Machine Learning Application to Combat Superbugs in Hospitals: A Primer to Infection Prevention Practitioners

Introduction

Healthcare-Associated Infections (HAIs) which defined as infections arising and developing during hospital stay or during the process of medical care in healthcare facilities. It is also defined as infections which are not present or incubating when the patient is hospitalized and are acquired after 48 hours of hospital stay [1]. HAIs represent the most serious threat to patient safety, and it also represent global public health concern [2]. HAIs have a significant clinical as well as financial impact due to prolonged hospitalization, increased mortality, and morbidity, increased antimicrobial resistance and increased direct costs for medical services [2]. Antimicrobial resistance is on the rise, raising worries about the impact on individuals with multidrug resistance bacteria [3]. As a result, significant efforts have been made to investigate the clinical outcomes of patients infected with such pathogens, which have shown higher mortality and treatment failure rates than those infected with susceptible isolates [3]. The rise of resistant hospital pathogens has posed a difficulty to providing high-quality inpatient treatment. The overuse of antibiotics in hospitals is largely to blame for this problem [4].

Resistant bacterial infections have a negative impact on the treatment outcomes, cost, disease spread, and sickness duration, offering a severe challenge to future chemotherapies [4]. The systematic collection of data on the occurrence of HAIs, analysis and transformation of the data into valuable information, and dissemination of this knowledge with those who may take action to avoid HAIs are all part of HAIs surviellance systems [5]. The first criteria in an infection preventionist’s minimum standard of practice are surviellance and epidemiology [5]. Already 40 years ago, many studies proved that there is 32% reduction in HAIs rates in hospitals with active surveillance programs compared with those without such programs [6]. The first goal of any surveillance system is to determine infection rates, infection sites, common pathogens, and antibiotic use, as appropriate empiric therapy is recognized to be the most crucial component in patient’s outcome. As a result, it is crucial to identify the microorganisms that cause infections as well as their antimicrobial resistance pattern to find the optimal antimicrobial treatment [6]. Surviellance in its conventional way, in which every patient’s file is reviewed for the presence of HAIs, is time consuming and labor intensive [5]. To improve the efficiency and strength of infection prevention and surveillance systems, information technology, data science and artificial intelligence have been recently applied. We need tools that help prediction, early diagnosis, surveillance, and treatment of HAIs to prevent human efforts of disease containment from being overwhelmed.

Definition of Artificial Intelligence and Machine Learning

Artificial intelligence (AI), which is defined as computer algorithms with cognitive-like characteristics such as learning capabilities, is already having an impact on our lives in a variety of ways [7]. In radiology, dermatology and pathology, AI- assisted image analysis has already established a significant position. In genomics, another data-intensive science, AI aids in the prediction of phenotypes from genotypes [7]. Also, AI has been applied in infectious disease management specially to aid the detection and prevention of diseases [7]. The application of AI in healthcare began with the creation of expert systems based on rules extracted from interviews with medical specialists and experts, which were then translated and programmed [8]. The first expert system in medicine was developed in 1976 aiming at suggesting antimicrobial treatment for severe bacterial infections [8]. Machine learning (ML) considered a subset of AI, demonstrates the experiential “learning” associated with human intelligence, while also having the ability to learn and improve its analysis via the use of computing algorithms [9].

These algorithms recognize patterns and effectively “learn” in order to teach the computer to make autonomous suggestions or decisions using vast volumes of data inputs and outputs. The machine can take and input and anticipate a result with enough repetitions and modifications to the algorithm [9]. The algorithm’s accuracy is then judged by comparing the output to a collection of known outcomes, which is then iteratively changed to perfect the capacity to anticipate future results [9]. The predictive capabilities of machine learning are rapidly being employed in the realm of healthcare. ML models have been presented and evaluated as potential answers to a range of challenges involving diagnostic errors, treatment errors, workflow inefficiencies and obstacles to value-based care as a convergence between health and data science [9].

Machine Learning Methods

ML is divided into three main categories: supervised learning, unsupervised learning, and reinforcement learning. The term “supervised learning” refers to algorithms that use labeled data as a training dataset. Labeled data are datasets in which the outcome of interest has already been determined; for example, to train an algorithm for sepsis prediction, we utilize a dataset in which patients are already classified as having sepsis or not. The algorithm will then select the best model to predict the desired outcome [8]. Unsupervised learning is the utilization of data without a specified or predefined outcome of interest. Algorithm are left to detect patterns and extract hidden structure from data on their own, with no expert labeling. Unsupervised learning is mostly used in medicine for clustering with the goal of discovering groups in data, such as related groups of patients based on clinical data [8]. Through trial and error, reinforcement learning algorithms uncover activities that provide the greatest rewards. In this category, the algorithm is set up to consider survival or a shorter hospital stay as a reward. The approach employs a training dataset to run several tests in order to generate the model with the highest reward [8].

ML in Infection Prevention and Control

AI and ML offer huge potential in Infection Prevention and Control (IPC) [10]. Its applications in IPC have enormous promise for implementing WHO core components. [10]. AI and ML have potential benefits in the three main areas highlighted by the WHO: 1- HAIs surviellance, 2- Improved laboratory diagnosis to facilitate IPC interventions, 3- Hand hygiene practice [10]. In HAIs surviellance, ML application have been used to monitor trends, identify clusters and outbreaks in a timely manner. It is also used in outbreak simulation to mitigate interventions. Also, ML is a very helpful tool in predicting the risk of nosocomial infections as nosocomial Clostridium difficile infection [10]. While more research is needed to validate these findings, this method has the potential to change HAIs surveillance and IPC [10].

ML data mining tools as well could use the clinical microbiology laboratory results to detect and predict clusters or outbreaks of multidrug resistant pathogens in healthcare settings [10]. AI and ML enhanced laboratory microscopy could speed up infection diagnosis and aid AMR prevention initiatives by facilitating targeted antibiotic management and IPC intervention [10]. Studies showed that gram stain interpretation with AI-assisted tools could lower cost and time with good accuracy [10]. Wearable technology using ML applications provide benefits for healthcare environment in general and IPC in specific in the form of supporting healthcare staff IPC education, audit and behavior change.

