Friday, April 30, 2021

Iris Publishers- Open access Journal of Pediatrics & Neonatal Care | Neonatal Survival Improvement in Dominican Republic through effective Collaboration of the Iberoamerican Society of Neonatology (SIBEN)

 


Authored by  Augusto Sola*

Abstract

Background: The Iberoamerican Society of Neonatology (SIBEN) dedicates efforts to facilitate the dissemination of knowledge and contributes to the well-being of NB in the Latin American region. In the Dominican Republic, the neonatal mortality rate was 17‰ in 2018, among the highest in Latin America. Through an agreement between the National Health System (NHS) of the country and SIBEN, actions were planned, developed and implemented to improve care of sick newborns (NB) at risk of dying.

Objective: To describe the actions implemented and to present the results obtained in the first year of collaborative work.

Methods: Multidimensional interventions in the context of continuous quality improvement of care in all public hospitals of the country where neonatal care is delivered. The main components of the comprehensive program were: detailed monitoring of vital statistics; situational diagnosis working in the field, including assessment of clinical management and procedures, education, NB and family issues, staff issues, infrastructure, equipment, and legal/regulatory and ethical issues, in order to institute an appropriate “hierarchy of interventions”. In addition, we performed root cause analysis (RCA) in deceased NB and incorporated data collection system in the neonatal units through SIBEN’s neonatal network. Finally, we also performed a preliminary cost analysis.

Results: The country’s neonatal mortality rate decreased from 17‰ in 2018 to 12.1‰ in 2019, with a relative risk reduction of 26%. There were improvements in infrastructure, equipment and staffing, together with modifications in clinical management and procedures and education and training. More than 600 neonatal health care professionals were trained, including nurses, neonatologists and neonatology residents.

By root cause analysis (RCA), of 511 infants who died, 54% were <1500 grams and pulmonary hemorrhage (PH) was the most frequent cause.

During 2019, 3,347 NB were admitted to 11 neonatal intensive care units (NICU) hospitals and reported to SIBEN’s Network. Comparing data from the first semester of 2019 with the second semester, mortality in the NICU’s decreased from 22.5% to 19%, detection of significant patent ductus arteriosus improved and PH frequency decreased. The cost of the program was approximately 1,100 dollars per each of the newborn whose life was saved.

Conclusion: One year after the collaborative agreement between SIBEN and NHS started, organization and delivery of care to sick NB in public hospitals of the Dominican Republic improved, and has led to a significant increase in neonatal survival. This was due to education and to definite improvements in the provision of neonatal intensive care, in a cost-effective manner.

Keywords: Neonatal mortality; Education; Neonatal health services

Abbreviations: NHS: National Health Service of the Dominican Republic; SIBEN: Iberoamerican Society of Neonatology; NB: Newborn; PH: Pulmonary hemorrhage; RCA: Root cause analysis; NICU: Neonatal intensive care unit

Introduction

In the Dominican Republic the population is 11,000,000, the birth rate is 18‰, with about 180,000 births per year [1], and the neonatal mortality in previous years has been >18‰. Of all births, 14% of NB are of low birth weight (<2,500 grams) and 1.5-2.3% are <1,500 grams. These rates are higher than the average for Latin America and the Caribbean [1,2]. More than 74% of children who die before 12 months of age are ≤ 28 days old [1]. In the first half of 2018, of a total of 1,961 infant’s deaths, 1,461 (74.5%) occurred before 28 days of age [1].

In this country >98% of births occur in hospitals [1,2] and two years ago, two maternity hospitals with a high number of births reported a very high neonatal mortality rate, 31-39‰ [3]. Likewise, the caesarean section rate in the Dominican Republic is >65% [4], with higher rates in the private sector than in the public sector.

In its mission to implement actions to reduce neonatal mortality rates, the National Health System (NHS) incorporated concrete measures to improve neonatal care. Among them, on October 31, 2018, they called upon SIBEN to collaborate in the efforts to improve the care of sick and at-risk neonates through various actions, including education of neonatal health care professionals. The agreement was signed by the general director of the NHS, Mr Chanel Rosa Chupany and the medical director of SIBEN, Augusto Sola.

SIBEN is a non-profit and public charity organization registered in the United States, under the federal tax and legal regulations of that country. Its main mission is to collaborate to improve neonatal care through education in the Latin American region [5]. In accordance with its bylaws, SIBEN dedicates its efforts to the diffusion of knowledge with an ethical approach, including equity, intersectoral and interdisciplinary methodologies, in order to identify and implement medical, human and social solutions for sick NB and their families. This has been done through various faceto- face and interactive educational methods in multiple regions of Latin America as demonstrated in multiple publications, some of which are listed in the bibliographic references [6,9].

The social, economic, preventive and nutritional actions that can have an effective impact in improving neonatal morbidity and mortality, if properly implemented, are multiple and have been described in detail [10-12]. Within this exhaustive and comprehensive framework, SIBEN focuses fundamentally on one aspect, aiming its actions directly towards improving the quality of intra-institutional care in three key periods for NB’s at risk of dying: the immediate prenatal period, the fetal-neonatal transition period and during the stay in neonatal intensive care. To do this, it implements and adapts, according to local needs and possibilities, programs to improve the quality of direct care, which have been widely described by others [13-19].

