Overcoming Healthcare Transportation Barriers: A Case Study

Transportation remains a major barrier in receiving cancer treatment in Canada. The situation is especially alarming for those living in rural areas and in the light of COVID pandemic, poses another risk in the long list of health challenges to patients with pre-existing conditions. In this dissertation we set out find a solution to this problem by providing a framework for a personalized healthcare transportation system tailored to the needs of this population. A three-step approach is proposed. First, a review of literature and initiatives employed by global transportation providers is conducted to identify major methods used for healthcare industry. Second, a transportation strategy is proposed, and key performance indicators identified through analysis of data and interviews with industry best practices in order to determine key aspects of such operations having the most impact on the overall service level. Finally, a discrete event simulation is provided and tested through various scenarios to understand how such operations would behave in real life and how they react as the environment evolves through time. A case study of a major nonprofit organization for whom this strategy was originally outlined is provided for further context. In the end, the key findings from this research are formulated as a decision-making tool for future guidelines in managing similar operations. Keywords: Transportation; Strategy; Simulation; Healthcare; Ride Sharing; Breast Cance

Genetic and Chemical Modifiers of EGFR Dependence in Non-Small Cell Lung Cancer

The term `oncogene addiction' has been used to describe the phenomenon whereby tumor cells exhibit singular reliance on an oncogene or oncogenic pathway for their survival, despite the accumulation of multiple genetic lesions. In non-small cell lung cancer (NSCLC), this principle is perhaps best exemplified with the finding that epidermal growth factor receptor (EGFR) mutations predict response to EGFR-targeted therapies and thus represent a dependency in the subset of tumors harboring these alterations. Yet while EGFR-mutant tumors often respond dramatically to EGFR inhibition, nearly 30% of cases are refractory to therapy at the outset, and all responsive patients ultimately develop resistance to therapy. A deeper understanding of the genetic underpinnings of EGFR dependence, and of the mechanisms by which EGFR-mutant cells can overcome addiction to EGFR, may improve clinical outcomes

Corticosteroids Administration Following COVID-19-induced Acute Respiratory Distress Syndrome. Is it harmful or Life-saving?

Until now, April 22, 2020, Covid-19 has been confirmed in 2471136 patients and 203 countries and territories with mortality rate over 169000 patients. Right now, there is no definite cure for it and developing treatments including vaccines and antiviral compounds are under evaluations for efficacy. Covid-19 infection can be mild, severe, or even critical. The symptoms may range from fever (the most common symptom), chills, fatigue and cough to decreased arterial oxygen saturation, changes in respiratory rate and dyspnea. The dyspnea in critically patients is more severe. In severe cases, respiratory failure, acute respiratory distress syndrome (ARDS) and septic shock have been reported. Septic shock is also associated with hypoxia and acidosis. ARDS is the most important cause of death in this group of patients. This feature of the disease may be caused by various factors, including inflammatory mediators and cytokine storm. The computed tomography (CT) imaging findings have shown that the lung with ARDS has a ground-glass appearance, in which white fluid-filled patches are seen inside the lung. The fluid inside these patches has a jelly state. Pathological samples obtained from lung tissue also indicate pulmonary damage, obvious destruction of pneumocytes and formation of a hyaluronan membrane, which more emphasized on ARDS occurrence. Cytokine storm caused by Covid-19 infection is a severe immune response. The occurrence of cytokine storm can lead to severe tissue damages. Pre-inflammatory factors are involved in this process and one of them is interleukin 6 (IL-6) which affects different cells. IL-6 performs various functions such as regulating body temperature, increasing the production of acute phase protein and differentiation of B cells. On the other hand, the production of interleukin 1 (IL-1) as an inflammatory mediator will be increased during cytokine storm, as well. IL-1 can cause fever and stimulating the production of hyaluronan which has been seen in fibrosis. Based on studies on SARS-CoV, rapid spread and proliferation of the virus as a result of delayed interferon-1 production and subsequent rapid accumulation of macrophages and monocytes may also be involved in tissue destructions and a similar mechanism might be seen in Covid-19 infection. When there is no proper immune system response, the virus causes extensive tissue damages, especially to organs where ACE2 is most commonly seen, such as the lungs. Therefore, since the lungs are damaged, efforts should be focused on suppressing the inflammation, managing the symptoms and theoretically any compounds that may help this inflammation subside could play an important role in reducing the incidence of ARDS and consequently the mortality rate. The use of corticosteroids in different phases of ARDS has been inconsistent with conflicting results. Corticosteroids exert their anti-inflammatory effects by regulating the signaling pathways on the membrane and inside the cells, stopping pre-inflammatory gene-related processes (genes responsible for producing pre-inflammatory factors). Furthermore, they are able to increase the production of anti-inflammatory mediators such as interleukin 10 (IL-10). Corticosteroids have been investigated in some clinical protocols for evaluation of their effectiveness in reducing inflammatory responses and cytokine storm. According to the guideline of World Health Organization (WHO), systemic corticosteroids should not be routinely used in viral pneumonia except in clinical trials. However, WHO has recommended that these compounds can be used in exacerbations of asthma and COPD, and septic shock, considering each patient's condition and assessing the benefits and risks. This guideline further states that the use of corticosteroids in similar conditions such as influenza may lead to secondary super infections and increase mortality rate. But in another study on SARS-CoV, the use of corticosteroids was associated with improvement in time to survival in severe patients and decrease in mortality rate. Delayed viral clearance is another concern. In a study on patients with MERS-CoV, the use of corticosteroids did not make a significant difference in mortality rate. However, its association with a delay in viral clearance from the lungs of patients was reported. Side effects are another limiting factors for use of corticosteroids in patients with Covid-19. A similar study in patients with SARS-CoV showed that use of higher doses of corticosteroids in such conditions could cause a corticosteroid-induced diabetes, with 36.3% of patients experiencing such complication. The guideline of Surviving Sepsis Campaign for the management of patients with Covid-19 has recommended the use of corticosteroids under the following conditions: 1) in patients with Covid-19 who are suffering from septic shock, the use of corticosteroids (low-dose) are preferred over not using it. The guideline notes that there is no difference in mortality rate and side effects. However, there is weak recommendation that using corticosteroids in these conditions can reduce the time of resolution of shock and ICU and hospital length of staying; 2) In cytokine storm, if the patient has not yet developed ARDS, corticosteroids are recommended in ways other than routine procedures, and if ARDS occurred, the use of these compounds is recommended over not using them. Lesser need of oxygen, improved radiographic findings and reduced length of staying in ICU and hospital are some of the advantages that this guideline has referred to. However, there is just a week recommendation over the use of these compounds in this guideline. Based on what has been discussed, it could be concluded that the use of corticosteroids in the current situation should be limited, since there are no significant benefits over their effectiveness. On the other hand, there is a risk in prolongation of viral clearance and secondary infections and mortality rate. The use of these compounds should be limited to clinical trials to further evaluate their effectiveness in this new found disease. The clinical conditions of patients should be carefully evaluated throughout the studies and close monitoring should be performed while discontinuing these drugs

Effect of vitamin C on coagulation factors and endothelium function in patients with sepsis

Objective: Sepsis is one of the leading causes of mortality in intensive care unit. Despite advances in its management, its mortality rate remains high. Recently, high dose of vitamin C in sepsis treatment has attracted the attention of researchers. In the current study, the impacts of 25 mg/kg of vitamin C every 6 hours as a bolus for 3 days were assessed in septic patients in intensive care unit (ICU). Methods: This was a prospective cohort study that was performed on adult patients with diagnosis of sepsis. Patients were assigned to control group (administration of placebo) or intervention group, i.e., those receiving a 25 mg/kg dose of vitamin C every 6 hours as a bolus for 3 days. Clinical data were recorded before and after the experiment. Also, plasma levels of antithrombin III, syndecan-1, fibrin degradation product (FDP), D-dimer, and C-reactive protein (CRP) were measured at 0, 24, 48, and 72 hours. Results: In septic patients receiving vitamin C, a significant upregulation of antithrombin III and significant decreases in the levels of syndecan-1 (at 48 hours; P-value=0.046 and at 72 hours; P-value=0.007), D-dimer and CRP were observed compared to the control. Reductions in sequential organ failure assessment (SOFA) score, in-hospital mortality, and ICU length of stay were seen in septic patients receiving vitamin C. Conclusion: Prescribing high dose of intravenous vitamin C can reduce the mortality of sepsis patients and reduce the length of stay in the ICU

