CONCLUSIONS: Treatment with IDegLira, vs IDeg and IGlar U100, resulted in lower rates of hypoglycaemia regardless of dosing time and definition of hypoglycaemia used. The choice of hypoglycaemia definition did not influence the results of analyses when stratified by age, sex and BMI.

Relationship between depression and diabetes in pregnancy: A systematic review.

AIM: To systematically review the literature on women with both diabetes in pregnancy (DIP) and depression during or after pregnancy. METHODS: In this systematic literature review, PubMed/MEDLINE and EMBASE were searched (13 November 2015) using terms for diabetes (type 1, type 2, or gestational), depression, and pregnancy (no language or date restrictions). Publications that reported on women who had both DIP (any type) and depression or depressive symptoms before, during, or within one year after pregnancy were considered for inclusion. All study types were eligible for inclusion; conference abstracts, narrative reviews, nonclinical letters, editorials, and commentaries were excluded, unless they provided treatment guidance. RESULTS: Of 1189 articles identified, 48 articles describing women with both DIP and depression were included (sample sizes 36 to > 32 million). Overall study quality was poor; most studies were observational, and only 12 studies (mostly retrospective database studies) required clinical depression diagnosis. The prevalence of concurrent DIP (any type) and depression in general populations of pregnant women ranged from 0% to 1.6% (median 0.61%; 12 studies). The prevalence of depression among women with gestational diabetes ranged from 4.1% to 80% (median 14.7%; 16 studies). Many studies examined whether DIP was a risk factor for depression or depression was a risk factor for DIP. However, there was no clear consensus for either relationship. Importantly, we found limited guidance on the management of women with both DIP and depression. CONCLUSION: Given the increasing prevalence of diabetes and depression, high-quality research and specific guidance for management of pregnant women with both conditions are warranted.

Design and characterization of a nanopore-coupled polymerase for single-molecule DNA sequencing by synthesis on an electrode array.

Scalable, high-throughput DNA sequencing is a prerequisite for precision medicine and biomedical research. Recently, we presented a nanopore-based sequencing-by-synthesis (Nanopore-SBS) approach, which used a set of nucleotides with polymer tags that allow discrimination of the nucleotides in a biological nanopore. Here, we designed and covalently coupled a DNA polymerase to an α-hemolysin (αHL) heptamer using the SpyCatcher/SpyTag conjugation approach. These porin-polymerase conjugates were inserted into lipid bilayers on a complementary metal oxide semiconductor (CMOS)-based electrode array for high-throughput electrical recording of DNA synthesis. The designed nanopore construct successfully detected the capture of tagged nucleotides complementary to a DNA base on a provided template. We measured over 200 tagged-nucleotide signals for each of the four bases and developed a classification method to uniquely distinguish them from each other and background signals. The probability of falsely identifying a background event as a true capture event was less than 1.2%. In the presence of all four tagged nucleotides, we observed sequential additions in real time during polymerase-catalyzed DNA synthesis. Single-polymerase coupling to a nanopore, in combination with the Nanopore-SBS approach, can provide the foundation for a low-cost, single-molecule, electronic DNA-sequencing platform.

Plication procedures-excisional and incisional corporoplasty and imbrication for Peyronie's disease.

Plication procedures for the correction of Peyronie's disease (PD) curvature are management options for PD patients. There are basically three types of procedures: excisional corporoplasty, incisional corporoplasty, and plication-only. This review is a compilation of English literature, peer-reviewed, published articles addressing these types of operations for Peyronie's curvature correction, not congenital curvature. According to the urology literature, this surgical type was initially used for correction of curvature associated with hypospadias repair or congenital penile curvature. The procedures also, for the most part, historically became an alternative for plaque excision and graft repair, because of the difficulty with such repairs and the often-resultant erectile dysfunction (ED). A brief section traces some of the origins of these various repairs, followed by a brief section on the selection criteria for these types of surgery for the patient with PD penile curvature. We also review the significant articles in which the three types were presented with modifications. Finally, several articles that compare the various surgical repairs are summarized in the order that they appear in the literature. These types of surgery have become a mainstay for the surgical correction of penile curvature due to PD.

Real-time single-molecule electronic DNA sequencing by synthesis using polymer-tagged nucleotides on a nanopore array.

DNA sequencing by synthesis (SBS) offers a robust platform to decipher nucleic acid sequences. Recently, we reported a single-molecule nanopore-based SBS strategy that accurately distinguishes four bases by electronically detecting and differentiating four different polymer tags attached to the 5'-phosphate of the nucleotides during their incorporation into a growing DNA strand catalyzed by DNA polymerase. Further developing this approach, we report here the use of nucleotides tagged at the terminal phosphate with oligonucleotide-based polymers to perform nanopore SBS on an α-hemolysin nanopore array platform. We designed and synthesized several polymer-tagged nucleotides using tags that produce different electrical current blockade levels and verified they are active substrates for DNA polymerase. A highly processive DNA polymerase was conjugated to the nanopore, and the conjugates were complexed with primer/template DNA and inserted into lipid bilayers over individually addressable electrodes of the nanopore chip. When an incoming complementary-tagged nucleotide forms a tight ternary complex with the primer/template and polymerase, the tag enters the pore, and the current blockade level is measured. The levels displayed by the four nucleotides tagged with four different polymers captured in the nanopore in such ternary complexes were clearly distinguishable and sequence-specific, enabling continuous sequence determination during the polymerase reaction. Thus, real-time single-molecule electronic DNA sequencing data with single-base resolution were obtained. The use of these polymer-tagged nucleotides, combined with polymerase tethering to nanopores and multiplexed nanopore sensors, should lead to new high-throughput sequencing methods.