ML in Prediction and Early Detection of HAIs

AI and ML are being used by researchers in public health surveillance to predict disease outbreaks and evaluate surveillance tools [11]. Identifying patients at increased risk of HAIs in ICUs is a serious public health concern. ML could improve patient risk classification and lead to more specific infection prevention and control study.

ML models could be made for surveillance of Blood Stream Infections (BSI), CD Infections (CDI), Urinary Tract Infections (UTI), pneumonia and Surgical Site Infections (SSI). Vab der Werff, et al. [12] developed a fully automated Surviellance algorithm for hospital acquired UTI using electronic health record (EHR) data. This study concluded that a fully automated surveillance algorithm based on artificial intelligence and machine learning to detect UTI symptoms from EHR had acceptable performance HAUTI compared to manual record review. Taylor, et al. [13] showed that machine learning algorithms accurately diagnosed positive urine culture results and accurately predict UTIs in emergency department.

Mancini, et al. [14] built a predictive model using a cloud platform (DSaaS), online and user-friendly platform, to predict Multi-Drug Resistant (MDR) UTI in hospitals. DSaas can help physicians to build easy prediction models that could help them to treat hospitalized patients. Their model is based on supervised ML regression and classification algorithms. They developed this model to assist in the antimicrobial stewardship program implemented in their hospital [14]. Nemati, et al. [15] developed an Artificial Intelligence Sepsis Expert (AISE) algorithm for early prediction of sepsis. Using data available in the ICU in real time, AISE can accurately predict the onset of sepsis in an ICU patient 4 to 12 hours prior to clinical recognition [15]. Many studies showed that ML based clinical decision support (CDS) tools embedded within electronic medical record improve early detection and therapy in patients with early blood stream infections and can predict septic shock [16].

Conclusion

Many studies suggest that machine learning algorithms outperforms conventional statistical approaches in term of predictive performance, implying that the machine learning approaches could be used to identify and predict patients at higher risk of HAIs at hospital admission, giving clinicians enough time to potentially prevent HAIs and mitigate their severity by targeting specific infection prevention and control interventions at high-risk groups in order to improve quality of care.

For more Articles on: https://biomedres01.blogspot.com/

 

Review on Evaluation of the Efficiency of Epidemiological Surveillance for Echinococcosis in the Kyrgyz Republic

Introduction

The work assessed the effectiveness of epidemiological surveillance of echinococcosis in the Kyrgyz Republic (KR), set out in the Order of the Ministry of Health of the KR № 666 “On strengthening measures to control and prevent echinococcosis and alveococcosis in the KR “ dated December 18, 2008, based on the following criteria: effectiveness anti-epidemic and preventive measures: epidemiological, social, economic, diagnostic and clinical, the degree of simplicity, the degree of acceptability and efficiency. The research materials were statistical reports of the Department of Disease Prevention and State Sanitary and Epidemiological Surveillance of the Ministry of Health of the KR. Were analyzed and systematized the legal norms governing the prevention and control of echinococcosis in dogs, and human protection, studied the laws and by-laws of the KR in the field of veterinary medicine, sanitary rules and norms, as well as epidemiological and epizootic reporting. Research methods: retrospective epidemiological, descriptive, analytical, statistical. Based on the favorable trend of many criteria characterizing the effectiveness of anti-epidemic and anti-epizootic measures, a preliminary conclusion can be drawn about the correct choice of organizational and methodological approaches in conducting epidemiological surveillance of echinococcosis in the KR and the following criteria are assessed: the effectiveness of antiepidemic and preventive measures is satisfactory, epidemiological effectiveness - low, social efficiency - high, economic efficiency - satisfactory, diagnostic and clinical efficiency - high, degree of simplicity - high, degree of acceptability - low, efficiency - high.

The years of potentially lost life in echinococcosis in the KR have been calculated. Echinococcosis is a zoonotic natural anthropurgic helminthiasis caused by tapeworms Echinococcus granulosus (Echinococcus) and Echinococcus multilocularis (Alveococcus). Human echinococcosis is a serious parasitic disease that affects both different segments of the population and different age groups [1,2]. Echinococcosis is widespread throughout the world, the prevalence of the population is higher in areas with developed pasture animal husbandry. The source of the pathogen for farm animals, pigs - dogs affected by larvae (hydatids) of echinococcus, for wild ruminants - wolves, foxes, jackals and arctic foxes, infested by the imaginal stage and excreting mature segments of this parasite with feces, and for carnivores - ruminants and pigs. The transmission factors of the pathogen are grass, various types of feed and water contaminated with segments and eggs of echinococci, excreted by dogs, wolves and other carnivores with feces and swallowed by ruminants and omnivores. The factor of transmission of echinococcus to definitive hosts is the organ affected by parasites. Shepherds, shepherds, fur breeders, hunters and other persons who have constant contact with the final hosts of echinococcus or alveococcus get sick more often [3,4]. Echinococcosis is an urgent socio-economic problem in the Central Asian region and the Kyrgyz Republic in particular. Echinococcosis subsequently leads to severe complications, both in the postoperative period and in the long-term.

Despite the long-standing struggle against these parasitic diseases, the Kyrgyz Republic still remains an unfavorable hyperendemic region in terms of the prevalence of echinococcosis, which has the status of a nationwide problem due to its wide distribution and huge economic damage to public health and animal husbandry [5]. Measures to combat hydatidosis are carried out in a complex way (by medical, veterinary, communal and hunting organizations). Mutual information about cases of hydatidosis in humans, farm and wild animals should be provided between medical and veterinary workers [6]. Recently, the epidemic situation of echinococcosis in the Kyrgyz Republic is quite tense. At the end of the 20th and the beginning of the 21st century, a sharp increase in the incidence of echinococcosis began throughout the territory of the Kyrgyz Republic, including among the child population [7,8]. This was the reason for the development of a new program of epidemiological surveillance, set out in the Order of the Ministry of Health of the Kyrgyz Republic No. 666 “On strengthening measures to combat and prevent echinococcosis and alveococcosis in the Kyrgyz Republic” dated 12/18/2008.The purpose of this work is to evaluate the effectiveness of epidemiological surveillance of echinococcosis in the Kyrgyz Republic.

