FUE Gp 21 Newsletter (DEDIC) 2021

Volume 1 Issue 1 November 2021 Group 21 DEDIC Drug Expert DIC “Guidelines for sickle cell disease 2021 update” p.1 “FDA Announcement” p.5 “Egyptian Healthcare Update 2021” p.7 “Relation Between Covid 19 And Vitamin D” p.9 “How to Be A Professional Pharmacist?” p.13 Under The Supervision Of: 51 South 90 St. - New Cairo Dr. Yasser Omar Mossad 01090667335 Editors: http://www.dedic.health 20173044 Islam Ismail 20171206 Khaled Ahmed 20173049 Khater Gomaa 20172684 Kholoud Khaled 20151687 Mai Ahmed

American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation The recommendations for hematopoietic stem-cell transplantation (HSCT) in patients with Sickle cell disease (SCD) are organized according to the principal SCD-related problems of concern, the patient's age, and the type 1 of transplantation being considered. The relevance of the patient's and family's preferences was emphasized throughout the discussion and recommendations. However, most of these suggestions are based on research with a low level of certainty. This lack of information emphasizes the significance of tailored patient care, which includes collaborative decision- making between the practitioner, the patient, and the patient's family. Furthermore, when it comes to transplantation, the balance of benefits and harms differs between children and adults, due to the increased risk of HSCT in adults with SCD and the potential gain in those with accumulated SCD-related comorbidities. As a result, it's crucial to account for patient and family preferences, as well as individual patient/family values and risk thresholds in the context of previous SCD experiences. Other evidence to inform decision criteria and considerations Because of a lack of knowledge about the risks and benefits of myeloablative vs nonmyeloablative or reduced-intensity conditioning (RIC) and alternative donor HSCT, the panel recognizes that there may be significant uncertainty or variability in how much people value the main outcomes of HSCT. Furthermore, there are no clear classification systems for determining whether a patient with SCD has severe disease or will experience specific SCD complications over the course of their life. As a result, accurately balancing a risk/benefit ratio of HSCT that takes into account an individual patient's lifetime experience can be difficult. However, it is assumed that not having SCD is preferable to having unpredictably debilitating complications that worsen with age. HSCT-specific harms, on the other hand, have been documented in several studies. Graft-versus-host disease (GVHD), infections, graft failure, infertility, vital organ injury, and death are among the complications. The methodologic considerations below go over these transplant-related risks in detail. Because these risks are not negligible, they must be weighed against the potential benefits, which include a cure for SCD. Because the extent and duration of HSCT benefit are unknown due to incomplete long- term follow-up data post-HSCT, the panel was unable to assess how significant the desired anticipated effects may be. Furthermore, the cost of transplantation versus standard of care has not been determined. Although the costs of HSCT are high in the short term, they could be offset by fewer hospitalizations, fewer transfusions, and the elimination of expensive SCD-specific medications if the procedure is successful. Furthermore, the potential gains from improved affected individuals' ability to attend school and work could help offset the long-term costs of HSCT. Because of concerns about patient trust, insufficient donor availability, preexisting comorbidities, and poor access to care, including lack of access to a transplantation facility, the feasibility of

