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Application of Drainage Position Ventilation and Real- Time Bedside Monitoring in Mechanical Ventilation of Patients Infected with nCov-19

Abstract

At present, the new coronavirus has spread to more than 200 countries and regions around the world. Up to now, no specific antiviral drugs are proved effective in defeating the new coronavirus, some measures, such as postural drainage ventilation, real-time bedside pulmonary ultrasound and chest electrical impedance monitoring may provide some new ideas for mechanical ventilation patients infected with new coronavirus.

Keywords

New coronavirus, ARDS, Mechanical ventilation, Bioelectrical impedance tomography, Pulmonary ultrasound

Etiology and Pathogenesis

The novel coronavirus (2019-nCoV) belongs to the beta genus of coronavirus, the S protein of the new coronavirus binds to the angiotensin-converting enzyme 2 (ACE2) receptor of human alveolar type II epithelial cells, and then enters into the cell to replicate and spread through respiratory droplets and contact [1].

Clinical Manifestation

Fever, dry cough and fatigue are the main symptoms of the people infected with novel coronavirus. Critically ill patients usually have dyspnea and (or) hypoxemia one week after the onset of the disease. Some patients can rapidly progress to acute respiratory distress syndrome, septic shock, uncorrectable metabolic acidosis, coagulation dysfunction and multiple organ failure [1].

Chest Imaging

Chest radiographs showed multiple small patch shadows and interstitial changes in the lungs, especially in the lateral pulmonary zone in the early stage of the patients infected with new coronavirus. Then it developed into multiple ground glass shadows and infiltration shadows in both lungs, and in severe cases, lung consolidation could occur [1-3].

Pulmonary Pathophysiology

Lung pathology showed focal hemorrhage and necrosis, marked proliferation of the type II alveolar epithelial cells in the lung tissue. Serous, fibrin exudates, and hyaline membrane formation were seen in the alveolar cavity; it could also be observed that the alveolar septal vascular congestion and edema, and some alveolar exudates organization and pulmonary interstitial fibrosis. Part of the bronchial mucosa epithelium was shed; mucus and mucus emboli could be seen in the bronchial lumen. A small number of alveoli were over-inflated, the alveolar septum was broken or the cysts were formed [4].

Thus, critically ill patients infected with new coronavirus may present abnormal pathophysiological changes such as obstructive ventilation disorder, lung gas exchange disorder, imbalanced ventilation blood flow ratio, and increased shunt.

Antiviral Therapy

During the emergency clinical trial of antiviral drugs, a number of randomized, double-blind, antiviral-placebo controlled studies have been carried out, but no antiviral drugs proved effective in treating the new coronavirus infection.

Mechanical Ventilation

Early and appropriate invasive mechanical ventilation is an important treatment for critically ill patients. In general, when PaO2/FiO2 is less than 150 mmHg, the effect of high flow oxygen therapy or noninvasive ventilation is not good, endotracheal intubation should be considered in time for invasive mechanical ventilation in severe and critical ill cases [2]. The strategies of lung protective mechanical ventilation and lung recruitment are implemented. If there is no contraindication, it is suggested to implement prone position ventilation at the same time. Prone position ventilation can improve oxygenation in patients with ARDS by increasing functional residual volume, improving ventilation/blood flow ratio (V/Q), reducing shunt (Qs/Qt), improving diaphragmatic movement and promoting secretion excretion. In the airway management, posture drainage and sputum suction by bronchoscope should be adopted to promote the sputum drainage and lung rehabilitation [2].

Lung Protective Mechanical Ventilation Strategy

The individualized strategy of mechanical ventilation is to adopt the most suitable methods or parameters in ventilation mode, lung recruitment, tidal volume, PEEP and mechanical ventilation posture for patients according to their different pathophysiological conditions, so as to achieve the best treatment effect. At present, low tidal volume, high PEEP, lung recruitment and prone position ventilation are widely used in patients infected with new coronavirus [2]. The characteristics of severe new coronavirus cases, such as inflammatory serous and fibrin exudate, exudate organization, pulmonary fibrosis, alveolar septum destruction, atelectasis and pulmonary bullae, coexist in the patients’ lung [4]. Large tidal volume is not suitable for patients infected with new coronavirus due to the potential mechanical ventilation lung injury [2]. The selection of PEEP should be guided by the best pulmonary mechanics, the reduction of pulmonary shunt, the improvement of oxygenation and the function of stable circulation, while the effect of pulmonary recruitment should be examined by CT, MRI, bioelectrical impedance tomography (EIT) and ultrasound imaging. In the process of lung recruitment, there is the possibility of lung over inflation and the original pulmonary injury aggravation, and the effect on the hemodynamics should be concerned at the same time. The optimal method, opportunity and parameters of lung recruitment have not been determined, but it is necessary to judge the potential of pulmonary reinflation under real-time bedside EIT and ultrasound pulmonary monitoring.

The Advantage of Real Time Bedside Monitoring of EIT and Ultrasound

The goal-oriented mechanical ventilation is to adjust the mechanical ventilation strategy in time with the aim of imaging, respiratory and oxygen dynamics monitoring, blood gas examination, the function of circulatory system and the condition of other organs [2]. Blood oxygen saturation, blood gas, hemodynamics and respiratory mechanics are still routine and convenient monitoring methods of mechanical ventilation. Traditional lung images, such as X-ray, CT, MRI, certainly have the characteristics of clear images and easy analysis and diagnosis, but they are complicated to operate under the special circumstances of isolation and transportation of patients infected with new coronavirus. The chest electrical impedance tomography cannot provide clear image, but it is convenient to operate and can be continuously imaged [5]. Ultrasound lung images also have unique advantages in the diagnosis of pneumonia and the effect of ventilation [6]. These two methods can be real-time bedside monitoring, which are simple and practical to guide lung recruitment, to diagnose pneumonia, and to evaluate the mechanical ventilation effectiveness. In addition, while monitoring respiratory mechanics and oxygenation parameters during mechanical ventilation, we should pay close attention to the corresponding changes in the circulatory system and make timely adjustments.

Electrical Impedance Tomography

Electrical Impedance Tomography (EIT) is to use the impedance changes of living organisms or biological tissues, biological organs, and biological cells under the action of a safe current below the excitability threshold to obtain the organism internal resistance rate of distribution and changing images through image reconstruction [5,7]. The resistivity of different tissues or the same tissue under different physiological and pathological conditions is different. The periodic changes of air and blood flow in the lungs together determine the changes in the electrical impedance of the chest. The advantage of EIT lies in the use of the rich physiological and pathological information carried by bio-impedance to obtain damage-free functional imaging and medical image monitoring. Chest X-rays and CT are widely used in the diagnosis of lung infections. But they cannot monitor lung lesions in real time, cannot measure lung ventilation status, and most importantly cannot be used in patients with severe pneumonia and respiratory failure who cannot easily access these examination, so their application are limited. Lung EIT, as a brand new medical imaging technology, which is different from traditional imaging technology and conventional lung function monitoring, has outstanding features such as injury-free, portable, low-cost, functional imaging, and image monitoring. EIT can real-time dynamic monitor the pulmonary ventilation and blood flow distribution, evaluate the effectiveness of clinical treatment methods such as mechanical ventilation by measuring electrical resistance under different ventilation conditions [5,7].

At present, the commonly used methods to monitor the effectiveness of lung recruitment strategy and the suitability of PEEP include arterial blood gas analysis, peripheral oxygen saturation, pulmonary and chest maximum compliance, static pressure volume curve and so on, but these methods cannot meet the requirements of dynamic monitoring of regional lung perfusion. A number of studies have showed that in mechanical ventilation patients with ARDS, EIT has been used to accurately measure the whole lung and regional lung ventilation distribution, to show the influence of PEEP changes on alveolar expansion and collapse by gradually increasing and decreasing PEEP level, and in the end to obtain the optimal value of PEEP, which improves the ratio of ventilation and blood flow (V/Q), and plays an important role in individulized lung protective ventilation strategy [5,7].

Pulmonary Ultrasound

Bedside lung ultrasound can be used for the diagnosis and differential diagnosis of various lung diseases by using a low-frequency convex probe of 3 to 5 MHz and a high-frequency linear probe of 8 to 12 MHz [8]. Normal lung ultrasound images include bat sign, lung sliding sign, and A-line. Pathological images mainly include abnormal pleural lines, pulmonary consolidation, interstitial syndrome, fragmentation sign, dynamic bronchial signs, pleural effusion and so on [9].

With the development of ultrasound technology, pulmonary ultrasound is gradually found to be of great value in diagnosing acute respiratory distress syndrome, pulmonary edema, pneumonia, pneumothorax, pulmonary embolism and so on [6,10,11]. It can be used to monitor the changes in lung ventilation, to guide clinical fluid management and evaluate prognosis, especially in patients with severe diseases. Since chest X-rays and CT examinations are unsuitable for rapid diagnosis of critical diseases due to the shortages of inconvenient carrying, radiation exposition, poor reproducibility, position limitations, and high costs, and compared with chest CT, bedside lung ultrasound has advantages of non-invasive, dynamic and repeatable observation of patients with lung disease.

The Advantage of Drainage Position Ventilation

At present, prone position mechanical ventilation is widely used in patients infected with new coronavirus, which may be helpful to the drainage of pulmonary inflammation and the reduction of pulmonary shunt volume [2]. So far, no effective antiviral drugs have been found in defeating new coronavirus, so drainage becomes an important treatment for pulmonary inflammatory lesions. Because of inflammatory lesions in different parts of the lung, prone position ventilation is not suitable for all patients, and it may be more beneficial to adopt drainage position mechanical ventilation combined with tracheal suction with the infected side of lung lesions upper side. For example, the lateral and head-down position mechanical ventilation with the inflammatory lung upper side according to the characteristics of pulmonary imaging of some patients infected with new coronavirus. The lateral prone position can be tried to improve the inflammatory side lung ventilation, reduce pulmonary shunt, increase blood reflux and improve hemodynamics. However, it is important to avoid excessive head down, which increases abdominal pressure on the chest cavity.

In summary, based on the autopsy, clinical manifestations, lung pathological characteristics and present treatment of the patients infected with the new coronavirus, this article describes some possible improvement measures for the mechanical ventilation strategy. We believe that postural drainage ventilation, real-time bedside pulmonary ultrasound and chest electrical impedance monitoring will improve the clinical treatment of critical patients based on the previous guidelines for ARDS treatment. These methods provide some new ideas for clinical treatment and need to be used and verified in future clinical work.

References

  1. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, et al. (2020) Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med.
  2. Lingzhong Meng, Haibo Qiu, Li Wan, Yuhang Ai, Zhanggang Xue, et al. (2020) Intubation and Ventilation amid the COVID-19 Outbreak: Wuhan’s Experience. Anesthesiology 132: 1317-1332. [crossref]
  3. Huang C, Wang Y, Li X, Ren L, Zhao J, et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395: 497-506.
  4. Qin Liu, Rongshuai wang, Guoqiang Qu, Yunyun wang, Pan Liu, et al. (2020) Gross Observation Report on the Autopsy of a nCov-2019 Pneumonia Death. Journal of Forensic Medicine (Chinese) 36: 21-23. [crossref]
  5. Hsu CF, Cheng JS, Lin WC, Cheng KS, Lin SH, et al. (2016) Electrical impedance tomography monitoring in acute respiratory distress syndrome patients with mechanical ventilation during prolonged positive end-expiratory pressure adjustments [J]. J Formos Med Assoc 115: 195-202. [crossref]
  6. Staub LJ, Mazzali Biscaro RR, Kaszubowski E, Maurici R (2019) Lung ultrasound for the emergency diagnosis of pneumonia, acute heart failure, and exacerbations of chronic obstructive pulmonary disease / asthma in adults: a systematic review and meta-analysis. J Emerg Med 56: 53-69. [crossref]
  7. Heines SJH, Strauch U, Van de Poll MCG, Paul MHJR, Dennis CJJB (2018) Clinical implementation of electric impedance tomography in the treatment of ARDS: a single centre experience [J]. J Clin Monit Comput. [crossref]
  8. Rouby JJ, Arbelot C, Gao YZ, Zhang M, Lv J, et al. (2018) APECHO Study Group. Training for lung ultrasound score measurement in critically ill patients. Am J Respir Crit Care Med 198: 398-401. [crossref]
  9. Lichtenstein DA (2015) BLUE-protocol and FALLS-protocol: two applications of lung ultrasound in the critically ill. Chest 147: 1659-1670.
  10. Chavez MA, Shams N, Ellington LE, Naithani N, Gilman RH, et al. (2014) Lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis. Respir Res 15: 50. [crossref]
  11. Long L, Zhao HT, Zhang ZY, Wang GY, Zhao HL (2017) Lung ultrasound for the diagnosis of pneumonia in adults: a meta-analysis. Medicine (Baltimore) 96: e5713. [crossref]

Thinking Climate – A Mind Genomics Cartography

Abstract

The paper deals with the inner mind of the respondent about climate change, using Mind Genomics. Respondents evaluated different combinations of messages about problems and solutions touching on current and future climate change. Respondents rated each combination on a two-dimensional scale regarding believability and workability. The ratings were deconstructed into the linkage between each message and believability vs. workability, respectively. Two mind-sets emerged,Alarmists who focus on the problems that are obvious to climate change, and Investors who focus on a limited number of feasible solutions.These two mind-sets distribute across the population, but can be uncovered through a PVI, personal mind-set identifier.

Introduction

Importance of the Weather and Climate

As of this writing, the concerns keep mounting about climate change, as can be seen in published material, whether the news or academic papers, respectively.As of this writing, the concerns keep mounting about climate change, as can be seen in published material, whether the news or academic papers, respectively.A search during mid-December 2020 reveal 416 million hits for ‘global warming,’ 350 million hits for ‘global cooling’ 886 million his for ‘weather storms’ and 608 million hits for ‘global weather change.’ The academic literature shows the parallel level of interest in weather and its changes. A retrospective of issues about climate change shows the increasing number of ‘hit’ over the past 20 years, as Table 1 shows. These hits suggest that issues regarding climate change are high on the list of people’s concerns.

Table 1a: Number of ‘hits’ on Google Scholar for different aspects of climate change.

Year

Global Warming Global Cooling Weather Storms

Global Weather Change

2000

14,900 22,300 8,370

34,300

2002

30,900 111,900 10,400

61,500

2004

39,900 126,00 13,100

75,300

2006

52,200 129,000 14,600

92,300

2008

82,200 132,000 19,600

111,000

2010

105,000 153,000 23,700

128,000

2012

112,000 154,000 26,700

137,000

2014

109,000 154,000 28,200

136,000

2016

96,300 131,000 27,900

114,000

2018

77,900 85,200 27,400

81,200

Table 1b: The four questions and the four answers to each question.

Question A: What climate impacts do people see today?
A1 Sea Levels are rising and flooding is more frequent & obvious
A2 Hurricanes are getting stronger and more frequent – just look at the news
A3 Heat Waves are damaging crops and the food supply
A4 Wildfires are more massive and keep burning down neighborhoods
Question B: What are the underlying risks in 20 years?
B1 Coastal property investments lose money
B2 Children will live in a much lousier world
B3 Governments will start being destabilized
B4 People will turn from optimistic to pessimistic
Question C: What are some actions we can take to avoid these problems?
C1 Right now, implement a global carbon tax
C2 Over time, transfer 10% of global wealth to an environment fund
C3 Create a unified global climate technology consortium for technological change.
C4 Build a solar shade that blocks 2% of sunlight
Question D: What’s the general nature of the system that will mitigate these risks today?
D1 $10trn to move all energy generation to carbon neutral
D2 $20trn to harden the grid and coastal communities
D3 $2trn to build a space based sunshade blocking 2% of sunlight.
D4 $0.02trn to spray particulate into atmosphere to block 2% of sunlight.

Beyond Surveys to the Inside of the Mind

The typical news story about climate changes is predicated on storytelling, combining historical overviews, current economic concerns, description of behavior from a social psychology or sociological viewpoint, and often adoom and gloom prediction which demands immediate action in ordertoday to be forestalled.All aspects are correct, in theory.What is missing is a deeper understanding of the inner thinking of a person when confronting the issue of climate change. There are some papers which do deal with the ‘mind’ of the consumer, usually from the point of view of social psychology, rather than experimental psychology [1].

Most conversations about climate change are general, because of the lack of specific knowledge, and the inability of people to deal with the topic in depth. The topic of climate change and the potential upheavals remains important, but people tend to react in an emotional way, often accepting everything or rejecting what sounds reasonable or what does not sound reasonable, respectively. The result is the ongoing lack of specific information, compounding the growth of anxiety, and the increasingly strident rejectionism by those who fail to respond to a believed impending catastrophe. Another result, just as inaction, is a deep, perplexing, often consuming discourse on the problem, written in way which demonstrates scholarship and rhetorical proficiency, but does not lead to insights or answers, rather to well justified polemics [2-6].The study reported here, a Mind Genomics ‘cartography’ delves into the mind of the average person, to determine what specifics of climate change are believable, what solutions are deemed to be workable, and what elements or messages about climate change engage a person’s attention. The objective is to understand the response to the notion of climate change by focusing of reactions to specifics about climate change, specifics presented to the respondent in the form of small combinations of ‘facts’ about climate [7-9].

Researchers studying how people think about climate follow two approaches, the first being the qualitative approach which is a guided, but free-flowing interview or discussion, the second being a structured questionnaire. The traditional qualitative approach requires the respondent to talk in a group about feelings towards specifics, or even talk an in in-depth, 1:1 interview. These are the accepted methods to explore thinking, so-called focus groups and in-depth interviews. Traditional discussion puts stress on the respondentto recall and state, or, in the language of the experimental psychologist, to produce and to recite. In contrast, the traditional survey presents the respondent with a topic, and asks a variety of questions, to which the respondent selects the appropriate answer, either by choice, or by providing the information.All in all, conventional research gives a sense of the idea, but from the outside in. Reading a book by research can provide extensive information from the outside. Some information from the inside can be obtained from comments by individuals about their feelings.Yet it will be… clearly from the outside, rather than a sense of peering out from the inside of the mind. The qualitative methods may reach into the mind somewhat more deeply because the respondent is asked to talk about a topic and must ‘produce’ information from inside. Both the qualitative and the quantitative methods produce valuable information, but information of a general nature. The insights which may emerge from the qualitative and quantitative methods have a sense of emerging from the ‘outside-in.’ That is, there is insight, but there is not the depth of specific material relevant to the topic, since the qualitative information is in the form of diluted ideas, ideas diluted in a discussion, whereas the quantitative information is structured description with a sense of deep specificity.