Objective

Describe the actions implemented by SIBEN in the Dominican Republic within the agreement with the NHS and present results obtained that led to the improvement of neonatal quality of care and neonatal survival in a cost-effective manner.

Methods

The program started at the end of 2018 within the framework of the SIBEN-NHS agreement and was based on the search for strategies and the implementation of actions to improve neonatal survival in the Dominican Republic by 2019.

All complex health interventions require a multidimensional approach and for this we established stages of diagnosis, planning and specific actions. The modality of the interventions was developed following the procedures described for the continuous improvement of quality of care [13-19]. As proposed by Deming and Shewhart, the “PDSA” cycle involves planning, doing, studying and acting [12]. These iterative cycles are based on the application of the best available evidence, the comparative evaluation of the results with permanent feedback and a collaborative process of mutual learning across all institutions. For all the stages we planned a dynamic interaction in order to adapt the strategies to the reality of each institution, to the identified findings and to the feasibility of change. We developed a “road map” that included the components described in this manuscript, actions to be implemented for each and their expected results. We summarize below the methods used related to vital statistics and neonatal survival, situational diagnosis, education, and information systems.

Vital statistics and neonatal survival

Number of births, neonatal mortality and prematurity rates were obtained from the General Epidemiology System (GEPIS) of the Ministry of Public Health (MPH) of the Dominican Republic [1]. We used these data to compare 2018 (pre-intervention) with 2019 (intervention in course). Statistical analysis included measures of effect with their respective confidence intervals.

Situational diagnosis

We planned to evaluate various basic aspects related to quality of neonatal care in the following areas: a) infrastructure, equipment and supplies (availability of O2 and compressed air, blenders, continuous positive airway pressure (CPAP), surfactant, respirators and others; b) human resource endowment and education (doctors, nurses and residents); c) use of protocols and procedures (name of the NB, family access, and diagnosis and treatment of prevalent diseases, including neonatal sepsis). This was carried out by SIBEN neonatologists and nurses in the maternity wards with the highest number of deliveries, in order to identify priority situations to be modified. The analysis of all the reports was carried out together with the local responsible MD’s and RN’s.

Education (October 2018 - December 2019)

Educational actions were planned according to SIBEN programs. The following were adapted locally so that most doctors and nurses could participate:

Dialogues SIBEN: An educational activity for doctors and nurses with an interactive and participatory approach.

Field activities (hospital visits): Sequential visits to all maternity wards to improve and modify management guidelines in inpatient care.

Residents: In agreement with the Ministry of Public Health and the Autonomous University, a training program was developed for all neonatology residents, in person or remotely, for training in neonatal topics relevant to neonatal survival.

Nursing: the SIBEN nursing chapter designed educational activities in practical workshops and in the field to improve the care of the NB and the performance of procedures.

Information systems

As the continuous improvement cycles require a fairly rapid sequence of “data - information - action”, we established two additional mechanisms for information, in addition to the evidence provided by GEPIS: i) analysis of neonatal deaths according to the standardized techniques of root cause analysis method [20,21], and ii) systematized data through SIBEN’s Neonatal Network.

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Iris Publishers- Open access Journal of Pediatrics & Neonatal Care | Reflections on How to Maintain and Improve Perinatal Care in the Midst of the COVID 19 Pandemic: Let’s not Forget Mothers and Newborn Babies!

 


Authored by Augusto Sola*

Abstract

Background: The current COVID-19 pandemic has become the most serious public health problem in the world. To respond to COVID-19 pandemia, many countries are using a combination of containment and mitigation activities, with solidarity efforts and resources and funds devoted to its prevention and intensive treatment. To date (April 6, 2020) there are about 1,360,000 confirmed cases and there have been 75,700 deaths reported in 205 countries. However, no serious harm has been reported in infants born to mothers with SARS-CoV-2. Current data suggest that vertical transmission of SARS-CoV-2 is at least uncommon. On the other hand, in many nations overall neonatal mortality rates remain high despite the fact that more than 50% of the neonatal deaths are reducible.

Objective: Analyze overall population mortality rates in the USA, China and in the 7 Latin American countries with the highest number of births to subsequently compare such data to: a) the mortality due to the COVID-19 pandemic to date, and b) to the current neonatal mortality rates and reducible neonatal mortality in the same regions of the world.

Methods: Data were obtained from several sources, including Federal Centers for Disease Control and Prevention; Johns Hopkins University and Global Health Observatory data repository. Data was compared through tables and descriptive measures. Estimations were performed to assess contribution of mortality due to COVID 19 to the overall mortality and to compare the population mortality and the neonatal mortality due to COVID 19 to neonatal mortality and to reducible neonatal deaths.

