A systematic review on multipotent carcinogenic agent, N-nitrosodiethylamine (NDEA), its major risk assessment, and precautions.

The International Agency for Research on Cancer has classified N-nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A of compounds that are probably harmful to humans. It is found in nature and tobacco smoke, along with its precursors, and is also synthesized endogenously in the human body. The oral or parenteral administration of a minimal quantity of NDEA results in severe liver and kidney organ damage. The NDEA required bioactivation by CYP450 enzyme to form DNA adduct in the alkylation mechanism. Thus, this bioactivation directs oxidative stress and injury to cells due to the higher formation of reactive oxygen species and alters antioxidant system in tissues, whereas free radical scavengers guard the membranes from NDEA-directed injury in many enzymes. This might be one of the reasons in the etiology of cancer that is not limited to a certain target organ but can affect various organs and organ systems. Although there are various possible approaches for the treatment of NDEA-induced cancer, their therapeutic outcomes are still very dismal. However, several precautions were considered to be taken during handling or working with NDEA, as it considered being the best way to lower down the occurrence of NDEA-directed cancers. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter the antioxidant line to cause malignancy in different parts of animal body along with its protective agents. Thus, revelation to constant, unpredictable stress situations even in common life may remarkably augment the toxic potential through the rise in the oxidative stress and damage of DNA.

Budget Impact Analysis of Intensification with iGlarLixi Compared to Alternative Treatment Strategies Among Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: The clinical benefits of treating patients with type 2 diabetes mellitus (T2DM) with fixed-ratio combination of insulin iGlar (iGlar) plus lixisenatide (iGlarLixi) were demonstrated in clinical trials and real-world evidence studies; however, its cost impact to healthcare payers is unknown. METHODS: A budget impact model was developed from a United States (US) payer's perspective for a hypothetical healthcare plan of 1 million people over a 1-year time horizon. In scenario analysis, patients with uncontrolled glycated hemoglobin (HbA1c) treated with 60 units or less of daily insulin (insulin cohort) or oral antidiabetic drugs (OADs) only (OAD cohort) were intensified to iGlarLixi/rapid-acting insulin (RAI)/glucagon-like peptide 1 receptor agonists (GLP-1RA) or iGlarLixi/iGlar/GLP-1RA, respectively. Model inputs from real-world data (RWD) included baseline market shares, proportion of patients intensifying to respective treatments, and dosing inputs; unit costs were obtained from published literature. One-way sensitivity analyses assessed the impact of individual parameters. RESULTS: Intensification with iGlarLixi resulted in the lowest incremental per member per month (PMPM) budget impact compared to other intensifying drugs (iGlar, RAI, and GLP-1RA). In the insulin cohort, the incremental PMPM cost for intensification with iGlarLixi ($0.03) was the lowest among intensifying drugs; GLP-1RA ($72.20) and RAI ($4.81). Similarly, the incremental PMPM cost for intensification with iGlarLixi was the lowest ($1.25) in the OAD cohort among intensifying drugs; GLP-1RA ($321.65) and iGlar ($114.82). In scenario analyses, when equal market intensification shares for iGlarLixi and GLP-1RA were explored, the incremental PMPM cost for iGlarLixi ($0.03) remained lower than GLP-1RA ($2.28) and RAI ($10.44) in the insulin cohort. CONCLUSIONS: Intensification with iGlarLixi was associated with lower costs compared to other treatment intensifications, as well as overall budget reductions compared to pre-intensification when considering cost savings attributable to reduction in HbA1c; therefore, its inclusion for the treatment of T2DM would represent a budget saving.

Neurophysiological and gait outcomes during a dual-task gait assessment in concussed adolescents.

