Low bone turnover associates with lower insulin sensitivity in newly diagnosed drug-naïve persons with type 2 diabetes

Context Bone turnover markers (BTMs) are lower in type 2 diabetes mellitus (T2D). The relationships between bone turnover, β-cell function, and insulin sensitivity in T2D are uncertain. Objective To investigate if fasting levels of BTMs in persons with T2D are associated with β-cell function or insulin sensitivity. Methods We defined three T2D phenotypes, the insulinopenic (low β-cell function, high insulin sensitivity), the classical (low β-cell function, low insulin sensitivity), and the hyperinsulinemic (high β-cell function, low insulin sensitivity) phenotypes, in the Danish Centre for Strategic Research T2D cohort using the homeostatic model assessment. We selected age- and gender-matched subgroups to represent the three T2D phenotypes, yielding 326 glucose-lowering treatment–naïve persons with T2D. Median values of BTMs between the three T2D phenotypes were compared. Regression models were applied to assess the association between BTMs, β-cell function, and insulin sensitivity adjusted for potential confounders. Results Median serum levels of procollagen type I N-terminal propeptide, C-terminal telopeptide of type I collagen, and osteocalcin were higher in the insulinopenic phenotype (52.3 μg/L, IQR 41.6, 63.3; 259.4 ng/L, IQR 163.4, 347.7; and 18.0 μg/L, IQR 14.4, 25.2, respectively) compared with the classical (41.4, IQR 31.0, 51.4; 150.4 IQR 103.5, 265.1; 13.1, IQR 10.0, 17.6, respectively) and the hyperinsulinemic (43.7, IQR 32.3, 57.3; 163.3, IQR 98.9, 273.1; 15.7 IQR 10.2, 20.8, respectively) phenotypes (all P < .01). These differences persisted after adjustment for age, sex, waist to hip ratio, or fasting plasma glucose (P < .01). Conclusion BTMs are lower in newly diagnosed persons with T2D characterized by low insulin sensitivity

Sex‐ and age group‐specific fracture incidence rates trends for type 1 and 2 diabetes mellitus

The incidence of major osteoporotic fractures has declined in men and women in Western countries over the last two decades. Although fracture risk is higher in persons with diabetes mellitus, trends of fractures remain unknown in men and women with diabetes. We investigated the trends in fracture incidence rates (IRs) in men and women with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) in Denmark between 1997 and 2017. We identified men and women aged 18+ years who sustained a fracture (excluding skull and facial fractures) between 1997 and 2017 using the Danish National Patient Registry. We calculated sex-specific IRs of fractures per 10,000 person-years separately in persons with T1D, T2D, or without diabetes. Furthermore, we compared median IRs of the first 5 years (1997–2002) to the median IRs of the last 5 years (2012–2017). We identified 1,235,628 persons with fractures including 4863 (43.6% women) with T1D, 65,366 (57.5% women) with T2D, and 1,165,399 (54.1% women) without diabetes. The median IRs of fractures declined 20.2%, 19.9%, and 7.8% in men with T1D, T2D, and without diabetes, respectively (p-trend <0.05). The median IRs decreased 6.4% in women with T1D (p-trend = 0.35) and 25.6% in women with T2D (p-trend <0.05) but increased 2.3% in women without diabetes (p-trend = 0.08). Fracture IRs decreased in men with both diabetes types and only in women with T2D, highlighting the need for further attention behind the stable trend observed in women with T1D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research

KCNV2-associated retinopathy: detailed retinal phenotype and structural endpoints-KCNV2 study group report 2

PURPOSE: To describe the detailed retinal phenotype of KCNV2-associated retinopathy.STUDY DESIGN: Multicenter international retrospective case series.METHODS: Review of retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), including qualitative and quantitative analyses.RESULTS: Three distinct macular FAF features were identified: (1) centrally increased signal (n = 35, 41.7%), (2) decreased autofluorescence (n = 27, 31.1%), and (3) ring of increased signal (n = 37, 44.0%). Five distinct FAF groups were identified based on combinations of those features, with 23.5% of patients changing the FAF group over a mean (range) follow-up of 5.9 years (1.9-13.1 years). Qualitative assessment was performed by grading OCT into 5 grades: (1) continuous ellipsoid zone (EZ) (20.5%); (2) EZ disruption (26.1%); (3) EZ absence, without optical gap and with preserved retinal pigment epithelium complex (21.6%); (4) loss of EZ and a hyporeflective zone at the foveola (6.8%); and (5) outer retina and retinal pigment epithelium complex loss (25.0%). Eighty-six patients had scans available from both eyes, with 83 (96.5%) having the same grade in both eyes, and 36.1% changed OCT grade over a mean follow-up of 5.5 years. The annual rate of outer nuclear layer thickness change was similar for right and left eyes.CONCLUSIONS: KCNV2-associated retinopathy is a slowly progressive disease with early retinal changes, which are predominantly symmetric between eyes. The identification of a single OCT or FAF measurement as an endpoint to determine progression that applies to all patients may be challenging, although outer nuclear layer thickness is a potential biomarker. Findings suggest a potential window for intervention until 40 years of age. (C) 2021 The Authors. Published by Elsevier Inc.Ophthalmic researc

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Aqueous dispersions of carbon black and its hybrid with carbon nanofibers