Findings: The average number of people dying every day from diverse causes in the 7 Latin American nations combined is 8,930, in the USA is approximately 7,880 and in China 26,000 people die every day. The contribution of the mortality due to COVID 19 to the general mortality to date is about 0,1-0,99 ‰. The number of persons who have died per day due to COVID 19 is estimated to be 120 in USA, and it was 37 in China, and this is reducible mortality. Neonatal mortality due to COVID-19 has occurred in 1 infant reported to date, and it seems to be extremely rare. In contrast, combining the yearly neonatal deaths from the 7 Latin American nations together with China and the USA, about 399 newborns die every day during one year. Close to 70,000 newborn infants die per year in the 7 Latin American countries with the largest populations. Eliminating neonatal reducible deaths by improving quality of perinatal care, there would be about 35,000 deaths less per year. In China and the USA decreasing reducible mortality could lead to at least 10,000 more infants surviving every year.

Conclusion: Significant efforts and funds are being dedicated to eliminate COVID 19 as a cause of death and they are starting to prove to be effective to eliminate or significantly reduce COVID 19 as a cause of reducible mortality. If reducible neonatal deaths were approached in a similar way, unnecessary and preventable neonatal mortality would cease to exist or be significantly reduced, with drastically less economic costs.

In addition, perinatal and neonatal care should not suffer by this pandemia. Long-term consequences of unnecessary termination of pregnancy, preventing breastfeeding and separation of the mother from the newborn can be very harmful. As pediatricians, neonatologists and neonatal nurses we must not distract our care efforts as this may negatively impact over perinatal well-being. Moreover, recommendations that contradict known evidence cannot and should not be made at this time

Keywords: COVID 19; Perinatal care; Neonatal mortality

Abbreviations: NICU: Newborn intensive care unit; CRP: C-reactive protein; PCT: Procalcitonin; EOBS: Early onset bacterial sepsis; WHO: World Health Organization; NEC: Necrotizing enterocolitis; BPD: Bronchopulmonary dysplasia; AMR: Antimicrobial resistance; NNT: Number needed to treat; SIBEN: Ibero american society of neonatology

Introduction

Novel coronavirus infection is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was named coronavirus disease 2019 (COVID-19) by the World Health Organization on January 7, 2020. The disease spread rapidly throughout China, and has now become a global pandemic. During the first 3 months of 2020, new major epidemic foci of (COVID-19) have been identified and are rapidly expanding in Europe, North America, Asia, and the Middle East, with the first confirmed cases identified more recently in developing African and Latin American nations.

To respond to COVID-19 pandemia, many countries are using a combination of containment and mitigation activities [1], but, today, it is currently difficult to estimate what the impact of this pandemic will be on global health. To date (April 6, 2020) there are about 1,360,000 confirmed cases and there have been 75,700 deaths reported in 205 countries [2]. These numbers will change in the coming weeks and, although projections could be made according to case fatality ratio data, they are still unpredictable.

A comprehensive report published by the Chinese Center for Disease Control and Prevention on 72,314 patients with COVID-19, showed that the case fatality ratio ranged from 2.9% in Hubei province to 0.4% in other Chinese provinces [3].

As COVID-19 has spread rapidly across the world, significant solidarity efforts and resources have been devoted to its prevention and intensive treatment of severely affected individuals and never before have so many of the world’s researchers focused so urgently on a single topic. The evidence and knowledge of this condition in only starting to be emerging at the present time, but there are still many unknowns and uncertainties.

Despite the sharp increase in the number of COVID-19 infections for the adult population, the incidence and clinical presentations of pediatric COVID-19 infections are varied and differ from those found in adult patients. Current data suggest that vertical transmission of SARS-CoV-2 is at least uncommon and that the virus may not pass to breast milk. Nevertheless, the neonatal population is of course vulnerable to this disease. However, the clinical course of the few infants born to mothers infected with SARS-CoV-2 reported to date varied in the available publications and only a few of them had severe illness and adverse courses that were clearly attributable to COVID 19 [4-9]. On the other hand, in many nations overall neonatal mortality rates are high and have improved too slowly during the last several years, even though it is known that in most places more than 50% of neonatal deaths are reducible deaths. When this viral pandemia ends, what lessons would we have learnt to act with sensitivity and energy in order to face and improve bad indicators of other stable and well understood pandemics, such as the reducible mortality of newborns in the world due to conditions for which prevention and treatment are well known?

Objective

This study aimed to analyze overall population mortality rates in the USA, China and in the 7 Latin American countries with the largest populations to subsequently compared such data to: a) the mortality due to the COVID-19 pandemic to date, and b) to the current neonatal mortality rates and reducible neonatal mortality in the same regions of the world.

Methods

Demographic, epidemiologic and mortality rates data were obtained from several sources, including Federal Centers for Disease Control and Prevention; Johns Hopkins University [10] and Global Health Observatory data repository - WHO [11]. The data gathered included total population and its mortality rates per year, COVID-19 deaths to date (April 6, 2020), live births per year and neonatal mortality rates, for the Latin American countries with the highest number of births, the USA and China. Data was compared through tables and descriptive measures. Estimations were performed to assess contribution of mortality due to COVID-19 to the overall mortality and also to compare mortality due to COVID-19 to neonatal mortality and to reducible neonatal deaths.