Tasks

- To determine the criteria for evaluating the effectiveness of epidemiological surveillance of echinococcosis;

- To conduct a comparative epidemiological analysis of these criteria for evaluating the effectiveness of epidemiological surveillance of echinococcosis;

- On the basis of the analysis carried out, to assess the effectiveness of epidemiological surveillance of echinococcosis in the Kyrgyz Republic.

Materials and Methods

Statistical reports of the Ministry of Health of the Kyrgyz Republic DPZiSSES served as the research materials. The legal norms regulating the implementation of the prevention and control of canine echinococcosis, and human protection were analyzed and systematized, the laws and by-laws of the Kyrgyz Republic in the field of veterinary medicine, sanitary rules and regulations, as well as epidemiological and epizootological reporting were studied. Research methods: retrospective epidemiological, descriptive, analytical, statistical.

Results and Its Discussion

As our studies show, the epidemiological situation of echinococcosis in the Kyrgyz Republic is rather ambiguous. Despite the introduction of a new epidemic surveillance program, the incidence of echinococcosis and alveococcosis continued to grow until 2014 and 2015, respectively, and it was under the new program that the peak incidence of both diseases was recorded. On the one hand, this is due to the increase in the quantity and quality of preventive examinations and examinations according to epidemic indications, as well as the introduction of new methods for diagnosing echinococcosis, which increased the detection of these parasitic diseases, which, in turn, affected the growth of infestation. This also explains the serious decline in incidence following the peak, also due to an increase in the quantity and quality of preventive and anti-epidemic measures, as well as the diagnosis and treatment of echinococcosis. On the other hand, it is impossible not to note the cyclicity characteristic of echinococcosis in 7-8 years. It is this cycle that can explain the observed decline in the incidence of this disease in the population. 2019 is the borderline, the lowest point of the cycle, after which there may be another growth characteristic of the beginning of the next cycle.

The trend towards an increase in the incidence of echinococcosis during the introduction of a new epidemiological surveillance program also does not inspire confidence in the effectiveness of the new epidemiological surveillance program for echinococcosis, but does not give a clear answer due to the increased detection rate. Despite this, the impact of the child population in the Kyrgyz Republic gives less controversial results. The increase in the proportion of childhood susceptibility to echinococcosis and alveococcosis in the Kyrgyz Republic, as well as the increase in the proportion of child susceptibility, indicate the low epidemic effectiveness of the new program for epidemiological surveillance of echinococcosis. It should be noted that this could also be affected by an increase in the detection of echinococcosis among the child population due to new diagnostic methods and an increase in preventive examinations, but in this case this is unlikely. Considering all of the above, we can conclude that this period is not enough for a full assessment of the effectiveness of anti-epidemic and preventive measures. For an accurate assessment, it is necessary to continue monitoring the incidence of echinococcosis in subsequent years in order to dismiss, or vice versa, confirm the role of cyclicity in the decline in incidence in the period after the introduction of a new program for epidemiological surveillance of echinococcosis.

However, during the implementation of the program, modern complex diagnostic methods and screening studies of the population were used, which helped to establish not only natural, but also anthropurgic foci of alveococcosis, as well as the proportion of children under 14 years of age with these invasions. Therefore, the effectiveness of preventive and anti-epidemic measures, as well as the epidemiological effectiveness of the current program for epidemiological surveillance of echinococcosis is not at a high, but at a satisfactory level.It is also impossible to discount the features of the clinical picture of echinococcosis, when the manifest stage of the disease is remote from the time of infection and manifests itself after many years of invasion with severe complications leading to disability and, often, death of the patient. A complete epidemiological characterization of the incidence of echinococcosis is possible only on the basis of the results of mass sero-epidemiological surveys of the population from risk groups (living in endemic areas or at occupational risk of infection with echinococcosis) [9]. Evaluation of social efficiency is also difficult for objective reasons.First, especially in remote regions, there is a serious problem with the registration of deaths from echinococcosis.

Patients after surgery with a diagnosis of echinococcosis and alveococcosis, after death, other diagnoses are made, such as: cirrhosis of the liver, hepatitis, liver failure, and therefore these cases are not included in the reporting form No. 1 of the State statistical reporting “Report on infectious and parasitic diseases” as dead from echinococoses. In this regard, the mortality rate from echinococcosis is slightly underestimated compared to the real situation. Secondly, due to the lack of criteria regulating indications for disability for echinococcosis, there is no way to evaluate it. But, even taking into account these two factors, the current program for the epidemiological surveillance of echinococcosis provides for more rational accounting, registration of morbidity and mortality from echinococcosis in medical institutions and centers of state sanitary and epidemiological surveillance with monitoring of reporting data horizontally and vertically, which, with relatively equivalent mortality rates, indicates a higher social efficiency of the new program for epidemiological surveillance of echinococcosis. Since during the operation of the new epidemic surveillance program the number of sanitary and educational activities carried out with the use of radio, TV, newspapers, seminars, conferences increased, many rural gatherings began to be held, etc., the number and quality of preventive and anti-epidemic measures increased, as well as however, more expensive diagnostic methods have been introduced, naturally, and the costs of implementing epidemiological surveillance have increased compared to the period before the introduction of the new program.