The Contribution of Mind Genomics

Mind Genomics is an emerging science, with origins in experimental psychology, consumer research, and statistics.The foundational notion of Mind Genomics is that we can uncover the ways that people make decisions about every-day topics using simple experiments, where people respond to combinations of messages abut the different aspects of the topic. These combinations, created by experimental design, present information to the respondent in a rapid fashion, requiring the respondent to make a quick judgment. The mixture of different messages in a hard-to-disentangle fashion, using experimental design, makes it both impossible to ‘game’ the system, and straightforward to identify which pieces of information drive the judgment.Furthermore, one can discover mind-sets of individuals quite easily, groups of people with similar pattern of what they deem to be important. The approach here, Mind Genomics, makes the respondents job easier, to recognize and react. The messages are shown to the respondent’s job easier, the respondents evaluate the combination, and the analysis identifies which messages are critical, viz, which messages about weather change are important. Mind Genomics approaches the problem by combining messages about a topic, messages which are specific. Thus, Mind Genomics combines the richness of ideas obtained from qualitative research with the statistical rigor of quantitative research found in surveys. Beyond that combination, Mind Genomics is grounded in the world of experiment, allowing the researcher to easily understand the linkage between the qualitatively, rich, nuanced information, presented in the experiment, and the reaction of the respondent, doing so in a manner which cannot be ‘gamed’ by the respondent, in a manner which reveals both cognitive responses (agree/disagree) and non-cognitive response (engagement with the information as measured by response time.)

Mind Genomics follows a straightforward path to understand the way people think about the everyday. Mind Genomics is fast (hours), inexpensive, iterative, and data-intensive, allowing for rapid, up-front analysis and deeper post-study analysis.Mind Genomics has been crafted with the vision of a system which would allow anyone to understand the mind of people, even without technical training. The grand vision of Mind Genomics is to create a science of the mind, a science available to everyone in the world, easy-to-do, a science which creates a ‘wiki of the mind’, a living database of how people think about all sorts of topics.

Doing a Simple Cartography – The Steps

Step 1 – Create the Raw Materials; Topic, Four Questions, Four Answers to Each Question

The cartography process begins with the selection of a topic, here the mind of people with respect to climate change. The topic is only a tool by which to focus the researcher’s mind on the bigger areas.

Following the selection of the topic, the researcher is requested to think of four questions which are relevant to the topic. The creation of these questions may sound straightforward, but it is here that the respondent must exercise create and critical thinking (got rid of word ‘some’), to identify a sequence of questions which ‘tell a story.’ The reality is that it takes about 2-3 small experiments, the cartographies,before the researcher ‘gets it,’ but once the researcher understands how to craft the questions relative to the topic, the researcher’s critical faculty and thinking patterns have forever changed. The process endows the world of research with a new, powerful, simultaneous analytic-synthetic ways to think about a topic, and to solve a problem.Once the four questions are decided upon, the researcher’s next task is to come up with four answers. The perennial issue now arises regarding ‘how do I know I have the right or correct answers?’ The simple answer is one does not. One simply does the experiment, finds out ‘what works,’ and proceeds with the next step of stimuli.After two, three, four, even five or six iterations, each taking 90 minutes, it is likely that one has learned what works and what does not. The iteration consists of eliminating ideas or directions which do not work, trying more of the type of ideas which do work, as well as other exploring other but related directions with other types of ideas.

It is important to emphasize the radically different thinking behind Mind Genomics, which is meant to be fast and iterative, and not merely to rubber stamp or confirm one’s thinking. Speed and iteration lead to a wider form of knowledge, a sense of the boundaries of a topic. In contrast, the more conventional and focused thinking lead to rejection or confirmation, but little real learning.

Step 2 – Combine the Elements into Small Vignettes that will be Evaluatedby the Respondents

The typical approach to evaluation would be to present each of the elements in Table 2 to the respondent, one element at a time, instructing the respondent to rate the element alone, using a scale.Although the approach of isolate and measure is appropriate in science, the approach carries with it the potential of misleading results, based upon the desire of most respondents to give the ‘right answer.’

Mind Genomics works according to an entirely different principle. Mind Genomics presents the answers or elements in what appear to be random combinations, but nothing could be further from the truth. The combinations are well designed, presenting different types of information. It will be the rating of the combination, and then the deconstruction of that rating into the contributions of the 16 individual elements which reveal the mind of the respondent.The experimental design simply ensures that the elements are thrown together in a known but apparently haphazard way, forcing the respondent to rely on intuitive or ‘gut responses,’ the type judgment which governs most of everyday life. Nobel Laureate Daniel Kahnemancalls this ‘System 1’ Thinking, the automatic evaluation of information in an almost subconscious but consistent and practical manner [10].

The underlying experimental design used by Mind Genomics requires each respondent to evaluate 24 different vignettes, or combinations, with a vignette comprising 2-4 elements. Only one element or answer to a question can appear in a single vignette, ensuring that a vignette does not present elements which directly contradict each other, viz., by comprising two elements from the question or silo, presenting two alternative and contradictory answers to the question. The experimental design might be considered as a form of advanced bookkeeping[11].

Many researchers feel strongly that every vignette must have exactly one element or answer from each question.Their point of view is that otherwise the vignettes are not ‘balanced’, viz., some vignettes have more information, some vignettes have less information. Their point of view is acceptable, but by having incomplete vignettes, the underlying statistics, OLS (ordinary least-squares) regression cannotestimate absolute values for coefficients. By forcing each vignette to comprise exactly one element or answer from each question, the OLS regression will not work because the system is ‘multi-collinear.’The coefficients can only be estimated in a relative sense, and not comparable across questions for the study, nor comparable across studies in the same topic, and of course not comparable for different topics.That lack of comparability defeats the ultimate vision of Mind Genomics, viz., to create a ‘wiki of the mind.’A further point regarding the underlying experimental design is that Mind Genomics explores a great deal of the design space, rather than testing the same 24 vignettes with each respondent.Covering the design space means giving up precision obtained by reducing variability through averaging, the strategy followed by most researchers who replicate or repeat the study dozens of times, with the vignettes in different orders, but nonetheless with the same vignettes. The underlying rationale is to average out the noise, albeit at the expense of testing a limited number of vignettes again and again.

Step 3 – Select an Introduction to the Topic and a Rating Scale

The introduction to the topic appears below. The introduction is minimal, setting up as few expectations as possible. It will the job of the elements to convey the information.

Please read the sentences as a single idea about our climate. Please tell us how you feel.

1) No way.

2) Don’t believe, and this won’t work.

3) Believe, but this won’t work.

4) Don’t really believe, but this will work.

5) I believe, and this will work.

The scale for this study is anchored at all five points, rather than at the lowest and at the highest point.The scale deals with both belief in that which iswritten, and belief that the strategy will work.The respondent is required to select one scale point out of the five for each vignette, respectively. The scale allows the researcher to capture both belief in the facts and belief in the solutions.

Step 4 – Invite Respondents to Participate

The respondents are invited to participate by an email. The respondents are member of Luc.id, an aggregator of online panels, with over 20 million panelists. Luc.id, located in Louisiana, in the United States, allows the researcher to tailor the specifications of the respondents. No specifics other than being US residentswere imposed on the panel. The respondents began with a short self-profiling classification questionnaire, regarding age and gender, as well as the answer to the question below:

How involved are you in thinking about the future?

1=Worried about my personal situation with my family

2=Worried about business stability

3=Worried about climate and ecological stability

4=Worried about government stability.

The respondent then proceeded to rate the 24 unique combinations from the permuted experimental design, with the typical time for each vignette lasting about 5-6 seconds, including the actual appearance time, and the wait time before the next appearance[12].The actual experiment thus lasted 2-3 minutes.

Step 6 – Acquire the Ratings and Transform the Data in Preparation for Model

In the typical project the focus of interest is on the responses to the specific test stimuli, whether there be a limited number of test vignettes (viz., not systematically permuted, but rather fixed), or answers to a fixed set of questions.The order of the stimuli or the test questions might be varied but there is a fixed, limited number. With Mind Genomics the focus will be on the contribution of the elements to the responses.Typically, the responses are transformed from a scale of magnitude (e.g., 1-5, not interested to interested), so that the data are binary (viz., 1-3 transformed to 100 to show that the respondents are not interested; 4-5 transformed to 0 to show that the respondent is interested.

As noted above, there are two scales intertwined, a belief in the proposition, and a belief that the action proposed will work. The two scales generate two new binary variables, rather than one binary variable:

Believe:Ratings of 1,2, 4 converted to 0 (do not believe the statements), ratings of 3,5 converted to 100 (believe the statements

Work (Efficacious) Ratings of 1,2,3 converted to 0 (do not believe the solution will work), ratings 4,5 converted to 100 (believe the proposed solution will work).

In these rapid evaluations we do not expect the respondent to stop and think. Rather, it turns out that ‘Believe’ is simply ‘’does it sound true?’ and Work” is simply ‘does it seem to propel people to solve the problem?Both of these are emotional responses. The end-product is a matrix of 24 rows for each respondent, one row for each vignette tested by that respondent. The matrix comprises 16 columns, one column for each of the 16 elements. The cell for a particular row (vignette) and for a particular column (element) is either 0 (element absent from that vignette) or 1 (element present in that vignette). The last four columns of the matrix are the rating (1-5), the response time (in seconds, to the nearest 10th of a second), and the two new binary values for the scales ‘Believe’ and ‘Work’ respectively (0 for not believe or not work, 100 for believe or work, depending upon the rating, plus a small random number < 10-5).

Step 7 – Create Two Models (Equations) for Each Respondent, a Model for Believe, and a Model for Work, and then Cluster the Respondents Twice, First for the Individual ‘Believe’ Models, Second for the Individual ‘Work’ Models

The experimental design underlying the creation of the 24 vignettes for each respondent allows us to create an equation at the respondent level for Believe (Binary) = k0 + k1(A1) + k2(A2) …. + k16(D4).The dependent variable is either 0 or 100, depending upon the value of the specific rating in Step 6.The small random number added to each binary transformed number ensures that there is variation in the dependent variable.

  1. Believe Models. For the variable Believe, applying OLS regression generates the 16 coefficients (k1 – k16) and the additive constant, for each of the 55 respondents. A clustering algorithm (k-means clustering, Distance = (1 – Pearson Correlation)) divides the respondents into two groups. We selected the two groups (called mind-sets) because the meanings of the two groups were clear. Each respondent was then assigned to one of the two emergent groups, viz., mind-sets,based on the respondent’s coefficients for Believe as a dependent variable[13].
  2. Work Models. A totally separate analysis was done, following the same process, but this time using the transformed variable ‘Work’.The respondents were then assigned to one of the two newly developedmind-sets, based only on the coefficient for work.

As a rule of thumb, one can extract many different sets of complementary clusters (mind-sets), but a good practice is to keep the number of such selected sets to a minimum, the minimum based upon the interpretability of the mind-sets. In the interests of parsimony, one should stop as soon as the mind-sets make clear sense.

Step 8 – CreateGroup Equations; Three Models or Equations, One for Believe, One for Work, One for Response Time

Create these sets of three models each for Total Panel, Male, Female, Younger (age 18-39), Older (age 40+), and the mind-sets.Theequations are similar in format, but not identical:

Believe = k0 + k1(A1) + k2(A2) … k16(D4)

Work = k0 + k1(A1) + k2(A2) … k16(D4)

Response Time=k1(A1) + k2(A2) … k16(D4)

For the mind-sets,create two models only.

Mind-Set based on ‘believe’:

Believe = k0 + k1(A1) + k2(A2) … k16(D4)

Response Time= k1(A1) + k2(A2) … k16(D4)

Mind-set based on ‘work’

Work =k0 + k1(A1) + k2(A2) … k16(D4))

Response Time =k1(A1) + k2(A2) … k16(D4).

Results

External Analysis

The external analysis looks at the ratings, independent of the nature of the vignettes, either structure or composition of the vignette in terms of specific elements. We focus here on a topic which is deeply emotion to some. The first analysis that we will focuses on the stability of the data for this deeply emotional topic. As noted above, the Mind Genomics process requires the respondent to evaluate a unique set of 24 vignettes. Are the ratings stable over time or is there so much random variability that by the time the respondent has completed the study the respondent is not paying any more attention, and simply pressing the rating button?We cannot plot the rating of the same vignette across the different positions for the same reason that each respondent tested a totally unique set of combinations. We can track the average rating, the average response time, and then the standard errors of both, across the 24 positions. If the respondent somehow stops paying attention, then the rating should show less variation over time.

Figure 1 shows the averages and standard errors for the two measures, the ratings actively assigned by the respondent, and the response time, not directly a product of the respondent’s ‘judgment,’ but rather a measure of the time taken to respond. The abscissa shows the order in the test, from 1 to 24, and the ordinate shows the statistic.The data show that the response time is longer for the first few vignettes (viz., test order 1-3), but then stabilizes.The data further show that for the most part, the ratings themselves are stable, although there are effects at the start and at the end. Figure 1 suggests remarkable stability, a stability that has been observed for almost all Mind Genomics studies, when the respondents are members of an on-line panel, and remunerated by the panel provided for their participation.

fig 1

Figure 1: The relation between test order (abscissa) and key measures. The top panel shows the analysis of the response times (mean RT on left, standard error of the mean on the right).The bottom panel shows the analysis of theratings (mean rating on the left, standard error of the mean on the right).

The second external analysis shows the distribution of ratings by key subgroups across all of the vignettes evaluated by each key subgroup. For each key subgroup (rows), Table 2 shows the distribution of the five scale points (A), distribution of the two scale points (3,5) points which reflect belief (3,5) distribution of the two scale points (4,5) reflecting positive feeling that the idea ‘works’ The patterns of ratings suggest that a little fewer than half the responses are believe or work. However, we do not know the specific details about which types of messages drive these positive responses. We need a different level of inquiry, an internal analysis into what patterns of elements drive the responses.

Table 2: Distribution of ratings on Net Believe Yes, and Net Work YES five-point scale, by key groups, and by key clusters of scale points.

 

Net Believe YES(% Rating 3 or 5)

Net Work YES(% Rating 4 or 5)

Total

45

44

Vignettes 1-12

43

43

Vignettes 13-24

47

45

Male

46

52

Female

44

36

Age 24x-9

47

49

Age 40+

43

38

Worry business

43

31

Worry about climate

50

52

Worry about family

45

48

Worry about government

43

39

Worry about ‘outside’ (business + climate)

43

35

Worry about ‘inside’ (family + government)

46

49

Belief – MS1

44

48

Belief MS2

47

40

Work – MS 3

46

47

Work – MS4

45

39

Internal Analysis – What Specific Elements Drive or Link with ‘Believe’ and ‘Work’ Respectively?

Up to now we have considered only the surface aspect of the data, namely the reliability of the data across test order (Figure 1), and the distribution of the ratings by key subgroup (Table 2). There is no sense of the inner mind of the respondent, about what elements link with believability of the facts, with agreement that the solution will work, or how deeply the respondent engages in the processing of the message, as suggested by response time. The deeper knowledge comes from OLS (ordinary least squares) regression analysis, which relates the presence/absence of the 16 messages to the ratings, as explicated in Step 8 above.

Table 3 shows the first table of results, the elements which drive ‘believability.’ Recall from the methods section that the 5-point scale had two points with the respondent ‘believing,’ and that these ratings (3,5) generated a transformed value of 100 for the scale of ‘believe’, whereas the other three rating points (1,2,4) were converted to 0.The self-profiling classification also provides the means to assign a respondent based upon what the respondent said was most concerning, worry about self (family, government), worry about other/outside (business, climate).Table 3 shows the additive constant, and the coefficients for each group. Only the Total Panel shows coefficients which are 0 or negative. The other groups show only coefficients which are positive. Furthermore, the table is sorted by the magnitude of the coefficient for the Total Panel.In this way, one need only focus on those elements which drive ‘belief’, viz., elements which demonstrate a positive coefficient. Elements which have a 0 negative coefficient are those which have no impact on believability. They may even militate against believability. Our focus is strictly what drives a person to say ‘I believe what I am reading.’

Table 3: Elements which drive ‘belief ’. Only positive coefficients are shown. Strong performing elements are shown in shaded cells.

table 3

We begin with the additive constant across all of the key groups in Table 3. The additive constants tell us the likelihood that a person will rate a vignette as ‘I believe it’ in the absence of elements. The additive constant is a purely estimated parameter, the ‘intercept’ in the language of statistics. All vignettes comprised 2-4 elements by the underlying experimental design. Nonetheless, the additive constant provides a good sense of basic proclivity to believe in the absence of elements. The additive constants hover between 40 and 50 with two small exceptions of 37 and 53. The additive constant tells us that the respondent is prepared to believe, but only somewhat. In operational terms, an additive constant of 45, for example, means that out of the next 100 ratings for vignettes, 45 will be ratings corresponding to ‘believe,’ viz., selection of rating points 3 or 5, respectively.The story of what makes a person believe lies in the meaning of the elements. Elements whose coefficient value is +8 or higher are strongly ‘significant’ in the world of inferential statistics, based upon the ‘T test’ versus a coefficient with value 0.There are only a few of these elements which drive strong belief.

The most noteworthy finding is that respondents in Q3 Inside (worried about issues close to them) start out with a high propensity to believe (additive constant = 53), but then show no differentiations among the elements. They do not believe anything. In contrast, respondents who say they worry about issues outside of them start with low belief (additive constant = 53), but there are a several of elements which strongly drive their belief (e.g., A4:Wild-Firesare more massive and keep burning down neighborhoods.)They are critical, but willing to believe in what they see, and in what is promised to them.  Table 4 shows the second table of results, elements which drive ‘work’. These elements generate positive coefficients when the ratings 4 or 5 were transformed to 100, and the remaining ratings (1,2,3) were transformed to 0. Only some elements give a sense of a solution, even If not directly a solution.The additive constants showdifferences in magnitude for complementary groups. Since the scale is ‘work’ vs. ‘not work’, the additive constant is the basic belief that a solution will work. The additive constant is higher for males than for females (52 vs. 36), higher younger vs. older (50 v 35), and higher for those who worry about themselves versus those who were about others (49 vs. 36).