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Thursday, April 29, 2021

Iris Publishers- Open access Journal of Online Journal of Modern Concepts in Material Science | Bending Properties of Graphene Reinforced Aluminium Matrix Composite Produced by Casting Process

 


Authored by Derya Dispinar*

Abstract

The use of graphene as reinforcement for many materials has become popular due to the enhanced properties it has. In this work, different casting methods were aimed to be used in order to produce graphene reinforced aluminum matrix composites. Sand casting, lost foam casting, die casting and squeeze casting methods were used. Graphene was added as layers and also in aluminum foils for incorporation of the reinforcer to the matrix. It was found that squeeze casting was the best method for the production of composite. Bending strength was increased 25-50% for 0.1 wt% graphene added A356 alloy.

Keywords: Aluminum; Graphene; Composite; Casting; Bending

Introduction

The term composite is defined by combining two materials at the macro level in order to enhance the best properties of two or more same or different groups of materials in a broad sense. In other words, they can be called materials consisting of different kinds of materials or phases which are combined with each other in order to obtain superior properties by improving each other’s weakness.

It is possible to classify composite materials in two classes according to the shapes of the constituent materials and components [1].

a) According to the type of matrix material;

• Plastic Matrix Composite

• Metallic Matrix Composite

• Ceramic Matrix Composites

b) According to the structure components;

• Particle Reinforced Composites

• Fiber Reinforced Composites

• Layered Composites

• Filled Composites

3XX series aluminum cast alloys contain silicon as the main

alloying element, are widely used in industry. With the addition of silicon to the aluminum, fluidity, weldability, mechanical properties are increased, as well as the ability to perform special processes such as heat treatment and modification are positively affected. Silicon content of the cast alloys is 25% maximum if the alloy is produced by powder metallurgy, the amount of silicon can be up to 50% by weight [2].

Graphene was first introduced in 1994 by Boehm [3] where the properties are summarized in Table 1.

Experimental

10 kg of A356 aluminum alloy charge was melted at 750°C in resistance furnace in SiC crucible. Moulds were prepared as lost foam, sand cavity and permanent moulds in the dimension of 120 mm length, 20 mm wide and 20 mm thickness in the shape of rectangular bars.

For the casting trials, two methods were used to add graphene to the cast piece. In the first method, graphene was placed in aluminum foil which was placed vertically in the mold cavity and the melt was poured. In the second method, graphene was added to the surface of the melt during pouring. For the lost foam castings, the graphene was added as layers in between the foams, and then the melt was poured. Thixoforging was also applied to the cast piece which was produced by casting and then heating the graphene reinforced sample to 630°C, held for 20 minutes and then forged under 220 bar pressure. For squeeze casting, after the melt was poured into the mould cavity together with graphene, the melt was pressurized at 150bar in the mould under 30 ton presses. All these methods were investigated in order to achieve higher wettability and homogeneous distribution of graphene into the matrix.

Samples were characterized by metallographic, SEM, EDS and CT scan analyzes. 3-point bending test was carried out for mechanical property determination.

Results

SEM images of the graphene found in the matrix are given in Figure 1. For many of the trials, particularly when aluminum foils were used, the graphene appeared to stay in between the foils and foil was not melted and graphene was not distributed into the matrix.

When thixoforging and squeeze casting was used, more sound and homogeneous structure was observed. The CT scan images of these samples are given in Figure 2. For the rest of the casting trials particularly lost foam and sand casting, highly porous cast parts with agglomerated graphene were observed.

The best composite production was achieved when squeeze casting was used. Three-point bending tests are given in Figure 3a. The dark data represents the alloy without any graphene addition and the light blues are the composites. Weibull analysis of the findings is given in Figure 3b. As can be seen, the scatter of the results is given by Weibull modulus where it is 6.48 and 3.69 for stress and displacement, respectively. The characteristic values were recorded from Weibull analysis and it was found that stress was 26,04MPa and displacement was 5,84mm. For the base alloy, these values correspond to 20.7MPa and 3.46 mm. According to these findings, by graphene addition, the stress was increased by 25.7% and displacement was enhanced by 68%. However, it is important to note that the bending results show a scatter which was based on the distribution of graphene into the matrix..

Conclusion

Production of graphene reinforced A356 alloy was quite challenging mainly due to the density difference and wettability of graphene. Different casting techniques were used to achieve good distribution of graphene into the matrix. Squeeze casting was found to be successful. The bending stress and displacement were enhanced by 25% by graphene addition to 356 alloys. The mechanical properties were scattered to do the inhomogeneous distribution of graphene and formation of porosity due to agglomeration.

