Melatonin: A potential protective multifaceted force for sepsis-induced cardiomyopathy.

Sepsis is a life-threatening condition manifested by organ dysfunction caused by a dysregulated host response to infection. Lung, brain, liver, kidney, and heart are among the affected organs. Sepsis-induced cardiomyopathy is a common cause of death among septic patients. Sepsis-induced cardiomyopathy is characterized by an acute and reversible significant decline in biventricular both systolic and diastolic function. This is accompanied by left ventricular dilatation. The pathogenesis underlying sepsis-induced cardiomyopathy is multifactorial. Hence, targeting an individual pathway may not be effective in halting the extensive dysregulated immune response. Despite major advances in sepsis management strategies, no effective pharmacological strategies have been shown to treat or even reverse sepsis-induced cardiomyopathy. Melatonin, namely, N-acetyl-5-methoxytryptamine, is synthesized in the pineal gland of mammals and can also be produced in many cells and tissues. Melatonin has cardioprotective, neuroprotective, and anti-tumor activity. Several literature reviews have explored the role of melatonin in preventing sepsis-induced organ failure. Melatonin was found to act on different pathways that are involved in the pathogenesis of sepsis-induced cardiomyopathy. Through its antimicrobial, anti-inflammatory, and antioxidant activity, it offers a potential role in sepsis-induced cardiomyopathy. Its antioxidant activity is through free radical scavenging against reactive oxygen and nitrogen species and modulating the expression and activity of antioxidant enzymes. Melatonin anti-inflammatory activities control the overactive immune system and mitigate cytokine storm. Also, it mitigates mitochondrial dysfunction, a major mechanism involved in sepsis-induced cardiomyopathy, and thus controls apoptosis. Therefore, this review discusses melatonin as a promising drug for the management of sepsis-induced cardiomyopathy.

Impact of magnesium supplementation on clinical outcome and disease progression of patients with diabetic nephropathy: a prospective randomized trial.

Background: Magnesium (Mg) deficiency is closely linked with proteinuria. Objectives: To assess the impact of oral Mg citrate supplementation on the clinical outcome of diabetic nephropathy (DN) patients. Design: This was a prospective, randomized, controlled, open-label study. Methods: Sixty DN patients were recruited from Nephrology and Endocrinology departments, Ain Shams University Hospitals, Cairo, Egypt. Patients were assigned by stratified randomization based on their Mg status, to either Mg citrate group, (n = 30), who received the standard regimen + oral Mg citrate 2.25 g/day or Control group, (n = 30), who received the standard regimen only. The primary endpoint was a change in urinary albumin to creatinine ratio (UACR) after 12 weeks. Secondary outcomes were insulin resistance, glycemic control, lipid profile, serum osteocalcin, quality of life (QoL) and Mg tolerability. Results: Out of a total of 60 patients enrolled, only 54 patients (26 in Mg citrate group and 28 in the control group) completed the study. Groups were comparable at baseline. The UACR median percent reduction was significantly higher in the Mg citrate group (-6.87%) versus (-0.9%) in the Control group, p = 0.001. After 12 weeks, the estimated glomerular filtration rate significantly improved in the Mg citrate group versus Control group (p = 0.001). Comparable change was observed in glycemic indices. Lipid profile significantly improved in the Mg citrate group versus Control group (p = 0.001). Serum osteocalcin levels significantly declined in the Mg citrate group (p = 0.001) versus control group. Regarding QoL, the total score and all domains significantly improved in the Mg citrate group compared to control. The Mg supplement was tolerable with only mild reported side effects that required no intervention. Conclusion: Oral Mg citrate supplementation improved microalbuminuria in DN patients. It also had favorable effects on serum osteocalcin, lipid profile and QoL with no reported major side effects. Trial registration: ClinicalTrials.gov identifier: NCT03824379.

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.

Comparison of Warfarin Initiation at 3 mg Versus 5 mg for Anticoagulation of Patients with Mechanical Mitral Valve Replacement Surgery: A Prospective Randomized Trial.

BACKGROUND: The increased warfarin sensitivity observed after mechanical mitral valve replacement (MVR) operations dictates clinical discretion in warfarin dose initiation. Evidence is still lacking with regard to anticoagulation management of MVR patients. OBJECTIVE: This study aimed to compare initiating warfarin at the recommended dosing regimen versus empirically lowered doses intended to account for the variation in warfarin sensitivity. METHODS: A prospective, single-blind, randomized, comparative study was conducted in postoperative MVR patients. Patients were randomly assigned to either the 5 mg group (n = 25) or the 3 mg group (n = 25) and were initiated on a 5 or 3 mg warfarin dose, respectively. Time to target international normalized ratio (INR), time in therapeutic range, occurrence of bleeding/thromboembolic events, and cost of bridging with enoxaparin were assessed for both groups. RESULTS: Target INR was achieved earlier in the 5 mg group than in the 3 mg group (p = 0.033), with a mean ± SD of 5.3 ± 2.0 and 6.6 ± 2.0, respectively (95% confidence interval of the mean difference 1.022-1.890). Bleeding events did not differ significantly between the two groups. The cost of enoxaparin consumption per patient was significantly higher in the 3 mg group versus the 5 mg group (p = 0.002). CONCLUSIONS: The initiation of warfarin at a 5 mg dose in MVR patients was more efficacious than the 3 mg dose in terms of time to reach the target INR. Moreover, the cost of enoxaparin bridging was significantly reduced with a 5 mg warfarin initiation dose. Bleeding events were comparable. GOV ID: NCT04235569, 22 January 2020.