HSCT is also complicated. In more recent years, feasibility of HSCT has substantially increased because of improvements in the process of donor-recipient HLA match requirements and less toxic conditioning regimens that are more suitable for patients with preexisting comorbidities. Because of improvements in the process of donor- recipient HLA match requirements and less toxic conditioning regimens that are more suitable for patients with preexisting comorbidities, the feasibility of HSCT has significantly increased in recent years. 2 Explanations and other considerations These recommendations take into account resource use, acceptability, feasibility, and health equity implications. When developing these recommendations, the American Society of Hematology (ASH) guideline panel acknowledged the variability in patient and provider knowledge, as well as their perceptions of harms vs benefits and other patient-important outcomes. The cost effectiveness of most interventions could not be assessed due to a lack of relevant data. Recommendations Recommendation 1. The ASH guideline panel suggests HLA-matched related HSCT rather than standard of care (hydroxyurea (HU)/transfusion) in patients with SCD who have experienced an overt stroke or have an abnormal transcranial Doppler ultrasound (TCD) (conditional recommendation. very low certainty in the evidence ⨁○○○). Remarks: • Consideration for transplantation should occur in all patients with neurologic injury who have a matched related sibling donor. • When considering transplantation for neurologic injury, children younger than age 16 years who receive matched sibling donor (MSD) HSCT have better outcomes than those older than age 16 years. Recommendation 2. For patients with frequent pain, the ASH guideline panel suggests using related matched allogeneic transplantation rather than standard of care (conditional recommendation, very low certainty in the evidence about effects ⨁○○○). Remark: • Consideration for transplantation should be given to patients who do not respond or have an inadequate response to standard of care, such as HU, new targeted therapies, or chronic transfusion therapies.

Recommendation 3. For patients with recurrent episodes of ACS, the ASH guideline panel suggests using matched related allogeneic transplantation over standard of care (conditional recommendation, very low certainty in the evidence about effects ⨁○○○). Remark: 3 • Consideration for transplantation should be given to patients who continue to have recurrent ACS despite optimal standard of care (eg, HU, L-glutamine, crizanlizumab, and chronic transfusion therapy). Recommendation 4. For patients with SCD with an indication for HSCT who lack an MSD, the ASH guideline panel suggests using transplants from alternative donors in the context of a clinical trial (conditional recommendation, very low certainty in the evidence about effects ⨁○○○). Remark: • Alternative donor transplantation has the potential to improve or resolve disease manifestations in patients with severe SCD. The risks related to transplantation complications should be balanced with benefits derived from successful transplantation. Recommendation 5. For allogeneic HSCT, the ASH guideline panel suggests using either total-body irradiation (TBI) ≤400 cGy or chemotherapy-based conditioning regimens (conditional recommendation, very low certainty in the evidence about effects ⨁○○○). Recommendation 6a. For children with SCD who have an indication for allogeneic HSCT and an MSD, the ASH guideline panel suggests using myeloablative conditioning over RIC that contains melphalan/fludarabine regimens (conditional recommendation, very low certainty in the evidence about effects ⨁○○○). Recommendation 6b. For adults with SCD who have an indication for allogeneic HSCT and an MSD, the ASH guideline panel suggests nonmyeloablative conditioning over RIC that contains melphalan/fludarabine regimens (conditional recommendation, very low certainty in the evidence about effects ⨁○○○).

Recommendation 7. In patients with an indication eligible for HSCT, the ASH guideline panel suggests using allogeneic transplantation at an earlier age rather than an older age (conditional recommendation, low certainty in the evidence about effects ⨁⨁○○). Remarks: 4 • Recommendations could not be made if an MSD was not available because of the paucity of available data. • The impact of age on HSCT outcome may also be affected by the conditioning regimen used. Recommendation 8. The ASH guideline panel suggests the use of HLA-identical sibling cord blood when available (and associated with an adequate cord blood cell dose and good viability) over bone marrow (BM) (conditional recommendation, very low certainty in the evidence about effects ⨁○○○). ⨁⨁⨁⨁ High certainty in the evidence about effects ⨁⨁⨁○ Moderate certainty in the evidence about effects ⨁⨁○○ Low certainty in the evidence about effects ⨁○○○ Very low certainty in the evidence about effects Reference: https://ashpublications.org/bloodadvances/article/5/18/3668/476988/American-Society-of- Hematology-2021-guidelines-for