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Iris Publishers- Open access Journal of Online Journal of Modern Concepts in Material Science | Hall Effect Phenomena

 


Authored by Thanassis Speliotis*

Opinion

The anomalous Hall Effect phenomenon has a long history behind it which is connected to the history of magnetism and electricity. In 1879 Erwin H. Hall, made a historic discovery [1] at the University of Baltimore, that when a conductor or semiconductor with current flowing in one direction was introduced to a perpendicular magnetic field H, a voltage could be measured at right angles to the current path. Later in 1881 he reported that this effect was ten times larger in ferromagnetic iron [2]. It is remarkable, though, that the first Hall discovery was made almost three decades prior to the electron discovery by J.J. Thomson in 1897. Since the transverse resistance (or Hall resistance), defined as UH/I, is proportional to H/n, where n is the sheet carrier density of the sample, the Hall effect provides a simple sophisticated method, that has been extensively used, to compute the carrier type (electron or hole), density, and the mobility of materials. The ability to calculate the carrier concentration in nonmagnetic conductors and semiconductors has played a critical role for the birth of semiconductor physics and solid state electronics. The second Hall discovery in ferromagnetic conductors is known as the anomalous Hall Effect (AHE) (Figure 1).

In ferromagnetic materials the resistivity of the sample in the direction that is perpendicular to external electric E and magnetic H field acquires an additional contribution due to the magnetization of the sample [4,5]:

where R0 is the Hall coefficient, Rs is the anomalous Hall coefficient, ρOH is the ordinary Hall resistivity and ρAH is the anomalous Hall resistivity.

The AHE is used today for the purposes of modern spintronics and is a unique tool for generating and controlling spin-polarized currents in complex magnetic nanoscale systems. The understanding of the mechanisms of the AHE is necessary for further developments in the field of spin Hall Effect and the related phenomena, which are based on propagation of pure spin currents without accompanying charge transport (Figure 2).

The recent progress in understanding the AHE from the approach of Berry phases and the topological structure of the electronic bands led to the point that many abstract quantities and objects in this part of quantum physics became measurable and achievable to explore experimentally.

Figure 2 clarifies the two main extrinsic contributions to AHE and spin Hall Effect (SHE) that are described below, specifically, skew scattering (a) and side-jump scattering (b). Both are caused by spin–orbit coupling (SOC), that is, the electron partially orbits around an impurity atom and thereby creates a small orbital moment, which depends on the spin through SOC. The impurity is not certainly magnetic, but a magnetization is mandatory to create a net voltage. (No net magnetic moment is essential for the SHE). The skew scattering changes the direction of the electron velocity v, creating a perpendicular component Δv and a net electron displacement TRΔv, where TR =l/v is the relaxation time.

Side-jump scattering does not amount to a perpendicular velocity component (Δv=0) but a finite displacement Δr.

Skew scattering is linear in the resistivity ρxx and dominates in rather pure metals, whereas side-jump scattering scales as ρ2 xx, and dominates in reasonably disordered metals. There is also an intrinsic (resistivity-independent) Hall contribution due to the Berry phase. This contribution influences the periodic electronic structure of the material.

In the 1980s it was found that when the charge carriers are confined to a two-dimensional (2D) film, the Hall resistance becomes quantized at h/(ve2), where h is the Planck constant, e is the electron charge, and v is a positive integer and H/n approaches precise values. This phenomenon was named the quantum Hall effect (QHE) [7] and the presence of an external magnetic field is necessary for its observation.

The spin Hall effect (SHE) predicted by Russian physicists Mikhail I. Dyakonov and Vladimir I. Perel in 1971 [8] involves the presence of spin accumulation on the edge of the surfaces of a sample carrying electric current. The opposite surface boundaries will have spins of opposite sign and thus it is equivalent to the classical Hall Effect. No magnetic field is needed for the SHE which is a purely spin-based phenomenon. Experimentally it was realized about 30 years later [9] in unstrained gallium arsenide and strained indium gallium arsenide semiconductors. The SHE belongs to the same family as the anomalous Hall Effect, that was already known in ferromagnetic materials and both originate from the spin-orbit interaction.

The quantum spin Hall (QSH) state is a state of matter proposed to exist in special, two-dimensional, semiconductors that have a quantized spin-Hall conductance and a vanishing charge-Hall conductance. In 1988, it was proposed that the existence of the QSH state shown theoretically in such an edge channel can exist on a two-dimensional lattice [10]. Then, almost 20 years later, the experimental demonstration of the presence of lossless edge channels in a HgTe/CdTe quantum well, which exhibits an integer quantum Hall effect in the absence of an external magnetic field, was reported [11] (Figure 3).

If one of the spin channels in the QSH effect system is silenced - by introducing ferromagnetism - it logically leads to the quantum anomalous Hall Effect (QAHE) which is a quantized version of the above mentioned AHE. It was later predicted that for a magnetically doped topological insulator Bi2Se3sub> thin film, the system should exhibit the QAHE with a quantized Hall resistance of h/e2 [13].

Topological Insulators (TIs) [14] are materials that are electrical insulators in the bulk, but can conduct electricity on their surface via special surface electronic states. They offer the chance to enlarge our understanding of materials physics and could lead to applications such as quantum computation.