However, given that at the moment the program of epidemiological surveillance of echinococcosis has shown satisfactory effectiveness of preventive and anti-epidemic measures, the economic efficiency is also at a satisfactory level. The introduction into wide practice of serological testing of patients suspected of being affected by echinococcosis, provided for by new methodological guidelines for the clinical and laboratory diagnosis and treatment of echinococcosis and alveococcosis, has made it possible to increase the detection rate and thus start the treatment of these parasitic diseases in a timely manner. This indicates a high diagnostic efficiency of the new program for epidemiological surveillance of echinococcosis. The text of the Order of the Ministry of Health of the Kyrgyz Republic No. 666 “On Strengthening Measures for the Control and Prevention of Echinococcosis and Alveococcosis in the Kyrgyz Republic” dated December 18, 2008 was executed in accordance with all the rules for compiling regulatory documentation, all terms and formulations used are of an exclusively legal and medical nature, do not have fuzzy wording or phrases with two meanings. Therefore, the degree of simplicity of the echinococcosis epidemiological surveillance program is assessed as understandable by specialists whose work duties are regulated by this regulatory document. In general, the surveillance system for echinococcosis is simple to implement. However, the omission of the implementation of anti-epidemic and antiepizootic measures depends on the qualifications of specialists, the degree of acceptability of administration employees, medical organizations and ordinary citizens. In medical institutions, the collection, processing, transmission and analysis of information, as well as keeping journals, compiling forms and reports according to the schemes provided for by the Order of the Ministry of Health of the Kyrgyz Republic No. 666, is carried out in a timely manner and on time. The system of registration, registration of new cases of infection and deaths from echinococcosis, as well as epidemiological investigations of each case of echinococcosis and identification of foci has been worked out, which ensures completeness, reliability, timeliness and high efficiency of epidemiological surveillance of echinococcosis.

Conclusion

1. After analyzing the data collected for the period before and after the introduction of epidemiological surveillance of echinococcosis, set out in the Order of the Ministry of Health of the Kyrgyz Republic No. 666 “On strengthening measures for the control and prevention of echinococcosis and alveococcosis in the Kyrgyz Republic” dated December 18, 2008, the following criteria were assessed

A. The effectiveness of anti-epidemic and preventive measures is satisfactory.

B. Epidemiological effectiveness is low.

C. Social efficiency is high.

D. Economic efficiency is satisfactory

E. The degree of simplicity is high

F. Efficiency is high

G. Diagnostic and clinical efficiency is high

H. The degree of acceptability is low

Therefore, based on the evaluation of the criteria characterizing the effectiveness of anti-epidemic and anti-epizootic measures for echinococcosis, we can conclude that the correct choice of organizational and methodological approaches in conducting epidemiological surveillance of echinococcosis, set out in the Order of the Ministry of Health of the Kyrgyz Republic No. 666 “On strengthening measures to combat and prevent echinococcosis and alveococcosis in the Kyrgyz Republic” from 12/18/2008.

2. Years of potentially lost life due to echinococcosis for the period from 2013 to 2019 in the Kyrgyz Republic amounted to 4331.9 years.

For more Articles on: https://biomedres01.blogspot.com/

 

Sars-Cov-2, Its Variants, and the Impact of Pandemic on Adolescent Mental Health

Introduction

COVID-19, a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), produced its first outbreak in Wuhan, the capital of Hubei province in China in December 2019, when it coincided with the Chunyun period, a period of high traffic around the Chinese Lunar New Year. It was very contagious and had no effective treatment, such that even after the lockdown of Wuhan, it still spread to the whole world and infected a huge percentage of the population, inflicting death, which led the World Health Organization to proclaim it a pandemic. As of today (June 16, 2022), according to the Johns Hopkins Coronavirus Resource Center, SARS-CoV-2 has caused 537,601,288 cases of infection worldwide, and 6,315,704 deaths.

Two and a half years after its outbreak, although dramatic efforts have been made to contain the pandemic, including vaccines, mask mandates, screening, testing, isolation (such as the recent Shanghai lockdown), the pandemic is still ongoing. SARS-CoV-2 has not just impacted health, it has also impacted the economy and almost every area of life worldwide. It has led to a sharp increase in unemployment, disruptions in the supply chain, like a baby formula shortage, and a surge in inflation, which is the highest it has been in the past four decades in the US [1] .On the other hand, huge progress has been made in the knowledge of the virus, as well as methods of prevention, detection, diagnosis, and treatment. At the same time, the pandemic, as well as responses to it, have revealed problems that have not been heavily researched before, like the psychological impact of isolation or even lockdown on adolescents, and more research and efforts are needed to address these problems. Here we provide some updated information focused on the virus and its variants, and we hope this pandemic will end in the near future.

SARS-CoV-2

Coronaviruses (CoVs) are a group of RNA viruses that belong to the family Coronaviridae within the order Nidovirales. They are enveloped viruses, with a single-stranded RNA genome, and a nucleocapsid. They can infect other vertebrates, including bats, birds, mice and other animals, in addition to human beings [2]. They can cause human respiratory infections, and the risk varies significantly. About 15% of cases of the common cold is caused by a coronavirus [3]. Till now, there have been three strain of coronavirus which have a very high morbidity and mortality in humans. In 2002- 2004, severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1) caused an outbreak in China, spread to 32 different countries and regions, and caused more than 8000 infections and 919 related deaths with a case fatality rate (CFR) of 11% [4]. Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus transferred from dromedary camels. MERS-CoV has been identified in several countries in the Middle East, Africa and South Asia. It was responsible for 2468 cases and 851 deaths with a CFR of 37.2% [5]. MERS-CoV did not fully adapt to human transmission, and most of the cases are due to spillover from camels [6]. In comparison with the other two coronaviruses, SARS-CoV-2 appears to be much more contagious and infectious. But the CRF is much lower than those of SARS-CoV-1 and MERD-Cov [7].

As for SARS-CoV-2, through comparing the data of the whole genomic sequence, the Wuhan strain is considered a new strain of β coronavirus with approximately 79% genetic similarity to SARS-CoV [8]. As it has a 96% similarity to a bat coronavirus, it is suspected to originate from bats [8-9]. SARS-CoV-2 has some features that allowed it to spread quickly and claim millions of lives. Its spike protein is coated with glycans, which help it evade the human immune system. The binding of the spike protein of the virus to the angiotensin-converting enzyme 2 (ACE2) of the host cell is necessary for both SARS-CoV-1 and SARS-CoV-2 for virus infection. It has been shown that SARS-CoV-2’s binding is 2-4 times stronger than that of SARS-CoV-1. For the merge of viral and cell membranes, both of these viruses use TMPRSS2 or cathepsin L (host protease). TMPRSS2, which is expressed abundantly on the outside of respiratory cells, is the faster route in, and SARS-Cov-2 uses TMPRSS2 more efficiently. Once inside the cells, the virus takes over the translation machinery effectively by three mechanisms. At the same time, it starts to remodel the cells. Some infected cells fuse with neighboring cells to form syncytia, which is not found in the SARS-CoV virus. The syncytia might live longer and produce more copies of the virus [10]. All these features result in the SARS-CoV-2 strain having high transmissibility and fatality.