Table 4: Elements which drive ‘work’. Only positive coefficients are shown. Strong performing elements are shown in shaded cells.

table 4

The key finding for ‘work’ is that there some positives on two strong ones. The respondents are not optimistic. There is only one element which is dramatic, however, D4, the plan to spray particulates into the atmosphere to block 2% of the sunlight. This element or plan performs strongly among males, and among the older respondents, 40 years and older, although in the range of studies conducted previously, coefficients of 8-10 are statistically significant but not dramatic, especially when they belong to only one element.  Our third group model concerns the response time associated with each element. The Mind Genomics program measured the total time between the presentation of the vignette and the response to the vignette. Response times of 8 seconds or longer were truncated to the value 8. OLS regression was applied to the data of the self-defined subgroups. The form of the equation for OLS regression was: Response Time = k1(A1) + k2(A2) … k16(D4). The key difference moving from binary rating to response time is the removal of the additive constant. The rationale is that we want to see the number of seconds ascribed to each element, for each group. The longer response times mean that the element is more engaging. Table 5 shows the response times for the total panel, the genders, ages, and the two groups defined by what they say worries them.Table 3 shows only those time coefficients of 1.1 second or more, response times or engagement times that are deemed to be relevant and capture the attention.The strongly engaging elements are shown in the shaded cells.

Table 5: Response times of 1.1second or longer for each element by key self-defined subgroups.

table 5

Table 5 suggests that the description of building something can engage all groups

$10trn to move all energy generation to carbon neutral

$20trn to harden the grid and coastal communities

Women alone are strongly engaged when a clear picture is painted, a picture at the personal level:

Coastal property investments lose money

Children will live in a much lousier world

Governments will start being destabilized.

One of the key features of Mind Genomics is its proposal that in every aspect of daily living people vary r in the way they respond to information. These different ways emerge from studies of granular behavior or attitudes, as well as from studies of macro-behavior or attitudes. Traditional segment-seeking research looks for mindsets in the population, trying to find them by knowing their geodemographics.  Both the traditional way of segmentation and the traditional efforts to find these segments in the population end up being rather blunt instruments. The traditional segmentation begins at a high level, encompassing a wide variety of different issues pertaining to the climate, the future, and so forth. The likelihood is minimal of finding the mind-sets with the clear granularity of these mind-sets is low, simply because in the larger scale studies there is no room for the granular, as there is in Mind Genomics, such as this study which deals with 16 elements of stability and destabilization.

Mind Genomics uses a simple k-means clustering divide individuals based upon the pattern of coefficients. The experimental design used in permuted form for each respondent allows the researcher to apply OLS regression to the binary-transformed data of each respondent.The k-means clustering was applied separately to the 55 models for Believe, and separately once again to the 55 models for Work.Both clustering programs came out with similar patterns, two mind-sets for each. The pattern suggested one be called ‘Investment focus’ and the other be called alarmist focus. The strongest performing elements from this study come from the mind-sets, classifying the respondent by the way the respondent ‘thinks’ about the topic, rather than how the respondent ‘classifies’ herself or himself, whether gender, age, or even self-chosen topic of major concern. The mind-sets are named for the strongest performing element. Group 1 (Believed MS1, Work MS4) show elementswhich suggest an ‘investment focus’.Group 2 (Believe MS2, Work MS3) shows elements which suggest an alarmist focus.

Table 6 shows the strong performing elements for the four mind-sets, as well as the most engaging elements for the mind-sets. The reader can get a quick sense of the nature of the mind-sets, both in terms of what they think(coefficients for Believe and for Work, respectively), as well as what occupies their attention and engages them (Response Time) [14].

Table 6: Strong performing coefficients for the two groups of emergent mind-sets after clustering on responses (Part1), and after clustering on response time, viz., engagement (Part 2).

table 6

The mind-sets emerging from Mind Genomics studies do not distribute in the simple fashion that one might expect, based upon today’s culture of Big Data. That is, just knowing WHO a person is does not tell us how a person THINKS. The reality is that there are no simple cross-tabulations or even more complex tabulations which directly assign a person to a mind-set.Topics such as the environment, for example, may have dozens of different facets. Knowing the mind of a person regarding one facet, one specific topic, does not necessarily tell us about the mind of that same person with respect to a different, but related facet.Table 7 gives a sense of the complexity of the distribution, and the probable difficulty of finding these mind-sets in the population based upon simple classifications of WHO is a person is.

Table 7: Distribution of key mind-sets (Investors, Alarmists).

 

Total

Investor (Belief) Investor (Work) Alarmist (Belief)

Alarmist (Work)

Total

56

30 24 26

32

Male

27

15 12 12

15

Female

29

15 12 14

17

Age24-39

31

14 12 17

19

Age40+

25

16 12 9

13

Worry aboutfamily

23

12 8 11

15

Worry about climate

12

8 4 4

8

Worry about government

11

7 6 4

5

Worry about business

10

3 6 7

4

Worry Other (business and climate)

21

10 12 11

9

Worry Self (Family, Government)

35

20 12 15

23

Invest from Believe

30

30 11 0

19

Invest from Work

24

11 24 13

0

Alarm from Work

32

19 0 13

32

Alarm from Believe

26

0 13 26

13

During the past four years authors Gere and Moskowitz have developed a tool to assign new people to the mind-sets. The tool, called the PVI, the personal viewpoint identifier, uses the summary data from the different mind-sets, perturbing these summary data with noise (random variability), and creating a decision tree based upon a Monte Carlo simulation. The decade PVI allows for 64 patterns of responses of six questions answered on a 2-point. The Monte simulation combined with the decision tree returns with a system to identify mind-set member in15-20 seconds.Figure 2 shows a screen shot of the PVI for this study, comprising the introduction, the additional background information stored for the respondent (option), and the six questions, patterns of answers to which assign the respondent immediately to the of the two mind-sets.

fig 2

Figure 2: The PVI for the study.

Discussion and Conclusion

The study described here has been presented in the spirit of an exploration, a cartography, a way to understand a problem without having to invoke the ritual of hypothesis. In most study of the everyday life the reality is that the focus should be on what is happening, not on presenting an hypothesis simply for the sake of conforming to a scientific approach which is many cases is simply not appropriate.The issue of climate change is an important one, as a perusalof the news of the day will reveal just about any day. The issues about the weather, climate change, and the very changes in ‘mother earth’ are real, political, scientific, and challenge all people. Mind Genomics does not deal with the science of weather, but rather the mind of the individual, doing so by experiments in communication.It is through these experiments, simple to do, easy to interpret, that we begin to understand the nature of people, an understanding which should not, however, surprise.The notion of investors and alarmists makes intuitive sense. These are not the only mind-sets, but they emerge clearly from one limited experiment, one limited cartography.One could only imagine the depth of understanding of people as they confront the changes in the weather and indeed in ‘mother earth.’ Mind Genomics will not solve those problems, but Mind Genomics will allow the problems to be discussed in a way sensitive to the predispositions of the listener, whether in this case the listener be a person interested in investment to solve the problem or the person be interested in the hue and the cry of the alarmist. Both are valid ways of listening, and for effective communication the messages directed towards each should be tailored to the predisposition of the listener’s mind. Thus, a Mind Genomics approach to the problem presents both understanding and suggestion for actionable solution, or at least the messages surrounding that actionable solution [2,15-19].

As a final note this paper introduces a novel way to understand the respondent’s mind on two dimensions, not just one. The typical Likert Scale presents the respondent with a set of graded choices, from none to a low, disagree to agree, and so forth. The Likert Scale for the typical study is uni-dimensional. Yet, there are often several response dimensions of interest.This study features two response dimensions, belief in the message, and belief that the solution will work.These response dimensions may or may not be intertwined.Other examples might be belief vs. action (would buy).By using a response scale comprising two dimensions, rather than one, it becomes possible to more profoundly understand the way a person thinks, considering the data from two aspects. The first is the message presented, the stimulus. The second is the decisions of the respondent, to select none, one, or both responses, belief in the problem and/or, belief that the solution will work

Acknowledgement

Attila Gere thanks the support of Premium Postdoctoral Research Program.

References

  1. Tobler C, Visschers VH, Siegrist M (2012) Addressing climate change: Determinants of consumers’ willingness to act and to support policy measures. Journal of Environmental Psychology 32: 197-207.
  2. Creutzig F, Fernandez B, Haberl H, Khosla R, Mulugetta Y,et al (2016) Beyond technology: demand-side solutions for climate change mitigation. Annual Review of Environment and Resources 41: 173-198.
  3. Lidskog R, Berg M, Gustafsson KM, Löfmarck E (2020) Cold Science Meets Hot Weather: Environmental Threats, Emotional Messages and Scientific Storytelling. Media and Communication 1: 118-128.
  4. Nyilasy G, Reid LN (2007) The academician–practitioner gap in advertising. International Journal of Advertising 26: 425-445.
  5. Reyes A (2011) Strategies of legitimization in political discourse: From words to actions. Discourse & Society 22: 781-807.
  6. Taleb NN (2007) The black swan: The impact of the highly improbable, Random house, Vol:2.
  7. Moskowitz HR (2012) ‘Mind genomics’: Theexperimental, inductive science of the ordinary, and its application to aspects of food and feeding. Physiology & Behavior 107: 606-613.
  8. Moskowitz HR, Gofman A, Beckley J, Ashman H (2006) Founding a new science: Mind Genomics. Journal of Sensory Studies 21: 266-307.
  9. Moskowitz HR, Gofman A (2007) Selling blue elephants: How to make great products that people want before they even know they want them. Pearson Education.
  10. Kahneman D (2011) Thinking, fast and slow. Macmillan.
  11. Box GE, Hunter WH, Hunter S (1978) Statistics for Experimenters, New York: John Wiley Vol: 664.
  12. Gofman A, Moskowitz H (2010) Isomorphic permuted experimental designs and their application in conjoint analysis. Journal of Sensory Studies 25: 127-145.
  13. Jain AK, Dubes RC (1988) Algorithms for Clustering Data. Prentice-Hall, Inc.
  14. Schweickert R (1999) Response time distributions: Some simple effects of factors selectively influencing mental processes. Psychonomic Bulletin & Review 6: 269-288.
  15. Acosta Lilibeth A, Nelson H Enano Jr, Damasa B Magcale-Macandog, Kathreena G Engay, Maria Noriza Q Herrera, et al. (2013) How sustainable is bioenergy production in the Philippines? A conjoint analysis of knowledge and opinions of people with different typologies. Applied Energy 102: 241-253.
  16. Lomborg B (2010) Smart solutions to climate change: Comparing costs and benefits. Cambridge University Press.
  17. Nerlich B, Koteyko N, Brown B (2010) Theory and language of climate change communication. Wiley Interdisciplinary Reviews: Climate Change 1: 97-110.
  18. Tol RS (2009) The economic effects of climate change. Journal of Economic Perspectives 23: 29-51.
  19. Warren R (2011) The role of interactions in a world implementing adaptation and mitigation solutions to climate change. Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 369: 217-241.

Differences between 5-Minute and 15-Minute Measurement Time Intervals of the CGM Sensor Glucose Device Using GH-Method: Math-Physical Medicine (No. 281)

Introduction

This paper describes the research results by comparing the glucose data from a Continuous Glucose Monitor (CGM) sensor device collecting glucose at 5-minute (5-min) and 15-minute (15-min) intervals during a period of 125 days, from 2/19/2020 to 6/23/2020, using the GH-Method: math-physical medicine approach. The purposes of this study are to compare the measurement differences and to uncover any possible useful information due to the different time intervals of the glucose collection.

Methods

Since 1/1/2012, the author measured his glucose values using the finger-piercing method: once for FPG and three times for PPG each day. On 5/5/2018, he applied a CGM sensor device (brand name: Libre) on his upper arm and checked his glucose measurements every 15 minutes, a total of ~80 times each day. After the first bite of his meal, he measured his Postprandial Plasma Glucose (PPG) level every 15 minutes for a total of 3-hours or 180 minutes. He maintained the same measurement pattern during all of his waking hours. However, during his sleeping hours (00:00-07:00), he measured his Fasting Plasma Glucose (FPG) in one-hour intervals.

With his academic background in mathematics, physics, computer science, and engineering including his working experience in the semiconductor high-tech industry, he was intrigued with the existence of “high frequency glucose component” which is defined as those lower glucose values (i.e. lower amplitude) but occurring frequently (i.e.. higher frequency). In addition, he was interested in identifying those energies associated with higher frequency glucose components such as the various diabetes complications that would contribute to the damage of human organs and to what degree of impact. For example, there are 13 data-points for the 15-minute PPG waveforms, while there are 37 data-points for the 5-minute PPG waveforms. These 24 additional data points would provide more information about the higher frequency PPG components.

Starting from 2/19/2020, he utilized a hardware device based on Bluetooth technology and embedded with customized application software to automatically transmit all of his CGM collected glucose data from the Libre sensor directly into his customized research program known as the eclaireMD system, but in a shorter time period for each data transfer. On the same day, he made a decision to transmit his glucose data at 5-minute time intervals continuously throughout the day; therefore, he is able to collect ~240 glucose data within 24 hours.

He chose the past 4-months from 2/19/2020 to 6/19/2020, as his investigation period for analyzing the glucose situation. The comparison study included the average glucose, high glucose, low glucose, waveforms (i.e. curves), correlation coefficients (similarity of curve patterns), and ADA-defined TAR/TIR/TBR analyses. This is his secondresearch report on the 5-minute glucose data. His first paper focused on the most rudimentary comparisons [1].

References 2 through 4 explained some example research using his developed GH-Method: math-physical medicine approach [2,3].

Results

The top diagram of Figure 1 shows that, for 125 days from 2/19/2020 – 6/23/2020, he has an average of 259 glucose measurements per day using 5-minute intervals and an average of 85 measurements per day using 15-minute intervals. Due to the signal stability of using Bluetooth technology, for the 5-min, it actually has 259 data instead of the 240 data per day.

IMROJ-5-3-516-g001

Figure 1. Daily glucose, 30-days & 90-days moving average glucose of both 15-minutes and 5-minutes.

The middle diagram of Figure 1 illustrates the 30-days moving average of the same dataset as the “daily” glucose curve. Therefore, after ignoring the curves during the first 30 days, we focus on the remaining three months and can detect the trend of glucose movement easier than “daily” glucose data chart. There are two facts that can be observed from this middle diagram. First, the gap between 5-min and 15-min is wider in the second month, while the gap becomes smaller during the third and fourth month. This means that the 5-min results are converging with the 15-min results.Secondly, both curves of 5-min and 15-min are much higher than the finger glucose (blue line). This indicates that the Libre sensor provides a higher glucose reading than the finger glucose. From the listed data below, the CGM sensor daily average glucoses are about 8% to 10% higher than the finger glucose.

5-min sensor: 118 mg/dL (108%)

15-min sensor: 120 mg/dL (110%)

Finger glucose: 109 mg/dL (100%).

The bottom diagram of Figure 1 is the 90-days moving average glucose. Unfortunately, his present dataset only covers 4 months due to late start of collecting his 5-min data; however, the data trend of the last month, from 5/19-6/23/2020, can still provide a meaningful trend indication. As time goes by, additional data will continue to be collected, his 5-min glucose’s 90-days moving trend will be seen more clearly.

Figure 2 shows the synthesized views of his daily glucose, PPG, and FPG.Here, “synthesized” is defined as the average data of 125 days.For example, the PPG curve is calculated based on his 125×3=375 meals. Listed below is a summary of his primary glucose data (mg/dL) in the format of “average glucose/extreme glucose”. Extreme means either maximum or minimum, where the maximum for both daily glucose and PPG due to his concerns of hyperglycemic situation, and the minimum for FPG due to his concerns of insulin shock. The percentage number in prentice is the correlation coefficients between the curves of 15-min and 5-min.

Daily (24 hours):15-min vs. 5-min

117/143vs. 119/144(99%)

PPG (3 hours):15-min vs. 5-min

126/135vs. 125/134(98%)

FPG (7 hours):15-min vs. 5-min

102/95 vs. 105/99 (89%).

Those primary glucose values between 15-min and 5-min are close to each other in the glucose categories. It is evident that the author’s diabetes conditions are under well control for these 4 months. However, by looking at Figure 2 and three correlation coefficients %, we can see that daily glucose and PPG have higher similarity of curve patterns (high correlation coefficients of 98% and 99%) between 15-min and 5-min, but FPG curves have a higher degree of mismatch in patterns (lower correlation coefficient of 89%). This signifies that his FPG values during sleeping hours have a bigger difference between 15-min and 5-min.

IMROJ-5-3-516-g002

Figure 2. Synthesized daily glucose, PPG, and FPG of both 15-minutes and 5-minutes.

Figure 3 are the results using candlestick model [4,5]. The top diagram is the 15-min candlestick chart and the bottom diagram is the 5-min candlestick chart. Candlestick chart, also known as the K-Line chart, includes five primary values of glucoses during a particular time period; “day” is used in this study. These five primary glucose data are:

Start: beginning of the day.

Close: end of the day.

Minimum: lowest glucose.

Maximum: highest glucose.

Average: average for the day.

Listed below are five primary glucose values of both 15-min and 5-min.

15-min: 108/116/86/170/120.

5-min: 111/116/84/173/118.

IMROJ-5-3-516-g003

Figure 3. Candlestick charts of both 15-minutes and 5-minutes.

By ignoring the first two glucoses, start and close, let us focus on the last three glucoses: minimum, maximum, and average. The 5-min method has a lower minimum and a higher maximum than the 15-min method. This is due to the 5-min method capturing more glucose data; therefore, it is easier to catch the lowest and highest glucoses during the day. The difference of 2mg/dL between 15-min’s average 120 mg/dL and 5-min’s average 118 mg/dL is only a negligible 1.7%.

Again, it is also obvious from these candlestick charts that the author’s diabetes conditions are under well control for these 4 months.

Conclusion

In summary, the glucose differences between 5-min and 15-min based on simple arithmetic and statistical calculations are not significant enough to draw any conclusion or make any suggestion on which are the “suitable” or better measurement time intervals. However, the author will continue his research to pursue this investigation of energy associated with higher-frequency glucose components in order to determine the glucose energy’s impact or damage on human organs (i.e. diabetes complications).

The author has read many medical papers about diabetes. The majority of them are related to the medication effects on glucose symptoms control, not so much on investigating and understanding “glucose” itself. This situation is similar to taming and training a horse without a good understanding of the temperament and behaviors of the animal. Medication is like giving the horse a tranquilizer to calm it down. Without a deep understanding of glucose behaviors, how can we truly control the root cause of diabetes disease by only managing the symptoms of hyperglycemia?

References

  1. Hsu, Gerald C. eclaireMD Foundation, USA (2020) Analyzing CGM sensor glucoses at 5-minute intervals using GH-Method: math-physical medicine (No. 278).
  2. Hsu, Gerald C. eclaireMD Foundation, USA(2020) Predicting Finger PPG by using Sensor PPG waveform and data via regression analysis with three different methods using GH-Method: math-physical medicine (No. 249).
  3. Hsu, Gerald C. eclaireMD Foundation, USA (2019) Applying segmentation pattern analysis to investigate postprandial plasma glucose characteristics and behaviors of the carbs/sugar intake amounts in different eating places using GH Method: math-physical medicine (No. 150).
  4. Hsu, Gerald C. eclaireMD Foundation, USA (2019) A case study of the impact on glucose, particularly postprandial plasma glucose based on the 14-day sensor device reliability using GH-Method: math-physical medicine (No. 124).
  5. Hsu, Gerald C. eclaireMD Foundation, USA. Comparison study of PPG characteristics from candlestick model using GH-Method: Math-Physical Medicine (No. 261).

