Neurological Manifestations of COVID-19: A Brief Update on the Cuban Context

Introduction

Despite of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered a respiratory virus, several neurologic manifestations can appear during acute COVID-19 [1]. At present, the increasing number of patients hospitalized with coronavirus disease involving the nervous system has attracted extensive attention, because of the short and long-term impact that it could represent on population health worldwide [2]. But certainly, it is too early to know accurately how to identify and manage appropriately these manifestations. Precise and targeted documentation of the neurological symptoms and signs of the cases and autopsies of the victims, may clarify the roles played by this pathogen in causing nervous system compromise [3]. Wide spectrums of neurological troubles related to COVID-19 are recently reported [4]. Clinical experience with this ill in different countries has shown some initial neurological abnormalities such as: headache, dizziness, convulsions, pathological wakefulness after sedation, confusion, alteration of consciousness, gustatory/olfactory disorders, spatial disorientation, neuromuscular disturbances, agitation and cognition impairment [5]. It has been suggested that SARS-CoV-2 neuroinvasion, neuroinflammation and impairment of the Blood Brain Barrier (BBB) are responsible for the neurological symptoms in humans [6].

These new properties exhibited by the virus are due to the occurrence of pathophysiological mechanisms that are not well understood yet. This picture is actually known in most of studies like Neuro-COVID and it can be divided in early and late clinically. It depends on variables associated with the timely medical attention, the virus strain and also with the hosts features like age, genetic background, comorbidities, sex and geographical location [6]. The most common neurological complications fell into three categories [7]
a) Central Nervous System (mostly inflammation-mediated): headache, delirium, seizures, infectious toxic encephalopathy, acute encephalitis, meningitis, cerebrovascular accidents and dysexecutive syndrome.
b) Peripheral Nervous System (mostly immune-mediated): dysosmia/anosmia, dysgousia/agousia, acute myelitis, Guillain-Barre syndrome, Miller Fisher syndrome, Polyneuritis cranialis; and
c) Musculoeskeletal (direct injury): atonia y paresis.

A considerable number of investigations have reported the presence of SARS-CoV-2 in the CSF (Cerebrospinal Fluid) and postmortem brain tissue of COVID-19 patients with encephalitis. However, there are contradictory findings that may indicate that the neurological complications are due to severe systemic inflammation and not the direct invasion of the brain. It has been suggested that pathogen could invade the CNS (Central Nervous System) via hematogenous route through the binding to its receptors on BBB endothelial cells, passing across them (which do not involve any viral replication) by transcytosis and finally reaching the brain. The other proposed mechanism involves infecting immune cells that express ACE2, such as monocytes, granulocytes, and lymphocytes (Trojan horse” mechanism) [8]. The infected immune cells may then carry SARS-CoV-2 to the CNS, where it can infect the brain; however, viral replication in this kind of cells needs to be confirmed. Another mechanism consists in passing through disrupted endothelial cells’ tight junctions (paracellular route). The virions may also reach the CNS via peripheral nerves, more specifically the olfactory sensory neurons. The high expression of ACE2 and the priming protease Transmembrane Serine Protease 2 (TMPRSS2) in sustentacular cells and stem cells of the olfactory epithelium and olfactory bulb, may allow for retrograde or antegrade transport into the CNS [8]. There is an urgent need to understand the pathophysiology of these disorders and develop disease-modifying therapies [1].

Early in the COVID-19 pandemic, patients have described lingering syndromes following acute infection, now called Long Covid. These syndromes often include predominant neurologic and psychiatric symptoms, like difficulty with memory, concentration and ability to accomplish everyday tasks, frequent headaches, alterations in skin sensation, autonomic dysfunction, intractable fatigue, delusions and paranoia in severe cases. This has raised the possibility that infection may accelerate or trigger future development of neurodegenerative diseases such as Alzheimer’s or Parkinson’s maladies. It is emphasizing that many people who experience Long Covid are less than 50 years old and were healthy and active prior to infection [1]. No information is yet available regarding neurodevelopmental trajectories in children, who usually experience mild COVID-19 and manifest few neurologic or psychiatric symptoms during or after acute illness. During the last two years, the Institute of Neurology and Neurosurgery of Cuba carried out studies on the neurological manifestations in convalescents from COVID-19 in Havana [9]. The objective was to evaluate the percentage of patients who suffered from this type of clinical picture, its intensity and possible persistence. Investigations of the effects were made through a retrospective survey in a mobile application designed by the Cybernetics Department of the Neuroscience Center of the country. In addition, brain electrical activity was explored through electroencephalography and some questionnaires were applied to determine the psychiatric alterations associated with COVID-19.

The inquiries were made in a language understandable to the patients in order to specify the alterations of the nervous system. Participants with neurological evidence prior to infection with SARS-CoV-2 were excluded from the study. The analyses showed a high frequency of symptoms such as headaches and loss of taste/ smell and chronic fatigue, diarrhea and cardiac arrhythmias were declared as occasional. In 2020, a high incidence of visual damage was found, since 20% of the individuals testified a decrease in visual acuity and 30% had dizziness related to the infection [9]. It should be noted that in both years, a high number of these alterations were notified in individuals who suffered from mild symptoms, even completely asymptomatic. Regarding to the residual manifestations, the persistence time is still not clearly known. Another study took place at the Pedro Kourí Institute of Tropical Medicine to measure the impact of SARS-CoV-2 infection; this time, it was demonstrated that neurological sequelae were the most frequent in the convalescent’s egresses from the institution. After recovery, the patients exhibited sleep and adjustment disorders, nervousness, anxiety, depression and chronic fatigue [10].

Based on the follow-up of the cases that manifested severe and critical stages, the persistence of neurological complications was confirmed up to six months after the onset of the disease (Long Covid). The results of the project also made possible to characterize the immunological behavior and to find evidence regarding to the future of Cuban anti-COVID-19 vaccines. In the case of the pediatric population in Cuba, some usual neurological alterations have been described, such as: encephalitis, excitability and lack of concentration. In January 2021, around 93% of all convalescents in the country had been fully evaluated [11]. The consultations with the highest attendance were pneumology and physiotherapy, which covered 50% of the cases respect to those of nephrology, cardiology, psychology and psychiatry. Currently the care protocol in these cases covers fourteen specialties.

Final Considerations

The unpredictable nature of the convalescence stage can be declared with complete certainty, since COVID-19 is a disease about which we still do not know more than we do. This occurs because the first cases recovered have just a few months, which is a little time to have a comprehensive vision and make an effective description of the stage. In this sense, the health system in Cuba, in addition to the multidisciplinary care and treatment of patients in acute periods of the disease, focuses on identifying and treating sequelae that persist during convalescence. In relation to early and late neurological manifestations, there is evidence of an increase in diagnoses worldwide. Taking into account the negative impact of these complications, a call for self-care and social responsibility is made in order to stop the spread of the pandemic.

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Primary Pulmonary Angiosarcoma in 25-Year Old Patient

Introduction

Angiosarcoma is a rare vascular tumor that originates from endothelial cells with a 1-2% incidence of all soft tissue sarcomas. Angiosarcoma is associated with poor prognosis attributed to a high rate of recurrence and metastasis with the lung being the common site of metastasis. Primary pulmonary angiosarcoma is an extremely rare tumor that presents with non-specific symptoms such as cough, weight loss, shortness of breath, and hemoptysis. We presented an interesting case of primary pulmonary angiosarcoma with an initial good outcome for 2 years following surgical and oncological management and unfortunately widespread metastasis on the third year of surveillance.

Case Report

A 25-year-old female with no significant past medical history presented to her general practitioner with hemoptysis. Initially, she was treated with a course of antibiotics for suspicion of community-acquired pneumonia. However, symptoms persisted she was investigated with chest radiography which didn’t reveal any normality. Then she was referred to the respiratory team for a more thorough investigation with a computed tomography (CT) scan. CT scan revealed a multilobulated mass measuring 3.2x3.0cm compressing the superior aspect of the left main pulmonary artery without infiltrating it. The mass extends posteriorly between the left main pulmonary artery and the descending aorta with the endobronchial segment that occludes the apico-posterior segmental bronchus, concern regarding the early invasion of the AP window was raised (Figure 1). The mass was FDG avid on Positron Emission Tomography (PET) which was carried out later to facilitate understanding the nature of the lesion and look for peripheral metastasis. No metastatic disease was seen and a CT-guided biopsy was positive for synaptophysin stain and CD 31 which are markers for neuroendocrine and vascular tumors respectively. Endobronchial ultrasound-guided biopsy (EBUS) was inconclusive, and a multi-disciplinary team (MDT) discussion recommended surgical excision of the tumor as it localizes and to get a proper tissue diagnosis.

Figure 1: CT images demonstrating left multilobulated mass measuring 3.2x3.0cm compressing the superior part of the left main pulmonary artery without infiltrating it and extends posteriorly between the left main pulmonary artery and the descending aorta with the endobronchial segment that occludes the apical segment of the bronchus posteriorly with concern about invasion to the aortopulmonary window.

After two months of thorough investigations, the patient was referred for surgery. The initial preparation was for pneumonectomy given the size, central position of the mass, and suspicion of vascular invasion. Cardiopulmonary bypass was made ready in the theatre room if required. At surgery, a left upper lobectomy with a pulmonary artery vascular sleeve resection and systematic lymph node dissection was ultimately performed via posterolateral thoracotomy. The patient was discharged with no post-operative complications 6 days after the operation. The histopathology examination from the resected lung reported a tumor comprised of solid sheets of malignant epithelioid cells that stained for ERG, synaptophysin, vimentin, and focally for CD31, with negative staining for cytokeratins, GATA3, and mesenchymal, melanocytic, germ cell, and lymphoid markers (Figure 2). There was no rearrangement of CIC, ESWR1, or FUS genes. A differential diagnosis of angiosarcoma and undifferentiated round cell sarcoma was given. Follow-up CT scan at 3, 6,12, and 24 months showing no recurrence. She also received a combination of chemotherapy (vincristine, doxorubicin, cyclophosphamide, ifosfamide) and cycles of radiotherapy. She remains under regular surveillance with regular CT scan screening. Unfortunately, on 30 months follow up a widespread disease recurrence was found.

Figure 2: Representative photomicrographs of the tumour cells and immunohistochemical staining.
A. A solid tumour comprising pleomorphic malignant epithelioid cells with prominent nucleoli and eosinophilic cytoplasm (Haematoxylin and Eosin staining, x200)
B. Vimentin immunohistochemistry demonstrating diffuse positivity (x100)
C. CD31 immunohistochemistry staining showing focal positivity within the tumour cells (x200).

Discussion

Angiosarcoma is a rare vascular tumour that arises from endothelial cells and has different subtypes such as cutaneous angiosarcoma, breast angiosarcoma, soft tissue angiosarcoma, lymphedema associated angiosarcoma, and radiation-induced angiosarcoma (Young, et al. [1]). Primary pulmonary angiosarcomas are extremely rare with only a few resected cases since the most pulmonary presentation is due to metastatic disease (Ren, et al. [2]). The aetiology of this tumour is still unknown (Young, et al. [1]). Primary pulmonary angiosarcoma has non-specific symptoms. It can present with hemoptysis, cough, weight loss, dyspnea, chest pain, fever and fatigue or even asymptomatic (Ren, et al. [2]). This lead to misdiagnosing primary pulmonary angiosarcoma especially since it affects a relatively younger age group and diagnosis can be made only when other symptoms related to distal metastasis occur. Radiologic features of primary pulmonary angiosarcoma include multiple nodules which can be calcified or noncalcified, infiltrates, consolidation and occasionally a solitary pulmonary nodule (Kim, et al. [3]). Patients with solitary lesions tend to do better compared to those with multiple lesions. Solitary nodules respond better to treatment while multiple lesions have a more rapidly progressive course (Ren, et al. [2]). Due to the various features of primary pulmonary angiosarcoma on CT scan, this can also be misinterpreted as an infection. Tang et al, have reported in a case that has been misdiagnosis due to the CT finding of left lower lobe ground-glass changes and lymphadenopathy especially with blood tests pointing toward that direction and their patient has been treated for tuberculosis Tang, et al. [4]. PET is considered to be valuable to rule out widespread metastasis at presentation as well as for close follow-up throughout the treatment course (Wilson, et al. [5]). Chest radiography can fail to detect primary pulmonary angiosarcoma as what happens with our patient.

Histopathology and immunochemistry were considered as the only means to diagnose pulmonary angiosarcoma. This can be obtained through CT guided or bronchoscopy guided and if these measures failed to provide a definitive diagnosis as with our case surgical resection will become necessary to provide tissue diagnosis which is the most effective diagnostic tool for primary pulmonary angiosarcoma Campione, et al.; (Kojima, et al. [6,7]). The presence of malignant endothelial cells constitute the hallmark of angiosarcoma, but the morphology is variable ranging from solid to Vaso formative and spindled to epithelioid (Wei et al. [8]). Angiosarcomas also typically express ERG and CD31 with variable expression of CD34 and Factor VIII (Wei et al. [8]). Our specimen was positive for ERG, synaptophysin, vimentin, and focally for CD31, hence, the diagnosis of angiosarcoma was favoured although, with genetic studies for CIC being negative.

There are no standard guidelines for the management of primary pulmonary angiosarcoma. Surgical resection, chemotherapy, radiotherapy or both have all been reported in the literature. However, none of these have been associated with the positive outcome which can lead to further research to establish a causal relation. Although there is a suggestion that early surgical resection for localized tumour can lead to a better outcome (Tang, et al. [4]). This has been proven false with our patient which radical surgical treatment has been offered very early in the disease course with aggressive chemoradiotherapy, yet there was widespread disease recurrence. In conclusion, primary pulmonary angiosarcoma is a very rare malignant tumour with a very poor prognosis and difficult diagnostic means. We present a young patient with a localized presentation of a malignant epithelioid primary pulmonary angiosarcoma, who developed widespread disease recurrence despite radial surgical management, chemotherapy, radiotherapy and close surveillance with serial CT scan every 6 months. This case highlights the importance of investigating a way to tackle this lethal tumour rather than following the same algorithm for localized pulmonary malignancy and highlights that diagnosis other than carcinoma should be considered in patients presenting at a young age, even with epithelioid morphology.

Conflict of Interest

The authors declared no potential conflicts of interest to research, authorship, and/or publication of this article.

