The Effect of Metformin on Chemotherapy-Induced Toxicities in Non-diabetic Breast Cancer Patients: A Randomised Controlled Study.

BACKGROUND AND OBJECTIVE: Breast cancer patients treated with adriamycin-cyclophosphamide plus paclitaxel (AC-T) are often challenged with serious adverse effects for which no effective therapies are available. Here, we investigated whether metformin, an antidiabetic drug with additional pleiotropic effects could favourably offset AC-T induced toxicities. PATIENTS AND METHODS: Seventy non-diabetic breast cancer patients were randomised to receive either AC-T (adriamycin 60 mg/m2 + cyclophosphamide 600 mg/m2 × 4 cycles Q21 days, followed by weekly paclitaxel 80 mg/m2 × 12 cycles) alone or AC-T plus metformin (1700 mg/day). Patients were assessed regularly after each cycle to record the incidence and severity of adverse events based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Moreover, baseline echocardiography and ultrasonography were done and repeated after the end of neoadjuvant therapy. RESULTS: Addition of metformin to AC-T resulted in significantly less incidence and severity of peripheral neuropathy, oral mucositis, and fatigue (p < 0.05) compared to control arm. Moreover, the left ventricular ejection fraction (LVEF%) in the control arm dropped from a mean of 66.69 ± 4.57 to 62.2 ± 5.22% (p = 0.0004) versus a preserved cardiac function in the metformin arm (64.87 ± 4.84 to 65.94 ± 3.44%, p = 0.2667). Furthermore, fatty liver incidence was significantly lower in metformin compared with control arm (8.33% vs 51.85%, p = 0.001). By contrast, haematological disturbances caused by AC-T were preserved after concurrent metformin administration (p > 0.05). CONCLUSION: Metformin offers a therapeutic opportunity for controlling toxicities caused by neoadjuvant chemotherapy in non-diabetic breast cancer patients. TRIAL REGISTRATION: This randomised controlled trial was registered on November 20, 2019 in ClinicalTrials.gov under registration number: NCT04170465.

Polymorphic renal transporters and cisplatin's toxicity in urinary bladder cancer patients: current perspectives and future directions.

Urinary bladder cancer (UBC) holds a potentially profound social burden and affects over 573,278 new cases annually. The disease's primary risk factors include occupational tobacco smoke exposure and inherited genetic susceptibility. Over the past 30 years, a number of treatment modalities have emerged, including cisplatin, a platinum molecule that has demonstrated effectiveness against UBC. Nevertheless, it has severe dose-limiting side effects, such as nephrotoxicity, among others. Since intracellular accumulation of platinum anticancer drugs is necessary for cytotoxicity, decreased uptake or enhanced efflux are the root causes of platinum resistance and response failure. Evidence suggests that genetic variations in any transporter involved in the entry or efflux of platinum drugs alter their kinetics and, to a significant extent, determine patients' responses to them. This review aims to consolidate and describe the major transporters and their polymorphic variants in relation to cisplatin-induced toxicities and resistance in UBC patients. We concluded that the efflux transporters ABCB1, ABCC2, SLC25A21, ATP7A, and the uptake transporter OCT2, as well as the organic anion uptake transporters OAT1 and OAT2, are linked to cisplatin accumulation, toxicity, and resistance in urinary bladder cancer patients. While suppressing the CTR1 gene's expression reduced cisplatin-induced nephrotoxicity and ototoxicity, inhibiting the expression of the MATE1 and MATE2-K genes has been shown to increase cisplatin's nephrotoxicity and resistance. The roles of ABCC5, ABCA8, ABCC10, ABCB10, ABCG1, ATP7B, ABCG2, and mitochondrial SLC25A10 in platinum-receiving urinary bladder cancer patients should be the subject of further investigation.

BCL11A Polymorphism in Egyptian Children with ß-Thalassemia: Relation to Phenotypic Heterogeneity.

