Clinical inertia is the enemy of therapeutic success in the management of diabetes and its complications: A narrative literature review

Diabetes mellitus is a chronic disease characterized by high social, economic and health burden, mostly due to the high incidence and morbidity of diabetes complications. Numerous studies have shown that optimizing metabolic control may reduce the risk of micro and macrovascular complications related to the disease, and the algorithms suggest that an appropriate and timely step of care intensification should be proposed after 3 months from the failure to achieve metabolic goals. Nonetheless, many population studies show that glycemic control in diabetic patients is often inadequate. The phenomenon of clinical inertia in diabetology, defined as the failure to start a therapy or its intensification/de-intensification when appropriate, has been studied for almost 20 years, and it is not limited to diabetes care, but also affects other specialties. In the present manuscript, we have documented the issue of inertia in its complexity, assessing its dimensions, its epidemiological weight, and its burden over the effectiveness of care. Our main goal is the identification of the causes of clinical inertia in diabetology, and the quantification of its social and health-related consequences through the adoption of appropriate indicators, in an effort to advance possible solutions and proposals to fight and possibly overcome clinical inertia, thus improving health outcomes and quality of care

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Is Climate Change Time-Reversible?

This paper proposes strategies to detect time reversibility in stationary stochastic processes by using the properties of mixed causal and noncausal models. It shows that they can also be used for non-stationary processes when the trend component is computed with the Hodrick-Prescott filter rendering a time-reversible closed-form solution. This paper also links the concept of an environmental tipping point to the statistical property of time irreversibility and assesses fourteen climate indicators. We find evidence of time irreversibility in greenhouse gas emissions, global temperature, global sea levels, sea ice area, and some natural oscillation indices. While not conclusive, our findings urge the implementation of correction policies to avoid the worst consequences of climate change and not miss the opportunity window, which might still be available, despite closing quickly

Exfoliated black phosphorus gas sensing properties at room temperature

Room temperature gas sensing properties of chemically exfoliated black phosphorus (BP) to oxidizing (NO2, CO2) and reducing (NH3, H-2, CO) gases in a dry air carrier have been reported. To study the gas sensing properties of BP, chemically exfoliated BP flakes have been drop casted on Si3N4 substrates provided with Pt comb-type interdigitated electrodes in N2 atmosphere. Scanning electron microscopy and x-ray photoelectron spectroscopy characterizations show respectively the occurrence of a mixed structure, composed of BP coarse aggregates dispersed on BP exfoliated few layer flakes bridging the electrodes, and a clear 2p doublet belonging to BP, which excludes the occurrence of surface oxidation. Room temperature electrical tests in dry air show a p-type response of multilayer BP with measured detection limits of 20 ppb and 10 ppm to NO2 and NH3 respectively. No response to CO and CO2 has been detected, while a slight but steady sensitivity to H-2 has been recorded. The reported results confirm, on an experimental basis, what was previously theoretically predicted, demonstrating the promising sensing properties of exfoliated BP

Response to NO<inf>2</inf> and other gases of resistive chemically exfoliated MoS<inf>2</inf>-based gas sensors

We report on the fabrication, the morphological, structural, and chemical characterization, and the study of the electrical response to NO2 and other gases of resistive type gas sensors based on liquid chemically exfoliated (in N-methyl pyrrolidone, NMP) MoS2 flakes annealed in air either at 150 °C or at 250 °C. The active material has been analyzed by scanning electron microscopy (SEM), and micro Raman and X-ray core level photoemission spectroscopies. SEM shows that MoS2 exfoliated flakes are interconnected between electrodes of the sensing device to form percolation paths. Raman spectroscopy of the flakes before annealing demonstrates that the flakes are constituted by crystalline MoS2, while, annealing at 250 °C, does not introduce a detectable bulk contamination in the expected form of MoO3. The sensor obtained by thermal annealing in air at 150 °C exhibits a peculiar p-type response under exposure to NO2. In line with core level spectroscopy evidences, this behavior is potentially ascribed to nitrogen substitutional doping of S vacancies in the MoS2 surface (nitrogen atoms being likely provided by the intercalated NMP). Thermal annealing the MoS2 flakes in air at 250 °C irreversibly sets an n-type behavior of the gas sensing device, with a NO2 detection limit of 20 ppb. This behavior is assigned, in line with core level spectroscopy data, to a significant presence of S vacancies in the MoS2 annealed flakes and to the surface co-existence of MoO3 arising from the partial oxidation of the flakes surface. Both p- and n-type sensors have been demonstrated to be sensitive also to relative humidity. The n-type sensor shows good electrical response under H2 exposure

A simple all-solution approach to the synthesis of large ZnO nanorod networks

Soft-lithography of Zn-loaded hydrogels and a subsequent hydrothermal growth process yield self-assembling networks of bridging ZnO nanorods (NRs). They are grown on seeding micropillars of ZnO until they touch, forming junctions that provide a preferred electrical path for the operative current of functional devices (e.g. gas senors)

High GADA titer increases the risk of insulin requirement in LADA patients: A 7-year follow-up (NIRAD study 7)

Objective: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. Methods: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. Results: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes ( P2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (PIC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients

Graphene Oxide as a Practical Solution to High Sensitivity Gas Sensing

Graphene and its related materials have attracted much interest in sensing applications because of their optimized ratio between active surface and bulk volume. In particular, several forms of oxidized graphene have been studied to optimize the sensing efficiency, sometimes moving away from practical solutions to boost performance. In this paper, we propose a practical, high-sensitivity, and easy to fabricate gas sensor based on high quality graphene oxide (GO), and we give the rationale to the high performance of the device. The device is fabricated by drop-casting water-dispersed single-layer GO flakes on standard 30 mu m spaced interdigitated Pt electrodes. The exceptional size of the GO flakes (27 mu m mean size and similar to 500 mu m maximum size) allows single GO flake to bridge electrodes. A typical p-type response is observed by testing the device in both reducing and oxidizing environments. The specific response to NO2 is studied by varying the operating temperature and the gas concentration. Sensing activity is demonstrated to be mainly mediated by the oxygen functional groups. A 20 ppb detection limit is measured. Besides illustrating a simple and efficient approach to gas sensing, this work is an example of the versatility of graphene oxide, accomplishing tasks that are complementary to graphene. adjacen

High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7).

OBJECTIVE: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. METHODS: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. RESULTS: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P&lt;0.0001 for both). A BMI of ≤25 kg/m2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P&lt;0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P&lt;0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P&lt;0.0001, OR=6.95). CONCLUSIONS: High GADA titer, BMI ≤ 25, ZnT8 and IA-2IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients