Evaluation of the efficacy and tolerability of alendronate versus denosumab in kidney transplant patients with reduced bone mineral density.

PURPOSE: To compare the effect of denosumab and alendronate on bone mineral density (BMD) in renal transplant recipients (RTRs) with low bone mass. METHODS: Patients were randomized to receive either denosumab subcutaneously (60 mg/6 months), oral alendronate (70 mg/week), or no treatment for 1 year. The three groups were prescribed daily calcium and vitamin D. Primary outcome was BMD assessed at lumbar spine, hip, and radius and measured by dual-energy X-ray absorptiometry (DEXA) at baseline and after 6 and 12 months. Adverse events and laboratory assessments (calcium, phosphate, vitamin D, renal functions, and intact parathyroid hormone) were monitored for all patients. Quality of life was assessed at baseline and after 6 and 12 months for all patients. RESULTS: Ninety RTRs were included in the study (30 in each group). Baseline clinical characteristics and BMD values were comparable in the three groups. After 12 months, lumbar spine T-score of patients treated with denosumab and alendronate showed a median increase of 0.5 [95% confidence interval (CI): 0.4-0.6] and 0.5 (95% CI: 0.4-0.8), respectively, and patients in the control group showed a decrease of -0.2 (95% CI: -0.3 to -0.1), p < 0.001. Denosumab and alendronate showed a significant comparable gain in T-scores at hip and radius versus a significant decrease in the control group. Adverse events and laboratory values were similar in the three groups. Both treatments resulted in comparable significant improvement in physical functioning, physical role limitations, vitality, and pain scores. CONCLUSION: Denosumab and alendronate showed comparable efficacy in improving BMD at all measured skeletal sites and were safe and well-tolerated, with no serious adverse effects reported in RTRs with low bone mass. The study was registered on ClinicalTrials.gov, number NCT04169698.

Effect of Clinical and Genetic Factors on the Development of Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting (CABG) in Egyptian Patients Receiving Beta-Blockers.

PURPOSE: Prophylactic beta-blockers are recommended to prevent postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). Polymorphisms in the beta-1 adrenergic receptor (ADRB1) and G protein-coupled receptor kinase 5 (GRK5) genes are associated with variable responses to beta-blockers. The aim of this study was to determine the clinical and genetic factors that influence the response to beta-blockers for POAF prophylaxis after CABG. METHODS: Patients undergoing isolated CABG and receiving prophylactic beta-blockers (n = 249) were prospectively recruited and followed up for 6 postoperative days. Genotyping of ADRB1 rs1801253, and 3 GRK5 SNPs (rs3740563, rs10787959, and rs17098707) was performed. RESULTS: Of the 249 patients, 52 patients (20.8%) experienced POAF. Age, hypertension, vasopressor use, calculated POAF risk score, GRK5 rs2230345 T-allele, and GRK5 rs3740563 A-allele were associated with POAF despite beta-blocker prophylaxis. The multivariate analysis revealed that age [odds ratio (OR) 1.06, 95% CI 1.02-1.11, p = 0.003] and GRK5 rs2230345 T-allele [OR 2.81, 95% CI 1.39-5.67, p = 0.004] were independent predictors of POAF after CABG despite beta-blocker prophylaxis. CONCLUSION: GRK5 rs2230345 T-allele carriers were less responsive than AA genotype carriers to prophylactic beta-blockers for the prevention of POAF after CABG. The study was registered on http://clinicaltrials.gov in March 2019, with trial registration number (TRN): NCT03871647.

Nicotinamide supplementation in diabetic nonalcoholic fatty liver disease patients: randomized controlled trial.