Fetal hemoglobin (HbF) is a potent genetic modifier of ß-thalassemia phenotype. B-cell lymphoma 11A ( BCL11A ) gene results in significant silencing of HbF. The aim of this study was to assess the prevalence of different BCL11A genotypes among a cohort of Egyptian children with ß-thalassemia and to correlate them to HbF and clinical severity score. Eighty-two children with ß-thalassemia (aged 12.95 ± 3.63 years) were recruited from the Pediatric Hematology Clinic, Ain Shams University. They were divided based on the clinical severity of ß-thalassemia into three subgroups: 20 mild (24.4%), 24 moderate (29.3%), and 38 severe (46.3%). Age, gender, age of diagnosis, initial HbF level, transfusion history, and history of splenectomy were assessed. Anthropometric measures, signs of anemia and hemosiderosis, and the severity score were determined. Laboratory investigations such as complete blood picture, ferritin, and single gene polymorphism genotyping of the rs11886868 were also performed. Our findings showed that 16 children had CC genotype (19.5%), 38 had TC genotype (46.3%), and 28 had TT genotype (34.1%) of the rs#. ß-thalassemia children with TT genotype had significantly higher severity scoring than the other two groups ( p < 0.001). Moreover, mean initial HbF was found to be lower in children with TT genotype followed by TC and CC genotypes ( p < 0.001). Increased γ-globin expression associated with BCL11A gene polymorphism is associated with better clinical severity of ß-thalassemia.

The Cardioprotective Effect of Vitamin D in Breast Cancer Patients Receiving Adjuvant Doxorubicin Based Chemotherapy.

PURPOSE: The primary objective of this study was to investigate the potential protective effect of Vitamin D (Vit D) on DOX induced cardio toxicity (DIC) in early breast cancer patients receiving adjuvant DOX based chemotherapy (AC). The secondary objective was to investigate the anti-inflammatory effect of Vit D by measuring serum IL-6 and its correlation with cardio toxicity. METHODS: This study was carried out on 150 newly diagnosed women with breast cancer who were planned to receive four cycles of adjuvant AC chemotherapy regimen (60 mg/m2 DOX and 600 mg/m2 cyclophosphamide) every 21 days. Study patients were randomized 1:1 into a control group treated with AC and a Vit D group treated with AC plus 0.5 µg of Vit D (Bon One 0.5 µg) orally once daily during the whole treatment course. The cardio protective effect of Vit D was assessed by measuring serum levels of Lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and anti-inflammatory Interleukin 6 (IL-6) at baseline, and after 4 cycles of AC in all study patients. RESULTS: Vit D supplementation in Vit D group patients was associated with a significant decrease (P < 0.001) in serum levels of LDH, cTnT, and IL-6 compared to the control group . CONCLUSION: The present work provides a promising clinical evidence to support the cardio protective effects of Vit D against DIC through attenuating the evoked pro-inflammatory cytokines induced by DOX.

Assessment of a new strategy for catalyzing deprescribing in community pharmacies.

BACKGROUND: Although community pharmacists have been actively engaged in patient care, their role in deprescribing is still restricted. OBJECTIVES: This study aimed to assess the effectiveness of a new educational approach designed to catalyze deprescribing in community pharmacies. METHODS: In this 4-month, randomized, controlled trial, 108 community pharmacies in Egypt were randomly and equally distributed to either the active or the control groups. Participants from the active group pharmacies received 31 deprescribing-related clinical case scenarios, designed according to the available deprescribing guideline and clinical experiences of an expert panel members, and delivered through WhatsApp. Then participants from both groups reported the incidence of potentially inappropriate medicines (PIMs), the frequency of deprescribing opportunities, and related pharmacist interventions. RESULTS: Pharmacists from the active group reported a considerably higher incidence of PIMs (20.87%) than that reported by pharmacists from the control group (5.03%). In addition, they made 1326 deprescribing-related interventions, of which 1022 (77.07%) were accepted and 641 (48.34%) were significant interventions. The proportions of cessation of drug therapy, reducing the dose, and persuasion of patients to accept deprescribing pharmacist interventions in the active group were 37.85%, 22.09%, and 10.63%, respectively. In contrast, 150 of 268 deprescribing-related interventions (55.97%) in the active group were accepted. The clinical value and type of deprescribing decision were statistically significant determinants for the acceptance of deprescribing decisions. The mean time needed to persuade the patient about deprescribing and the cost saved per patient across the active and the control groups were 5.09 ± 3.54 minutes versus 10.03 ± 6.19 minutes and 17.88 ± 9.60 U.S. dollars versus 4.49 ± 2.44 U.S. dollars, respectively. CONCLUSION: The intervention proposed improved the frequency and clinical value of deprescribing decisions.