FDA Announcement for 2021 5 The U.S. Food and Drug Administration approved the first interchangeable biosimilar product to treat certain inflammatory diseases. Cyltezo (adalimumab-adbm), originally approved in August 2017, is both biosimilar to, and interchangeable with (may be substituted for), its reference product Humira (adalimumab) for Cyltezo’s approved uses. Cyltezo is the second interchangeable biosimilar product approved by the agency and the first interchangeable monoclonal antibody. Once on the market, approved biosimilar and interchangeable biosimilar products can Monoclonal Antibody play a role in facilitating access to treatments for many serious health conditions. “The biosimilar and interchangeable approval pathway was created to help increase access to treatment options for patients with serious medical conditions,” said Acting FDA Commissioner Janet Woodcock, M.D. “We continue to be steadfast in our commitment to provide patients with alternative high-quality, affordable medications that are proven to be safe and effective.” Cyltezo is approved for the following indications in adult patients: • Moderately to severely active rheumatoid arthritis. • Active psoriatic arthritis. • Active ankylosing spondylitis (an arthritis that affects the spine). • Moderately to severely active Crohn’s disease. • Moderately to severely active ulcerative colitis; and • Moderate to severe chronic plaque psoriasis. • Moderately to severely active polyarticular juvenile idiopathic arthritis in patients two years of age and older • Pediatric patients six years of age or older with Crohn’s disease. Biological products, generally derived from a living organism, include medications for treating many serious illnesses and chronic health conditions. A biosimilar is a biological product that is highly similar to, and has no clinically meaningful differences from, a biological product already approved by the FDA (also called the reference product). Patients can expect the same safety and

effectiveness from the biosimilar as they can from the reference product. Interchangeable biosimilar products can be expected to produce the same 6 clinical result as the reference product in any given patient and, for biological products administered more than once to an individual, the risk in terms of safety or diminished efficacy of switching between the two products is not greater than the risk of using the reference product without such switching. An interchangeable biosimilar product may be substituted for the reference product without the prescriber having to change the prescription. The substitution may occur at the pharmacy, subject to state pharmacy (laws which vary by state), a practice commonly called “pharmacy-level substitution” — similar to how generic drugs are substituted for brand name drugs. Biosimilar and interchangeable biosimilar products may cost less than the brand-name medicine. Cyltezo, offered in a single-dose, pre-filled glass syringe (40 mg/0.8 mL, 20 mg/0.4 mL), is administered subcutaneously (under the skin) under the guidance of a physician. The most serious known side effects with Cyltezo are infections and malignancies (cancers). The most common expected adverse reactions are upper respiratory and sinus infections, injection site reactions, headache and rash. Like Humira, the labeling for Cyltezo contains a BOXED WARNING to alert health care professionals and patients about an increased risk of serious infections that may lead to hospitalization or death. The boxed warning also notes that lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, including adalimumab products. The drug must be dispensed with a patient Medication Guide that describes important information about its uses and risks. The FDA granted approval of Cyltezo to Boehringer Ingelheim on October 15, 2021. Cyltezo® is not commercially available in the U.S. at this time, but its commercial license will begin on July 1, 2023. References: - https://www.fda.gov/news-events/press-announcements/fda-approves-cyltezo-first-interchangeable- biosimilar-humira - https://www.boehringer-ingelheim.us/press-release/us-fda-approves-cyltezo-adalimumab-adbm-first- interchangeable-biosimilar-humira

Egyptian Healthcare Update 2021 Additional 260 Million LE allocated to healthcare in Egypt in FY2020/2021 7 due to COVID-19 CAIRO - 23 May 2021: Dr. Hala El-Said, Minister of Planning and Economic Development, approved raising allocations to the healthcare sector by LE260 million in current fiscal year 2020/2021 to increase hospitals' capacity of intensive care beds to 1,000 and introduce further 500 ventilators. It is noted that the healthcare's share in the FY2020/2021 budget was initially worth LE93.5 billion, while that of the upcoming fiscal year's budget is planned to be LE108.8 billion, according to the Ministry of Finance in April. The minister explained that there is a growth in public investments directed to the projects of the Ministry of Health in the next fiscal year 2021/2022, for them to amount to LE 47.5 billion, an increase of 205% compared to FY20/2021, including projects of the Decent Life presidential initiative. El-Said explained that the most important programs and initiatives of the health sector in the next fiscal year are to provide the necessary funds to enter service hospitals and to accelerate the rates of implementation of health facilities under construction and development to quickly enter service and start to benefit citizens from them. \"It is intended to complete 23 hospitals, the completion rate of which is currently 77%, as well as the initiative of the National Project for Self-Sufficiency in Plasma Derivatives, which aims to establish 20 plasma collection centers and a central strategic store,\" El-Said explained.