BACKGROUND: Gait deficits are common after concussion in adolescents. However, the neurophysiological underpinnings of these gait deficiencies are currently unknown. Thus, the goal of this study was to compare spatiotemporal gait metrics, prefrontal cortical activation, and neural efficiency between concussed adolescents several weeks from injury and uninjured adolescents during a dual-task gait assessment. METHODS: Fifteen concussed (mean age[SD]: 17.4[0.6], 13 female, days since injury: 26.3[9.9]) and 17 uninjured adolescents (18.0[0.7], 10 female) completed a gait assessment with three conditions repeated thrice: single-task walking, single-task subtraction, and dual-task, which involved walking while completing a subtraction task simultaneously. Gait metrics were measured using an inertial sensor system. Prefrontal cortical activation was captured via functional near-infrared spectroscopy. Neural efficiency was calculated by relating gait metrics to prefrontal cortical activity. Differences between groups and conditions were examined, with corrections for multiple comparisons. FINDINGS: There were no significant differences in gait metrics between groups. Compared to uninjured adolescents, concussed adolescents displayed significantly greater prefrontal cortical activation during the single-task subtraction (P = 0.01) and dual-task (P = 0.01) conditions with lower neural efficiency based on cadence (P = 0.02), gait cycle duration (P = 0.03), step duration (P = 0.03), and gait speed (P = 0.04) during the dual-task condition. INTERPRETATION: Our findings suggest that several weeks after injury concussed adolescents demonstrate lower neural efficiency and display a cost to gait performance when cognitive demand is high, e.g., while multitasking, suggesting that the concussed adolescent brain is less able to compensate when attention is divided between two concurrent tasks.

Pythagorean fuzzy entropy measure-based complex proportional assessment technique for solving multi-criteria healthcare waste treatment problem.

With the increasing risk to human health and environmental issues, the selection of appropriate management and treatment of healthcare waste has become a major problem, especially in developing countries. There are various alternatives to dispose of health care waste. The important is to assess the best alternative among them. The assessment of each alternative should be done based on public health, psychological, economic, environmental, technological, and operational aspect. The selection of the best health care waste treatment (HCWT) alternative is a complicated, multi-criteria decision-making (MCDM) problem involving numerous disparate qualitative and quantitative features. Hence, in this research article, the MCDM method is presented for estimating and choosing the best alternative of HCWT by COPRAS technique in a Pythagorean fuzzy set (PFS). Here, in this paper, first of all, a new entropy measure on PFSs is proposed and its validity is studied. Thereafter, the MCDM technique Complex Proportional Assessment (COPRAS) is discussed in which the criteria weights are assessed by the proposed entropy measure and score function to enhance an efficacy and efficiency of the proposed technique. Furthermore, the above-defined technique is employed to resolve the real-life problem to obtain the best treatment alternative to disposal of the health care waste. Finally, sensitivity analysis is presented to rationale the proposed viewpoint for prioritizing HCWT alternatives.

A new approach to airway assessment-"Line of Sight" and more. Recommendations of the Task Force of Airway Management Foundation (AMF).

Assessment of airway is recommended by every airway guideline to ensure safe airway management. Numerous unifactorial and multifactorial tests have been used for airway assessment over the years. However, there is none that can identify all the difficult airways. The reasons for the inadequacy of these methods of airway assessment might be their dependence on difficult to remember and apply mnemonics and scores, inability to identify all the variations from the "normal", and their lack of stress on evaluating the non-patient factors. Airway Management Foundation (AMF) experts and members have been using a different approach, the AMF Approach, to overcome these problems inherent to most available models of airway assessment. This approach suggests a three-step model of airway assessment. The airway manager first makes the assessment of the patient through focused history, focused general examination, and focused airway assessment using the AMF "line of sight" method. The AMF "line of sight" method is a non-mnemonic, non-score-based method of airway assessment wherein the airway manager examines the airway along the line of sight as it moves over the airway and notes down all the variations from the normal. Assessment of non-patient factors follows next and finally there is assimilation of all the information to help identify the available, difficult, and impossible areas of the airway management. The AMF approach is not merely intubation centric but also focuses on all other methods of securing airway and maintaining oxygenation. Airway assessment in the presence of contagion like COVID-19 is also discussed.