Multidisciplinary approach for improvement of immunotherapy utilization in solid tumors with H MSI /dMMR –An action plan from a single oncology center

Immune checkpoint inhibitors such as nivolumab and pembrolizumab are approved by Food and Drug Administration for patients diagnosed with metastatic solid tumors with high microsatellite instability (MSI) or mismatch repair deficient (dMMR). The prognosis of these patients is generally poor, that is why it is very essential to identify the targeted patients who can benefit from immunotherapy. Pembrolizumab is approved in our institution for this indication. In order to ensure proper utilization of available resources, we decided to make a pilot retrospective review to evaluate pembrolizumab utilization, to identify the problems we are facing then to set an action plan through multidisciplinary approach. Based on the results we set recommendations. This paper is innovative and the first in kind. It could be used as guidance for other centers using immunotherapy and could be applied for other drugs as well to ensure best practice, patient safety and maximize utilization of resources.

Effective Pharmacist led interventional strategies to improve outcomes in hypertensive patients: a narrative review

The role of pharmacist intervention as a cost-effective alternative to physician in disease management is increasingly been recognized. Studies have demonstrated that pharmaceutical care can improve drug therapy as well as patient satisfaction in chronic health conditions including cardiovascular diseases. This study is aimed to review and outline a comprehensive pharmaceutical care plan from the randomized controlled trials previously conducted to assess the impact of pharmacist-managed care on disease outcomes in hypertensive patients. Compared with usual care, the pharmaceutical intervention involved patient evaluation, patient education and counselling, medication review and management, patient monitoring and follow-up, and feedback to the primary physician as major strategies.

The Economic Burden of Post-transplant Events in Renal Transplant Recipients

Kidney transplantation (KT) is considered the optimum treatment choice for end stage renal disease (ESRD) both from a clinical and economic perspective. The incidence of acute rejection (AR) from KD could differ according to different patient and donor characteristic, as well as, the type of immunosuppressant agent allocated. Thus, it is crucial to carefully examine the costs associated with the type of immunosuppressant agents as they directly affect the clinical outcomes of recipients. Tacrolimus which is one of the Calcineurin inhibitors (CI) have proven a huge success in kidney transplantation and are considered the cornerstone therapy post transplantation. Since the expiry of its patent in 2008, generic versions have been introduced in the market. While it has been widely accepted in the medical community to switch from brand to generic drug products provided that they have proven therapeutic bioequivalence, the switch has been documents to be sensitive case with particular products which are characterized by a narrow therapeutic index (NTI). Their concern is that most of the bioequivalence studies are conducted in health volunteers’ whom do not suffer any comorbidity which is not the case in real life settings. González et al., 2017 note that this conversion affected its dose and blood levels which lead to the occurrence of acute rejection episodes due to under immunosuppression and report that infectious adverse events occurred as a result of over immunosuppression. Another important observation that there was a post serum creatinine increase after the formulation conversion and also patients experienced greater incidence of magnesium wasting, and more episodes of rejection which led to greater institutional costs of care. These findings highlight that cost containment policies need to be revisited especially with NTI drugs as their extra monitoring costs might actually off-set the savings of the generic product in the short term.

A Cross Sectional Observational Study to Assess Pharmacists Perspective and General Health Wellbeing During COVID-19 Pandemic in Saudi Arabia

Introduction: COVID-19 pandemic impacted all countries negatively. Regulatory bodies in Saudi Arabia and worldwide set a firm policies and guidelines to protect their nationals and residents from the virus. Pharmacists play a major role in health care. This study aims to assess pharmacists prospective and general health wellbeing during COVID-19 pandemic in Saudi Arabia. Methods: We conducted a cross sectional observational study using a quantitative survey-based methodology. Data was collected from May to July 2020. Results: We were able to enrol 381 pharmacists working in different practice settings as governmental hospitals, healthcare centers, private hospitals and community pharmacies. The acceptable knowledge level score is 13 (60%) that has been reached by about 37% of participants. Male and female had similar scores. Level of knowledge among regions was variable, southern region scored the least with a mean score of 12.89 ± 3.91 and eastern region scored the highest level with a mean score of 15.07 ± 2.86. There was a significant correlation between knowledge level, region of residency and level of experience. The maximum total awareness score was 7, the mean score was 5.18 ± 1.65. There was a statistically significant correlation between awareness level and the region of residency variable. The general health questions section included 9 questions. The minimum score was 9, the maximum was 36 and the mean score was 17.51 ± 7.34. The higher the score indicate the worsening of the general health. There is a strong correlation between gender, experience and the general health wellbeing. Men had better general health compared to women p<0.001 and participants with range of experience 6-10 years had a lower level of general health. Conclusion: COVID-19 still has a negative impact worldwide. Maintaining awareness and education is essential to keep the protective measures as possible. In addition, there is a need to address the impact of COVID-19 on pharmacist's mental health to act accordingly.