El-Said added that the health sector initiatives within the 2021/2022 plan include developing critical and urgent care departments in hospitals, expanding the availability of intensive care beds, as well as implementing the objectives of the “Women's Health” initiative to provide the best service for breast cancer patients by raising the efficiency of medical staff and developing the infrastructure to ensure treatment quality. 8 Dr. Hala El-Said indicated that the health sector initiatives include enhancing the capacity of health facilities to provide medical services in a distinguished manner in light of confronting the Coronavirus, increasing coverage rates in university hospitals at the governorate level, and enabling them, and creating an electronic health record for all visitors. Regarding the plan to develop the Egyptian family during FY2021/2022, El-Said explained that it aims to improve population characteristics, control population growth, and work to raise the efficiency of 125 integrated hospitals. Moreover, the plan aims to operate 200 sewing workshops attached to Al- Takamol hospitals, providing and making available family planning methods, operating 20 family development centers, in addition to financing 350,000 micro-projects, and automating family planning services and linking databases together. Reference: https://www.egypttoday.com/Article/3/104198/Additional-LE260M-allocated-to-healthcare-in-Egypt-in- FY2020-2021

Relation Between Covid 19 And Vitamin D The COVID-19 epidemic has triggered a global public health emergency. Little is known about the infection's protective factors. As a result, preventative health interventions to lower the risk of infection, progression, and severity are critical. This review discussed 9 the possible roles of vitamin D in reducing the risk of COVID-19 and severity. Moreover, this study determined the correlation of vitamin D levels with COVID-19 cases and deaths in 20 European countries as of 20 May 2020. In European countries, there was a significant negative connection (p = 0.033) between mean vitamin D levels and COVID-19 cases per million population. However, there was no substantial link between vitamin D and COVID-19 mortality in these countries. Some retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find the correlation when confounding variables are adjusted. Several studies demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections and pneumonia. These include direct inhibition with viral replication or with anti-inflammatory or immunomodulatory ways. Vitamin D supplementation was found to be both safe and efficacious against acute respiratory tract infections in the meta-analysis. As a result, persons who are at a higher risk of vitamin D deficiency during this worldwide pandemic may consider taking vitamin D supplements to keep their levels at the recommended range (75–125 nmol/L). In conclusion, there is not enough evidence on the association between vitamin D levels and COVID-19 severity and mortality. Therefore, randomized control trials and cohort studies are necessary to test this hypothesis. A recent data reported the antiviral effects of vitamin D, which can hinder viral replication directly, and also be effective in an anti-inflammatory and immunomodulatory way. SARS-CoV-2 appears to predominantly exploit immune evasion during infection, Vitamin D's putative involvement in preventing acute respiratory tract infections was also examined in this review. Furthermore, the available studies that determined the role of vitamin D in COVID-19 have been discussed. PubMed, Google Scholar, Web of Science, Scopus, Cochrane Central Register of Controlled Trials.