Human βhsp90 as adjuvant in HCV Recombinant vaccine

There are more than 350 million individuals with hepatitis C in the world. One of the important problems in vaccine project is development of effective and suitable adjuvant in human vaccines. At present research we applied human βHsp90 protein as an adjuvant in recombinant HCV vaccine design. The thermal vector of pGP1-2 was used for human heat shock protein 90 expression. This protein injected to BalbC mice as an adjuvant together with recombinant protein of HCV core. The combination of these proteins was used and we evaluated the humoral and cellular immunity and the cytokine secretion of inguinal and popliteal lymph nodes lymphocytes were analyzed in vitro and ex vivo conditions. So the combination of Core protein together with hsp90 induced total IgG and IgG2a secretion. The spleen lymphocytes proliferation were increased equal to serum IgG2a level that was constant in second time bleeding with significant different to complexes with freund’s adjuvant. At first IL-4 and IL-5 cytokines were increased, after one week it decreased. Production of IL-4 showed there was no hypersensitivity reaction after vaccine injection

Genome size, morphological and palynological variations, and heterostyly in some species of the genus Linum L. (Linaceae) in Iran

Heterostyly is the occurrence of flowers with different sexual organ arrangements in different plants of the same species. This floral polymorphism occurs in four sections of genus Linum. The present study compares the morphological, palynologycal and genome size (C-value content) characteristics in the long-styled and short-styled plants in three Linum species, that is, Linum austriacum L., Linum album Ky.ex Boiss. and L. glaucum Boiss. & Nöe . 15 qualitative and quantitative morphological characters from both vegetative and reproductive organs of these plants were studied. A higher mean value of the plant height, size of the basal leaves width, flower leaves width, calyx length, sepal length and petal length occurred in the long-styled plants, while the mean value of branch number, basal leaves length, flower leaves length, calyx width, pedicel length and sepal length was higher in the short-styled plant populations. T-test analysis of morphological characters showed significant difference (p<0.05) for some of the characters studied. Principal coordinate analysis (PCoA) plot of long-styled and short-styled plant populations based on all morphological characters also separated these two kinds of plants in the three species studied. The pollen obtained from the mature buds was prepared for light microscopy (LM) and scanning electron microscopy (SEM). The polar and equatorial views of the pollen grains were similar in the long-styled (Ls) and short-styled (Ss) plants but the aperture shape differed in these populations. C-values obtained by flow cytometry, differed in the long-styled and short- styled plants of the species studied. The analysis of variance (ANOVA) test performed among the three Linum species showed a significant difference in 2C-value content. Positive significant correlation was observed between 2C-value and northern distribution of the Linum species studied, while a negative significant correlation occurred with eastern distribution.Key words: Heterostyly, Linum, morphology, palynology, genome size

Effect of Ephedrine on Pain and Hemodynamic Status on Injection of Propofol

Background: Propofol is one of the drugs most commonly used during induction of anesthesia. The induction dose of propofol can lead to hemodynamic changes such as hypotension and bradycardia. Pain on injection is another side effect of propofol. The purpose of this study was to evaluate the effect of two different doses of ephedrine on hemodynamic status and pain on injection of propofol compared to lidocaine and placebo.Methods: In the present study, 100 patients were enrolled. A 22 gauge cannula was inserted into the veins on the non-dominant hand of all patients. The patients were randomly allocated to 4 groups and 10 ml/kg of saline was administered over 10 minutes from each of the cannulas. Then, patients received either of these pretreatments: 2 ml of Saline (group S); 2 ml lidocaine 2% (40 mg) (group L); Ephedrine (30 ug/kg) (group E1); or Ephedrine (70 ug/kg) (group E2). After 30 seconds all patients were administered 2.5 mg/kg of propofol with a rate of 1 ml per second. The patients were asked to give a score from 0 to 10 (0 = no pain and 10 = most severe pain) every 5 seconds until loss of consciousness. Systolic and diastolic pressures and heart rate were recorded before induction of anesthesia, before intubation, and 1, 3, and 5 minutes after intubation.Results: Systolic, diastolic, and mean arterial pressure and heart rate following induction in E1 and E2 groups were higher than S and L groups (P < 0.001). There were no differences in systolic, diastolic, and mean arterial pressure and heart rate 1, 3, and 5 minutes after intubation between groups. Lidocaine and both doses of ephedrine reduced pain on injection of propofol similarly.Conclusions: Lidocaine and high and low doses of ephedrine reduce the intensity of pain on injection of propofol. Small doses of ephedrine attenuate blood pressure and heart rate reduction after induction of anesthesia with propofol