Variants

Compared with DNA viruses, RNA viruses have higher mutation rates, ranging from 10-6 to 10-4 substitutions per nucleotide, per round of copying. After its outbreak, more than 4000 SARS-CoV-2 mutation have been detected. The viral variants are the product of mutations which come from transcription or translation errors during viral replication [11]. “Some variants are variants of concern (VOCs), which refer to variants with an alteration in the S protein Receptor Binding Domain (RBD), which significantly improves the binding capability, leading them to have a high transmissibility, increased morbidity, or increased immune evasion”. In Figure 1 shows some variants and their clade, and all VOCs [11]. According to the WHO, previous circulating VOCs include Alpha, Beta, Gamma, Delta variants, and the Omicron variant is listed as the currently circulating VOC (access on June 19, 2022). Each of these 5 variants, at some point in time, have been related to a dramatic increase in COVID-19 cases among several nations at the same time.

Figure 1: Variants of SARS-Cov-2, including all VOCs, which are in red rectangles, and their clade. This figure is modified from SARS-CoV-2 variants and vulnerability at the global level [11].

Omicron

Like any other virus, random mutations accumulate in SARSCoV- 2. S protein S1 subunit is the hot spot of mutation which can change the virus’s virulence, transmissibility, and immune evasion [12]. The Omicron variant was first detected in Gauteng province in South Africa in the middle of November 2021 [13]. On Nov 26, 2021, WHO designated this variant (B.1.1.529) a VOC [14]. Now, it is the dominant variant in all nations. It carries more than 60 alterations, deletions, and insertion mutations, a high percentage of them found in other VOCs, and at least 32 mutations in the S protein. It has 15 mutations in the RBD, some of them in viral replication proteins, like NSP12 and NSP14 [15-16]. The specific changes in the S protein (mutations in RBD, and N-terminal), make it more transmissible, even among vaccinated people15, as studies demonstrated that mutations in RBD are responsible for the escape from neutralized antibodies induced by vaccine [17]. The early double time for Omicron was 1.2 days, and for Delta was 1.5 days. Now, it is clear that it is substantially more spreadable, and the infection rates in Omicron were four time higher than that of the wild type, and the better interaction between the ACE2 receptor and S protein of the Omicron variant is the reason that Omicron has a higher infection rate than other VOCs. For the virulence of this variant, Omicron infection has milder symptoms and much less severe cases. The risk of hospitalization is less than that of the Delta variant. Vaccination, especial the booster, can significantly reduce the rate of being hospitalized and the rate of fatality [15].

The Impact of Covid-19 on Adolescent Mental Health

Since the start of pandemic, significant effort has been exerted to contain the spread of the virus. Isolation, quarantine, and even lockdown of huge cities like Shanghai all impact the mental health of the whole population. Quarantines and lockdowns are states of isolation that are psychologically painful and unpleasant for anyone who experiences them. Adolescents, who are at higher risk of developing mental health problems than adults, may be more vulnerable to the adverse effects of isolation [18]. They could not accurately identify the veracity of information about the COVID-19 pandemic due to the rapid flood of complex information on the Internet, and they had to study online at home as their schools had been closed. Thus, they may easily develop feelings of loss of control, negative emotions and behaviors, and their relationship with their parents may also be affected [19-20]. The repercussions of COVID-19 on adolescents’ mental health are mainly manifested in three aspects: emotion, behavior, and parent-child relationship. First, since the outbreak of the pandemic, the incidence of emotional problems in adolescents has increased. For example, in one study, researchers have shown that changes in adolescents’ emotional conditions were mentioned by 85.7% of the parents, manifested as boredom, worry, irritability and nervousness [21].

In another study, scholars have reported that Wuhan adolescents’ anxiety symptoms were significantly higher than in other urban areas during the epidemic [22]. Other studies have shown a feeling of isolation, apathy, and increased irritability among adolescents [19,23]. Moreover, there is also research suggesting that COVID-19 might influence adolescents’ adjustment in a cascading fashion, and adolescents whose parents are infected, served as first-line medical staff, or died due to COVID-19 might experience more severe mental health impacts than other adolescents [22]. Second, negative emotions can also result in greater irritability, aggressiveness and oppositional behaviors among adolescents [19]. The most frequent symptoms were regressive behaviors, oppositional behaviors, loss of appetite, and inattention [21,24]. During the lockdown, most parents also reported a change in their children’s behavioral condition. The changes reported were behavioral problems (reported by 44.2% of parents), sadness (reported by 43.7% of parents) and laziness (reported by 44.3% of parents) [25]. Third, home isolation dramatically increases the amount of time parents spend with their children and changes the parent-child relationship. Compared with non-COVID-19, 31.4% of families reported an increase in parent-child conflict in the last month.

In the context of COVID-19, parents are faced with greater financial pressure, which might lead to bad temper and an overreliance on less effective parenting approaches. Researchers found that Wuhan adolescents’ parents were less warm and supportive and showed more emotional rejection toward their children compared to other urban areas during the Wuhan epidemic [22]. As a result, the relationship between parents and children may be strained by the outbreak. In addition, the shift from offline to online, whether at work or at school, has significantly increased the amount of time parents and children spend on electronic devices, which has also led to more parent-child conflicts.

Conclusion

Currently, huge numbers of people are still infected every day, including those who are vaccinated. However, most of them display mild symptoms, and the number of related hospitalizations and deaths every week is relatively low (2140 deaths last week in the US). In most countries, like China, India, and America, which have large populations, most people are vaccinated, and are receiving the booster. The impact of pandemic on the economy is decreasing. On the other side, the emergence of new variants of SARS-Cov-2 is continuing. With intensive research still ongoing, the development of more effective vaccines, and the cooperation of the whole world, we will ultimately win the war against the virus.