Vitamin D and mechanisms to decrease viral infections Recent reviews have revealed some of the mechanisms by which vitamin D reduces the risk of microbial infections. Vitamin D reduces the risk of viral infection and mortality through a variety of ways. Vitamin D may play a role in reducing the incidence of COVID-19 infections and death, according to a recent review. These comprise 10 maintaining of cell junctions, and gap junctions, increasing cellular immunity by decreasing the cytokine storm with influence on interferon γ and tumor necrosis factor α and regulating adaptive immunity through inhibiting T helper cell type 1 responses and stimulating of T cells induction . Vitamin D supplementation was also found to enhance CD4+ T cell count in HIV infection. One of the major manifestations of severe SARS-CoV-2 infection is lymphopenia . In both the mouse models and in human cell lines, vitamin D exerted activity in lung tissue and played protective effects on experimental interstitial pneumonitis . Several in vitro investigations have shown that vitamin D plays an important role in local \"respiratory homeostasis,\" either by increasing the production of antimicrobial peptides or by directly interfering with respiratory virus proliferation. As a result, vitamin D deficiency may have a role in ARDS and heart failure, which are symptoms seen in COVID-19 patients who are critically unwell. As a result, vitamin D deficiency increases the renin-angiotensin system (RAS), which can lead to CVD and a reduction in lung function. People with such comorbidities account for a higher percentage of severe ill cases in COVID-19 . Although, many studies supported the immunomodulatory characteristics of vitamin D and its significant role in the maintenance of immune homeostasis; well-designed randomized controlled trials are required to elucidate the plausible role of vitamin D in protective immune responses against respiratory microbes and in preventing various types of acute respiratory tract infections.

The relevance of vitamin D to COVID-19 Yet, it is important to fully elucidate the virulence mechanisms of COVID-19, several cellular mechanisms including Papain-like protease (PLpro)-mediated replication, dipeptidyl peptidase-4 receptor (DPP-4/CD26) binding, disruption of M- protein mediated type-1 IFN induction and MDA5 and RIG-I host-recognition evasion 11 have been recognized in the closely-related COVID-MERS virus . Human DPP-4/CD26 has been shown to interact with the S1 domain of the COVID-19 spike glycoprotein, implying that it could be a significant virulence factor in Covid-19 infection.. There is also an indication that maintaining of vitamin D may reduce some of the unfavorable downstream Correlation of vitamin D levels with COVID-19 cases and deaths in the European population The number of COVID-19 cases and deaths per one million of the population in 20 European nations (Table 1) were taken from the worldwide coronavirus pandemic data portal at https://www.worldometers.info/coronavirus/ for 20 May 2020 (all countries after peak). The data for these 20 countries' mean serum vitamin D concentrations came from a prior study. In Pearson's correlation coefficient test, a significant correlation (r = -0.477, p = 0.033) was observed between mean concentrations of vitamin D and number of COVID-19 cases/1 M population (Table 1). While the relationship between mean vitamin D concentrations and the number of COVID-19 deaths/1 M population was not significant (r = -0.357, p = 0.123). In the present analysis, the negative correlation between vitamin D levels and COVID-19 cases is stronger than that (r = -0.444, p = 0.050) observed on 8 April 2018 (most countries before the peak) in a previous analysis . However, the current study's negative link of vitamin D with COVID-19 mortality appears to be less substantial than the prior study's (Table 1). There is a good chance that a cause–effect relationship exists. Differences in age distribution, demographic makeup, pre-existing medical disorders, and drug usage variations could all be confounding variables that impact the association.

Countries Mean 8 April 2020 20 May 2020 vitamin D Iceland (nmol/L) Cases/1 M Death/1 M Cases/1 M Death/1 M population population population population 12Norway 57 65 4736 18 5287 29 Sweden 73.3 Finland 67.7 1123 19 1530 43 Denmark 65 UK 47.4 834 68 3124 380 Ireland 56.4 Netherlands 59.5 449 7 1163 55 Belgium 49.3 Germany 50.1 933 38 1920 97 France 60 Switzerland 46 895 105 3690 526 Italy 50 Spain 42.5 1230 48 4932 319 Estonia 51 Czech Republic 62.5 1199 131 2595 336 Slovakia 81.5 Hungary 60.6 2019 193 4818 790 Turkey 51.8 Portugal 39 1309 25 2131 98 Average 56.8 ± 10.6 Correlation (r) 1671 167 2782 431 p-value 2686 103 3548 219 Table 1 2306 292 3750 535 3137 314 5980 596 893 18 1359 48 488 9 773 28 125 0.4 709 51 93 6 372 48 453 10 1810 50 1289 37 2101 115 1393.4 ± 1129.9 80.4 ± 94.6 2718.7 ± 1632.3 239.7 ± 233.3 −0.444 −0.438 −0.477 −0.357 0.050 0.053 0.033 0.123 References: https://www.sciencedirect.com/science/article/pii/S1876034120305311 https://clinicalmolecularallergy.biomedcentral.com/articles/10.1186/s12948-020-00139-0