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.

Midodrine improves clinical and economic outcomes in patients with septic shock: a randomized controlled clinical trial.

BACKGROUND: Prolonged use of intravenous (IV) vasopressors in patients with septic shock can lead to deleterious effects. AIMS: This study assessed the impact of midodrine administration on weaning off IV vasopressors and its economic value. METHODS: It is a prospective randomized controlled study of 60 resuscitated patients with septic shock who demonstrated clinical stability on low-dose IV vasopressors for at least 24 h. Participants were randomized into two groups: norepinephrine (IV norepinephrine) and midodrine (IV norepinephrine + oral midodrine 10 mg thrice a day). A cost comparison was applied based on the outcomes of both groups. RESULTS: The median duration of norepinephrine administration in the midodrine and norepinephrine groups was 4 and 6 days, respectively (p = 0.001). Norepinephrine weaning time was significantly less in the midodrine versus norepinephrine groups (26 and 78.5 h, respectively; p < 0.001). Mortality was 43.3% versus 73.3% in the midodrine and norepinephrine groups, respectively (p = 0.018). The mean length of stay was comparable in the two groups. The midodrine group showed cost-saving results versus the norepinephrine group. CONCLUSION: The use of midodrine in septic shock patients significantly reduced IV norepinephrine duration, weaning period during the septic shock recovery phase, and mortality. Thus, the use of midodrine is dominant with less cost, better outcome and a cost-saving option in terms of budget impact analysis. This study was registered at clinicaltrials.gov (NCT 03,911,817) on April 11, 2019.

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.

The impact of cholecalciferol on markers of vascular calcification in hemodialysis patients: A randomized placebo controlled study.

BACKGROUND AND AIM: Vascular calcification is an independent risk factor for cardiovascular diseases and all-cause mortality in end stage renal disease, and particularly in hemodialysis patients. Vitamin D deficiency has been shown to be associated with vascular calcification among this category of patients. Cholecalciferol or vitamin D3; the native inactivated 25-hydroxy vitamin D [25(OH)D], has been proposed to have a good impact on vascular calcification and vitamin D deficiency. However, clinical data is still limited. METHODS AND RESULTS: A prospective, randomized, placebo-controlled study was carried out to evaluate the effect of oral cholecalciferol on vascular calcification and 25(OH)D levels in hemodialysis patients. A total of sixty eligible hemodialysis patients were randomly assigned to either a treatment group (Oral 200.000IU Cholecalciferol per month) or a placebo group, for 3 months. Serum 25-hydroxy vitamin D (25(OH)D), fetuin-A, fibroblast growth factor (FGF-23), osteoprotegerin (OPG), calcium, phosphorus, their product (CaXP) and intact parathyroid hormone (iPTH) levels, were all assessed at baseline and at the end of the study. ClinicalTrials.gov registration number: NCT03602430. Cholecalciferol significantly increased serum levels of 25(OH)D and fetuin-A in the treatment group (p-value < 0.001), while no significant difference was observed in the placebo group. Cholecalciferol administration showed no effect on either FGF-23 or OPG. None of the treatment group patients experienced any adverse effects. CONCLUSION: Cholecalciferol was shown to be an effective, tolerable, inexpensive pharmacotherapeutic option to overcome vitamin D deficiency, with a possible modulating effect on fetuin-A, among hemodialysis patients. CLINICALTRIALS. GOV REGISTRATION NUMBER: NCT03602430.

Coenzyme Q10 administration has no effect on sICAM-1 and metabolic parameters of pediatrics with type 1 diabetes mellitus.