For more Articles on: https://biomedres01.blogspot.com/

 

Functioning and Disability in Alzheimer’s Disease

Opinion

Alzheimer’s disease (AD) corresponds to a complex neurodegenerative disorder that leads to a progressive decrease in brain metabolism functionally and morphologically (Deture, et al. [1-3]). Their presentation is progressive and chronic, with a subsequent loss of cognitive function (Justin M Long [3]). AD is the most common form of dementia and may contribute to 60- 70% of cases (WHO [4]). The majority of cases occur after age 65, comprising late-onset AD (LOAD), while cases occurring earlier than age 65 are considerably rarer, constituting less than 5% of all cases and are termed early-onset AD (EOAD) (Alzheimer’s, Long [3,5]). In addition, the risk of AD is 60% to 80% dependent on hereditary factors, with more than 40 genetic risk loci associated with AD already identified (Tanzi [6]). Also, the APOE alleles have the strongest association with the disease (Scheltens, et al. [7,8]). Moreover, in recent years, it is fast becoming one of the most costly, deadly, and burdensome diseases of this century (Scheltens, et al. [5,7]). The most recent data indicate that, by 2050, the prevalence of dementia will double in Europe and triple worldwide, and that estimate is three times higher when based on a biological definition of the disease (Scheltens, et al. [7]). Functionality is conceptualized as the ability of a person to carry out the activities necessary to achieve wellbeing through the interrelation of their fields: biological, psychological (cognitive and affective) and social (Hopper [9]).

Under this definition, the International Classification of Functioning, Disability and Health (ICF) proposes a conceptual framework that establishes a standard language to describe health and its different dimensions (WHO [10]). It was approved by the (WHO [10]), and since then, it has had high applicability in the field of health rehabilitation (Hopper [9]). (Figure 1) lists the three components of this model: body functions and structures, activity and participation. The first component is related to physiological and psychological functions and anatomical elements; the second component refers to the individual execution of tasks and activities; the third component is related to the development of social situations (WHO [10]). Functional impairment is a core symptom of AD (Arrighi, et al. [11,12]). The most precise indicator of functional deterioration is the decrease in the performance of activities of daily living (ADL) (Arrighi, et al. [11,13,14]). A report using ICF has pointed out that activity and participation are restricted to domestic life, self-care and mobility, communication, interaction, and social relations (Muò, et al. [13]). In addition, subjects who appeared more compromised on the Mini-Mental State Examination (MMSE) and Global Deterioration Scale (GDS) showed more significant function impairment, activity limitation, and participation restriction (Muò, et al. [13]).

Figure 1: International Classification of Functioning, Disability, and Health (ICF) (WHO 2001).

Executive dysfunction and decreased general measures of cognitive functioning have also been reported to be associated with decreased ability to perform instrumental ADLs (Pereira, et al. [15]). ADLs are affected progressively and hierarchically associated with cognitive decline, but substantial variability persists between individuals and the relative order of affected items (Arrighi, et al. [11]). It has also been pointed out that there are disability profiles with restricted patterns of time use in a variety of domains encompassing both compulsory and discretionary activity, accompanied by a significant increase in a passive activity, such as sleeping during the day or sitting in front of the television (Lomax, et al. [16]). Also, restrictions in the social and environmental contexts of the patient’s life and diminished levels of subjective enjoyment have been associated with their pattern of daily use of time (Hopper, et al. [9,16]). Currently, the ICF consists of 1,424 mutually exclusive categories that, taken together, cover a complete and comprehensive spectrum of human experience and are organized as a hierarchical structure of 4 levels differentiated from least to greatest precision (WHO [17]). The ICF categories are indicated using alphanumeric codes with which it is possible to classify functioning and disability, both at the individual and population levels.

According to this hierarchical structure, the highest-level category (4th) shares the attributes of the lowest level category (1st) to which it belongs. In addition, ICF qualifiers are used to quantify the magnitude of a problem in the different ICF categories, which are mathematically weighted quality descriptors that record the presence or severity of a problem at the bodily, personal, or social level (WHO [10]). Thus, a problem can suppose a deterioration, a limitation or a restriction that can be qualified from 0 (no problem: 0-4%), 1 (slight problem: 5-24%), 2 (moderate problem: 25-49%) , 3 (severe problem: 50-95%) to 4 (total problem: 96- 100%). For their part, environmental factors are quantified with a negative or positive scale that indicates the extent to which an environmental factor acts as a barrier or facilitator (WHO [17]). The ICF is a helpful tool for describing health status in patients with AD since it highlights important aspects of daily life that are not usually considered in activities of daily living scales, such as communication, social relationships, and recreation and leisure (Badarunisa, et al. [9,12,18]).

For more Articles on: https://biomedres01.blogspot.com/

 

Gastric Barotrauma ERCP-Related

Mini Review

A 73-year-old woman was referred to us for endoscopic biliary drainage of obstructive jaundice due to a pancreatic mass diagnosed by abdominal computed tomography (CT) scan (Figure 1A). Endoscopic Retrograde CholangioPancreatography (ERCP) was performed with CO2 insufflation under general anesthesia. Wire-guided cannulation of the papilla was gently attempted with the long route because of the distorted anatomy of the descending duodenum (Figure 1B) and was suddenly stopped by the anesthesiologist when blood came from the aspiration tube. Withdrawing the duodenoscope, petechial lesions and deep longitudinal actively oozing mucosal tears were seen in the lesser curvature of the stomach from the angulus (Figure 1C) to the gastroesophageal junction, consistent with gastric barotrauma. This gastric “cat scratch” is a rare phenomenon that, following LaPlace’s law, arises when sudden high gaseous pressure leads to increased wall tensions. It occurs in the lesser gastric curvature probably because this part of the stomach has a lower capacity for distension, owing to the lack of mucosal folds and the presence of the gastrohepatic ligament [1]. At the end of the procedure the patient immediately experienced epigastric pain and abdominal distention without any sign of perforation. This is the first case report showing gastric barotrauma during ERCP.

Figure 1:

A. Abdominal computed tomography showing double-duct sign: the combined dilatation of the common bile duct and pancreatic duct, caused by pancreatic mass.

B. Wire-guided cannulation of the papilla with the long route at x-rays.

C. Petechial lesions and deep longitudinal actively oozing mucosal tears in the lesser curvature of the stomach at the angulus and the gastroesophageal junction (Figure D).