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Ventricular Septal Defect in Eight Holstein Calves in a Large Dairy Herd

Introduction

In this clinical case series report, we aimed to present clinical findings concerning congenital ventricular septal defect (VSD) in a commercial dairy herd in Iran (Behroozi Dairy Complex, approximately 3000 dairy cattle, Tehran, Iran) and to differentiate between VSD and respiratory diseases in Holstein calves. The VSD is an abnormality in both human and animal hearts in which the heart wall (septum) that divides the heart into two separate parts (left and right ventricles) is not fully developed during embryogenesis [1]. As a result, a hole is formed between heart ventricles leading to disturbed and abnormal blood flow into the heart that cause heart failure. Genetic background has been proposed as a main cause of VSD in humans. However, in a recent study [2], it was concluded that maternal stressful life had a significant role in the development of heart disorders especially VSD in offspring.

Case Presentation and Discussion

In previous reports concerning VSD in Holstein calves, only one calf has been identified with VSD [3,4]. However, according to our observations in a large dairy herd, we suggest that VSD occurs more frequently and that it could be confused with respiratory diseases at least in some cases. In the current case report, eight Holstein calves (5 females and 3 males) were diagnosed initially for respiratory diseases but were further examined for the probability of heart defects. Consequently, the VSD was diagnosed and observed by postmortem necropsy in all 8 calves. The Figures 1 & 2 illustrate the hole position with different sizes obtained from culled/dead calves with VSD in a large dairy farm (Behroozi Dairy Complex, approx. 3000 dairy cattle, Tehran, Iran). The calves diagnosed with VSD ranged from 1 to 90 days of age, indicating that this phenomenon occurs in different young ages. As the VSD is a congenital disorder, its severity can be affected by the hole diameters. This implies that calves with a smaller hole in the septum might live without any problem unless the hole becomes large enough to seriously compromise the heart function as calf ages. Therefore, disorder detection and calf culling, or death may occur in a variety of ages. Like the age, the VSD was not sex-dependent either and it occurred in both female and male calves. Moreover, exploring parity in the incidence of VSD revealed no differences between cows or heifers.

Figure 1: The hole position (VSD) is illustrated when observed in culled/dead calves in a large dairy farm (Behroozi Dairy Complex, Tehran, Iran).

Figure 2: The hole position with different size in another case of VSD in another calf (Behroozi Dairy Complex, Tehran, Iran).

As noted, the symptoms of VSD were primarily similar to those of the respiratory diseases. Hyperpnea, lethargy, anorexia and poor growth are common clinical symptoms of VSD. Clinically, substantial alterations occur in heartbeat frequency and sound in the VSD cases. For instance, the heart beats faster and a thrill can be detected when the right or left side of the thorax is palpated. The heart auscultation showed an audible murmur in all affected calves with different degrees of VSD. The body temperature was normal in the VSD cases, whereas in respiratory diseases, the body temperature is almost high (> 39.3 °C). As such, the early diagnosis of VSD in calves can be helpful in managing these animals and provide an opportunity to distinguish it from respiratory diseases. As a result, the useless antibiotics therapy should be avoided. Finally, the right calf culling time can be decided upon. As noted above, mothers exposed to stressful life during pregnancy had higher risks of VSD development in offspring. It has been reported that maternal lifestyle as well as excessive body mass possess potential roles in increasing congenital heart defects in babies [5]. Suboptimal calf welfare may occur when dams are exposed to stresses and diseases during pregnancy [6]. Overall, it is suggested that gestation is a critical phase for both dam and fetus and that all pressures must be minimized during this period. Overcrowding, hyperthermia, and nutritional deficiency are the most common stressors in ruminant farms worldwide.

As a result, optimizing the pregnant and dry cow environment by reducing stress might reasonably decrease congenital disorders, and hence, improve the productivity and sustainability of commercial dairy herds.

Conclusion

Eight cases of the Ventricular Septal Defect (VSD) were diagnosed and reported in the present study in a large dairy herd in Iran. The VSD is a common heart abnormality leading to culling or death of young calves. Hyperpnea, lethargy, and poor growth are its most common symptoms, but they should be differentiated from the similar symptoms in respiratory diseases. Palpation of the right side of thorax would be useful for the early diagnosis of VSD. Controlling stress in late gestation and attention to herd genetics programs could be helpful in minimizing congenital heart problems. Consequently, preventing calf culling or death will benefit the commercial dairy herds’ economy.