How to Be A Professional Pharmacist??? First of all we should talk about professionalism and should know its real meaning to be aware of what we should do or what will be our next steps we will have to take in order to use this professionalism in our career which is Pharmacy. 13 So, professionalism in some meanings that defined by MERRIAM WEBSTAR is it is a set of attitudes and behaviors believed to be appropriate to a particular occupation When we consider professionalism in the pharmacy career or any career by the way, we should look to the ethical side which should be present in our life totally in everything. As professionalism and ethics are on the same way, support each other and are so important, so by applying this part and shed the light on it, so we should as professional pharmacists have some basic principles of medical ethics: 1. Respect for patient autonomy. 2. Not inflicting harm on patient. 3. A positive duty to contribute to the welfare of patients 4. Justice or face treatment of patient. - Pharmacist should face ethics dilemmas too. - Pharmacist shouldn’t think only or work for money as it’s the most important thing by any means or above patient’s interest.

- Agree on inappropriate prescribing. When you work to be a professional pharmacist, you should know that Someone who is professional is competent in their discipline, takes pride in their work and keeps up to date with what they need to know. Pharmacist should be patient centered too, as Someone who is patient 14 centered; always puts the interests of their patients and especially their safety first, listens to their patients and is responsive to their needs and preferences. They are: 1. Setting education and training standard 2. Revising standards of professional practice 3. Informing future developments on continuing fitness to practice 4. Considering how to respond to complaints As this qualifications, attitudes, and behavior you take by working on yourself will make you different and unique in your profession that put you in the category of the professional pharmacists. We can say a Pharmacist is professional or describe him as a star when this criterion is applied to him too: Pharmacist is a care giver, decision maker, entrepreneur, researcher, communicator, teacher, have good memory, Ability to accurately interpret prescriptions, Is Detail-oriented, Is a businessperson, Serves as a front-line educator, Knowledgeable, patience and, lifelong learner; who never get bored from gaining information and searching for it to put any new knowledge in his agenda to be comprehensive with the greatest number of information and knowledge . In addition to the previous things, Professional pharmacist should have some: - Honesty and Integrity - Altruism - Professional presence - Professional stewardship

- Dedication and commitment to excellence - Professional competence - Personal values - Extracurricular activity 15 - Communication - Empathy Pharmacist should be professional in his communication with his patients by: showing respect, compassion, empathy, by being helpful, active listener, understanding, by taking in consideration about their privacy and patient's perspective, he should remember everything about their medical history and not to provide misinformation. To be professional with his peers is an important thing too to succeed, Pharmacist should: -Be supportive. -Help problem solve (Bounce ideas off each other). -Share experience. AND ALWAYS REMEMBER References: 1. https://www.mvorganizing.org/what-qualities-should-a-pharmacist-have/ 2. General Pharmaceutical Council. Patient-centred professionalism in pharmacy: a review of the standards of conduct, ethics and performance, April 2015 3. Health and Care Professions Council. Professionalism in healthcare professionals research report, 2014 4. Goleman D. Emotional Intelligence: why it can matter more than IQ, 1996



For Inquiries feel free to cotact us through: 01090667335 dedic.health http://www.dedic.health