BACKGROUND: Nicotinamide has been reported to protect against liver steatosis and metabolic imbalances in nonalcoholic fatty liver disease (NAFLD) in animal models. OBJECTIVES: The objective was to investigate the efficacy and safety of nicotinamide supplementation in diabetic NAFLD patients. DESIGN: This is a prospective randomized controlled open label study. METHODS: Seventy diabetic NAFLD patients were randomly assigned either to the nicotinamide group (n = 35) who received nicotinamide 1000 mg once daily for 12 weeks in addition to their antidiabetic therapy or the control group (n = 35) who received their antidiabetic therapy only. The primary outcome was improvement in steatosis score, while secondary outcomes included assessment of liver stiffness, liver enzymes, lipid profile, insulin resistance, serum malondialdehyde, serum adiponectin, and patients' quality of life (QOL). RESULTS: Only 61 patients completed the study; 31 in the nicotinamide group and 30 in the control group. Comparisons between groups and within groups revealed nonsignificant changes in steatosis and fibrosis scores. However, significant reduction was observed in liver enzymes with a median decrease in alanine transaminase of 26.6% versus 0.74% in nicotinamide and control groups, respectively. After 12 weeks of treatment, the nicotinamide group showed significantly lower levels of low-density lipoprotein cholesterol (p value = 0.004), total cholesterol (p value = 0.006), and insulin resistance marker (p value = 0.005) compared with control. Serum triglycerides, malondialdehyde, and adiponectin levels were all comparable between the two groups. Regarding QOL, a significant improvement was detected in the total scores and the activity and fatigue domains scores. CONCLUSION: Nicotinamide at a dose of 1000 mg daily was tolerable, improved metabolic abnormalities and QOL of diabetic NAFLD patients with no effect on liver fibrosis or steatosis. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov and given the ID number: 'NCT03850886'. https://clinicaltrials.gov/ct2/show/NCT03850886.

Exploring SARS-CoV-2 Spikes Glycoproteins for Designing Potential Antiviral Targets.

Till today, the globe is still struggling with the newly emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and known as coronavirus disease 2019 (COVID-19). It has resulted in multiple fatalities from SARSs all around the world. A year after the global pandemic, the World Health Organization (WHO) has reported more than 79 million confirmed cases of COVID-19 and over 1.7 million deaths, making it one of the worst and most difficult pandemics encompassed in the modern history. The ongoing triad of escalating infections, mortality, and economic loss has urgently called for recognizing SARS-CoV-2 cell entry mechanisms as a crucial step in the initial stages of infection and to which possible interventional strategies should be targeted. To mediate host cell infections, Coronaviruses utilize the immunogenic studded spikes glycoproteins on its surface as a key factor for attachment, fusion, and entrance to host cells. Herein, we shed the light on a potential strategy involving disruption of SARS-CoV-2 S protein interaction with host cell receptors through design of neutralizing antibodies targeting receptor binding domain in S1 subunit, small peptide inhibitors, peptide fusion inhibitors against S2, host cell angiotensin converting enzymes 2 (ACE2), and protease inhibitors, aiming to pave the way for controlling viral cell entrance. In this review, we also highlight the recent research advances in the antiviral drugs that target the highly exposed spike protein, aiming to stem the COVID-19 pandemic.

Evaluation of the effect of N-acetylcysteine on the prevention and amelioration of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled study.

PURPOSE: The aim of the current study was to evaluate the effect of N-acetylcysteine (NAC) on the incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN) in breast cancer patients. METHOD: A prospective randomized controlled open label study was conducted on 75 breast cancer patients receiving adjuvant paclitaxel 80 mg/m2 weekly for 12 weeks. Eligible patients were randomized to either the low dose group; 1200 mg daily NAC, the high dose group; 1200 mg NAC twice daily or the control group; received paclitaxel only. The primary endpoint was the incidence of different grades of PIPN using National Cancer Institute's common toxicity criteria for adverse event (NCI-CTCAE) while secondary endpoints were the severity of PIPN using modified total neuropathy score (mTNS), quality of life (QOL) using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTX) subscale, serum nerve growth factor (NGF), and serum malondialdehyde (MDA). RESULTS: At the end of the 12-week period, the incidence of grade (2, 3) peripheral neuropathy was significantly lower in the high dose group (28.6%) compared to the low dose group (61.9%) and the control group (100%), p value < 0.001. A significant improvement in the mTNS and QOL scores was observed after 6 and 12 weeks in the high dose group and the low dose group compared to the control, p value < 0.001. Significantly higher levels of serum NGF in the high dose group and lower level of serum MDA in the high dose and the low dose group were observed. CONCLUSION: Oral NAC (1200 mg once and twice daily) might reduce the incidence and severity of PIPN and improve the patients' QOL. TRIAL REGISTRY: Clinical Trial.gov registration number: NCT03492047.

Effect of Genetic and Nongenetic Factors on the Clinical Response to Mineralocorticoid Receptor Antagonist Therapy in Egyptians with Heart Failure.