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The Importance of Just in Time (JIT) Methodology and its Advantages in Health Care Quality Management Business – A Scoping Review

Introduction

The logistics management of Modular integrated construction (MIC) (Mohamed Hussein, et al. [1]) has always been a major barrier to the wider adoption of (MIC). Nonetheless this challenge can be tackled by the application of lean techniques namely justin- time (JIT). Numerous studies have identified and evaluated the critical factors (CFs) required to implement JIT. The results indicate that all the 42 CFs are important for applying JIT of (Mohamed Hussein, et al. [1]) which seven are highly significant for successfully implementing JIT in (MIC). The results of the randomized trial strongly support (Christopher M, et al. [2]) the efficacy of just-in-time evidence-based reminders as a means of changing clinical practice among home health nurses who are geographically dispersed and spend much of their time in the field. Both the basic and the augmented interventions greatly increased the practice of evidence-based care according to patient records in the areas of patient assessment and instructions about HF disease management. While not all results were statistically significant at (Christopher M, et al. [2]) conventional levels intervention effects were positive in virtually all cases and effect magnitudes frequently were large (Figure 1).

Figure 1: Worldofagile.com [32].

The JIT and stockless approach to provider supplier relationships (Lynch D [3]) has proven to be a win-win proposition for the partners that have implemented it in many manufacturing industries and health care organizations as well. This strategy will fundamentally impact the entire cost structure within the hospital supply distribution chain. The sweeping changes the health care industry experienced during the 1980s are leading creative materiel managers to seize the initiative to improve the current operating (Lynch D [3]) costs of their hospitals. They do not want to be left behind “holding the inventory.” JIT leads to waste reduction improves productivity and (Kaswan S, et al. [4]) provides highquality patient care. The practical implementation of JIT depends on vital factors known as enablers. Grey Relational Analysis (GRA) has been used in the present study to rank enablers and ranks were further validated using the fuzzy technique for (Kaswan S, et al. [4]) order of preference by similarity to ideal solution (TOPSIS) and sensitivity analysis. Clinical nurse educators are expected to (White, et al. [5]) prepare students for the realities of practice while providing meaningful learning experiences.

However, shortened patient stays in the acute care setting often lead to wasted and useless effort for both instructors and students. The application of Just-in-Time principles offers a viable and alternative solution for clinical (White, et al. [5]) practice preparation in today’s rapidly changing healthcare environment. Different organization around the globe are using 5S (Ahsan Siddiqui [6]) and 7 Muda methodology to get benefits for improvement of their health care system. The step-by-step process of 5S and 7 Muda methodology is smart way to start monitor, finish and follow up the broken health system in several countries. Lean management and Lean six sigma methodology has shown promising results to improve the quality of health care system. Lean six sigma methodology works by reducing 8 wastes including overproduction, inventory, waiting, Motion, Transportation, rework, over processing and non-utilized talent. The 5 (Ahsan Siddiqui [6]) principles of lean model include value, value stream, flow, pull and perfection.

Healthcare providers are critical to disaster response (Ahsan Siddiqui [7]) throughout the world. Increasingly, there are government and nongovernment sponsored opportunities for providers to participate in disaster response as members of disaster response teams. Training opportunities on-line and in-person are readily available but not usually for a specific disaster at the time it occurs. Just-in-time disaster specific training prepares providers for imminent deployment for a real-time disaster. Particularly for disaster response (Ahsan Siddiqui [7]) in an austere environment just-in-time disaster specific training optimizes preparation and response.

Methods

The Author of this article has chosen the scoping review of the 37 articles and the websites to discuss details about the Just in time methodology. Scoping review focuses more on to discuss the 10 benefits/advantages of the JIT methodology and the 10 steps to perform JIT methodology. The author has chosen subject and words to find out the which organization should use the JIT methodology and some of the disadvantages of the JIT methodology. Articles are specially selected from the PubMed NIH website focusing only on healthcare JIT methodology. Just-in-time (JIT) has been a popular operation strategy partly (Ahsan Siddiqui [8]) because of its success in the Japanese automobile industry. Various benefits such as inventory reduction improved operations efficiency and faster response have been studied widely in previous studies. Therefore, successful implementation of JIT is vital to many companies. The major contribution (Ahsan Siddiqui [8]) of this paper lies in the discussions of the successful factors as a practical guide to implement JIT systems.

As we enter a new era of technological capacity for (Inbal NS [9]) delivering Just-in-time adaptive intervention (JITAIs). It is critical that researchers develop sophisticated and nuanced health behavior theories capable of guiding the construction of such interventions. Despite the increasing use and appeal of JITAIs, a major gap exists between the growing (Inbal NS [9]) technological capabilities for delivering JITAIs and research on the development and evaluation of these interventions (Figure 2). During the current recession economy around the globe, (Ahsan Siddiqui [10]) it is wise to choose the quality tools such as KAIZEN for the growth of organizations. Toyota motors, BMW Germany, Ford motors USA, other companies are using the KAIZEN tool to organize their organization, reduce the waste and increase the profits.

Figure 2: Marketbusinessnews.com [33].