The aqueous dispersions of a special type of carbon black (CB) in 1 M lithium bis(trifluoromethanesulfonimide) electrolyte is mainly controlled by the affinity of the aqueous electrolyte towards the CB particles rather than the particle size. In spite of its small particle size (30 nm), this type of CB forms a three-dimensional open network which is rheologically and electrically percolated at a relatively high threshold (2.0 wt%) with enhanced rheological and electrical properties. At this percolating threshold, replacing a trace amount of CB with equivalent carbon nanofibers (CNFs) produces hybrid dispersions with higher electrical conductivity and comparable rheological behavior to pure CB dispersions. This hybrid dispersion is dominated by a cooperatively supporting network, which is wired by the flexible filamentous nanofibers so that it is able to recover the conductivity loss under flow conditions due to flow-induced breaking up of the conductive pathways of CB and presumably sustain a higher load of active materials. This finding suggests hybrid dispersions as a promising precursor in the formulation of electrode suspensions for aqueous semi-solid redox flow cells. 2018 The Royal Society of Chemistry.M. Youssry would like thank Cabot Corporation, USA and 3M, France for providing, respectively, the carbon black and lithium salt, and Dr Nasr Bensalah for helping in conducting the impedance spectra. We would like to thank the staff of Central Lab Unit at Qatar University for performing SEM and Raman spectra. This work was partially supported by an internal grant (QUST-CAS-SPR-2017-6) from Qatar University

Development of a polyacrylamide-based mud formulation for loss circulation treatments

Loss circulation materials in the last two decades have witnessed a lot of developments and implementations. New technologies and materials are introduced to treat various types of loss zones. However, the success rate is still very low due to many uncertainties in the selection of types and particle size of the bridging materials. In addition, there are many operational restrictions such as the risk of plugging and pumping difficulties when large size of particle is needed, especially in deep-water drilling. In this study, polyacrylamide (PAM) crosslinked with polyethylenimine (PEI) is introduced as polymer-based mud for loss circulation treatment. The PAM/PEI systems have wide applications in water shutoff for high water production zones and are known for their strong gel and exceptional rheological properties. This study provides a rheological method for screening of PAM/PEI-based drilling formulation with optimized molecular weight and concentrations. Comparative analysis of rheology of non-crosslinked and crosslinked polyacrylamide with other drilling fluids additives as well as proper mixing procedures are provided. The results achieved in this study are used as a strong tool to design a polymer-based mud with competitive rheological properties which achieved an 80% reduction in fluid loss when compared with other conventional loss circulation materials.The authors would like to thank the Qatar National Research Fund (a member of Qatar Foundation) for funding this study, this paper was made possible by an NPRP Grant # NPRP10-0125-170240. The authors also thank SNF Floerger Group, France, for providing the materials for the tests. The statements made herein are solely the responsibility of the authors.Scopu

Loss circulation in drilling and well construction: The significance of applications of crosslinked polymers in wellbore strengthening: A review

Loss circulation is one of the major concerns in drilling and well construction. The uncontrolled flow of fluids into formation while drilling or primary cementing lead to substantial non-productive time (NPT). The methods of wellbore strengthening (WS) maximize the pressure that the wellbore can withstand before fractures is initiated or propagated, which is the key parameter in prevention and mitigation of loss circulation. The cross-linkable polymers among various loss circulation materials (LCM) are considered an efficient plugging material that can seal wide range of fracture sizes, strengthen the wellbore and provide solution for lost circulations under extreme drilling conditions. This paper reviews the applications of wellbore strengthening and summarizes various filed practices used for preventive and corrective treatment of loss circulations. The paper highlights the development of crosslinked polymers for wellbore strengthening and the significance of using acrylamide polymer systems as LCM. The review also covers the application of commercially available types of polymers and crosslinkers and their performance in high pressure/high temperature (HPHT) wells. The loss circulation in geothermal drilling, and in challenging HPHT is discussed. The types of formations cause loss circulation, the methods of locating loss zones, and summary of recent literatures on the effect of crosslinking process on gelation time, thermal stability and formation damage is also included.This paper was made possible by an NPRP Grant # NPRP10-0125-170240 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors.Scopu

A comprehensive rheological study for a flowing polymer-based drilling fluid used for wellbore strengthening

Loss circulation encountered in highly fractured formations, depleted reservoir, or HP/HT intervals is the root cause of many problems plaguing the oil and gas sector for many years. High pore pressure narrows the window of safe drilling, while in depleted reservoir fracture pressure is remarkably reduced, which may lead to a lower pressure-bearing capacity. Therefore, a proper predrill wellbore strengthening strategy is needed to anticipate wellbore issues and design drilling fluids that strengthen unstable formations. This study benefits from the successful applications of polymers in water shut-off. Whereas polymers are used to entirely plugs high water productive zones, the flowing polymer-based mud (PBM) is proposed and evaluated to enhance wellbore strengthening. Based on the API drilling fluids testing procedures, varied polyacrylamide/polyethyleneimine PAM/PEI systems were tested and ammonium chloride (NH4Cl) is added as a retarder to control gelling time as need. Base fluid formulated with PAM/PEI was optimized to attain the desired rheological properties. Weighting and other commercial essential additives were also added, and the formula is tested for rheology, stability, and sealing efficacy. Our proposed PBM formula with proper concentration of polymer in water and optimized PAM to PEI ratio is found to be highly competitive in comparison with the conventional methods of loss circulation prevention and wellbore strengthening techniques. This paper introduces an innovative design for a flowing polymer-based mud (PBM) for wellbore strengthening and provides wide-range of assessment. Moreover, the essential rheological characteristics revealed in this study for several PAM/PEI mud systems under various conditions can set the stage for wide application of these muds globally where tremendous reduction in drilling non-productive time (NPT) can be achieved.This paper was made possible by an NPRP Grant # NPRP10-0125-170240 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors.Scopu