For more Articles on: https://biomedres01.blogspot.com/

 

Assessment of Target Volume Definition for Contemporary Radiotherapeutic Management of Retroperitoneal Sarcoma: An Original Article

Introduction

Soft tissue sarcomas are relatively rare and comprise a heterogeneous group of malignancies. While the most common localization for soft tissue sarcomas includes the limbs, a considerable proportion occur in the retroperitoneum. Soft tissue sarcomas include a variety of histologic subtypes such as liposarcomas, undifferentiated-unclassified tumors, and leiomyosarcomas. Among the group of soft tissue sarcomas, retroperitoneal sarcomas deserve utmost attention since they represent a heterogeneous and relatively rare group of tumors originating from mesenchymal cells with considerably high rates of local recurrence and mortality. Surgery has been the principal mode of management for retroperitoneal sarcomas, however, complete surgical removal may not be achievable particularly in the setting of large tumor sizes and involvement of nearby critical structures. In an attempt to improve therapeutic outcomes, the use of radiation therapy (RT) has been addressed [1-7]. Surgical resection with negative margins may be challenging to achieve in some circumstances and neoadjuvant or adjuvant therapeutic strategies may be considered. RT may be utilized as a local treatment option, however, adverse radiation effects should be considered [1-7]. Critical advances in the millennium era for improved RT outcomes include sophisticated technologies along with state of the art irradiation techniques [8-46]. Accuracy and precision in target volume definition may be considered as a more important aspect of state of the art radiotherapeutic strategies to comply with these contemporary improvements. An overwhelming majority of RT centers currently make use of Computed Tomography (CT) simulation for radiotherapeutic management of retroperitoneal sarcomas. Clearly, CT remains to be a viable imaging modality for this purpose, however, incorporation of other imaging modalities such as Magnetic Resonance Imaging (MRI) may lead to improved target definition. Herein, we evaluate multimodality imaging based RT target definition for radiotherapeutic management of retroperitoneal sarcomas.

Materials and Methods

Herein, we had the purpose of investigating whether any improvement may be achieved through the incorporation of multimodality imaging in the target volume definition process for radiotherapeutic management of retroperitoneal sarcoma. To achieve this goal, a thorough appraisal has been utilized to shed light on this important aspect. We have carried out thorough comparative investigation of RT target volume definition. To be utilized for actual treatment and comparison purposes, a ground truth target volume was outlined individually by board certified radiation oncologists. Patients who have been allocated to RT for retroperitoneal sarcoma were included, and decision making for RT has been performed on a multidisciplinary basis. At the outset, alternative treatment strategies and protocols have been thoroughly discussed. Synergy (Elekta, UK) linear accelerator (LINAC) has been utilized for treatment delivery. Selected patients underwent CT-simulation at the CT-simulator. After the CT-simulation process has been completed, acquired images have been transferred to the contouring workstation. Outlining of structure sets including treatment volumes and critical structures comprised an important aspect of RT planning. Treatment volume determination has been performed by either the CT-simulation images only or by fused CT and MR images. A comparative analysis has been performed for evaluation of treatment volume determination by CT only and with incorporation of CT-MR fusion based imaging.

Results

Patients with retroperitoneal sarcoma referred to Department of Radiation Oncology, Gulhane Medical Faculty, University of Health Sciences were assessed for treatment volume definition by either CT-only imaging or by CT-MR fusion based imaging in this original research article. Lesion size, localization and association with critical structures, and disease extent were among the considered tumor associated characteristics. Also, we individually took into account the patient ages, symptoms, and performance status before radiotherapeutic management of retroperitoneal sarcoma. The reports by American Association of Physicists in Medicine (AAPM) and International Commission on Radiation Units and Measurements (ICRU) have also been considered for improved treatment planning. Radiation physicists played a significant role in generation of optimal RT plans by taking into account the recent informatory guidelines and clinical experience. Considered parameters in RT planning included the critical organ dose limitations, tissue heterogeneity, electron density, CT number and HU values in CT images. Primary aim of treatment planning was to achieve optimal treatment volume coverage while respecting the preset critical organ dose limitations. Modern treatment equipment has been used for irradiation, and we made use of contemporary image guidance strategies such as kilovoltage cone beam CT and electronic digital portal imaging for optimal setup verification. As the primary outcome of this study, the ground truth target volume was observed to be identical with CT-MR fusion based imaging for precise RT of retroperitoneal sarcoma.

Discussion

Although relatively rare, retroperitoneal sarcomas comprise a heterogeneous group of tumors originating from the mesenchymal cells. They may be typically associated with high rates of local recurrence and resultant mortality. While the main therapeutic option includes surgical resection to achieve optimal treatment results, complete removal of the tumor may not be achieved in some patients particularly when the tumor is large and in intimate association with surrounding critical structures. Within this context, RT may be considered in selected patients as another local therapeutic approach [1-7]. The primary objective of irradiation is eradication of as many tumor cells as possible without damage to normal tissues. However, achieving an optimal therapeutic ratio by RT may be hampered by critical organ dose constraints and the desired ablative doses of irradiation may sometimes not be administered due to the risk of excessive radiation induced toxicity. Several contemporary RT techniques and strategies have been developed recently to improve the toxicity profile of radiation delivery. Nevertheless, target definition has gained more importance and relevance with the availability of contemporary RT strategies. In this context, target definition for optimal RT planning is an indispensable component of sophisticated RT approaches. Meanwhile, CT-simulation is the most frequently used procedure for RT planning in a plethora of cancer centers. Cross sectional imaging with thin CT slices has clearly improved target and critical organ definition for radiotherapeutic management, however, incorporation of additional imaging with MRI may further refine this critical procedure. Fusion of CT-simulation and MR images may allow for exploiting the advantage of multimodality imaging. Indeed, the addition of MRI to CT images has been demonstrated to improve RT planning for a variety of cancers [47-80]. At this standpoint, we cordially believe that this study may add to the accumulating data on this subject and may have pertinent clinical implications for utilization of multimodality imaging for optimal RT of retroperitoneal sarcoma. We conclude that our study indicates improvement in treatment volume determination for precise RT of retroperitoneal sarcoma by integration of MRI in RT target definition process albeit with the requirement for further supporting evidence.