This prospective cohort study evaluated the association between the renin angiotensin aldosterone system genotypes and response to spironolactone in 155 Egyptian patients with heart failure with reduced ejection fraction (HFrEF). Genotype frequencies for AGT rs699 were: CC = 16%, CT = 48%, and TT = 36%. Frequencies for CYP11B2 rs1799998 were: TT = 33%, TC = 50%, and CC = 17%. After 6 months of spironolactone treatment, change in the left ventricular ejection fraction (LVEF) differed by AGT rs699 (CC, 14.6%; TC, 7.9%; TT, 2.7%; P = 2.1E-26), and CYP11B2 rs1799998 (TT, 9.1%; TC, 8.7%; CC, 1.4%; P = 0.0006) genotypes. Multivariate linear regression showed that the AGT rs699 and CYP11B2 rs1799998 polymorphisms plus baseline serum potassium explained 71% of variability in LVEF improvement (P = 0.001), 63% of variability in serum potassium increase (P = 2.25E-08), and 39% of the variability in improvement in quality of life (P = 2.3E-04) with spironolactone therapy. These data suggest that AGT and CYP11B2 genotypes as well as baseline serum K are predictors of spironolactone response in HFrEF.

Clinical Pharmacist-Provided Services In Iron-Overloaded Beta-Thalassaemia Major Children: A New Insight Into Patient Care.

Iron-overloaded ß-thalassaemia major (BTM) children have high risk of delayed sexual/physical maturation, liver/heart diseases and reduced life expectancy. The lifelong need to use iron chelators, their unpleasant administration, side effects and lack of awareness regarding iron overload risks all hamper BTM patient compliance to iron chelators. This study evaluated the impact of clinical pharmacist-provided services on the outcome of iron-overloaded BTM children. Forty-eight BTM children were randomly assigned to either control group, who received standard medical care, or intervention group, who received standard medical care plus clinical pharmacist-provided services. Services included detection of drug-related problems (DRPs) and their management, patient education regarding disease nature and iron chelators, as well as providing patient-tailored medication charts. After six months of study implementation, there was a highly significant difference between the control and intervention groups in serum ferritin (SF) (mean: 3871 versus 2362, µg/l, p = 0.0042), patient healthcare satisfaction (median: 24.47 versus 90.29, p < 0.0001) and quality of life (QoL) (median: 49.84 versus 63.51, p = 0.0049). The intervention group showed a decline from baseline to the end of study in DRPs (64-4), the number of non-compliant patients (24-3) and mean SF levels (3949-2362 µg/l, p < 0.0001). Clinical pharmacist-provided services can positively impact the outcome of BTM children.

Clinical study evaluating pregabalin efficacy and tolerability for pain management in patients undergoing laparoscopic cholecystectomy.

OBJECTIVES: To evaluate the efficacy and tolerability of pregabalin in postoperative pain management after laparoscopic cholecystectomy (LC). PATIENTS AND METHODS: A prospective, randomized, placebo, controlled, double-blinded study was conducted at Anesthesia Department, Laparoscopy Surgery Unit, Ain Shams University Hospital. Ninety patients with ASA physical status I-II scheduled for elective LC under general anesthesia were included. Patients were randomly assigned to the following groups (n=30 each): pregabalin group (P), received 150 mg pregabalin capsules 2 hours preoperatively, 12 hours postoperatively, and twice daily for 2 days; gabapentin group (G), received 1200 mg gabapentin capsules (400 mg, ×3) 2 hours preoperatively, 12 hours postoperatively, and 400 mg three times daily for 2 days; and control group (C), received placebo capsules. Postoperative pain scores were recorded on a visual analogue scale. The following data were recorded: total daily pethidine and diclofenac consumption, numeric sedation score, and the postoperative nausea, vomiting, and dizziness scores. RESULTS: The 24-hour pethidine consumption was significantly lower (P<0.001) in both pregabalin and gabapentin groups versus control. Both groups had significantly less (P<0.001) patients with postoperative nausea, vomiting, sedation, and dizziness versus control. Overall patient satisfaction with pain management was significantly higher (P<0.001) in pregabalin group versus gabapentin or control groups. CONCLUSIONS: Gabapentin 1200 mg and pregabalin 150 mg are effective and safe analgesics for reducing postoperative pain in LC. The perioperative oral administration of pregabalin 150 mg in patients undergoing LC is an effective and safe method of analgesia with a low incidence of adverse effects and reduces postoperative pethidine consumption.