The effectiveness of pharmacist-based coaching inimproving breast cancer-related health behaviors: A randomized controlled trial

Background: Although pharmacists are trusted and easily accessible by the public, their role in changing health behaviours related to breast cancer has been rarely investigated. Objective: To investigate the effectiveness of pharmacist-based coaching in improving BC-related health behaviors and knowledge in females, and to measure the comfort level toward this program. Methods: This was a randomized controlled study carried out in community pharmacies in Egypt. Pharmacies included were asked to enroll 240 females into a trial, then equally allocate them into either active or control arms, and provide 12 weekly face-to-face coaching sessions to those assigned to the active arm. Pharmacists were also asked to survey females and fill a standardized data collection form at baseline, in the middle of coaching, at the end of coaching, and three months after coaching. Results: The proportions of doing high physical activity, practicing healthy diet, and practicing breast self-exam three months after the end of coaching programme across the active and control arms were 52.17% versus 17.09% (p=0.002), 62.60% versus 28.20% (p=0.003), and 81.73% versus 23.07% (p=0.005), respectively. The mean scores of knowledge on BC symptoms, risk factors, and detection methods three months after coaching across the active and control arms were 4.10±2.47 versus 2.72±1.19 (p=0.038), 4.25±2.20 versus 3.28±1.48 (p=0.020), and .34±1.80 versus 1.72±0.68 (p=0.001) respectively. While most of the females participated in the active arm were comfortable toward the financial 94.78% and social 88.69% sides of the program, more than one-third (34.78%) of the participants were uncomfortable toward the competency of coaches. Conclusion: Despite the need for some modifications, BC-related health behaviors and knowledge can be improved through pharmacist-based health coaching (AU)

Assessment and analysis of outpatient medication errors related to pediatric prescriptions.

BACKGROUND: Medication errors are the errors that impact the efficacy and safety of the therapy. The impact of medication errors is higher for certain subjects, such as pediatrics, who require more attention. Hence, the current study aimed to investigate the types and frequency of outpatient medication errors of pediatric subjects related to different prescription types. METHODS: A cross-sectional study was carried in several community pharmacies to record the medication errors found in outpatient pediatric prescriptions by gathering data from the outpatient prescriptions besides direct counseling with the subjects and their parents. Many medical resources (disease and drug-related) were used for checking the different aspects of medication errors. The data collection process included a preprepared sheet containing several items representing the medication errors in addition to a counseling session. Data were expressed as percentages and compared through the Chi-square test for results of handwritten and computerized prescriptions. RESULTS: 752 outpatient pediatric prescriptions were recruited in the study as they involve medication errors. Among the highest percentage of medication errors was the absence of essential data in the prescription, such as diagnosis, age, and weight. The duration of the therapy and contraindication for some of the prescribed medications were among the highest recorded errors. Among the critical errors were the drug interaction and drug duplication that directly affect the drug's efficacy and safety. There was a significant difference between computerized and handwritten prescriptions regarding the number of medication errors related to each type. CONCLUSION: Medication errors related to outpatient pediatric prescriptions vary from one to another prescription with predominant errors that influence the therapy's safety or efficacy. The role of patient counseling and prescription checking is critical for improving patient therapy.

Community pharmacists' needs, education, and readiness in facing COVID-19: Actions & recommendations in Egypt.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) outbreak is considered one of the most important public health crises all over the world and in Egypt. Community pharmacists represent the third largest health care professional group after physicians and nurses. Community pharmacists are expected to be fully prepared at the frontline of defending their community needs by limiting the spread of COVID-19 via different pharmaceutical care services. AIM: This study aimed to evaluate the sources of knowledge and readiness of community pharmacists in facing COVID-19 early outbreak in Egypt. METHODS: A descriptive cross-sectional study was performed via a self-administered online google form questionnaire during the early period from 14 April to 3 June 2020. The questionnaire focused on; evaluating education level, sources of information, and readiness of Egyptian community pharmacists in the COVID-19 pandemic crisis. RESULTS: A total of 318 community pharmacists from Egypt participated in this questionnaire. About half of the surveyed pharmacists reported that they were frequently consulted and that their patients were seeking consultation regarding COVID-19 management more than 10 times per day. More than half of the pharmacists reported using social media as a source of information and knew the right social distancing recommendations. Regarding protective measures, only a quarter of pharmacists disclosed the availability of personal protective equipment (PPE). Nevertheless, the majority of pharmacists significantly reported some initial lack of support either inform of recommendations or PPE supply. CONCLUSION: The study revealed the dependence of community pharmacists on social media as the main source of information and the lack of early awareness of evidence-based practice resources. Community pharmacists were in need of more initial support to achieve better satisfaction, patient counselling and infection control. Corrective measures were promptly undertaken to support and satisfy the Egyptian community pharmacists' initial awareness and readiness facing COVID-19.