Unusual Sella Mass: Pituitary Abscess (PA)

Abstract

Pituitary abscess (PA) caused by an infectious process is a rare cause of Sellar mass. The clinical features and radiological appearance of PA as an intra- or supra-sellar mass are similar to many other pituitary lesions, and so they are often misdiagnosed as pituitary tumor.

70% of cases occur in a previously healthy pituitary gland. These are classified as primary pituitary abscesses, persumbly secondary to either hematogenous spread or as an extension from an adjacent infective focus such as meningitis, sphenoid sinusitis, Cavernous sinus thrombophlebitis or contaminated cerebrospinal fluid (CSF) fistula.

The rest are secondary abscesses, and arise from pre-existing lesions, such as an adenoma, apoplexy in a tumor, a craniopharyngioma, or a complicated Rathke’s cleft cyst and lymphoma. The risk factors are for PA are immunosuppression, previous irradiation or surgical procedures to the pituitary gland [1].

In almost 50% of cases, the pathogenic microorganism causing the infection is not isolated. A history of recent meningitis sinusitis or head surgery can be the source [2].

Correct diagnosis before surgery is difficult and is usually confirmed intra- or post-operatively. The early surgical intervention allows appropriate antibiotic therapy and hormone replacement resulting in reduced mortality and morbidity. A long term follow-up is recommended because of the high risk of recurrence and of postoperative hormone deficiencies.

Keywords

Pituitary abscess, Papilledema, Panhypopituitarism, Rathke’s cleft cyst, Propionibacterium acnes

Introduction

A pituitary abscess (PA) represents 0.2%-0.6% of all pituitary lesions and can be life threatening. It can have a prolonged disease course. The first case was reported by Heslop in 1848, and so far, <300 cases have been reported worldwide [3]. It is an infectious process that presents as a mass in the Sella. Clinical features and the radiological appearance of the PA as an intra or suprasellar mass are similar to many other pituitary lesions, so it is often misdiagnosed as a cystic pituitary tumor, craniopharyngioma, and Rathke’s cyst. It can be life-threatening if not appropriately diagnosed or treated, and the outcome is difficult to predict. Fortunately, the majority of the cases have a chronic course. The disease has a higher prevalence in females between the age of 12 to 76 years. The average period it takes to diagnose from the onset of symptoms is around 8 years.

PA can occur as a primary disease or can be secondary to infections caused by either hematogenous spread or as an extension from an adjacent infected tissue such as meningitis, sphenoid sinusitis, Cavernous sinus thrombophlebitis or contaminated cerebrospinal fluid fistula 70% of cases occur in a previously healthy pituitary gland. These are classified as primary pituitary abscesses, and the rest are secondary abscesses that arise from pre-existing lesions, such as an adenoma, apoplexy in a tumor, a craniopharyngioma or a complicated Rathke’s cleft cyst and lymphoma [4].

In almost 50% of cases, the pathogenic microorganism causing the infection cannot be isolated. A history of recent meningitis sinusitis or head surgery can be the source [2].

Correct diagnosis before surgery is difficult and is usually confirmed intra- or post-operatively. The early surgical intervention allows appropriate antibiotic therapy and hormone replacement resulting in reduced mortality and morbidity. A long term follow-up is recommended because of the high risk of recurrence and postoperative hormone deficiencies.

We present 2 cases of pituitary abscess in young women. One presented with bilateral papilledema and the other with panhypopituitarism. Both had a sellar mass on an MRI scan, and the diagnosis was made intra-operatively. Microbiological culture in both cases was positive for Propionibacterium acnes (P.acnes). P.acnes is a gram-positive organism, a part of the normal skin microbe. This organism is most commonly isolated from wounds following craniotomies after Staphylococcus aureus and streptococcus epidermidis. Low-grade infections can manifest between 3-36 months.

Case 1

A 14-year old South Asian girl presented with a one-month history of worsening frontal headaches that occurred daily, associated with vomiting, nausea, lethargy, photophobia, and sleep disturbance. Aside from well-controlled asthma, she has been previously healthy. There was no recent travel history or infectious contacts. On examination, she appeared alert and active. She had bilateral papilledema, suggesting raised intracranial pressure (ICP). She was apyrexial and systemically well. Her cerebral magnetic resonance imaging (MRI) scan revealed a soft tissue mass in the pituitary fossa extending up towards the optic chiasm, with mild edema in the optic nerve and tracts. The scan also showed an enlarged pituitary gland and thickened stalk. The findings suggest an inflammatory process like hypophysitis, particularly Langerhans cell histiocytosis (LCH) because of her age. There were no other features of LCH. She had a normal liver US and skeletal survey. She had no symptoms of Diabetes insipidus. Her pituitary hormones were normal, including the stimulated cortisol. Her Prolactin was elevated. Her serum sodium and osmolality were normal. Her ESR was slightly raised, but autoantibodies, serum tumor markers, ACE, and the Quantiferon tuberculosis test were negative. Her IgG4 subclass was normal (Table 1). The formal ophthalmology review did not show evidence of bilateral papilledema. Her symptoms improved with oral analgesics, and steroid treatment was not initiated.

Table 1: Results at initial presentation.

                    Short Synacthen test

Time T=0 T-30 T=60
Cortisol (nmol/L) 186 452 594

                   Baseline tests

Test Result Normal range
IGF-1(nmol/L) 47.9 18.3 to 63.5
TSH (mU/L) 1.62 0.51-4.3
T4 (pmol/L) 13.3 10.8-19
LH (IU/L) 4.3 Follicular phase 2-13

Mid cycle 14-6

Luteal phase 1-11

FSH (IU/L) 1.8 Follicular phase 4-13

Mid cycle 5-22

Luteal phase 2-8

Postmenopause>25

ACTH (ng/L) <3 0-50
Prolactin (mU/L) 806 102-496
Serum Na mmol/L 144 133-146
Serum Osmolality mOsmo/Kg 293 282-300
Random Urine Osmolality mOsmo/Kg 475 100-1400
LDH (u/L) 188 120 to 300
HCG (IU/L) <1 0-1
alpha Fetoprotein (kU/L) 1 0-10
C-Reactive protein (mg/L) 1.5 0-5
ESR (mm/h) 28 1-12
Complement C3 (g/l) 1.1 0.75-1.65
Complement C4 (g/l) 0.29 0.14-0.54
Antinuclear antibodies Negative
Angiotensin convert enzyme (U/L) 42 16-85
IgG4 (g/L) 0.04 0-1.3

 

A repeat MRI scan 3 months later discussed in a multidisciplinary meeting was reported to suggest Rathke’s cleft cyst abscess/ Pituitary abscess (Figures 1 and 2). She underwent a trans-sphenoidal endoscopic pituitary biopsy for diagnosis. The appearances suggested a Rathke’s left cyst and a pituitary abscess. Immunostaining for ACTH, FSH, LH, growth hormone, TSH and Prolactin, chromogranin, synaptophysin, and collagen IV was consistent with anterior pituitary tissue. Microbiological culture on prolonged incubation was positive for Propionibacterium with no acid-fast bacilli growth. TB culture was also negative. She received a 6-week course of antibiotics, including 2 weeks of intravenous ceftriaxone and oral metronidazole followed by 4 weeks of oral co-amoxiclav. Her headaches and vomiting deteriorated after biopsy with a peak CRP of 218 mg/L, which resolved following medical treatment. Imaging with MRI and baseline pituitary function blood tests has since been repeated following the 6 weeks to assess the management’s effectiveness, which showed normal results. The patient reported the resolution of headaches and able to resume full-time schooling.

fig 1 414

Figure 1: MRI at presentation.

fig 2 414

Figure 2: MRI 3 months after transphenoidal surgery.

Case 2

29 years old Caucasian fine arts student presented to the emergency department with fever, headaches, profuse sweating, tiredness, and blurring of vision. Her symptoms, particularly headaches, had worsened over the last 12 months. She had noticed polydipsia and polyuria. She also had amenorrhoea for twelve months. She was treated at her local hospital twice in the preceding 3 years with symptoms of headaches, fever, weight loss, and vomiting. She had a lumbar puncture 3 times to rule out a possibility of central nervous system infection. On both occasions, she was discharged home after empirical treatment with antibiotics for suspected meningitis. There was no other past medical history. There was no recent travel history or infectious contacts. She was not on any regular medications.

The initial pituitary MRI and contrast-enhanced MRI scan revealed the absence of the posterior pituitary bright spot and a thickened pituitary stalk with a deviation of infundibulum to the right. There was a homogenous hyperintense area within the pituitary gland with no discernable pituitary tissue. This area was hypointense on T2 (Figures 3-5). The differential diagnosis was apoplexy, hypophysitis or a proteinaceous cystic lesion replacing or compressing the pituitary gland. The optic nerves and the chiasm appeared normal. Her investigations confirmed her to have hypopituitarism with Diabetes insipidus (Table 2). Her lumbar puncture showed no CSF abnormality. Her tumor markers and Quantiferon for tuberculosis were negative. The case was discussed in multidisciplinary meeting (MDT) and with empirical diagnosis of hypophysitis, she was started on prednisolone with the replacement of deficient hormones, including Desmopressin. She showed no improvement in her clinical symptoms. A 3 month interval scan showed an increase in the size of the pituitary gland with further thickening of the stalk and optic chiasm displaced superiorly. After the second discussion in MDT, she had a pituitary biopsy. During surgery, soft yellow-white pus-like material was drained after dural incision. The microscopy showed necrotic material with a little amount of compressed anterior pituitary gland, chronic inflammation, and no evidence of adenoma or granuloma or giant cells was found. No acid-fast bacilli or organisms were seen on gram staining, and the culture for TB was negative. There was scanty growth of Propionibacterium acneformis. Her interval scan 3 months later showed complete resolution of the non-enhancing T1 hypertense pituitary tissue with a further decrease in the size of the pituitary gland. She remains on full hormones replacement. She had an insulin tolerance test that confirmed her growth hormone deficiency, and she is now on growth hormone replacement. She remains on hydrocortisone, Thyroxine, female hormone replacement, and Desmopressin.

fig 3 414

Figure 3: MRI at presentation.

fig 4 414

Figure 4: MRI 3 months later.

fig 5 414

Figure 5: MRI post-surgery.

Table 2: Results at initial presentation.

                   Short Synacthen test

Time T=0 T-30
Cortisol (nmol/L) 148 169

                   Baseline tests

Test Result Normal range
IGF-1(nmol/L) 12.7 11.9-40.7
TSH (mU/L) 1.35 0.27-4.20
T4 (pmol/L) 5.3 10.8-25.5
LH (IU/L) 3.1 Follicular phase 2-13

Mid cycle 14-96

Luteal phase 1-11

FSH (IU/L) 5.1 Follicular phase 4-13

Mid cycle 5-22

Luteal phase 2-8

Postmenopause>25

Oestradiol (pmol/L) <92 92-1462
Prolactin (mU/L) 577 102-496
Serum Na mmol/L 142 133-146
Serum Osmolality mOsmo/Kg 301 275-295
Random Urine Osmolality mOsmo/Kg 154 100-1400
CSF-b HCG (IU/L) <2 <2
CSF-alpha fetoprotein (µg/L) <1 <1
C-reactive protein (mg/L) 1.4 0-5
ESR (mm/h) 3 1-12
Antinuclear antibodies Negative
IgG4 (g/L) <0.01 0-1.3

Discussion

A pituitary abscess is an infectious process characterized by the accumulation of purulent material in the sella turcica. It is rare, and can be a life-threatening condition unless promptly diagnosed and treated. We report 2 cases of secondary pituitary abscess in young women. The first case was due to abscess in the Rahtke’s cleft cyst (RCC), and the second was Pituitary gland abscess with a history of otitis media and repeated lumbar punctures for presumed meningitis.

The clinical presentation of PA is nonspecific, such as headaches, pituitary hypofunction, and visual disturbances, whereas the infection can be discreet and inconstant [5,6]. Symptoms can be acute, subacute, or chronic, explaining the late diagnosis; in some cases. Visual disturbance, including hemianopia, can be present in 50% of cases. Headache without a particular pattern is a regular feature (70-90%) and can be debilitating. Anterior pituitary hypofunction due to destruction and necrosis of the gland is the commonest presentation resulting in fatigue and amenorrhoea (54-85%). In one series, 28 out of the 33 patients had anterior pituitary hypofunction. Pituitary hormone deficiencies persist in the majority of patients following treatment Up to 70% of patients with PA can have central Diabetes insipidus. In contrast, fever with signs of meningeal irritation is reported in 25% of cases [5].

MRI is the imaging of choice for the pituitary lesions. PA can present as a suprasellar mass (65%) or as an intrasellar mass (35%). A typical PA appears as a single cystic or partially cystic mass that is hypointense on T1-weighted image and hyperintense in T2-weighted image. It can show a rim of enhancement after contrast gadolinium. The posterior pituitary bright spot is mostly absent in majority of the cases (Wang et al.). The lesion’s signal depends on protein, water, lipid content, and whether there is hemorrhage. Imaging can also show the invasion of an adjacent anatomical structure, peripheral meningeal enhancement, thickening of the pituitary stalk, and paranasal sinus enhancement [6].

Diffusion-weighted magnetic resonance imaging (DWI) is widely used to differentiate cerebral abscess from other necrotic masses. Brain abscesses typically show high intensity on DWI with decreased apparent diffusion coefficient (ADC) value in their central region. The high intensity on DWI is useful but not specific to PA because pituitary apoplexy can also exhibit high intensity on DWI [7]. The accuracy of DWI in PA remains controversial. In the Wang et al. case series, PA was misdiagnosed in one-third of the case [6]. The radiological differential diagnosis includes, Rathke’s cleft cyst, cystic pituitary adenoma, arachnoid, and dermoid cysts, metastases, glioblastoma multiforme, chronic hematoma, and multiple sclerosis [8]. Rathke’s cleft cyst mainly can mimic a pituitary abscess [9]. RCC is the second most common incidentaloma after adenomas and accounts for 20% of incidental pituitary lesions at autopsy. The incidence of RCCs in children was reported to be much lower than in adults. However, the prevalence is now believed to be much higher, especially among those with the endocrine-related disorder [10]. Gunes et al. reported the radiological appearance of RCC on MRI in 13.5% of the children who underwent MRI for the investigation of endocrine-related disorders. Patients with RCC are usually asymptomatic, but symptomatic RCC is more common in females in both adult and pediatric populations [11]. RCC can cause significant morbidity such as headache, visual disturbances, chemical meningitis, endocrine dysfunction (hypothyroidism, menstrual abnormalities, diabetes insipidus, adrenal dysfunction, and very rarely apoplexy). Short stature, growth deceleration, delayed puberty are also reported in children and adolescents.

The diagnosis of PA in most cases can only be confirmed after surgical exploration, due to overlapping of clinical signs, symptoms, imaging, and laboratory findings with other sellar lesions. Signs of inflammation are present in less than a third of the patients. The PA should be included in the differential diagnosis of patients with headaches or signs of pituitary dysfunction and patients with pituitary mass who develop signs of meningeal inflammation.

The main treatment for PA in patients with mass effect is Transsphenoidal excision (TSS) with decompression of sella and antibiotic therapy. This can result in the resolution of visual abnormalities. Treatment is effective for typical symptoms such as fever, headache, and visual changes. Patients with shorter duration of symptoms and those with primary abscess have better improvement in their pituitary dysfunction. Majority of the patients remain with pituitary dysfunction even after the treatment.

Antibiotic therapy should to started promptly even in the patients who are waiting for microbiology and histological confirmation for about 4–6 weeks [1,12]. Empirical treatment with ceftriaxone is indicated until the results are available. Hormone replacement is commenced depending on the hormone deficits including stress dose glucocorticoid therapy. Hypocortisolemia should be recognized among patients presenting with sellar masses, as early diagnosis and treatment improve survival and endocrinological outcome. Patients who suffer from the pituitary abscess may eventually have a good quality of life if they are diagnosed and treated early. A craniotomy is reserved for larger lesions with the suprasellar extension or where transsphenoidal surgery is ineffective [13]. In a series published with 66 patients, 81.8% of patients recovered completely, 12.1% of patients had at least one operation for recurrence, and only one patient had died [14].

There are widespread pathogenic microorganisms in abscesses. These include Gram-positive bacteria, Gram-negative bacteria, anaerobes, and fungi [8,11]. Streptococcus and Staphylococcus are the most predominant Grampositive bacteria, whereas Escherichia coli, Mycobacterium, and Neisseria have also been reported [3,10,11]. Aspergillus fumigatus is mostly isolated in cases of secondary PA. Immunosuppressed patients mostly have Candida and Histoplasma. Cultures are positive only in 50% of cases; therefore, broad-spectrum antibiotics are given as empirical treatment. The pathogen identification is important for the therapeutic management [15].

Both patients had culture-positive for Propionibacterium acnes (P. acnes). This organism is seated deeply in the pilosebaceous glands, mainly in the scalp and face. It is a slow-growing, pleomorphic, non-spore-forming gram-positive anaerobic bacillus that is a universal component of the normal skin microbiota. It is usually considered a contaminant of blood cultures but occasionally can cause serious infections, including postoperative central nervous system (CNS) infections. P. acnes are the most commonly isolated organism after Staphylococcus aureus and Staphylococcus epidermidis following craniotomies. In the presence of heavy infiltrates, the Gram stain is not reliable. Gram stain is only positive in about 10.5% of clinically significant infections with moderate growth. P. acnes behave in a less aggressive manner than other postsurgical organisms and only accounts for a small fraction of CNS infections [16]. P. acnes abscesses typically follow craniotomy, shunts, access to reservoirs, trauma, and foreign bodies. Granulomatous responses have been documented in the CNS following P. acnes infections.

P. acnes grow slowly in the laboratory. This can cause in a delay in diagnosis, missed diagnosis, or delay in treatment if specimens are not cultured for an extended period. Cultures may not grow for as long as 14 days, so samples should be held beyond the usual 5 to 7 days. Gram stain may not be a reliable technique for the rapid diagnosis of P. acnes infections. When there is evidence of an abundant inflammatory response in the Gram-stained smear, a more careful evaluation of cultures must be performed. Polymerase chain reaction for the 16S rRNA or mass spectrometry can be a useful tool for rapid identification and typing of P. acnes following recovery in culture. Propionibacterium is susceptible to antibiotics used for the treatment of anaerobic infections, including penicillin, erythromycin, lincomycin, and clindamycin, but not metronidazole, which is notably ineffective against P. acnes [17].