SWOT tool helps administration to simplify the challenges an organization is facing and would face in the future to write and implement the corrective actions for improvement. SWOT analysis also helps to identify the (Ahsan Siddiqui [10]) 7 Muda wastes of the organization to reduce the wastes to make the organization reliable productive and profitable. Canonical correlation analysis was used to test five hypotheses. (Sadao S, et al. [11]) The results indicated that

a) There was not a significant relationship between the use of JIT practices alone and manufacturing performance,
b) There was a very strong relationship between JIT practices and infrastructure practices
c) The combination of JIT management and infrastructure practice was related to manufacturing performance
d) Infrastructure by itself is sufficient to explain manufacturing performance and
e) Manufacturing performance was [11] related to competitive advantage. The worsening global economy following the burst [12] of the dotcom bubbles in 2001 the financial tsunami in 2008. And the incessant rise in customer demand for better services have all contributed to shrinking profit margins for businesses around the world. One successful solution has been the adoption of Just-in-Time manufacturing systems which involve many functional areas of a firm such as manufacturing, engineering, marketing, and purchasing among others.

Just-in-Time Logistics extends the JIT concept in manufacturing to business logistics an area (Kee h, et al. [13]) that has been observed to account for more than 30 per cent of sales revenue for some firms. The price of alirocumab would have to be reduced (Dhruv S, et al. [14]) considerably to be cost-effective. Because substantial reductions already have occurred, we believe that timely independent cost effectiveness analyses can inform clinical and policy discussions of new drugs as they enter the market. Compared with a statin alone the addition of alirocumab cost $308 000 (UI, $197 000 to $678 000) per QALY. Compared with the combination of statin and ezetimibe replacing ezetimibe with alirocumab cost $997 000 (UI, $254 000 to dominated) per QALY. (Dhruv S, et al [14]) Incremental cost effectiveness ratio in 2018 U.S. dollars per quality-adjusted life-year (QALY) gained. JIT is a philosophy that can be applied to inventory (Kinney Bill C, et al. [15]) management operations to reduce waste achieve cost savings maximize space and improve quality of care. In the healthcare environment a prime vendor program is essential to a successful JIT program.

With the advent of a prime vendor program at Naval Hospital, Oakland, the advantages offered by JIT become available. JIT is an innovative approach to inventory management that has been successfully applied in the healthcare industry. The authors examine JIT and how (Bill C, et al [15]) this philosophy can further the goals of the prime vendor program and increase quality of care (Figure 3) (Tables 1-4).

Figure 3: SPSS diagram shows 30 websites & journal articles discusses about 10 principles (steps) of jit- just in time and agrees to the following 10 points: CIPS.org [34].

Table 1: 30 Websites & Journal Articles Discusses About 10 Principles (Steps) Of Jit- Just in Time and Agrees to The Following 10 Points CIPS.org [34].

Table 2: 30 Websites & Journal Articles Discusses About 10 Advantages of Jit- Just in Time And Agrees To The Following 10 Points: (Valleybox.com 2021).

Table 3: 30 Websites & Journal Articles Discusses About Who Should Use Jit – Just in Time and Agrees To The Following 06 Points: (Bluecart.com 2021).

Table 4: 30 Websites & Journal Articles Discusses About 06 Disadvantages of Jit- Just in Time and Agrees to The Following 06 Points (Netsuite.com 2021).

Results

There are four tables providing details about the 10 steps of the JIT methodology and its benefits/advantages. Remaining two tables provide the details about who should use the JIT methodology and its disadvantages. Author has provided the data analysis and diagrammatic presentation by using SPSS software. Four diagrams show the bar charts and the frequencies of the 30 articles of the steps, advantages, disadvantages and who should use the JIT methodology. Just-in-time (JIT) a management concept which requires (Whitson Daniel [16]) the delivery of a service or a product only upon demand can be used by hospitals as a tool for minimizing expenditures in logistics. This system offers a variety of benefits such as continuity in process flows minimization of works-in- process and finished goods inventory and the removal of bottlenecks in the production line.

Some of the areas wherein the JIT system (Whitson Daniel [16]) can be applied include central supply materials management and pharmacy nursing units and physician practices. During the time of recession and economic instability (Ahsan AS [17]) most of the organizations are looking to save money. The seven quality tools and other 29 administrative quality tools help the organizations to identify the problem, its root cause analysis and implement the corrective action to obtain the best possible result. By the literature review of the PESTEL/PESTLE analysis tool it helps the organization to focus on 6 important factors to grow the business. 6 important factors include political focus on health care, (Ahsan AS [18]) economic challenges, social factors, technological factors, legal factors, and the environmental factors. The present work provides important difficult and easy (Kaswan MS, et al. [19]) to implement JIT elements in healthcare services.