An emergency plan for management of COVID-19 patients in rural areas.

AIMS OF THE STUDY: To describe the experience of six hospitals in the management of COVID-19 patients in rural areas through an assessment of proportions, types and clinical outcomes of remote clinical interventions. METHODS: This was a prospective observational study conducted in six Egyptian hospitals over a period five months. An emergency response was implemented in each hospital in order to connect clinical pharmacists with COVID-19 patients living in rural areas. Pharmacists used phone calls and social media applications, such as WhatsApp® to conduct two types of interventions; (a) Proactive interventions and (b) outcome-based interventions. IBM SPSS V26 was used for data analysis. RESULTS: Of the 418 patients included, 351 (83.97%) recovered, 60 (14.35%) were hospitalised and 7 (1.67%) were deceased. Medication orders per patient, high-alert medications per patient and prescribing errors per patient were 5.82, 1.45 and 0.74, respectively. Telepharmacy teams conducted 3318 phone calls, 2116 WhatsApp® chats and 1128 interventions, of which 812 (71.92%) were process-based and 316 (27.98%) were outcome-based. Among these interventions, four significant determinants of improvement in clinical outcomes were found: substitution of a prescribed drug (Adjusted odds ratio [AOR] = 4.03; 95% confidence interval [CI], 2.54-5.87), adding a drug to the prescription (AOR = 3.15; 95% CI, 1.87-4.76), advice the patient to stop smoking (AOR = 3.53; 95% CI, 1.98-5.17) and cessation of drug therapy (AOR = 3.11; 95% CI, 1.25-4.55). The most common medications involved in drug-related interventions were Hydroxychloroquine, Azithromycin and Paracetamol. CONCLUSION: Our findings demonstrate significant impact of the remote pharmacist interventions on both medicines use and clinical outcomes of COVID-19 patients in rural areas. Pharmacists in developing countries should be supported to implement remote clinical services to provide patients in rural places with optimal care.

The effectiveness of pharmacist-based coaching in improving breast cancer-related health behaviors: A randomized controlled trial.

Background: Although pharmacists are trusted and easily accessible by the public, their role in changing health behaviours related to breast cancer has been rarely investigated. Objective: To investigate the effectiveness of pharmacist-based coaching in improving BC-related health behaviors and knowledge in females, and to measure the comfort level toward this program. Methods: This was a randomized controlled study carried out in community pharmacies in Egypt. Pharmacies included were asked to enroll 240 females into a trial, then equally allocate them into either active or control arms, and provide 12 weekly face-to-face coaching sessions to those assigned to the active arm. Pharmacists were also asked to survey females and fill a standardized data collection form at baseline, in the middle of coaching, at the end of coaching, and three months after coaching. Results: The proportions of doing high physical activity, practicing healthy diet, and practicing breast self-exam three months after the end of coaching programme across the active and control arms were 52.17% versus 17.09% (p=0.002), 62.60% versus 28.20% (p=0.003), and 81.73% versus 23.07% (p=0.005), respectively. The mean scores of knowledge on BC symptoms, risk factors, and detection methods three months after coaching across the active and control arms were 4.10±2.47 versus 2.72±1.19 (p=0.038), 4.25±2.20 versus 3.28±1.48 (p=0.020), and .34±1.80 versus 1.72±0.68 (p=0.001) respectively. While most of the females participated in the active arm were comfortable toward the financial 94.78% and social 88.69% sides of the program, more than one-third (34.78%) of the participants were uncomfortable toward the competency of coaches. Conclusion: Despite the need for some modifications, BC-related health behaviors and knowledge can be improved through pharmacist-based health coaching.