Patients with PA should be followed up with serial MRI of the pituitary, hormonal profile and visual fields at 3, 6, and 12 months after surgery. The recurrence rate is variable and depends on the nature of the abscess (primary or secondary. The majority of relapses are associated with either an immunological defect or previous pituitary surgery [12,18].

Conclusion

We presented 2 cases of unusual sellar mass from an abscess in an adolescent and a young adult due to P. acnes, both responded well to treatment.

The pituitary abscess should be included as the differential diagnosis of patients with a sellar or a suprasellar mass, headaches, pituitary dysfunction, and meningeal inflammation.

The diagnosis is difficult before surgery because of overlapping clinical signs, radiological and laboratory findings with other sellar lesions.

Broad-spectrum antibiotics should be started empirically even before the culture results are available.

Culture is positive only in 50% of cases, and in case of unusual bacteria like P. acnes, an extended culture is required for the confirmation of the diagnosis.

Pituitary dysfunction should be recognized and appropriately treated particularly glucocorticoid replacement.

Transsphenoidal surgery is the treatment of choice and this is followed by pronged 4-6 weeks of broad-spectrum antibiotic therapy.

Early and efficient surgical and medical management results in lower mortality and higher recovery of pituitary hormone function.

Patients should be followed up with MRI imaging, assessment of the hormone replacement if required, and visual field assessment because of a chance of recurrence.

References

    1. Lin Y, Lin F, Liang Q, Li Y, Wnag Z, et al. (2017) Pituitary abscess: report of two cases and review of the literature. Neuropsychiatr Dis Treat 13: 1521-1526. [crossref]
    2. Furnica RM, Lelotte J, Duprez T, Maiter D, Alexopoulou O, et al. (2018) Recurrent pituitary abscess: case report and review of the literature. Endocrinol Diabetes Metab Case Rep 17-0162. [crossref]
    3. Kummaraganti S, Bachuwar R, Hundia V, et al. (2013) Pituitary abscess: A rare cause of pituitary mass lesion. Endocrine Abstracts 31: 1. [crossref]
    4. Al Salamn JM, Al Agha RAMB, Helmy M, et al. (2017) Pituitary abscess. BMJ Case Rep 2016-217912. [crossref]
    5. Nordjoe YE, Igombe SRA, Laamrani FZ, Jroundi L, et al. (2019) Pituitary abscess: two case reports. J Med Case Rep 13: 342.
    6. Wang Z, Gao L, Zhou X, Guo X, Wang Q, Lian W, Wang R, Xing B, et al. (2018) Magnetic resonance imaging characteristics of pituitary abscess: a review of 51 cases. World Neurosurg 114: e900-e902. [crossref]
    7. Xu XX, Li B, Yang HF, Du Y, Li Y, Wang WX, et al. (2014) Can diffusion-weighted imaging be used to differentiate brain abscess from other ring-enhancing brain lesions? A meta-analysis. Clin Radiol 69: 909-915. [crossref]
    8. Corsello SM, Paragliola1 RM, et al. (2017) Differential diagnosis of pituitary masses at magnetic resonance Imaging. Endocrine 58: 1-2.
    9. Coulter IC, Mahmood S, Scoones D, Bradey N, Kane PJ, et al. (2014) Abscess formation within a Rathke’s cleft cyst. J Surg Case Rep 11: 105. [crossref]
    10. Vasilev V, Rostomyan1 L, Daly AF, Potorac J, Zacharieva S, et al. (2016) Bonneville JF and Becker A. Pituitary ‘incidentaloma’: neuroradiological assessment and differential diagnosis. European Journal of Endocrinology 175: R171-R18. [crossref]
    11. Güneş A, Güneş SO (2020) The neuroimaging features of Rathke’s cleft cysts in children with endocrine-related diseases. Diagn Interv Radiol 1: 61-67. [crossref]
    12. Vates GE, Berger MS, Wilson CB, et al. (2001) Diagnosis and management of pituitary abscess: a review of twenty-four cases. J Neurosurg 95: 233-241. [crossref]
    13. Karagiannis AKA, Dimitropoulou F, Papatheodorou A, Lyra S, Seretis A, Vryonidou A, et al. (2016) Pituitary abscess: a case report and review of the literature. Endocrinol Diabetes Metab Case Rep [crossref]
    14. Ling X, Zhu T, Luo Z, Zhang Y, Chen Y, Zhao P, Si Y (2017) A review of pituitary abscess: our experience with surgical resection and nursing care. Transl Cancer Res 6(4): 852-859.
    15. Achermann Y, Goldstein EJC, Coenye T, Shirtliff ME, et al. (2014) Propionibacterium acnes: from Commensal to Opportunistic Biofilm-Associated Implant Pathogen. Clin Microbiol Rev 27: 419-440. [crossref]
    16. Chung S, Kim JS, Seo SW, Ra EK S, Joo SI, Kim SY, Park SS, Kim EC, et al. (2011) A Case of Brain Abscess Caused by Propionibacterium acnes 13 Months after Neurosurgery and Confirmed by 16S rRNA Gene Sequencing. Korean J Lab Med 31(2): 122-126. [crossref]
    17. Yacoub AT, Khwaja S, Daniel L, et al. (2015) Propionibacterium acnes Causing Central Nervous System Infections: A Case Report and Review of Literature. Infectious Diseases in Clinical Practice 23: 60-65. [crossref]
    18. Batool SM, Mubarak F, Enam SA, et al. (2019) Diffusion-weighted magnetic resonance imaging may be useful in differentiating fungal abscess from malignant intracranial lesion: Case report. Surg Neurol Int 10: 13. [crossref]

A Safety Signal’s Significance with the COVID-19 Coronavirus

Introduction

The global pandemic involving COVID-19 (coronavirus) has produced unprecedented challenges for the medical, healthcare providers and our world community. The World Health Organization (WHO 2020) initially declared COVID-19 a pandemic, pointing to the over numerous cases of the coronavirus illness in over a hundred countries and territories around the world and the sustained risk of further global spread [1,2]. The term pandemic is most often applied to new influenza strains, and the Centers for Disease Control and Prevention (CDC) use it to refer to strains of virus that are able to infect people easily and spread from person to person in an efficient and sustained manner. Such a declaration refers to the spread of a disease, rather than the severity of the illness it causes. A pandemic declaration can result in increased levels of stress, anxiety, panic and levels of functional depression for some individuals [3]. Recognized is the realization that these unusual circumstances create significant uncertainty and unease in the professional and personal lives of health care professionals and their patients.

Definition of a Safety Signal

“Safety signals” are learned cues that predict the nonoccurrence of an aversive event. As such, safety signals are potent inhibitors of fear and stress responses. Investigations of safety signal learning have increased over the last few years due in part to the finding that traumatized persons are unable to use safety cues to inhibit fear, making it a clinically relevant phenotype.

The coronavirus has traumatized some which has been recognized as a state of heightened fear or anxiety in environments globally. This symptom has been conceptualized as a generalization of the fear conditioned during the traumatic experience that becomes resistant to extinction. As opposed to danger learning where a cue is paired with aversive stimulation, safety learning involves associating distinct environmental stimuli also known as safety signals that can be used an applied when aversive events occur as in a global pandemic.

During periods of high stress such as during this Covid-19 pandemic, fear often permeates the lives of many because if the unknown nature of this illness. This occurs because of the absence of a learned safety signal. Such safety signals can inhibit fear responses to cues in the environment. As such, safety signals are only learned when the subject expects danger but it does not necessarily occur. More fundamental to the clinical importance of a safety signal is the distinction between safe and dangerous circumstances. Thus, identifying the mechanisms of safety learning represents a significant goal for basic neuroscience that should inform future prevention and treatment of trauma and other anxiety disorders.

With COVID-19 global pandemic, the World Health Organization (2020) continues to ask countries to “take urgent and aggressive action.” World leaders continue holding international teleconferences with health officials to address the most effective way to protect the public and develop public health policy for the coronavirus that has caused multiple illnesses and deaths worldwide.

Transitioning the Pandemic

The urgency has created stressful life experiences for all ages that pose the potential for illness resulting for some in disabling fear, a hallmark of anxiety and stress-related disorders [4]. Researchers at Yale University and Weill Cornell Medicine report on a novel way that could help combat such anxiety experienced at times like these. When life events as the spread of the Corvid 19 triggers excessive fear and the absence of a safety signal. In humans, a symbol or a sound that is never associated with adverse events can relieve anxiety through an entirely different brain network than that activated by fear and worry. Each individual must find their own “safety signal” whether that is a mantra, song, a person, or even an item like a stuffed animal that represents the presence of safety and security.

The Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO), and other reputable agencies have advocated on how to address the coronavirus by washing hands frequently, avoid sharing personal items, and maintaining social distance from others beyond immediate family.

While it’s still unclear exactly how much of the current coronavirus outbreak has been fueled by asymptomatic, mildly symptomatic, or pre-symptomatic individuals, the risk of contagion exists. A yet to be published article in the CDC journal “Emerging Infectious Disease” (CDC 2020) reports that the time between cases in a chain of transmission is less than a week, with more than 10% of patients being infected by someone who has the virus but does not yet have symptoms according to Dr. Luren Meyers, a professor of integrative biology at UT Austin, who was part of a team of scientists from the United States, France, China and Hong Kong examining this viral threat.

Earlier this year, researchers in China published a research letter in the Journal of the American Medical Association, outlining a case of an asymptomatic woman in Wuhan, China who reportedly spread the virus to five family members while traveling to Anyang, China-all of whom developed COVID-19 pneumonia. The sequence of events suggests that the coronavirus may have been transmitted by the asymptomatic carrier,” [5].

Prevention Interventions

Coordinated regional efforts are underway under the direction of the Centers for Disease Control and Prevention (CDC) that provides guidelines aimed at prevention intervention. Each individual should make the effort to create one’s own “safety signal” by following the recommendations of the CDC (2020). Know how it spreads and that there is currently no vaccine to prevent coronavirus disease (COVID-19). Critical for prevention is avoided exposing the virus. The virus is thought to spread mainly from person-to-person. Between people who are in close contact with one another. Through respiratory droplets produced when an infected person coughs or sneezes. These droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs.

Disinfecting by washing hands often with soap and water for at least twenty seconds especially after you have been in a public place or after blowing your nose, coughing, or sneezing. If soap and water are not readily available, use a hand sanitizer that contains at least 60% alcohol. Cover all surfaces of your hands and rub them together until they feel dry. Avoid touching the eyes, nose, and mouth with unwashed hands Put distance between yourself and other people if COVID-19 is spreading in your community. This is especially important for people who are at higher risk of getting immune compromised illness.

Health care calls for “sheltering in place” are effort to provide primary prevention it’s important to stay home to slow the spread of COVID-19, and if you must go out, practice personal quarantine. While we stay home, don’t let fear and anxiety about the COVID-19 pandemic become overwhelming. Managing mental health issues can be aided by taking breaks from watching, reading, or listening to news stories and social media. It remains important to take the time to connect with others. Networking with friends and loved ones over the phone or via video chat about the thoughts and feelings experienced during this pandemic is very important to maintain mental health daring three times. Employ the use mindful meditation, eating healthy meals, exercising regularly, and getting plenty of sleep.

Take steps to protect yourself and others. Stay sheltered in place especially when you’re sick. Shelter in place means to seek safety within the building one already occupies, rather than to evacuate the area or seek a community emergency shelter. The American Red Cross says the warning is issued when “chemical, biological, or radiological contaminants which would include exposure to the coronavirus.

Efforts must be made to cover one’s mouth and nose with a tissue when you cough or sneeze or use the inside of your elbow. Throw used tissues in the trash. Immediately wash your hands with soap and water for at least 20 seconds. If soap and water are not readily available, clean your hands with a hand sanitizer that contains at least 60% alcohol.

It is important to wear a facemask for your own health as well as the health of others. Everyone should wear a facemask when they are around other people (e.g., sharing a room or vehicle) and before entering a healthcare provider’s office. If someone is not able to wear a facemask due to breathing difficulties, then these individuals should cover all coughs and sneezes, and people who are caring for theme should wear a facemask when they enter ones room. Wear a facemask when caring for someone who is showing any signs or symptoms of respiratory infection and fever.

When considering the anxiety and apprehension individuals may experience with the vulnerabilities of the present pandemic and future epidemics of this proportion, patient medical education can provide a buffer against the Prevention interventions that include cleaning and disinfecting objects and surfaces that are touched regularly. This includes tables, doorknobs, light switches, countertops, handles, desks, phones, keyboards, toilets, faucets, and sinks. If surfaces are dirty, clean them: Use detergent or soap and water prior to disinfection. With first signs of symptoms, take advantage of Virtual Care in an effort to minimize unnecessary visits to an emergency room or health care provider’s office, which can also decrease the spread of illness and/or infection of many conditions, including COVID-19. Finally, each individual is encouraged to establish one’s own “safety signal” by adhering to the multiple precautions that include the guidelines developed and promoted by the World Health organization and the Centers for Disease Control and Prevention (CDC 2020).

References

  1. Centers for Disease Control (2020) Coronavirus Disease 2019 (COVID-19).
  2. World Health Organization (2020) Coronavirus disease 2019 (COVID-19): Situation Report-38.
  3. Miller TW (2015) Problem Epidemics in Recent Times. Health & Wellness. Lexington Kentucky: Rock point Publisher Incorporated.
  4. Miller TW (2010) Handbook of Stressful Transitions across the Life Span. New York: Springer Publishers Incorporated.
  5. Huang C, Wang Y, Li X, et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395: 497-506.

Self-Recovery of Pancreatic Beta Cell’s Insulin Secretion Based on 10+ Years Annualized Data of Food, Exercise, Weight, and Glucose Using GHMethod: Math-Physical Medicine (No. 339)

Abstract

The author was inspired from reading two recently published medical papers regarding pancreatic beta cells insulin secretion or diabetes reversal via weight reduction. The weight reduction is directly related to the patient’s lifestyle improvement through diet and exercise. He has published six medical papers on beta cells based on different stages in observations of his continuous glucose improvements; therefore, in this article, he will investigate food ingredients, meal portions, weight, and glucose improvement based on his 10+ years of collected big data.

Here is the summary of his findings:

  1. His successful weight reduction, from 220 lbs. in 2010 to 171 lbs. in 2020, comes from his food portion reduction and exercise increase.
  2. His lower carbs/sugar intake amount, from 40 grams in 2010 to 12 grams in 2020, is resulted from his learned food nutrition knowledge and meal portion reduction, from 150% in 2010 to 67% in 2020.
  3. His weight reduction contributes to his FPG reduction, from 220 mg/dL in 2010 to 104 mg/dL in 2020. His carbs/sugar control and increased walking steps, from 2,000 steps in 2010 to ~16,000 steps in 202, have contributed to his PPG reduction, from 300 mg/dL in 2010 to 109 mg/dL in 2020. When both FPG and PPG are reduced, his daily glucose is decreased as well, from 280 mg/dL in 2010 to 108 mg/dL in 2020.
  4. His damaged beta cell’s insulin production and functionality, most likely, have been repaired about 16% for the past 6 years or 27% in the past 10 years at a self-repair rate of 2.7% per year.

The conclusion from this paper is a 2.7% annual beta cells self-repair rate which is similar to his previously published papers regarding his range of pancreatic beta cells self-recovery of insulin secretion with an annual rate between 2.3% to 3.2%.

To date, the author has written seven papers discussing his pancreatic beta cell’s self-recovery of insulin secretion. In his first six papers [1-7], he used several different “cutting angles” or “analysis approaches” to delve deeper into this complex biomedical subject and achieved consistent results within the range of 2.3% to 3.2% of annual self-recovery rate.

He used a quantitative approach with precision to discover and reconfirm his pancreatic beta cell’s health state by linking it backwards step-by-step with his collected data of glucose, weight, diet, and exercise. He has produced another dataset for a self-repair rate of 2.7% which is located right in the middle between 2.3% and 3.2% from his previous findings.

In his opinion, type 2 diabetes (T2D) is no longer a non-reversible or non-curable disease. Diabetes is not only “controllable” but it is also “self-repairable”, even though at a rather slow rate. He would like to share his research findings and his persistent efforts from the past decade with his medical research colleagues and to provide encouragement to motivate other T2D patients like himself to reverse their diabetes conditions.

Introduction

The author was inspired from reading two recently published medical papers regarding pancreatic beta cells insulin secretion or diabetes reversal via weight reduction. The weight reduction is directly related to the patient’s lifestyle improvement through diet and exercise. He has published six medical papers on beta cells based on different stages in observations of his continuous glucose improvements; therefore, in this article, he will investigate food ingredients, meal portions, weight, and glucose improvement based on his 10+ years of collected big data.

Methods

Background

To learn more about his developed GH-Method: math-physical medicine (MPM) research methodology, readers can review his article, Biomedical research methodology based on GH-Method: math-physical medicine (No. 54 and No. 310), in Reference [1] to understand his MPM analysis method.

Diabetes History

In 1995, the author was diagnosed with severe type 2 diabetes (T2D). His daily average glucose reached 280 mg/dL with a peak glucose at 398 mg/dL and his HbA1C was at 10% in 2010. Since 2005, he has suffered many kinds of diabetes complications, including five cardiac episodes (without having a stroke), foot ulcer, renal complications, bladder infection, diabetic retinopathy, and hypothyroidism.

As of 9/30/2020, his daily average glucose is approximately 106 mg/dL and HbA1C at 6.1%. It should be mentioned that he started to reduce the dosage of his three different diabetes medications (maximum dosages) in early 2013 and finally stop taking them on 12/8/2015. In other words, his glucose record since 2016 to the present is totally “medication-free”.

Beginning on 1/1/2012, he started to collect his weight value in the early morning and his glucose values four times a day: FPG x1 in the early morning and PPG x3 at two hours after the first bite of each meal. Since 1/1/2014, he also started to collect his carbs/sugar amount in grams and post-meal walking steps. Prior to these two dates, especially during the period of 2010 to 2012, the manually collected biomarkers and lifestyle details were scattered and unorganized. Therefore, those annualized data from 2010 to 2012 or 2014 were guesstimated values with his best effort. It should be further mentioned that on 1/1/2013, he began to reduce his dosages of three diabetes educations step by step. By 1/1/2015, he was only taking 500 mg of Metformin for controlling his diabetes conditions. Finally, he completely ceased taking Metformin on 12/8/2015; therefore, since 1/1/2016, his body has been completely free of any diabetes medications.