Pharmacotherapeutic Considerations in the Management of Hypertensive and Diabetic COVID-19 Patients

The COVID-19 disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 has emerged as a pandemic inflicting more than 229 million people over the globe. Preexisting illnesses including diabetes, hypertension, and cardiovascular diseases are known to increase the risk of developing severe disease course and mortality. Likewise, COVID-19 potentiates the risk of acute cardiovascular events, multiorgan damages and, poor glycemic control among the patients. Special pharmacotherapeutic considerations are, therefore, essential for optimal treatment of COVID-19 patients with chronic comorbidities. In this editorial, we have summarized and interpreted the current information and guidelines about the need for pharmacotherapy adjustment in COVID-19 patients with hypertension and type II diabetes. Diabetic and hypertensive patients with mild to moderate COVID-19 disease should be encouraged to continue their usual medications with frequent monitoring. However, the choice of antidiabetic drugs needs to be reviewed in severe diseases.

The impact of moderate combination exercise on HbA1c, IL-6, and TNF in type 2 diabetic and non-diabetic subjects: an interventional non-randomized clinical trial

Introduction: The main causes of worldwide increase in prevalence of type 2 diabetes are the daily consumption of excessive number of calories and sedentary lifestyle. Diabetes is usually accompanied by hypertension, lipid disorders and obesity that are considered as risk factors for developing diabetes. This study is designed to assess the benefit of a combined exercise programme (cardio “aerobic” and resistance) on HbA1c and the inflammatory markers (IL-6, and TNF) in type 2 diabetic (T2D) and non-diabetic (ND) subjects. Materials and methods: This is an interventional non randomized clinical trial conducted from 2016 to 2019 at exercise physiology laboratory at De Montfort University (DMU). Our target volunteers are T2D (HbA1c > 6.4), and ND (HbA1c < 5.8) with age group from 18-60 years old who are fit and able to do exercise. No restriction on weight. HbA1c, weight, BMI, waist and lung capacity were measured at baseline and at the 12th exercise session. In each exercise session the participant performed a combined exercise program consists of 30 min of resistance exercise followed by 20 min moderate cycling to be done twice a week for 6 weeks. Results: We enrolled 17 T2D intervention group 4 female and 13 male and 8 ND control group 5 female and 3 male. In both groups there was a significant reduction in HbA1c level after 6 weeks (P= 0.000). In T2D there were a significant weight reduction that decreased from (92.0± 4.3) to (90.0±4.5), (P< 0.001), BMI reduction that decreased from (30.8± 1.0) to (30.2± 0.9), (P< 0.001). In ND, the changes in weight reduction and BMI level were not significant. In T2D the changes in IL-6 level were only significant after the last exercise session. It was increased from 1.79±0.4 to 3.88±1.9 pg/ml (P=0.002), while it was not significant in ND group. In T2D and ND subjects, the changes in TNF level were insignificant. Conclusion: Development of combination exercise programs as a non-pharmacological intervention for diabetic and non-diabetic population are essential to decrease the prevalence of diabetes worldwide. In addition to conduction of public awareness events for proper implementation.

Fourth Pharmacoeconomics International Masterclass: Vital Initiative

The annual Pharmacoeconomics International Masterclass has been organized by Global Healthcare Activities Academy (GHAA) every year since 2017, to enrich the knowledge of healthcare professionals and provide them with the necessary tools to maximize the quality of the healthcare services provided around the world. ​ The topics discussed in the Masterclass were choosen to cover as many aspects as possible from different stakeholders whether they were healthcare practitioners, academics, pharmaceutical companies or policy makers. The masterclass is divided into four main session topics, each including more specific sub-topics. The main session topics are the novel values in health economics, the alternative access models for innovative treatment, the pharmaceutical pricing techniques and lastly, the role of academia in PE development. As the principles of pharmacoeconomics gain more appreciation and acceptance around the world, the Arabic world is starting to take steps towards the implementation of these principles, with countries starting to establish official HTA organization and publishing official guidelines. Taken these changes into account, defining “value” in an accurate, inclusive manner is vital to assure maximum benefit and cost-containment. More concepts regarding quality adjusted life years, novel values, gene replacement therapy values, managing entry agreements, reference and value based pricing were discussed. The Pharmacoeconomics International Masterclass is a vital and important element for the introduction and development of pharmacoeconomics principles in the Middle East. The benefit of the masterclass comes from the fact that year after year, more in-depth issues are discussed, and bigger challenges are tackled. From the introduction to pharmacoeconomics principles in the 1st masterclass to the discussion of novel values and optimizing the healthcare services provided, each year the topic is more relevant and more crucial for the application of health economics principles in the area. With two paper already published based on discussions and recommendations in the previous masterclasses, the 4th Pharmacoeconomics International Masterclass is expected to produce many fruitful insights and helpful recommendations.