For more Articles on: https://biomedres01.blogspot.com/

 

Mental Depression©

Pharmaceutical Drugs Can Cause Permanent Harm

A person depressed is immersed in gloom. For them, everything is bad, they see no hope. They are constantly exhausted. Their glass is always half empty and all the traffic lights are at red. They may well blame someone. They drag down all those close to them and can cause mental depression in others. This is a common plight that is not cured by modern pharmaceutical medicine or drug wielding psychiatrists. A doctor will prescribe an anti-depressant drug to help the patient cope. All that does is switch off part of the brain and prolonged consumption causes permanent brain damage. If they stop taking the drug, stress increases and in fear they become more drug dependant. Good business for the pharmaceuticals. There is no known drug that repairs thoughts. The brain is the hardware, in computer terms, and thoughts are the software. Depression is a software problem. Emotions can be chemically stimulated but there is no control. For example, alcohol shifts the mood towards extraversion and caffeine can shift the other way with an inability to relax and that causes harm. Thoughts out of control are dangerous. At one extreme a person can think they are invincible and at the other commit suicide. No doctor should ever consider mood shifting for medical healing.

The only way to manage thoughts is conversation. We used to follow the explanations of Sigmund Freud and snigger at the technique of a patient on the psychiatrist’s couch until the drug makers took over and repaired the brain chemically. If a patient was not helped by one drug, they were given an alternative with the explanation that they were not responding properly, the patient’s fault. This suited the doctors who are called general practitioners with ten minutes to process each patient. A conversation about a person’s troubles could take an hour. The patient, who was helpless, hence their depression, never complained other than to often demand a stronger dose. Long term follow-ups confirmed that the person was now coping. To cope with life was regarded as a cure. Drug dependency had been caused (Figure 1).

Figure 1.

The Spectrum of Emotions

Below is a diagram of the spectrum of emotions. I used this first in an article about The Life Switch. When the mood is below normal, there is no healing. A depressed person is not just unhappy, they are ill. Aches and pains get worse. The immune system does not work. Add drugs to the helpless body and the immune system completely packs in (Figure 2). I observe, watch and listen to patients treated by Calsonic. A few weeks ago, a hunch that Cell Sonic is anti-depressant was confirmed. I visited St James Clinic in Birmingham to meet two lady professors from Poland when were interested in our technology. https://stjamesxh-clinic.com/. Here we are outside. I am the old man in a bow tie (standard garb for a professor) (Figure 3). The directors of St James are Hieu Tran standing between the ladies and Syed Ahmed on my left. The visiting professors are from Rzeszów University. Agnieszka Banas-Ząbczyk is on the left in the picture and Marta Kopańska is in the middle of the group. Both ladies were treated twice by the machine which at St James is called CS1. I explained what the machine does and how we understand it works on the body. The discussion then centred on the CS1 (Cell Sonic) making the patient feel happy. Hieu told of a miserable man who never smiled being seen after a treatment to be smiling. He told his friends it was the machine that did it.

Agnieszka said the same. She felt lifted, relaxed and welcomed more treatments. Marta agreed. Agnieszka said that neurons were being sent into the brain. Here is the machine (Figure 4). St James [1] have developed a standard procedure to treat the spine regardless of what the patient came to the clinic for. In the photo below, Hieu is showing the lady what to do. She is in the process of buying a machine for her own clinic (Figure 5). The protocol is 1,000 pulses at energy level 4.The treatment takes about five minutes with the machine banging at four a second. It can be felt but is not painful. Indeed, the patient enjoys the treatment. Three forces are emitted by the shock head (called a wand in America): pressure, electrical field and light. The spine is connected to the brain and all the organs (Figure 6). By treating the spine with Cell Sonic all the organs receive an electrical boost from the electrical field. There is no direct contact with an electrical charge from the machine (Figure 7). Credit and thanks are given to Dr Jerry Tennant for these illustrations [2]. His book and lectures on “Healing is Voltage” are first class (Figure 8-12). The frequencies needed to stimulate the cells and the related emotions are fully served by Cell Sonic because every pulse is a bang covering a full range of frequencies from high to low.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

Figure 9.

Figure 10.

Figure 11.

Figure 12.

The very high frequencies are attained by the short rise time of a Cell Sonic pulse lasting a billionth of a second, the time taken for electricity to travel 1 mm as it shorts across the gap in the electrode of the shock head. The resulting sound and flash of lightning is the same as a thunderstorm but smaller. Here below is an explanation of shockwaves taken from HMT, a Swiss company I represented in Britain before they went out of business twenty years ago. Their problem was that doctors demanded endless clinical trials costing the company more than they could afford until they ran out of money. I then formed Cell Sonic and have avoided the pitfalls that beset HMT. The electrohydraulic system is far superior to other methods. Also important is the means of switching the high voltage passing through the electrode. Cell Sonic uses the fastest possible. Slower methods such as a cascade of thyristors cannot achieve the high frequencies needed to restore body cells. Breaking kidney stones is one thing. Generating cell restoration is another and only Cell Sonic has the frequency range needed [3,4].

Conclusion

The discovery that Cell Sonic reduces and helps remove mental depression is a valuable addition to the medical tool kit. Drugs are not used so there are no side effects. The effects have been observed for ten years and reported to me from different continents. In some cases, patients with brain disease are being treated with pulses aimed directly into the brain. Whether this is better than sending the neurons to the brain through the spinal cord remains to be seen. The brain is surrounded by bone as is the spinal cord, so the pressure and light parts of the pulse have little effect. That leaves the electrical field and in bursts of a billionth of a second at low energy levels, no side effects are detected. The mental improvements are accumulative. When the person grows new brain tissue or other parts of the brain take over from the parts damaged by drugs, the person is lifted into the upper half of the emotional spectrum where the immune system becomes active and thus starts the upward spiral of feeling better because the body is healing. When pain is stopped, proper sleep allows the immune system to work and the person is lifted out of gloom into a bright, smiling day.

For more Articles on: https://biomedres01.blogspot.com/