Besides this work justifies the application of decision-making tool (AHP, BWM) for the prioritization of JIT elements in the health care sector. This work also facilitates the proper management of inventory items together with the reduction in various Lean wastes with the proper implementation (Kaswan MS, et al. [19]) of JIT in healthcare. The reduction in various associated wastes leads to cleaner surrounding and lesser environmental degradation. This study examines the transformation of manufacturing industry (Krishnamurthy A [20]) to Just in Time (JIT) manufacturing and mass customization. The main objective is to identify strategies that will accelerate the realization of information technology enabled on demand services. Manufacturing and service systems are compared in terms of the similarities and differences with respect to issues related to their design planning and performance evaluation. These comparisons show that problems related to portfolio optimization workforce optimization and resources allocation are important in both manufacturing and (Krishnamurthy A [20]) service systems suggesting that the similarities be exploited to develop strategies for on demand services.

A new form of relational exchange commonly referred (Gary LF, et al. [21]) to as the “just-in-time” (JIT) exchange relationship has been adopted and implemented by many original equipment manufacturers (OEMs) and suppliers of component parts-materials during the past several years. The authors attempt to expand understanding of

a) How JIT exchanges compare with other forms of exchange between suppliers of component parts-materials and OEMs,
b) What conditions are most conducive to the initiation of JIT exchanges and
c) What key factors (Gary LF, et al. [21]) are likely to influence the success or failure of initiated JIT exchanges. We conclude that in a hospital with a sophisticated material (Epstein R, et al. [22]) management information system OR managers will probably achieve greater cost reductions from focusing on negotiating less expensive purchase prices for items than on trying to link the OR information system with the hospital’s material management information system to achieve just-intime inventory control.
Because expensive items typically have different models and sizes each of which is used by a hospital less often than this for almost all items there will be (Epstein R, et al. [22]) no benefit to making daily adjustments to the order volume based on booked cases. There are two keys to JIT supplier logistics that is taking control (Harry G [23]) of inbound deliveries and establishing quick feed-back loops. Various models have been proposed to investigate the improvement and learning processes the JIT system seeks to foster. To maximize the probability of success of a JIT program it is also necessary to put proper incentive systems in place that encourage employees and management to implement the desired changes and to redefine areas of responsibility throughout the organization. The extension of JIT across firms thus creates (Harry G [23]) mutual dependencies between supplier and customer and hence incentives to cooperate to resolve problems and increase efficiency (Figures 4-6).

Figure 4: SPSS Diagram Shows 30 Websites & Journal Articles Discusses About 10 Advantages of Jit- Just In Time And Agrees To The Following 10 Points: Valleybox.com [35].

Figure 5: SPSS Diagram Shows 30 Websites & Journal Articles Discusses About Who Should Use Jit – Just In Time And Agrees To The Following 06 Points: (Bluecart.com, 2021).

Figure 6: (Netsuite.com 2021).

Discussion

The analysis was conducted in a systematic manner and (Gary Jarrett [24]) compared the anticipated benefits with benefits validated in other industries from the implementation of JIT. In this particular study the cost and benefit outcomes achieved from a health care JIT implementation were compared with those achieved by the manufacturing service and retail industries. Chiefly, it was found that the health service market must be restructured to encourage greater price competition among priorities. A new standardization process (Gary Jarrett [24]) should eliminate duplication of products and realize substantial savings. Nurse executives need to review what is working in (Jacobs SM, et al. [25]) other industries to see if similar techniques and philosophies can help the healthcare industry. The authors review the manufacturing philosophy supporting the just-in-time JIT method and apply some of its (Jacobs SM, et al. [25]) principles to healthcare to improve operations and operating margins.

Describes one approach to meeting the health‐care cost reduction (Heinbuch SE [26]) challenge through the hospital materials management function. Highlights the value of taking a proactive stance to meet the challenge, transferring technology across industry sectors such as employing a just‐in‐time inventory management system in clinical areas of hospital materials (Heinbuch SE [26]) management and adopting a win‐win managerial philosophy. Features a case study to demonstrate the ideas in practice. With the implementation of the recent Healthcare Reform Act (Bhushan K [27]) and the increased scrutiny on the soaring costs of healthcare medical plans are looking for ways to optimize workflows and reduce costs. Titan Healthcare is a large non-profit integrated healthcare company located in Arizona New Mexico, Nevada, Colorado, and Texas. They provide health insurance coverage and a broad range of comprehensive health care.

From a pharmacy inventory (Bhushan K [27]) perspective expectation for the system is to significantly reduce inventory costs and increase service levels to their members. With the recent public focus on health care reform hospitals (Yitteck Walker [28]) are under more pressure than ever to be more cost efficient. In order to accomplish these hospitals must explore new business models that will help them reduce costs while at the same time increasing productivity. The just-in-time (JIT) inventory system is selected in this project as a potential cost saving strategy for hospitals. This project explores the feasibility of adopting a JIT inventory system (Yitteck Walker [28]) in a hospital setting through a detailed review and comparison of 20 articles. Lean management aims to add value to the patient (Tomasz K [29]) and the healthcare unit by eliminating superfluous and non-value adding activities. The purpose of the article is to discuss the implementation of lean management/lean healthcare solutions to the healthcare units thanks to the use of a value-adding Just-in-Time (JIT) method in hospital inventory management. The article is based on [29-39] an up-to-date subject literature and was conducted by means of desk research analysis.