The surface of a TI hosts symmetry-protected gapless Dirac electrons with spin direction locked perpendicular to their momenta. When doped with magnetic elements such as Cr, Mn etc, TIs can host a large variety of magnetic phases, such as ferromagnetic, paramagnetic, noncolinear, and spin glass phases, due to various types of exchange interactions between the magnetic impurities in presence of the surface and bulk states. The magnetically doped TIs have received intensive experimental attention, and the work on ferromagnetic (FM) order in Cr-doped (Bi,Sb)2Te3 thin films has led to the discovery of quantum anomalous Hall effect (QAHE) [15].

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Wednesday, April 28, 2021

Iris Publishers- Open access Journal of Online Journal of Complementary & Alternative Medicine | Longitudinal follow-up Study of the Intrarenal Hemodynamics and Pulmonary Function in Patients with T2DM

 


 Authored by Lian Qun Jia*

Abstract

Purpose: The main aim of this study is to long-range assess incidence of diabetic kidney disease (DKD) and pulmonary function in patients with type 2 diabetes mellitus (T2DM) during 2000 and 2015.

Methods: 60 subjects newly diagnosed with T2DM were divided into two groups according to their arterial resistivity index (RIs) (≤0.7 and >0.7). These patients underwent tests designed to assess the early changes in pulmonary function and intrarenal haemodynamics associated with diabetes, the results of which were compared to corresponding test results for the same group of patients between 2000 and 2015. The endpoints of the study were the between-group differences in the changes in the pulmonary functional parameters, the mean kidney arterial RI in the bilateral interlobular renal arteries, and the indicated renal functional parameters (BUN, Cr, AER, and UACR).

Results: The subjects with RIs ≤0.7 displayed significantly better pulmonary function in the year 2000 than subjects with RIs >0.7. Moreover, subjects in the former group displayed improvement and smaller decreases in their pulmonary functional parameters from 2000 to 2015 compared to subjects in the latter group. Additionally, subjects in the former group displayed improvement and smaller increases in their renal functional parameters, i.e., their BUN and Cr, and their AERs and UACRs from 2000 to 2015 compared to subjects in the latter group. The incidence of DKD in the group with RIs ≤0.7 (6/25, 24.00%) was significantly lower than that in the group with RIs >0.7 (23/45, 65.71%) (P<0.05).

Conclusion: The renal functional parameters, the right kidney RI may also serve as a predictor of diabetes-related changes in pulmonary function and renal injury in the future.

Keywords:Type 2 diabetes mellitus; Diabetic kidney disease; Pulmonary function; Intrarenal haemodynamics; Resistivity index

Abbrevations:Neurodegenerative disorders; Hypnosis; well-being; Embodiment; Relaxation; Complementary therapy

Introduction

The prevalence of T2DM is increasing worldwide, particularly in Asian countries [1]. Patients with T2DM develop abnormalities related to glucose and lipid metabolism, phenomena associated with multiorgan dysfunction. Moreover, T2DM has been identified as an independent risk factor for cardiovascular disease, as affected patients have a two-fold higher risk of developing cardiovascular disease than unaffected patients [2], and leads to the development of vascular diseases such as DN and DR [3], which are the leading causes of end-stage renal disease (ESRD) and acquired blindness, respectively [4]. New terminology describing kidney disease attributable to diabetes has been introduced in recent guidelines (National Kidney Foundation, 2007), which stipulate that the term ‘DN’ should be replaced by ‘DKD’, a major long-term microvascular complication of diabetes characterized by functional, structural and clinical abnormalities of the kidneys caused by diabetes that is highly prevalent among patients with the disease.

More than 3 decades ago, researchers established that patients with T2DM had less alveolar gas exchange capacity than healthy subjects [5]. However, hyperglycaemia-induced pulmonary vascular injury is a complication of T2DM that has been overlooked by researchers attempting to devise treatments for the numerous complications associated with the disease. Obesity, smoking, vascular disease, and prolonged diabetes are also significant contributors to reductions in lung function, and ex-smokers display clinically significant chronic air flow obstruction [6].

Colour doppler ultrasound (CDU), a modality that is widely used in a variety of medical fields, evaluates blood flow velocity based on shifts in Doppler signals [7]. Patients with hyperglycaemia and uncontrolled blood pressure have significantly increased blood flow compared to patients with systemic hypertension without diabetes (as estimated by CDU) [8]. The Doppler RI [PSV − PED/ PSV] that reflects intrarenal vascular resistance has been widely used to quantify the alterations in renal blood flow that may develop in renal disease [9].

To the best of our knowledge, no studies have used the intrarenal haemodynamics (RI) to predict changes in pulmonary function and intrarenal haemodynamics in patients with T2DM without DKD.

Methods

Subjects

The patients were included in the study: 1) patients with a diagnosis of T2DM, as defined by the guidelines of the American Diabetes Association [10]; 2) patients with no history of smoking, pulmonary disease, or recent viral illnesses; 3) patients without hepatopathy, nephropathy, hyperuricaemia, or gastrointestinal disease; and 4) patients likely to comply with the guidelines of the study who were able to visit our hospital for periodic assessments. The patients were excluded from the study: 1) patients with T1DM, as well as patients with gestational diabetes and patients who were lactating; 2) patients with inadequate renal function and other renal conditions that may affect intrarenal haemodynamics, such as urolithiasis, urinary infections, and large renal cysts; 3) patients whose liver function were abnormal or with the class III or IV heart failure or a history of coronary angioplasty, or myocardial infarction within 6 months before enrolling in the study; 5) patients with DKD and hypertension (patients receiving antihypertensive drugs).