Other Research Results

Recently, a Danish medical research team has published an article on JAMA which emphasizes a strengthen lifestyle program can reverse” T2D. This program includes a weekly exercise (5-6 times and 30-60 minutes each time), daily walking more than 10,000 steps using smart phone to keep a record, personalized diet and nutritional guidance by healthcare professionals, etc. The observed results from this Danish report are patientsoverall HbA1C reduction of 0.31%, and their diabetes medication dosage reduction from 73% to 26%.

DiRECT research report from UK also indicated that an aggressive weight reduction program can induce improvement on diabetes conditions. This UK program includes low-calories diet for 3-5 months with 825-853 K-calories per day, plus daily walking of 15,000 steps per day. The observed results from this UK report are patientsoverall HbA1C reduction of 0.9%, weight reduction of 10 kg (or 22 lbs.), and reduced diabetes medication dosage as well.

The Author’s Approach

Inspired by the results from the two European studies and based on his own collected big data over the past 10+ years, from 2010 to 2020, he decided to conduct a similar research on his own. He has separated his 10+ years data into two periods. The first period of 5 years, from 2010 to 2014, with partially collected and partially guesstimated data under different degrees of medication influence, and the second period of 6 years, from 2015 to 2020, with a complete set of collected raw data stored in software and severs without any medication influence.

His trend of thoughts include a sequence from cause to consequence as listed below from top to bottom:

  • Food and meal’s portion %
  • K-calories per day
  • Weight (lbs.)
  • FPG (mg/dL)
  • Carbs/sugar intake (grams)
  • Walking
  • PPG (mg/dL)
  • Daily glucose (mg/dL)

He has further conducted nine calculations of correlation coefficient based on the above parameters to examine the degree of connections between any 2 elements of these total 8 parameters. It should be mentioned that the correlation coefficients can only be done between two data sets, or two curves.

More importantly, in addition to examining the raw data, he also placing an emphasis on the annual change rate percentage, its trend, and their comparisons of these 8 parameters.

Results

Figure 1 shows his background data table which includes his calculated annual averages of the 8 parameters plus proteins, fat, and daily K-calories, based on his daily data collected during 2010 to 2020.

fig 1

Figure 1: Background data table.

Figure 2 depicts the annual change rate percentage of his food (meal portion %, K-calories, and carbs/sugar) and his weight. In this figure, meal portion and weight have similar change rates which means the less he eats, the lighter his weight. Also, carbs/sugar amount and K-calories have similar change rates which means the less his K-calories, the less his carbs/sugar intake amount.

fig 2

Figure 2: Annual change rates of Weight and Food (meal portion, K-calories, and carbs/sugar).

Figure 3 illustrates the similar trend of annual data of his weight and three food components (meal portion, K-calories, and carbs/sugar amount).

fig 3

Figure 3: Annual change rates of Weight and Food (meal portion, K-calories, and carbs/sugar).

Exercise is a missing component from this figure which is also essential on weight reduction. The more he eats, the higher intake amounts of his K-calories and his carbs/sugar as well. During the past decade on his effort for weight reduction, he has focused on reducing both of his meal portion percentage and carb/sugar intake amount. As a result, he was able to reduce his weight from 220 lbs (100 kg) and his average glucose from 280 mg/dL in 2010 to 171 lbs. (78 kg) and 106 mg/dL in 2020 (without any medication).

Figure 4 reflects the annual change rate percentage of his daily glucose, weight and carbs/sugar amount. In this figure, the change rates of his glucose and weight are remarkably similar, almost a mirror image, which indicates the lower his weight, the lower his glucose. This finding matches the two European studies and the common knowledge possessed by healthcare professionals. The reason for the obviously mismatched change rates between carbs/sugar and glucose or weight is due to the missing component of exercise which is equally important on glucose reduction.

fig 4

Figure 4: Annual change rates of Weight, Glucose, and Carbs/sugar.

Figure 5 focuses exclusively on the relationships among data of glucose, carbs/sugar, and exercise. The positive correlation coefficient between glucose and carbs/sugar is expressed by these two similar moving trends. On the other hand, the negative correlation coefficient between glucose and exercise (walking) is expressed by these two opposite moving trends.

fig 5

Figure 5: Annual data of Weight, Glucose, and Carbs/sugar.

Figures 6-8 collectively collective together to show the 9 sets of calculated correlation coefficients among those 8 listed elements in above section of Methods. A better illustration of these three figures can be found in a table, where all of the calculated correlations are above 90%, which means they are highly connected to each other (Figure 9). Even the correlation of -89% between glucose and walking exercise is also extremely high in a negative manner.

fig 6

Figure 6: Correlation coefficients among Weight, K-calories, meal portion.

fig 7

Figure 7: Correlation coefficients among Weight, Glucose, Carbs/sugar.

fig 8

Figure 8: Correlation coefficients among PPG, Carb/sugar, Walking, FPG, Weight.

fig 9

Figure 9: A combined data table of 9 correlation coefficients among 8 elements.

Figure 10 reveals the detailed annual change rates of 8 elements for a 10+ year period from 2010 to 2020. It should be pointed out that his average change rates within 6 years from 2015 through 2020 are 2.7% per year for both FPG and PPG, and 3.4% for daily glucose. This conclusion is similar to his six previously published papers regarding his pancreatic beta cell’s self-recovery rate of insulin secretion. Most likely, his beta cells insulin production and functionality have been repaired about 16% during the past 6 years or 27% during the past 10 years at a self-repair rate of 2.7% per year.

fig 10

Figure 10: A combined data table of annual change rates of 7 elements, especially glucose change rates of 2.7%.

Here is the summary of his findings:

  1. His successful weight reduction, from 220 lbs. in 2010 to 171 lbs. in 2020, comes from his food portion reduction and exercise increase.
  2. His lower carbs/sugar intake amount, from 40 grams in 2010 to 12 grams in 2020, is resulted from his learned food nutrition knowledge and meal portion reduction, from 150% in 2010 to 67% in 2020.
  3. His weight reduction contributes to his FPG reduction, from 220 mg/dL in 2010 to 104 mg/dL in 2020. His carbs/sugar control and increased walking steps, from 2,000 steps in 2010 to ~16,000 steps in 202, have contributed to his PPG reduction, from 300 mg/dL in 2010 to 109 mg/dL in 2020. When both FPG and PPG are reduced, his daily glucose is decreased as well, from 280 mg/dL in 2010 to 108 mg/dL in 2020.
  4. His damaged beta cell’s insulin production and functionality, most likely, have been repaired about 16% for the past 6 years or 27% in the past 10 years at a self-repair rate of 2.7% per year.

Summary

To date, the author has written seven papers discussing his pancreatic beta cell’s self-recovery of insulin secretion. In his first six papers [2-7], he used several different “cutting angles” or “analysis approaches” to delve deeper into this complex biomedical subject and achieved consistent results within the range of 2.3% to 3.2% of annual self-recovery rate.

He used a quantitative approach with precision to discover and reconfirm his pancreatic beta cell’s health state by linking it backwards step-by-step with his collected data of glucose, weight, diet, and exercise. He has produced another dataset for a self-repair rate of 2.7% which is located right in the middle between 2.3% and 3.2% from his previous findings.

In his opinion, type 2 diabetes (T2D) is no longer a non-reversible or non-curable disease. Diabetes is not only “controllable” but it is also “self-repairable”, even though at a rather slow rate. He would like to share his research findings and his persistent efforts from the past decade with his medical research colleagues and to provide encouragement to motivate other T2D patients like himself to reverse their diabetes conditions.

References

  1. Hsu, Gerald C. eclaireMD Foundation, USA. “GH-Method: Methodology of math-physical medicine, No. 54 and No. 310.”
  2. Hsu, Gerald C. eclaireMD Foundation, USA. “Changes in relative health state of pancreas beta cells over eleven years using GH-Method: math-physical medicine (No. 112).”
  3. Hsu, Gerald C. eclaireMD Foundation, USA. “Probable partial recovery of pancreatic beta cells insulin regeneration using annualized fasting plasma glucose via GH-Method: math-physical medicine (No. 133).”
  4. Hsu, Gerald C. eclaireMD Foundation, USA. “Probable partial self-recovery of pancreatic beta cells using calculations of annualized fasting plasma glucose using GH-Method: math-physical medicine (No. 138).”
  5. Hsu, Gerald C. eclaireMD Foundation, USA. “Guesstimate probable partial self-recovery of pancreatic beta cells using calculations of annualized glucose data using GH-Method: math-physical medicine (No. 139).”
  6. Hsu, Gerald C. eclaireMD Foundation, USA. “Relationship between metabolism and risk of cardiovascular disease and stroke, risk of chronic kidney disease, and probability of pancreatic beta cells self-recovery using GH-Method: Math-Physical Medicine (No. 259).”
  7. Hsu, Gerald C. eclaireMD Foundation, USA. “Self-recovery of pancreatic beta cell’s insulin secretion based on annualized fasting plasma glucose, baseline postprandial plasma glucose, and baseline daily glucose data using GH-Method: math-physical medicine (No. 297).”

Disease, Duration and Death

Abstract

Life has always been threaten by diseases, calamities, catastrophes leading to death caused by various known or unknown, animate or inanimate objects in human’s relatively medium life span. Ever since the documentation of the human history, it is well known that man loved their body and prefer to live in accordance with their wishes. When rationale judgment became prominent after the experiences and observations of life and death events, they started searching remedies such as medicine. This is how medicine evolved since our early civilization. With the development of reason, logic, observation, experimentation and practical application, we learned tremendous ways of saving body, brain and behavior. However, as time passes human environment changes unpredictably leading to change in human behavior and attitude towards objects/materials and living beings. It is not only a matter of physical, biological or cosmic change but also behavior of everything that brought unprecedented events such as unexpected war, epidemic, catastrophes etc. leading to death [1,2]. Measurement of several physical parameters of human and universal bodies has become routine but various functions/characters in relation to time has yet to measure fully. This is the point we fall short to save humans promptly resulting high number of unexpected loss of life such as in COVID-19 pandemic. Among 1554960 covid-19 infected population in more than 209 countries, territories and two conveyances 5.9% died, and among the deaths more than 80% occurring in just 10 countries (USA, Spain, Italy, Germany, France, China, Iran, UK, Belgium, Netherlands) of the world in the last three months duration [2].

Disease is an abnormal architecture/anatomy, function, condition of the body and mind in a specific duration. Many times and circumstances death occurs due to unprecedented cause, behavior or ignorance. Therefore, it is essential to know the unknown environment and diverse nature and behavior of human beings to diagnose epidemicity of the disease. Despite vast scientific discoveries and new achievement, there is a big hole in the measurement of core human behavior and intelligence. Human body, intelligence and behavior plays a great role in the defense mechanism as well as association in the causation, development, cessation of disease in specific duration in specific place/s. So far we are devoid of the precise knowledge on the creation of covid-19 however many scientists have been trying to explore the mystery of the occurrences, nature and impact on the human population of the globe [3].

The duration or natural course of illness or diseases is important in the management of cases, carrier as well as prevention of complications and death [4]. Alert researchers identify the key factors of the disease when there is sudden rise of cases of similar features in a short period. Ignorance about the nature of pathogen and ignorance of the general population about the disease leads to higher number of deaths in a very short duration. Lack of alertness in changing behavior and environment of the disease in the population further complicates its management and increases the number of deaths. The challenge of the new disease, ignorance on the part of environment and human behavior help to expand disease dimensions in terms of time, place and person.

Opportunities such as chance, experience, observation and experimentation lead to discovery and development of medicine and care system that can make our life easier, comfortable and lengthier. This is the beauty of medical discipline, research and practice in human population. A dynamic patience where a body and brain searches a remedy continuously in response to disease is probably the best stimulus to initiate new knowledge, skills, practice to cure patient and prevent death. Lack of precise knowledge of duration and the nature of the disease is biggest obstacles in managing covid-19 at present and many more diseases that are possible in the future. Following the spread of disease and management of the patient (source) meticulously in global environment, recording the evidences and continuous sharing among the fellow researchers and responsible individuals are the most important aspects of pandemic control.

Alertness, continuous searches, dynamic patience can help humans to increase its capacity to deal with covid-19 pandemic. Change in seasonality in different geographical regions may affect duration of the diseases and distribution of death in humans. This demands thinking globally and acting globally.

Keywords

Covid-19, Death, Disease, Duration, Pandemic

References

  1. Riedel S (2004) Biological warfare and bioterrorism: a historical review. BUMCProceedings17: 400-406. [crossref]
  2. Covid-19 Coronavirus Pandemic, Worldometer. Accessed on April 09, 2020, 16:30 GMT.
  3. Zhou P, Yang X, Wang X, Hu B, Zhang L, et al. (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature579: 270-273. [crossref]
  4. Rothan HA,ByrareddySN (2020) The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of Autoimmunity109: 102433. [crossref]

Telemedicine: Enabling Patients with Arrhythmias in Self-Care Behaviors

Abstract

The study, Telemedicine: Enabling Patients with Arrhythmias in Self-Care Behaviors study is designed for early recognition and treatment of an arrhythmia and optimizing patients’ medication, activity, and arrhythmia self-efficacy. Telemedicine is a method which allows health care professionals to evaluate, diagnose, and treat patients within their homes and remote locations [1]. Connecting with patients via video and telephone visits allows the caregiver access and assists the patient in improving self-care behaviors and self-efficacy in managing arrhythmias [1,2]. This pilot telemedicine study provides earlier diagnosis of abnormal arrhythmias and increased patient involvement and self-efficacy of one’s health care solutions [2]. The Telemedicine: Enabling patients in Self-Care Behaviors study started in February 2020, prior to the onset of the Covid 19 pandemic. The study has been placed on hold since March 17, 2020. In a response to the Covid-19 pandemic (separate from this study) multiple medical and nursing practices have adopted telemedicine to maintain ongoing care appointments [3]. The study displays the complementing use of three survey tools (Medication Understanding and Self-Efficacy Tool, Functioning Self Efficacy Scale, and Arrhythmia Specific questionnaire in Tachycardia an Arrhythmia) with monitoring devices (loop recorders, Kardia-TM, pacemakers and cardioverter defibrillators-ICDs) coupled with telephone and video visits to pinpoint arrhythmia changes and exact patient reactions and discussion to reinforce self-efficacy behaviors.

Keywords

Telemedicine, arrhythmia, self-efficacy, behavior.

Introduction

The purpose of the study, Telemedicine: Enabling Patients with Arrhythmias in Self-Care Behaviors (T:EPASB) is to provide an alternative to in person visits, decreased the time of diagnosis and treatment of an arrhythmia via the internet, and enable patients to improve self-efficacy of arrhythmia care behaviors. Self-efficacy can be defined as the individual’s belief in oneself to handle a set of circumstances or changes in physical or mental well-being [2].

The first outcome of the study is to determine if subjects in a telemedicine program for the care of cardiac arrhythmias have  any difference in [1] time of arrhythmia recognition [2], time of arrhythmia diagnosis by a healthcare provider, and [3] time of treatment initiation compared with patients enrolled in standard care for cardiac arrhythmias. The second outcome of the study examines subjects’ self-efficacy of medication use, functional self-efficacy, and arrhythmia self-efficacy. A data collection tool was utilized with a simplistic check off system used to mark when one recognized changes in symptoms such as increased palpitations, fatigue, activity intolerance, shortness of breath, and any other change in symptoms associated with an arrhythmia. The tool allowed for quick responses to these symptoms with self-initiated blood pressure check, heart rate check, increased fluids, or taking an additional beta blocker, sitting down and resting, and calling the electrophysiology (EP) office for advice (Appendix A).

Background Information

University based tertiary care clinics, which  treat  irregular heart rhythms, are known as arrhythmia clinics and formally called electrophysiology departments [4]. These departments have been in existence prior to the early 1960’s and their technology has continued to evolve over time. The need to meet with patients and discuss  their abnormal and irregular heart rhythms has entailed prescribing medications to slow the heart rate, prescribing medications to eliminate abnormal heart rhythms, and implanting devices to further control the heart rhythms, known as pacemakers (PPM) and implantable cardioverter-defibrillators (ICDs) [4]. The continued improvement in technology and expansion of such departments has led to a need for increased numbers of patient appointments, dual appointments for arrhythmia management and pacemaker or ICD management, and coordinated appointments with other cardiology sub-specialties [5]. This increased frequency and duration of appointments places stress upon patients with longer drives, wait times, financial stressors of parking, food, and gas costs in reaching such appointments [6]. With such stressors, a need for computer assisted video visits has evolved [6]. The monitoring  of  arrhythmias  involves  home  monitoring via external disposable monitors which are affixed on  the chest wall, small implanted monitors (loop recorders), and utilizing the monitoring features of permanent pacemakers (PPMs) or implantable cardioverter defibrillators (ICDs).

Review of literature

The T:EPASB is based upon studies showing improved clinical outcomes with the use of telemedicine. The TRUST trial compares the use of a telephone video conference to conventional in person visits with individuals with ICDs. The TRUST trial determined the efficacy and safety for monitoring ICDs and the reduction of in person visits [7,8]. This study displayed an adverse event rates of 10.4 for each group [7,10] and no difference in the telemedicine versus the in person visit group.

The Poniente trial determined there was no difference in arrhythmia detection and functional capacity in monitoring elderly patients with pacemakers via home monitoring compared with in person monitoring [9]. The CHOICE AF was a pilot study to test the feasibility of brief telephone-based program to target improving cardiovascular risk factors and health related quality of life in patients with atrial fibrillation [11], showing great potential for a telephone- based program.

A study by Ryan et. al. (2018) [13] verified the efficacy of theory based Integrated Theory of Health Behavior Change (ITHBC) intervention utilizing a cellular phone application to increase women’s initiation and long-term maintenance of osteoporosis self-management behaviors. This study takes a chronic disease state, osteoporosis, and combines ITHBC prompted behaviors with a cellular phone application to assist women in behavior change. Suter et. al. (2011) [14] used self-efficacy as a key component in managing one’s health noting patient empowerment in the management of chronic disease conditions such as diabetes mellitus and heart failure. The study identified the essence of telemedicine in its ability to empower patients with skills in managing one’s chronic health condition.

Theoretical Framework

Integrated Theory of Health Behavior Change (ITHBC) was used in guiding this study as it notes the importance in assisting individuals in becoming increasingly involved in their own health care [2]. This theory links a relationship between the way one views one’s own health care and an overall sense of wellness. Dr. Ryan’s study of those with chronic health care diagnosis’ and improving specific health care behaviors highlighted the need to 1) have a change in how one reacts followed by 2) one’s resultant behavior with an improved sense of wellness (when assisted with behavior changes). Essential components for behavior change include a desire to change, self- reflection, positive social-influence and support required in creating the change [2].