Impact of activated monocyte and endothelial dysfunction on coagulopathy in Egyptian adult beta thalassemic patients.

The mechanism of the well observed hypercoagulability and high incidence of Thromboembolic Events (TE) in ß- thalassemia patients has not been fully elucidated. This study aimed to evaluate evaluate the endothelial dysfunction and monocyte activation among adult Egyptian ß-thalassemic patients and assess their role in the hypercoagulability and development of TE. A total of 40 adults patients with bthalassemics and 20 healthy age and sex-matched controls were assessed for endothelial dysfunction using serum Von Willebrand Factor Antigen (VWFAg) and for monocytic activation using flow cytometric assessment of CD14 monocyte microparticles and CD11b activated monocytes. The VWF:Ag level was significantly higher among thalassemic patients (P<0.001) and was positively correlated to development of TE (P<0.05). There was no significance difference for CD14 between patients and controls (P>0.5) and CD11b was higher in controls (P=0.004) with no significant correlation between both and TE development (P>0.05). VWF:Ag is increased in thalassemic patients and could be used as a risk factor for thrombosis in these patients, while no identified role of activated monocytes in thrombotic tendency in such patients.

PD1 expression on bone marrow T-cells in newly diagnosed Egyptian AML patients: Correlation with hematological parameters, aberrant antigens expression, and response to induction therapy.

Background: Programed cell death protein 1 (PD-1) is a key mediator for the development of T cell exhaustion that develops in response to persistent antigen stimulation. Aim: In this study, we measured PD1 expression on CD3 positive bone marrow T-lymphocytes in newly diagnosis AML patients and its relation to clinical/ prognostic outcomes in addition to response to induction therapy (day 28). Methods: This study was conducted on 59 newly diagnosed AML patients and 20 healthy controls. Complete blood counts, flow cytometry using acute leukemia panel in addition to PD1 monoclonal antibodies were performed on bone marrow lymphocytes (CD3+), whereas cytogenetic/molecular studies were used to determine risk group. The patients' remission status following induction therapy was determined. Results: PD1 was brightly expressed in 91.5% of the cases than control sample with highly significant difference (P = .001). A cutoff of 3.5 for mean fluorescence intensity was used to divide patients into two groups (higher vs normal PD1 expression). A significant difference between the two groups regarding platelet count and aberrant CD7 expression (P = .007 and .023, respectively) was found. Those normally expressed PD1 respond better to induction therapy. Conclusion: PD1 expression on BM T-cells had a predictive value and providing an immunotherapeutic target for AML.

Metformin may protect nondiabetic breast cancer women from metastasis.

Metformin, a widely prescribed oral hypoglycemic agent, has recently received a big interest because of its potential antitumorigenic effects in different cancer types. The present study investigated the impact of adding metformin to breast cancer adjuvant therapy in nondiabetic women on, insulin like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), insulin, fasting blood glucose (FBG), the molar ratio of IGF-1 to IGFBP-3, homeostatic model assessment of insulin resistance (HOMA-IR) and metastasis. 102 women with newly diagnosed breast cancer were divided into 2 main groups, a control group and a metformin group. All women were treated with adjuvant therapy, according to the protocols of Ministry of Health and Population and National Cancer Institute, Egypt. Moreover, the women in the metformin group received 850 mg of metformin twice daily. Blood samples were collected at baseline, after chemotherapy (CT), after 6 months of hormonal therapy (6-HT) and 12 months of hormonal therapy (12-HT) for analysis of serum IGF-1, IGFBP-3, insulin, FBG and cancer antigen 15-3 (CA15-3). Metformin resulted in a significant reduction of IGF-1, IGF-1: IGFBP-3 molar ratio, insulin, FBG and HOMA-IR. On the other hand, metformin caused a significant increase of IGFBP-3. Moreover, metformin significantly decreased the numbers of metastatic cases after 6-HT. Metformin may have potential antitumor and antimetastatic effects that need further clinical investigations. This may be attributed to either the significant increase of the apoptotic inducer IGFBP-3 or/and the significant reduction of mitogenic insulin, IGF-1, free bioactive IGF-1, FBG and HOMA-IR.