Study design

154 adult patients with T2DM (82 males and 72 females) were initially diagnosed with the disease in 2000 and were subsequently divided into two separate groups according to their RIs (≤0.7 or >0.7); however, we were able to locate only 60 of these patients (32 males, 28 females) in 2015. These patients’ pulmonary functional parameters, RIs, UACRs, AERs, and BUN and Cr levels were measured in 2015 and compared to corresponding values measured in 2000.

Study assessments and endpoints

Blood specimen collection and laboratory testing: Venous blood samples were collected between 6 and 8 AM following a fasting period of at least 8 hours and used for measurements of FPG levels, HbA1c levels, and renal functional parameters (BUN, Cr). For this procedure, 5 ml of venous blood was placed in a glass tube, stored at room temperature for at least 10 min, and then centrifuged (3000 r/min) for 10 min to separate the plasma from the serum, the latter of which was stored at -70 °C in a cryogenic refrigerator. BUN and Cr levels were measured according to the instructions of the corresponding research kits. All the specimens were used for measurements of the above parameters within 1 week of collection.

Urine sample collection and laboratory tests: Urine output was quantified via a single 24-h urine collection. Urinary albumin concentrations were measured using a double-antibody radio immunoassay with a sensitivity of 0.5 mg/l, an intra-assay coefficient of variation of 4.5%, and an inter assay coefficient of variation of 5.3% within the range of 10-50 mg/l.

Pulmonary function measurements: The indicated pulmonary functional parameters (VC%, FVC%, FEV1%, PEF%, MVV%, TLC%, the FEV1/FVC% ratio, DLCO%, and the DLCO/VA% ratio) were measured using a spirometer. We used the measuredto- expected value ratios and the percentages of the predicted value to eliminate the influence of age, height, and weight on the results. The subjects were asked to remain seated and rest quietly for at least 30 min before testing. The pulmonary function tests were performed 3 times, and the best of 3 acceptable readings for each parameter was used in the analysis. Spirometry and pulmonary functional analysis were performed by trained professionals.

Intrarenal haemodynamic parameter measurements: We measured the indicated intrarenal haemodynamics parameters (PSV, EDV, and RI) in the bilateral interlobular renal arteries of subjects who had fasted for at least 8 h by Doppler sonography after documenting the subjects’ blood pressures and pulse rates. The examinations were performed after the subjects had rested for 15 min and with each subject in the supine position, as described previously. Colour duplex Doppler sonography was used to examine the vasculature of the left and right renal parenchyma and the main trunk of the renal artery. If no abnormalities in kidney size or vasculature structure were noted, 3 pulsed Doppler measurements were initiated in the interlobar arteries located at the center of the kidney, as well as in the arteries located at its upper and lower poles, within 5 minutes. The pulsed Doppler sampling gate was located in the interlobar arteries, and the angle of insonation, which was measured as precisely as possible, was kept under 60 °C. The PSV and EDV were documented in centimeters per second, and the RI was calculated as (PSV – EDV) / PSV. For each recording, the RI was measured only when at least 3 consecutive waveforms with similar appearances were observed. A mean of 3 RI measurements was obtained for each kidney. All examinations were performed in duplicate by the same operator, who had no knowledge of the two groups (diabetes or control) [11, 12].

Statistical analysis

Measurement data were expressed as the mean ± SD, and numerical data were expressed as percentages. Statistical analysis was conducted using the SPSS statistical package (Version 17.0, SPSS Inc. Chicago, IL, USA). Differences in categorical variables between the two groups were evaluated using the chi-square test; differences in continuous variables between the two groups were evaluated using the independent-samples t test; before and after treatment within-group differences in continuous variables were assessed using the paired-sample t test. P<0.05 was considered statistically significant.

Results

Pulmonary and renal function were assessed in patients with T2DM who were organized into separate groups according to their RIs. Subjects with RIs ≤0.7 had significantly better pulmonary (VC%, FVC%, FEV1%, PEF%, MVV%, TLC%, the FEV1/FVC% ratio, DLCO%, and the DLCO/VA% ratio), renal function (the AER and UACR and Cr, and BUN) in 2000 than subjects with RIs >0.7. Moreover, subjects in the former group displayed improvements and smaller decreases and increases in their pulmonary and renal functional parameters between 2000 and 2015, respectively, compared to subjects in the latter group. Additionally, the incidence of DKD in the group with RIs ≤0.7 (6/25, 24.00%) was significantly lower than that in the group with RIs >0.7 (23/35, 65.71%) (P<0.05) (Table 1).