Continent Catheterizable Vesicostomy: An Alternative Surgical Modality for Pediatric Patients With Large Bladder Capacity.

OBJECTIVE: To present a modified technique and early outcomes of a continent catheterizable vesicostomy in pediatric patients with either flaccid neurogenic bladder or intractable voiding dysfunction and large capacity bladder. METHODS: Six patients underwent the procedure from October 2014 to December 2015. A 4-cm Pfannenstiel incision was made, avoiding intraperitoneal dissection. After adequate mobilization, a 2-cm vertical flap at the dome of the bladder was identified and tubularized over a 12Fr catheter with 4-0 vicryl suture. The tubularized flap was then intussuscepted into the bladder with four 4-0 polydioxanone sutures, creating a continent mechanism. The catheterizable channel was then tunneled to the umbilicus, the channel ostomy matured, and the cystotomy closed in two layers. RESULTS: The median patient age was 8 (interquartile range [IQR] 12) years. All patients had urinary dysfunction requiring drainage from etiologies that included Eagle-Barrett syndrome (n = 2), Noonan syndrome (n = 1), Lennox-Gastaut syndrome (n = 1), and Spina bifida (n = 2). Median hospital length of stay was 8 (IQR 3) days. One patient had a superficial wound infection treated with antibiotics, and 1 patient required balloon dilation of the catheterizable channel at 3 months postoperatively, secondary to difficulty self-catheterizing. Five patients were successfully self-catheterizing at last follow-up. Median follow-up was 6 (IQR 5) months and there were no intra- or perioperative complications. CONCLUSION: Continent catheterizable vesicostomy is a novel technique for urinary drainage in patients with large bladder capacity that spares use of the appendix or ileum. Early results are encouraging, providing a catheterizable channel through the umbilicus without urinary leakage between catheterization.

Composition homogeneity in InGaAs/GaAs core-shell nanopillars monolithically grown on silicon.

Alloy composition homogeneity plays an important role in the device performance of III-V heterostructures. In this work, we study the spatial composition uniformity of n-In0.12Ga0.88As/i-In0.2Ga0.8As/p-GaAs core-shell nanopillars monolithically grown on silicon. Cross sections extracted along the axial and radial directions are examined with transmission electron microscopy and energy-dispersive X-ray spectroscopy. Interestingly, indium-deficient segments with width ∼5 nm are observed to develop along the radial ⟨112̅0⟩ directions in the InGaAs layers. We attribute this spontaneous ordering to capillarity effect and difference in group-III adatom diffusion lengths. The slight fluctuation in indium content (∼4%), however, does not induce any noticeable misfit defects in the pure wurtzite-phased crystal. In contrast, the heterostructure exhibits excellent alloy composition uniformity along the axial [0001] direction. Furthermore, abrupt transitions of gallium and indium are seen at the heterointerfaces. These remarkable properties give rise to extraordinary optical performances. Lasing is achieved in the core-shell nanopillars upon optical pump despite the observed alloy composition fluctuation in the radial directions. The results here reveal the potential of the InGaAs-based core-shell heterostructures as efficient optoelectronic devices and high-speed heterojunction transistors directly integrated on silicon.

Nanophotonic integrated circuits from nanoresonators grown on silicon.

Harnessing light with photonic circuits promises to catalyse powerful new technologies much like electronic circuits have in the past. Analogous to Moore's law, complexity and functionality of photonic integrated circuits depend on device size and performance scale. Semiconductor nanostructures offer an attractive approach to miniaturize photonics. However, shrinking photonics has come at great cost to performance, and assembling such devices into functional photonic circuits has remained an unfulfilled feat. Here we demonstrate an on-chip optical link constructed from InGaAs nanoresonators grown directly on a silicon substrate. Using nanoresonators, we show a complete toolkit of circuit elements including light emitters, photodetectors and a photovoltaic power supply. Devices operate with gigahertz bandwidths while consuming subpicojoule energy per bit, vastly eclipsing performance of prior nanostructure-based optoelectronics. Additionally, electrically driven stimulated emission from an as-grown nanostructure is presented for the first time. These results reveal a roadmap towards future ultradense nanophotonic integrated circuits.

Tailoring the optical characteristics of microsized InP nanoneedles directly grown on silicon.

Nanoscale self-assembly offers a pathway to realize heterogeneous integration of III-V materials on silicon. However, for III-V nanowires directly grown on silicon, dislocation-free single-crystal quality could only be attained below certain critical dimensions. We recently reported a new approach that overcomes this size constraint, demonstrating the growth of single-crystal InGaAs/GaAs and InP nanoneedles with the base diameters exceeding 1 µm. Here, we report distinct optical characteristics of InP nanoneedles which are varied from mostly zincblende, zincblende/wurtzite-mixed, to pure wurtzite crystalline phase. We achieved, for the first time, pure single-crystal wurtzite-phase InP nanoneedles grown on silicon with bandgaps of 80 meV larger than that of zincblende-phase InP. Being able to attain excellent material quality while scaling up in size promises outstanding device performance of these nanoneedles. At room temperature, a high internal quantum efficiency of 25% and optically pumped lasing are demonstrated for single nanoneedle as-grown on silicon substrate. Recombination dynamics proves the excellent surface quality of the InP nanoneedles, which paves the way toward achieving multijunction photovoltaic cells, long-wavelength heterostructure lasers, and advanced photonic integrated circuits.