Therapy Related Acute Myeloid Leukemia in Solid Tumors: Two Pediatric Case Reports and Review of the Literature

Introduction: Therapy-related acute myeloid leukemia is devastating late effects in solid tumors. The most frequent and lethal secondary malignancy is secondary acute myeloid leukemia t-AML. t-AML is a sequel of specific chemotherapeutic agents, specifically alkylating agents, and topoisomerase II inhibitors, commonly used in treating solid tumors. t-AML is relatively rare with a poor prognosis. Case reports: We are reporting two cases of t-AML. Case 1: A 13-year-old girl presented with left hand swelling in 2014. Biopsy confirmed the diagnosis as Ewing sarcoma. She started a chemotherapy regimen that contained alkylating agents and epipodophyllotoxins. In 2017, local recurrence occurred, and she received salvage chemotherapy (ifosfamide, carboplatin, and etoposide) followed by amputation of the left 4th finger. In 2020, she had a second local recurrence with unexplained prolonged neutropenia. Diagnosis of t-AML was confirmed by bone marrow aspiration. Case 2: A 5-years-old boy presented with an abdominal mass in July 2006. It was diagnosed as rhabdomyosarcoma and treated with alkylating agents. He showed a good response to the treatment initially. In September 2007, prolonged pancytopenia, neutropenia, and thrombocytopenia occurred. Diagnosis of t-AML was confirmed by bone marrow aspiration as it showed mild dysplastic, moderate marrow fibrosis. Conclusion: t-AML is of growing interest to the pediatric oncologist and requires further studies to develop pathways for leukemogenesis. We discussed two cases to highlight the importance of designing treatment regimens for solid tumors associated with t-AML.

Local experience for managing oncology services during COVID-19 pandemic in a tertiary care hospital in Saudi Arabia

The COVID-19 pandemic led to several critical challenges that impacted the healthcare system worldwide. Many guidelines have been developed internationally and nationally aiming to minimize the risk of infection and its sequential complications. Cancer patients on active treatment are at higher risk to get infected either due to the disease itself or the cancer treatment and other comorbid diseases. In this manuscript we share our local experience while delivering oncology services during the COVID-19 pandemic at Prince Sultan Military Medical City in Riyadh, Saudi Arabia.

Re-challenge with High Dose Methotrexate vs. Reduced Dose After Methotrexate Toxicity in Pediatric Osteosarcoma:Case Report

Introduction: Methotrexate (MTX), a classic antifolate, is one of the most widely used and well-studied anticancer agents. High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is one of the standard therapies for osteosarcoma. High-dose methotrexate (HDMTX) can exert significant toxicity and requires complex pharmacokinetic monitoring and leucovorin rescue. The side effect profile of MTX varies markedly according to the dose. Regimens containing MTX are classified as high, intermediate, or low-dose. High-dose methotrexate (HD-MTX; 12 g/m2) is a part of the golden standard therapy for pediatric osteosarcoma (OS). Risk factors associated with MTX toxicity in children with OS are not well defined. Case Presentation: We report here a case of pediatric osteosarcoma with nephrotoxicity associated with delayed MTX excretion who was successfully managed using supportive measures that encouraged us to re-challenge with a full dose of MTX then we reduced the dose to 50% to attain the final critical decision about continuation or changing the regimen of treatment for the patient. Our patient developed moderate renal complications during therapy that improved with supportive care, so we challenged with more cycles of a high dose MTX, but the patient developed serious renal complications. A reduced dose of MTX with 50% was given successfully without any renal impairment. Conclusion: Methotrexate toxicity that might not occur during the initial courses of high-dose MTX is not a predictive of the tolerability of further courses and re-challenging with HDMTX is risky, but reduced dose methotrexate is a good option rather than changing the regimen, with good tolerability and rapid clearance of HDMTX. HDMTX-induced renal impairment occurs in a low percentage of patients with osteosarcoma and can be managed successfully by maximum supportive care. MTX clearance can be affected by gender and age.