Methods and Materials

The study is a prospective randomized controlled study, in which informed consent was obtained. Randomization included subjects picking from sealed envelopes which were numbered, labelled with a folded card within each envelop stating either standard versus telemedicine visits. The University of Michigan Hospital IRB number: IRB00001995.

Inclusion/Exclusion Criteria:

JCRM-3-2-307-g001

Methods

The study was introduced to the subjects during an initial meeting with an explanation of the study and an explanation of the consent. After the informed consent was obtained, the subjects were randomized into telemedicine or standard in person six- month visits.

With the initial visit, surveys were completed with telemedicine and standard visit groups. Telemedicine subjects received monthly visits for three consecutive months and standard received a six month return visits (Appendix B-study schematic). Interventions provided to the telemedicine group included discussion and reinforcement of medication, functional activity and arrhythmia self-efficacy, guided discussion, and social support.

The surveys utilized were the Medication Understanding and Self-Efficacy Tool, Functioning Self Efficacy Scale, and Arrhythmia Specific questionnaire in Tachycardia an Arrhythmia (MUSE, FSES, ASTA) surveys. All three surveys were provided on the first day of the study to each study group subject and on the last day of the study for each study group subject. Key questions were compared with a calculation of the mean for these questions, comparing the standard group with the telemedicine group. (Appendix C, D, E– MUSE, FSES, and ASTA surveys).

There were chart reviews and analysis of monitored data from devices  revealing  onset  of  arrhythmias,  times  of  diagnosis’  and treatments in the telemedicine group compared with the standard group. The T:EPASB utilizes the null hypothesis to demonstrate no difference in time of recognition of an arrhythmia, time to diagnosis and treatment of the arrhythmia, between the telemedicine group as compared with the standard group. The null hypothesis is be used in the Medication Understanding and Use Self- Efficacy (MUSE), ASTA (Arrhythmia Specific questionnaire in Tachycardia and Arrhythmia) and FSES (Shortened Functional Self Efficacy Scale) surveys. A paired T test with the difference in the means of answers to survey questions was utilized in calculating a P value for select survey questions (Appendix C).

Measures

Arrhythmias can be multifactorial and can cause no perceived symptoms versus serious symptoms such as palpitations, fast and pounding heart beats, sweating, chest pain and or pressure, anxiety, fear, and depression [15]. One single survey may not capture the data experienced by the subject and not every survey relates to the self- efficacy of these perceived events. The MUSE survey gives information on medication compliance, cost barriers, number of medications, physicians and pharmacies and hospitalizations. The FSES gives a scale of the subject’s self- efficacy to cope with the arrhythmia and day to day functioning. The ASTA survey is the most specific survey to arrhythmias and the symptoms associated with arrhythmias; but does not reflect the medications or functional capabilities.

The MUSE survey was tested for validity and reliability in measuring   patients’ self-   efficacy   in   understanding   and   using prescription medications [12]. FSES displayed good internal consistency and satisfactory criterion and convergent validity in assessing the degree of confidence self-functioning while facing decline in health and function [16]. ASTA, displayed content validity for all items, and internal consistency [17].

Data Collection Sheet and Demographics:

JCRM-3-2-307-g002

Pilot Study Results

From late February 2020 to March 2020, 9 patients were enrolled in the Telemedicine study and randomized to either standard visits or telemedicine visits. Three patients declined the study, one patient noted he would join the study, but only if he received a Kardia monitoring device (he was not enrolled in the study as this could not be guaranteed and he noted his intention of simply gaining the Kardia device) and was not enrolled due to ethical concerns.

All subjects signed the informed consent and received copies of the protocol and consent, including the clause that they may drop out of the study. Each subject was given instruction on filling out surveys and were given the opportunity to answer questions by the nurse practitioner (NP) in clinic and the research assistant. The surveys were reviewed and scored by the research assistant and double scored with the author of the study. The surveys pinpointed the overall arrhythmia burden, degree to which subjects felt the arrhythmia, and physical and mental coping levels in relation to the arrhythmia. The surveys gave the caregiver (Nurse Practitioners and Physician Assistants within the EP clinic) specific areas to discuss, reinforce, and empower the subject in arrhythmia behavior change. The time of recognition, diagnosis and treatment of arrhythmias was deferred due to the Covid 19 pandemic and this monitoring data is attained only for daily arrhythmia management.

Appendix D gives the overview of all survey results for T:EPASB. The overview gives the researcher a quick glimpse of any problem areas such with decreased self-efficacy of medication use, or functional capacity or arrhythmia knowledge and understanding.

Results of the MUSE survey show near complete compliance in medication use with only one missed dose of medications from one subject. MUSE tallied results also show no financial constraints to medication obtainment in all nine subjects. There was a 0.8679:1 ratio with number of number of physicians treating to number of medical diagnosis; with a mean of 2.89 physicians prescribing medications to a mean of 3.33 medical diagnosis for the 9 subjects evaluated (Appendix B). When combining the surveys, key data becomes clear. The subjects scoring the lowest functional status self-efficacy, subject 5a and subject 9a with scores of 43 and 44 respectively, scored 37 and 54 respectively on the ASTA arrhythmia burden survey. One can note poor functional self-efficacy, but not necessarily related to arrhythmia burden in subject 5a, while poor functional self-efficacy may be related to a higher arrhythmia burden in subject 9a. Another complementing data point will be specific arrhythmia logs within monitoring- devices; once this deferred data is allowed within the study. Another interesting finding is the subject 8a who has a high arrhythmia burden noted with ASTA of 46, but a very good FSES score of 64.

Discussion

The T:EPASB pilot study has shown the importance of offering an alternative to conventional in person visits, offering counseling in  managing  one’s  self-efficacy  for  arrhythmia  care,  and  providing reinforcement and social support in managing one’s arrhythmia care. The study illustrates the importance of gathering complementing data on arrhythmia management including medication use and understanding, functional self-efficacy, and arrhythmia self-efficacy. The triad of these surveys provides an excellent overview of one’s arrhythmia self-efficacy. With such data, the medical and nursing provider may offer patient specific counseling. There is an advantage of having a specifically timed event, match a corresponding subject’s complaint. The use of implanted and portable monitoring data gives an excellent overview of the subject’s associated heart rhythm abnormality. The MUSE survey used alone gives a false sense that there may not be any need for any reinforcement of self-efficacy of medication or arrhythmia understanding. When this survey is coupled with the FSES and ASTA, trends begin to develop and specific areas of intervention, such as improved daily activity levels, decreased arrhythmia burdens via medications or activity, utilization of beta or calcium channel blockers, increased fluids, and or activity training to improve arrhythmias may be discussed. The surveys when used  together  display  specific  areas  to  improve  subject’s  knowledge, one’s confidence and self-efficacy in arrhythmia management. Those with higher arrhythmia burdens in which the subject feels palpitations, fatigue, and side effects have a greater need for intervention which strengthen self-efficacy and social support for medication use, functional activities and arrhythmia management [16,17]. This pilot T:EPASB study continues to show great potential and will likely mimic the TRUST, CHOICE-AF and Poinete trials in identifying, diagnosing, and treating arrhythmias with no difference in timing of these events with telemedicine compared with in person follow up visits with prompt device monitoring. The study has already helped to pinpoint areas of difficulties with arrhythmias, medications, and functional capacity. Via interventions such as affirming knowledge, counselling medication usage, and validating activity and exercise efforts and knowledge, the caregiver  may  help  improve  the  subjects’  overall  functional  capacity in coping with one’s arrhythmia. The study’s evaluated questions have not reached significant p values, as the study has been Anecdotally, the overall response to telemedicine has been very positive with comments like, “this is so much better”, “I can concentrate on what you are teaching me, without the long drive” and “this information seems to stick much better, when I learn it at home” and “can we make more telemedicine appointments”. The T:EPASB study can in no way be fully assessed at this early point, but its potential to assist in improving patients’ self-efficacy via increased patient interaction, reinforcement of arrhythmia details, and social support will surely lead to further studies using telemedicine and a triad of survey tools.

Authorship:

Kathleen Fasing, DNP-c, MS,

ACNP Madonna University,

Livonia MI

University of Michigan, Staff ACNP, Ann Arbor, Michigan

kfasing@med.umich.edu

DNP Project Chair: Patricia Clark, DNP, RN, ACNP-BC,

ACNS- BC, CCRN, Madonna University,

pclark@madonna.edu

DNP Project Member: Rachel Mahas, PhD, MS, MPH,

Madonna University, rmahas@madonna.edu

DNP Project Member: Vicki Ashker, DNP, MSA, RN,

CCRN, Madonna University, vashker@madonna.edu

Milwaukee- Self Management Science for your great research on self- efficacy and your ITHBC theory and allowing its use.

Sara Carmel- Ben Gurion University of Negev- Public Health Faculty Member- for your behavior research and functional self- efficacy tool and allowing its use.

Ulla Walfridsson RN, PhD-Division of Nursing Science; Dept of Medicine & Health Sciences, Linkping, Sweeden- for sharing your incredible arrhythmia assessment tool and allowing its use.

Sangeeta Lathkar-Pradhan- Research Assistant for ongoing support and patience.

Rachel Wessel- Research Assistant for exacting perseverance.

Hakan Oral, MD- University of Michigan EP Director- thanks for believing in me.

Dr. Patricia Clark- DNP committee lead and advisor and patience extraordinaire.

My husband- Gregory Fasing BSN, RCIS- for his forever support.

Acknowledgements

Thank you so much for all who assisted in this project including and in equal acknowledgement.

Polly Ryan PhD, RN, CNS-BC – University of Wisconsin

References

  1. Kay, Misha, Santos, Takane (2010) Telemedicine opportunities and development in member states, Global observatory for eHealth series, virtualhospital.org.uk. (1,2). [crossref]
  2. Ryan, P. (2009) Integrated theory of health behavior change: Background and intervention development, Clinical Nurse Specialist, 23 (3): 161-172. (3, 5,18,19). [crossref]
  3. Lovett-Rockwell, K. & Gilroy, A. (2020) Incorporating telemedicine as part of COVID-19 Outbreak response systems, The American Journal of Managed Care, 26 (4): 147-148. Doi.org/10.37765/ajmc.,(4). [crossref]
  4. Fozzard (2011) History of basic science in cardiac electrophysiology, Cardiac electrophysiologycinics, 3, 1, 1-10. Doi:10.1016/j.ccep.2010.10.010,(6,7). [crossref]
  5. Phend, C. (2020) Telehealth shaping up for Covid-19- Cardiology illustrates what specialties can do to be ready, Medpage today.,(8).
  6. Maffei, R., Hudson, Y. & Skim Dunn, M. (2008) Telemedicine for urban uninsured: A pilot Framework for specialty care planning sustainability, J E health, 14(9), 925- 931 [crossref]
  7. Dalouk,  K.,  Gandhi,  N.,  Jessel,  P.,  MacMurdy,  K.  et.  al.  (2017)  Outcomes   of telemedicine  videoconferencing  clinic  versus   in-person   clinic   follow-up for implantable cardioverterdefibrillator recipients, Circulation arrhythmia electrophysiology, 10, (11,13).
  8. Varma, N., Epstein, A., Irimpen, A., Schweikert, R., & Love, C. (2010) Efficacy and safety of automatic remote monitoring for implantable cardioverter-defibrillator follow-up: The Lumos-T safely reduces routine office device follow-up, TRUST trial, Circulation, 122: 325332.,(12). [crossref]
  9. Lopez-Villegas, A., Catalan-Matamoros, D., Robles-Musso, E., & Peiro, S. (2015) Effectiveness of pacemaker tele-monitoring on quality of life, functional capacity, event detection and workload: The PONIENTE trial, Geriatrics and gerontology international, 16 (11).,(14). [crossref]
  10. Varma, N. & Ricci, R. (2013) Telemedicine and cardiac implants: what is the benefit? European heart journal, 34 (25), 1885-1895.(15).
  11. Lowres, N., Redfern, J., & Freedman, S. (2014) Choice of health options in prevention of cardiovascular events for people with  atrial  fibrillation  (CHOICE  AF):  A  pilot study, European journal of cardiovascular nursing, doiorg.proxy.lib.umich. edu/10.1177/14745114549687. (16). [crossref]
  12. Cameron, K., Ross, E., Clayman, M., Bergeron, A., et. al. (2010) Measuring patients’ self-efficacy in understanding and using prescription medication, PatientEducation Couns, 80 (3); 372376. Doi: 10.1016/j.pec.2010.06.029.,(17,21). [crossref]
  13. Ryan, P., Papanek, P., Csuka, M., Brown, M., et. al. (2018) Background and method of the striving to be strong study, a RCT test the efficacy of a mhealth self-management intervention, Contemporary Clinical Trials, 71, 80-87.,(16). [crossref]
  14. Suter, B., Suter, W. N., & Johnston, D. (2011) Theory-based telehealth and patient empowerment, Population Health Management, 14 (2).,(19). [crossref]
  15. Withers, K., Wood, K., Carolan-Rees, G, Patrick, H., et.al. (2015) Living on a knife edge- the daily struggle of coping with symptomatic cardiac arrhythmias, Health quality life outcomes, 13:86.,(20). [crossref]
  16. Tovel, H. & Carmel, S. (2015) Functional Self-Efficacy Scale- FSES: Development, evaluation, and contribution to well-being, Research on aging, 1-22. Doi: 10.1177/0164027515596583. (16,22,24). [crossref]
  17. Walfridsson, U., Arestedt, K., & Stromberg, A. (2012) Development and validation of a new arrhythmia-specific questionnaire in tachycardia and arrhythmia (ASTA) with focus on symptom burden, Health quality life outcomes, 10-44, doi: 10.1186/1477- 7525-10-44.,(23,25). [crossref]

Appendix A. Data Collection Tool- Aid for patient at home.

JCRM-3-2-307-g003

2 points each for every activity noted along the vertical axis; showing an activity taken due to the symptom noted on the horizontal axis. Subject to keep weekly log of number of symptoms and number of points for response activities.

Appendix B: Study Schematic

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Appendix C: Three Surveys

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Walfridsson, U., Arestedt, K., & Stromberg, A. (2012) Development and validation of a new arrhythmia-specific questionnaire in tachycardia and arrhythmia (ASTA) with focus on symptom burden, Health quality life outcomes, 10-44, doi: 10.1186/1477- 7525-10-44.,(23,25).

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Appendix D: Scores of completed surveys:

Survey Scores: Key- Muse– Shows any difficulty in taking; or understanding medications. FSES

highest the better functional status; highest possible =65. ASTA– the highest the worse arrhythmia burden, symptoms, and mental and physical QOL.

JCRM-3-2-307-g019

Appendix D. – Answers to the above scores

Muse Survey Answers

Question 1– How many prescriptions medications do you take regularly?

Mean= 5.33 medications; Median 4 Medications; Mode 5 medications with a low answer of 2 and high answer of 19 medications.

Question 2– During the past have you forgotten to take any medication? “Only 1 yes.

Question 3– In the past did you not fill or stop taking the prescription due to cost? All answered no.

Question 4– In a typical month how many pharmacies do you use; including mail order? Six subjects answered 1/ 3 subjects answered 2.

Question 5– Have you been admitted to the hospital in the past six months? –Three subjects -yes.

Question 6– How many physicians prescribed medications for you in the past year? – mean answer 2.89.

Question 7– How many medical conditions which you are receiving treatment? – mean answer 3.33

FSES Shortened Survey * Higher scores showing better functional status

This survey gained very differing results for patient. Two subjects scored the total possible of 65 points indicating the best functional status and answered 5 (maximal score) for all 13 questions. One subject answered 3 for each of the 13 questions with a score of 39 and indicating day to day function was exactly in the middle of the survey. Other subjects gave a variable scoring with specific areas and gave a scattered response, depending upon the question. Two of the subjects gave responses in the 2 range, or lower level of functional capabilities. Scores listed in 1a-9a order: 65/ 57/ 53/ 65/ 43/ 39/ 63/ 64/ 44.

ASTA Survey The survey is scored into three categories- presence of arrhythmia, symptoms associated with the arrhythmia and Health related Quality of life (QOL)- both mental and physical. Higher the score- the higher the arrhythmia burden, more symptoms and more impact on the health related QOL. Scores listed in 1a- 9a order: 39/39/38/21/37/50/21/46/54.

Appendix E.

Average Scores Pre and Post (n=9)

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When two pandemics meet

Abstract

The COVID-19 pandemic has emerged in the middle of another pandemic which is far from under control: the cardiometabolic syndrome pandemic. Recently published data suggests patients with obesity are at a higher risk of being hospitalized and placed on a mechanical ventilator for COVID-19 than patients with a normal body weight. We discuss the pathophysiology behind this relationship and the implications in the global fight against COVID-19.

Keywords

COVID-19; coronavirus; obesity; cardiometabolic syndrome.

No one single mechanism is responsible for disease progression into severity in COVID-19 cases as in almost all diseases -chronic or not, transmissible or not-. We as scientists are trained to observe, identify differences and similarities between cases and arrive at possible explanations called hypothesis that can help the scientific community to develop effective strategies to combat the illness.

To this day several factors have been identified and when put together they tell a storyline that sums up the pathophysiology of severity in COVID-19 shown in Figure 1.

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Figure 1. Schematic representation of shared pathophysiology in COVID-19 cases with underlying metabolic illness. [1]. DIC: Disseminated Intravascular Coagulation.