Discussion

The results of this study indicate that in addition to renal functional parameters, the combination of the right kidney RI and the GFR may also be a good predictor of changes in pulmonary function in patients with diabetes, as well as a more sensitive indicator of changes in pulmonary function in such patients during the pre-clinical stages of DKD than the UACR or AER.

Renal Doppler RIs are widely used to evaluate blood flow in renal parenchymal diseases. RIs, which reflect intrarenal vascular resistance, a measure of vascular compliance [9], are also widely used to quantify changes in renal blood flow that may be attributable to renal diseases. Interestingly, previous studies have shown that renal Doppler sonography is an effective noninvasive and inexpensive means of screening for renovascular hypertension correctable via treatment with captopril [13]; therefore, we evaluated intrarenal haemodynamics by examining the RI using Doppler sonography.

The mechanisms underlying the occurrence of lung damage in diabetes are not fully understood. Thus, hyperglycaemia damages the lung, collagen is less susceptible to proteolysis because of nonenzymatic glycosylation of proteins in the lungs and chest wall, leading to its accumulation in lung connective tissue. This process is triggered mainly by hyperglycaemia and is thus more pronounced in patients with poor glycaemic control than in patients with good glycaemic control. In addition, nonenzymatic glycosylation of proteins in the lungs decreases lung compliance [14,15]. Clinically, loss of microvascular reserve in the lung may be associated with an increased risk of hypoxia in acute or chronic pathological lung conditions, such as pneumonia, asthma, chronic obstructive pulmonary disease, and congestive heart failure. Moreover, microvascular abnormalities frequently contribute to histological changes in the lung parenchyma, such as nodular fibrosis [15].

Systemic inflammation is another concern in patients with diabetes. Systemic inflammation induced by oxidative stress is associated with endothelial dysfunction in patients with diabetes [16-18]. Additionally, insulin resistance can alter lung volume and mechanical function via mediators such as leptin [15] and may independently cause airflow obstruction in a manner similar to that in which peripheral airway inflammation causes air flow obstruction in asthma [19]. Lung CO transfer capacity is significantly affected by the integrity of the lung capillary endothelium, a finding that supports that idea that clinicians should devote more attention to pulmonary vascular changes. The reports on lung function testing in patients with diabetes that have been published during the last 15 years have focused predominantly on pulmonary microangiopathy. The lung functional parameters that are related specifically to pulmonary microangiopathy include pulmonary capillary blood volume and CO transfer capacity [20]. Niranjan V found that TLC, FVC, FEV1, and VC values were significantly lower in patients with type 1 diabetes than in healthy subjects [21]. The results pertaining to the correlations between HbA1c and pulmonary function that were noted in previous studies were inconsistent. Two studies noted weak associations between HbA1c and spirometric parameters and strong correlations between diabetes duration and pulmonary function [22,23]. Another cross-sectional population study noted that plasma glucose levels were negatively correlated with FVC and/or FEV [24].

The precise mechanisms underlying DKD development are unknown; however, several theories exist regarding the specific processes that affect haemodynamics in DKD. Haemodynamic changes in diabetic kidneys have been the focus of considerable research. Renin-angiotensin system (RAS) activation reportedly

induces intrarenal haemodynamic abnormalities in diabetes [25]. Taniwaki H and colleagues demonstrated that the intrarenal RAS may be activated in diabetes and subsequently facilitate increases in the RI and that RAS activation may be impacted by poor glycaemic control. In addition, these authors showed that blocking RAS activation with captopril may reduce intrarenal vascular resistance in diabetes [26].

Elevated RIs have been reported to be associated with vascularinterstitial diseases, including DKD (but not glomerulopathies). Increased RIs may be reflective of decreased tissue and vascular compliance, as well as increased vascular resistance [9]. However, the early stages of DN are associated with an increased GFR and variable increases in renal plasma flow and the filtration fraction in both clinical and experimental settings. Diabetic hyper perfusion and hyperfiltration at the nephron level are characterized by disproportionate decreases in afferent arteriolar resistance. These changes may also be reflected by increased RIs. RIs are measured by duplex Doppler sonography [27]. Biopsy studies involving children have shown that basement membrane thickening and mesangial expansion in the kidney develop prior to the onset of microalbuminuria [28]. Doppler sonography apparently does not replace renal biopsy but is a readily applicable and noninvasive tool for investigating renal haemodynamics and a credible means of exploring renal structures for the purpose of collecting both morphologic and physiologic data for the study of renal blood flow in children [29]. To our knowledge, our study is the first to use the RI to predict changes in renal function in the preclinical stage of DKD, results similar to those of the study by Pelliccia P, which involved children [29].

However, there is no general agreement with respect to the significance and predictive value of the renal RI in patients with DKD. Researchers have performed several studies regarding the application of Doppler sonography for the evaluation of intrarenal haemodynamic abnormalities in adults with DKD [9,30]; however, studies regarding the preclinical stage of DKD (in which renal function is normal) in adults are still lacking. In our study, we aimed to explore whether Doppler sonography could be used to detect alterations in the renal RI in adults with diabetes who had normal renal function.

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