Conclusion

To conclude, just in time methodology (JIT) is a lean methodology to provide economic comfort to the organization. JIT has proven that it could save lot of wastes for the organization and provided affective savings for the organization. The method to get the benefit is to order only what is needed and do not waste the time and money in inventory stocks. Toyota motors, Apple, McDonald and others are successful organizations taking huge benefits from the JIT methodology from decades. Small businesses should practice JIT methodology, which is convenient to use and sensible, easy to implement in the organizations.

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Impact of Automaticity Skills on Students’ Success in O-Chem I

Opinion

The Texas Networking for Science Advancement (NSA) team previously reported in this journal on how student’s automaticity ability (what can be done without the use of a calculator) influences their success in general chemistry [1,2]. The published general chemistry statistics for the MUST (Math-Up Skills Test) consistently support that this assessment is highly reliable (KR-20 > .80), has good internal consistency (Cronbach’s alpha > .85), and the Cohen’s d for the MUST is consistently > 1.0 indicating a large effect size for a population of over 10,000 [2]. Given these statistics, the NSA team turned its attention to how do automaticity skills assessed by the MUST reflect students’ success in first-semester organic chemistry (O-Chem I), a course commonly referred to as the “pre-med killer” or the hardest pre-med course. If you ask a student who has taken organic chemistry what they recalled most about the course, there is a slim chance you would hear them reference mathematics. However, mathematics does exist in O-Chem in forms that reflect lessons from the foundation courses that students have taken and passed, like general chemistry and calculus. Some example lessons in O-Chem that need calculations include:

 Drawn chemical structures/empirical formulas and calculating the molecular weight

 PH determination

 Enthalpy and entropy to determine endothermic/exothermic reaction conditions

 Bond dissociation energies of molecules

 Kinetics and rate equations

 Energy of activation with the Arrhenius equation

 Percent yield, weight/weight%, volume/volume%

 Conversions factors (mole to mmol) or concentrations

 J-splitting in nuclear magnetic resonance (NMR) spectra

 Molar extinction coefficient (Ɛ) from Beer-Lambert equation in UV-Vis

 Change in wavelength in infrared spectroscopy bands when groups shift positions

Knowing that MUST skills are linked to success in general chemistry, led the NSA team to investigate how students’ arithmeticautomaticity ability might lead to a better understanding of whom will succeed in O-Chem I. In this study, the MUST was given to O-Chem I students (n = 99, no incompletes or withdrawals were considered in the analysis) at the beginning of a semester at two Texas universities, one public Hispanic Serving Institution (HSI) and one private Hispanic-emerging institution. The MUST scores were then matched to the respective students’ final course grades and compared. A copy of the 12 min, 20-question MUST is available in Williamson, et al. [3]. Surprising was that these results continued to mimic those of general chemistry students (Figure 1). The left side of Figure 1 depicts three groups (I – III) of students. The MUST mean and SD are 9.99 (5.50). Group I students (bottom, blue group) are those who scored above average (> 13 of 20 questions) on the MUST. Students in group II (middle, orange group) are those who scored in the average group range (7-13 correct questions), and group III (top, green group) consists of students who scored < 7 correct. On the right side of (Figure 1), the two groups U and S reflect those who completed O-Chem I successfully (grades of A, B, or C) and those who did not attain at least a grade of C or a numerical average of > 69.5%. We did not hypothesize that there would be any relationship between students’ MUST scores and their success in O-Chem I, but as can be seen, almost all group I students were successful in O-Chem I as were most of the students in the average group.

Figure 1: Alluvial diagram comparing MUST scores to completion level of O-Chem I students. Left vertical bar identifies three MUST groups (I = above average scores, II = average scores, and III = below average scores). Right vertical bar identifies two student groups (U = unsuccessful and S = successful). Alluvial diagram source: https://rawgraphs.io/learning/how-to-makean- alluvial-diagram/#01-paste-your-data.

About half of group III students (identified the first week of class!) failed to successfully complete O-Chem I and are therefore not allowed to progress to O-Chem II and probably have a slim chance of continuing the pre-med track. Mathematics and underlying thought processes are prevalent in some form in most chemistry courses, including organic chemistry. Success on the MUST goes beyond basic arithmetic understanding and reflects what students have “overlearned.” Processing an ability to retain certain facts in long-term memory provides an edge to succeed in O-Chem I. It is students’ prior knowledge that continues to be the most predictive factor of determining success in the next course. The knowledge a student brings to the next course is always confronted with new applications that must be incorporated into their chemical repertoire, but as has again been shown, the more arithmetic facts that can be correctly recalled without the use of a calculating device, the more successful on the average students will be. The MUST is a fast, simple assessment of students’ arithmeticautomaticity ability that can be used to determine those who are predicted to struggle in only 12 min. the first day of class.

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