But how does this scenario come to be? The answer comes from a previous pandemic that has been around for many years: the Cardiometabolic Syndrome (CMS) pandemic. CMS is defined by a combination of metabolic disorders that include diabetes mellitus, systemic arterial hypertension, central obesity, and dyslipidemia. All these conditions lead to elevated heart disease risk, which in turn is the leading cause of death in first world countries and doesn´t fall far behind in the rest of the world as well. This global epidemic to some doesn´t seem so scary being that it cannot be transmitted through droplets or by touching “infected” surfaces. Thisidea, however, isn´t completely true. The first risk factor for this group of diseases is being overweight or obesity, and this is in a sense “transmitted”. Eating habits are a cultural phenomenon, and from one generation to the next, families and communities pass on grocery lists, recipes and pantry contents. As of 2019 the global mean prevalence of obesity was measured at 19.5%. This number has almost tripled since 1975 and is currently the number one risk factor associated with premature death. Obesity as a risk factor for disease usually means it leads to chronic diseases such as the ones previously mentioned, but nowadays we are observing a different consequence of being overweight. An elevated body mass index has become a high-risk factor for severity in COVID-19 cases. [2]

Table 1 shows the evidence on the previous statement. A study by Zheng et al of 214 patients in Wuhan, China with laboratory confirmed COVID-19 showed that the presence of a Body Mass Index (BMI) >25 kg/m2 was associated with a near-6 fold increased risk of severe illness, even after adjusting for age and other comorbidities. [3] Of 4,103 COVID-19 cases in New York City the chronic condition which conferred the strongest association with critical illness was obesity, with 39.8% of hospitalized patients having obesity. [4]

Table 1. Epidemiological studies on COVID-19 outcomes and obesity related risk-factors

Author, Region and Date

Subjects

Findings

Z. Wu [7]
Mainland China
Updated Feb 11, 2020

72,314 suspicious cases of COVID-19
44,672 lab-confirmed cases

2.3% Case-Fatality Rate
Mild cases 81%
Severe cases 14%
Critical cases 5%

S. Garg [8]
USA (COVID-NET)
March 1-30, 2020

1,482 hospitalized patients

89% of patients had one or more underlying conditions:
Hypertension 49.7%
Obesity 48.3%
Chronic lung disease 34.6%
Diabetes Mellitus 28.3%
Cardiovascular disease 27.88%

Among patients 18-49 years-old obesity was the most prevalent underlying condition (59%).

P. Goyal [9]
New York City, US
Mar 3-27, 2020

First 393 cases of COVID-19 adults hospitalized in New York

Patients who required invasive mechanical ventilation were more likely to be male, have obesity and elevated liver-function and inflammatory markers.

S. Richardson [10]
New York, USA
Mar 1 – Apr 4, 2020

5,700 hospitalized patients

Most common comorbidities among hospitalized patients:
Hypertension 56.6%
Obesity 41.7% – (Morbid obesity 19%)
Diabetes Mellitus 33.8%

G. Grasselli [11]
Milan, Italy
Feb 20 – Mar 18, 2020

73 patients in intensive care unit

Over 80% of patients in ICU were overweight or had obesity.
Normal weight – 19%
Overweight – 51.9%
Obesity 1 – 15.4%
Obesity 2 – 11.5%
Obesity 3 – 1.9%

Zheng [3]
Wenzhou, China
Jan 1 – Feb 29, 2020

214 patients with lab confirmed COVID-19
Ages 18-75

A BMI equal to or greater than 25 kg/m2 was associated with a 6-fold increased risk of severe illness.
This risk remained significant even after adjusting for age and other comorbidities.

Petrilli [4]
New York
Mar 1 – Apr 7, 2020

4,103 cases of COVID-19
1,999 hospitalized

The chronic condition with the strongest association to critical illness was obesity.
39.8% of hospitalized patients had obesity.

Qingxian [12]
Mainland China
Jan 11 – Feb 16, 2020

383 patients admitted to a hospital in Shenzen

After adjusting for age, sex, disease history and treatment the overweight group was 2.42 times more likely to develop severe pneumonia.

A. Simonnet [5]
Lille, France
Feb 27 – Apr 5, 2020

124 patients admitted to ICU for COVID-19.
Compared to control group from 2019

Obesity was significantly more frequent among cases of COVID-19 (47.6%) compared to control group (25.2%).
The median BMI of patients requiring intubation was 31.1 kg/m2 compared to 27 kg/m2 in the patients who did not require intubation.
In individuals with a BMI ³35 kg/m2 the odds ratio for intubation was 7.36 compared to individuals with a normal BMI.

Among 124 patients admitted for COVID-19 to a hospital in Lille, France 47.6% had obesity. Patients with a BMI of greater than 35 kg/m2 were 7.36 times more likely to require a ventilator than patients with a BMI of less than 25 kg/m2. [5] In Milan more than 80% of 73 patients treated in an ICU were overweight or had obesity, when the rates of overweigh and obesity in Italy are only 35.4% of the population. [6]

Two main explanations play a role in this complicated infectious disease in association with weight problems. The first one is the chronic inflammatory state it conveys. Recent studies have found that adipose tissue secretes extracellular vesicles that function as vectors which can modify cellular function in the recipient through the information they carry. Data suggests that this mechanism is used by fat to induce monocyte differentiation into active macrophages and high secretion of IL-1 and TNF-α among other cytokines. [13] The second one is the fact that patients with obesity have been found to have higher concentrations of pro-thrombotic factors as compared to normal-weight controls. Some of these altered parameters include higher D-dimer, fibrinogen and factor VII; as well as lower fibrinolysis because of higher plasminogen activator inhibitor-1. [14]

Besides increased inflammatory cytokines, obesity englobes several pathophysiological factors which affect the risk and outcomes of patients with COVID-19. In the respiratory tract obesity may cause pulmonary restriction, decreased pulmonary volumes and ventilation-perfusion mismatching. Patients with obesity are more likely to present diabetes mellitus and atherosclerosis which may be complicated by COVID-19. Additionally, there is limited data on the right dosing of antimicrobials in obesity and bioavailability of drugs used to treat patients with this disease may be affected by altered protein binding, metabolism and volume of distribution. [15]

On the other hand, new information is developing every day concerning COVID-19 cases and more data is suggesting that bad prognosis is linked to thromboembolic events caused by inflammation, hypoxia and coagulation abnormalities. One study by Klok et alstudied 184 Intensive Care Unit (ICU) patients with confirmed COVID-19, and found that 31% showed thrombotic complications, of which 81% was due to pulmonary embolism. [16] When we put two and two together, the relationship becomes apparent. Obesity is a clear catalyzer for severe COVID-19 cases. In a country like Mexico, where the prevalence for overweight and obesity in over 20-year-olds is 75.2%, this relationship is very threatening. [17]

It seems that the best way to prevent bad outcomes from this novel disease (as well as from infectious diseases in general) is to be in good health prior to contracting it in the first place. As for those patients who already suffer from CMS or one of its components, preventive treatment is our main recommendation. These patients should be at optimal glycemic, systemic arterial pressure and cholesterol level goals. A study by Carter et al also suggests that vitamin D deficiencies (also more common in patients with obesity) have been linked to worse cytokine storms. To this end, physical activity as well as sun exposure is effective ways to boost vitamin D levels. [18]

This sound reasonable, right? Well, reasonable doesn´t always mean achievable in all populations. Vulnerable communities around the world are struggling every day just to have access to general medical attention. These communities are also at an increased risk of exposure to COVID-19. Working from home is a privilege that is unavailable for many people from a lower socio-economic status. Social distancing is considerably more difficult for people living in overcrowded neighborhoods. Emerging epidemiological studies in the U.S. suggest a disproportionate burden of illness and higher death rates among minority groups. [9]

Currently there is no gold standard treatment for COVID-19, however, all this data suggests that global efforts need to be directed towards prevention and education. Pre-existing conditions need to be under control and lifestyle habits should be aimed towards getting enough exercise and a proper nutrition. [19,20]

References

  1. Xiong M, Liang X, Wei YD (2020) Changes in Blood Coagulation in Patients with Severe Coronavirus Disease 2019 (COVID‐19): A Meta‐Analysis. Br J Haematol.[crossref]
  2. Blüher M (2019)Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol15:288-298.
  3. Zhou F, Yu T, Du R, Fan G, Liu Y et al. (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet.395: 1054-1062. [crossref]
  4. Petrilli CM, Jones SA, Yang J, Rajagopalan H, O’Donnell LF, Chernyak Y, Horwitz LI (2020) Factors associated with hospitalization and critical illness among 4,103 patients with COVID-19 disease in New York City. medRxiv.
  5. Simonnet A, Chetboun M, Poissy J, Raverdy V, Noulette J et al. (2020) Intensive Care COVID‐19 and Obesity study group. High prevalence of obesity in severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) requiring invasive mechanical ventilation. Obesity.[crossref]
  6. Zangrillo A, Beretta L, Scandroglio AM, Monti G, Fominskiy E (2020) Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy. Crit Care Resusc.[crossref]
  7. Wu Z, McGoogan JM (2020) Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. Jama.[crossref]
  8. Garg S (2020) Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019—COVID-NET, 14 States, March 1–30, 2020. MMWR. Morbidity and Mortality Weekly Report 69.
  9. Goyal P, Choi JJ, Pinheiro LC, Schenck EJ, Chen R, Jabri A, Hoffman KL (2020) Clinical Characteristics of Covid-19 in New York City. New England Journal of Medicine..[crossref]
  10. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T et al. (2020) Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA.[crossref]
  11. Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L et al. (2020) Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. Jama. [crossref]
  12. Qingxian C, Fengjuan C, Fang L, Xiaohui L, Tao W et al. (2020) Obesity and COVID-19 severity in a designated hospital in Shenzhen, China. China.
  13. Kim A, Shah AS, Nakamura T (2018) Extracellular Vesicles: A Potential Novel Regulator of Obesity and Its Associated Complications. Children 5: 152.[crossref]
  14. De Pergola G, Pannacciulli N (2002) Coagulation and fibrinolysis abnormalities in obesity. J Endocrinol Invest25: 899-904.[crossref]
  15. R Huttunen, J Syrja¨nen (2013) Obesity and the risk and outcome of infection. International Journal of Obesity37: 333-340.[crossref]
  16. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, GommersDAMPJ et al. (2020) Incidence of thrombotic complications in critically ill ICU patients with COVID-19. ThrombosisResearch.[crossref]
  17. Romero-Martínez M, Shamah-Levy T, Vielma-Orozco E, Heredia-Hernández O, Mojica-Cuevas J et al. (2019) Encuesta Nacional de Salud y Nutrición (Ensanut 2018): metodología y perspectivas. salud pública de México 61: 917-923.
  18. Carter SJ, Baranauskas MN, Fly AD (2020) Considerations for obesity, vitamin D, and physical activity amidst the COVID‐19 pandemic. Obesity.
  19. Smith JA, Judd J (2020) COVID‐19: Vulnerability and the power of privilege in a pandemic. Health Promotion Journal of Australia 31: 158.[crossref]
  20. Ahmed F, Ahmed NE, Pissarides C, Stiglitz J (2020) Why inequality could spread COVID-19. The Lancet Public Health5: 240.[crossref]

Differences between 5-Minute and 15-Minute Measurement Time Intervals of the CGM Sensor Glucose Device Using GH-Method: Math-Physical Medicine (No. 281)

Introduction

This paper describes the research results by comparing the glucose data from a Continuous Glucose Monitor (CGM) sensor device collecting glucose at 5-minute (5-min) and 15-minute (15-min) intervals during a period of 125 days, from 2/19/2020 to 6/23/2020, using the GH-Method: math-physical medicine approach. The purposes of this study are to compare the measurement differences and to uncover any possible useful information due to the different time intervals of the glucose collection.

Methods

Since 1/1/2012, the author measured his glucose values using the finger-piercing method: once for FPG and three times for PPG each day. On 5/5/2018, he applied a CGM sensor device (brand name: Libre) on his upper arm and checked his glucose measurements every 15 minutes, a total of ~80 times each day. After the first bite of his meal, he measured his Postprandial Plasma Glucose (PPG) level every 15 minutes for a total of 3-hours or 180 minutes. He maintained the same measurement pattern during all of his waking hours. However, during his sleeping hours (00:00-07:00), he measured his Fasting Plasma Glucose (FPG) in one-hour intervals.

With his academic background in mathematics, physics, computer science, and engineering including his working experience in the semiconductor high-tech industry, he was intrigued with the existence of “high frequency glucose component” which is defined as those lower glucose values (i.e. lower amplitude) but occurring frequently (i.e.. higher frequency). In addition, he was interested in identifying those energies associated with higher frequency glucose components such as the various diabetes complications that would contribute to the damage of human organs and to what degree of impact. For example, there are 13 data-points for the 15-minute PPG waveforms, while there are 37 data-points for the 5-minute PPG waveforms. These 24 additional data points would provide more information about the higher frequency PPG components.

Starting from 2/19/2020, he utilized a hardware device based on Bluetooth technology and embedded with customized application software to automatically transmit all of his CGM collected glucose data from the Libre sensor directly into his customized research program known as the eclaireMD system, but in a shorter time period for each data transfer. On the same day, he made a decision to transmit his glucose data at 5-minute time intervals continuously throughout the day; therefore, he is able to collect ~240 glucose data within 24 hours.

He chose the past 4-months from 2/19/2020 to 6/19/2020, as his investigation period for analyzing the glucose situation. The comparison study included the average glucose, high glucose, low glucose, waveforms (i.e. curves), correlation coefficients (similarity of curve patterns), and ADA-defined TAR/TIR/TBR analyses. This is his secondresearch report on the 5-minute glucose data. His first paper focused on the most rudimentary comparisons [1].

References 2 through 4 explained some example research using his developed GH-Method: math-physical medicine approach [2,3].

Results

The top diagram of Figure 1 shows that, for 125 days from 2/19/2020 – 6/23/2020, he has an average of 259 glucose measurements per day using 5-minute intervals and an average of 85 measurements per day using 15-minute intervals. Due to the signal stability of using Bluetooth technology, for the 5-min, it actually has 259 data instead of the 240 data per day.

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Figure 1. Daily glucose, 30-days & 90-days moving average glucose of both 15-minutes and 5-minutes.

The middle diagram of Figure 1 illustrates the 30-days moving average of the same dataset as the “daily” glucose curve. Therefore, after ignoring the curves during the first 30 days, we focus on the remaining three months and can detect the trend of glucose movement easier than “daily” glucose data chart. There are two facts that can be observed from this middle diagram. First, the gap between 5-min and 15-min is wider in the second month, while the gap becomes smaller during the third and fourth month. This means that the 5-min results are converging with the 15-min results.Secondly, both curves of 5-min and 15-min are much higher than the finger glucose (blue line). This indicates that the Libre sensor provides a higher glucose reading than the finger glucose. From the listed data below, the CGM sensor daily average glucoses are about 8% to 10% higher than the finger glucose.

5-min sensor: 118 mg/dL (108%)

15-min sensor: 120 mg/dL (110%)

Finger glucose: 109 mg/dL (100%).

The bottom diagram of Figure 1 is the 90-days moving average glucose. Unfortunately, his present dataset only covers 4 months due to late start of collecting his 5-min data; however, the data trend of the last month, from 5/19-6/23/2020, can still provide a meaningful trend indication. As time goes by, additional data will continue to be collected, his 5-min glucose’s 90-days moving trend will be seen more clearly.

Figure 2 shows the synthesized views of his daily glucose, PPG, and FPG.Here, “synthesized” is defined as the average data of 125 days.For example, the PPG curve is calculated based on his 125×3=375 meals. Listed below is a summary of his primary glucose data (mg/dL) in the format of “average glucose/extreme glucose”. Extreme means either maximum or minimum, where the maximum for both daily glucose and PPG due to his concerns of hyperglycemic situation, and the minimum for FPG due to his concerns of insulin shock. The percentage number in prentice is the correlation coefficients between the curves of 15-min and 5-min.

Daily (24 hours):15-min vs. 5-min

117/143vs. 119/144(99%)

PPG (3 hours):15-min vs. 5-min

126/135vs. 125/134(98%)

FPG (7 hours):15-min vs. 5-min

102/95 vs. 105/99 (89%).

Those primary glucose values between 15-min and 5-min are close to each other in the glucose categories. It is evident that the author’s diabetes conditions are under well control for these 4 months. However, by looking at Figure 2 and three correlation coefficients %, we can see that daily glucose and PPG have higher similarity of curve patterns (high correlation coefficients of 98% and 99%) between 15-min and 5-min, but FPG curves have a higher degree of mismatch in patterns (lower correlation coefficient of 89%). This signifies that his FPG values during sleeping hours have a bigger difference between 15-min and 5-min.

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Figure 2. Synthesized daily glucose, PPG, and FPG of both 15-minutes and 5-minutes.

Figure 3 are the results using candlestick model [4,5]. The top diagram is the 15-min candlestick chart and the bottom diagram is the 5-min candlestick chart. Candlestick chart, also known as the K-Line chart, includes five primary values of glucoses during a particular time period; “day” is used in this study. These five primary glucose data are:

Start: beginning of the day.

Close: end of the day.

Minimum: lowest glucose.

Maximum: highest glucose.

Average: average for the day.

Listed below are five primary glucose values of both 15-min and 5-min.

15-min: 108/116/86/170/120.

5-min: 111/116/84/173/118.

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Figure 3. Candlestick charts of both 15-minutes and 5-minutes.

By ignoring the first two glucoses, start and close, let us focus on the last three glucoses: minimum, maximum, and average. The 5-min method has a lower minimum and a higher maximum than the 15-min method. This is due to the 5-min method capturing more glucose data; therefore, it is easier to catch the lowest and highest glucoses during the day. The difference of 2mg/dL between 15-min’s average 120 mg/dL and 5-min’s average 118 mg/dL is only a negligible 1.7%.

Again, it is also obvious from these candlestick charts that the author’s diabetes conditions are under well control for these 4 months.

Conclusion

In summary, the glucose differences between 5-min and 15-min based on simple arithmetic and statistical calculations are not significant enough to draw any conclusion or make any suggestion on which are the “suitable” or better measurement time intervals. However, the author will continue his research to pursue this investigation of energy associated with higher-frequency glucose components in order to determine the glucose energy’s impact or damage on human organs (i.e. diabetes complications).

The author has read many medical papers about diabetes. The majority of them are related to the medication effects on glucose symptoms control, not so much on investigating and understanding “glucose” itself. This situation is similar to taming and training a horse without a good understanding of the temperament and behaviors of the animal. Medication is like giving the horse a tranquilizer to calm it down. Without a deep understanding of glucose behaviors, how can we truly control the root cause of diabetes disease by only managing the symptoms of hyperglycemia?

References

  1. Hsu, Gerald C. eclaireMD Foundation, USA (2020) Analyzing CGM sensor glucoses at 5-minute intervals using GH-Method: math-physical medicine (No. 278).
  2. Hsu, Gerald C. eclaireMD Foundation, USA(2020) Predicting Finger PPG by using Sensor PPG waveform and data via regression analysis with three different methods using GH-Method: math-physical medicine (No. 249).
  3. Hsu, Gerald C. eclaireMD Foundation, USA (2019) Applying segmentation pattern analysis to investigate postprandial plasma glucose characteristics and behaviors of the carbs/sugar intake amounts in different eating places using GH Method: math-physical medicine (No. 150).
  4. Hsu, Gerald C. eclaireMD Foundation, USA (2019) A case study of the impact on glucose, particularly postprandial plasma glucose based on the 14-day sensor device reliability using GH-Method: math-physical medicine (No. 124).
  5. Hsu, Gerald C. eclaireMD Foundation, USA. Comparison study of PPG characteristics from candlestick model using GH-Method: Math-Physical Medicine (No. 261).