Background: Endothelial dysfunction (ED) plays a key role in the development and progression of microvascular and macrovascular complications in pediatrics with type 1 diabetes mellitus (T1DM). Coenzyme Q10 (CoQ10) is a nutraceutical with a known anti-inflammatory and anti-oxidant activity. This study was conducted to evaluate the potential effect of CoQ10 on ED and various metabolic parameters. Methods: This prospective randomized open-label pilot study was conducted on 49 T1DM pediatric patients. Seven healthy non-diabetic pediatric subjects who didn't receive treatment were included as a control group. Eligible patients were randomly allocated into either group I (n = 25); received 100 mg of CoQ10 in addition to standard treatment or group II (n = 24); received standard treatment only. The levels of; soluble intracellular adhesion molecule-1 (sICAM-1), glycated hemoglobin (HbA1c), fasting blood glucose (FBG), lipid profile, serum creatinine and liver function tests were assessed for both groups at baseline and after 3 months of treatment. Results: At baseline, compared to an age-matched healthy control group sICAM-1 levels were significantly elevated in group II diabetic patients (276.5 (231.6-320.66) vs 221.8 (177.9-267.1 ng/ml), p = 0.042. After 3 months of treatment no significant difference was observed in sICAM-1, HbA1c, FBG, lipid profile, serum creatinine and liver function tests between the two study groups. A positive correlation was found between sICAM-1 and HbA1c throughout the study (r = 0.308, p = 0.0054). Conclusion: Administration of CoQ10 for 3 months in T1DM pediatric patients was well tolerated but had no favorable effect on ED or metabolic parameters.

Impact of lipophilic vs hydrophilic statins on the clinical outcome and biomarkers of remodelling in heart failure patients: A prospective comparative randomized study.

AIMS: There are insufficient direct comparative studies addressing the impact of the type of statin on their respective efficacy in heart failure (HF). The aim of the current study was to compare the effects of lipophilic (atorvastatin) vs hydrophilic (rosuvastatin) on left ventricular function, inflammatory and fibrosis biomarkers in patients with chronic HF. METHODS: This was a prospective, randomized, comparative, parallel study. A total of 85 patients with chronic HF optimized on guideline directed therapy were randomized to receive either atorvastatin 40 mg (n = 42) or rosuvastatin 20 mg (n = 43) for 6 months. Baseline and follow-up assessment included 2D echocardiography, measurement of N-terminal pro-brain natriuretic peptide, interleukin-6 and soluble suppression of tumorigenicity 2 (sST2) levels, liver enzymes and lipid profile. RESULTS: The increase in left ventricular ejection fraction was significantly higher in the atorvastatin group compared to the rosuvastatin group (6.5% [3-11] vs 4% [2-5], P = .006). The reduction in left ventricular end diastolic and end systolic volume was comparable between the 2 groups. The decrease in sST2 levels in pg/mL was significantly higher in the atorvastatin compared to the rosuvastatin group (-255 [-383 to -109.8 vs - 151 [-216 to -69], P = .003). There was a significant reduction in N-terminal pro-brain natriuretic peptide and interleukin-6 levels in both groups, yet the reduction was comparable in both groups. CONCLUSION: The study results suggest that lipophilic atorvastatin is superior to hydrophilic rosuvastatin in increasing left ventricular ejection fraction and reducing fibrosis marker sST2 in HF patients. Trial registration ID: NCT03255044, registered on 21 August 2017.

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.

Impact of Rutin and Vitamin C combination on oxidative stress and glycemic control in patients with type 2 diabetes.

AIM: This study aimed to investigate the effect of Vitamin C alone and in combination with Rutin on the glycemic control, insulin resistance, lipid profile and oxidative stress markers in patients with type 2 diabetes. METHODS: A prospective, randomized, controlled study conducted on 53 type 2 diabetes patients randomized into 3 groups; (group A) 20 received Rutin with vitamin C, (group B) 20receivedvitamin C and (group C)13 received antidiabetic treatment only. Fasting Blood Glucose (FBG), Hemoglobin A1c (HbA1c), fasting insulin, Malondialdehyde, Superoxide dismutase, Lipid profile and patients' quality of life (QOL) using SF-36 questionnaire were assessed in all patients at baseline and after 8 weeks. RESULTS: At baseline, the 3 groups were comparable while FBG was lower in group C versus group A and B (p = 0.0021). After 8 weeks, a significant reduction was observed in % change of FBG in groups A and B versus group C (p = 0.0165, 0.0388 respectively). Low Density Lipoprotien-cholesterol (LDL-c) and Total cholesterol (TC) levels significantly improved in group B versus baseline (p = 0.0239,0.0166 respectively). QOL, physical functioning and energy domains improved significantly in group A versus group C (p = 0.0049, 0.0253 respectively), while role limitation to physical health and to emotional problem improved significantly in group B versus group C (p = 0.0267,0.0280 respectively). CONCLUSION: Vitamin C supplementation alone or with Rutin significantly reduced the % change of FBG compared to controls but had no effect on HbA1c, FBG,TC, fasting insulin and HOMA-IR or oxidative stress in T2DMpatients. CLINICAL TRIAL REGISTRATION NUMBER: NCT03437902.

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.

Pentoxifylline and vitamin E reduce the severity of radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients: a randomized, controlled study.

The purpose of this study was to assess the impact of pentoxifylline and vitamin E on the incidence and severity of radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients. This is a prospective, randomized, controlled study. Head and neck cancer patients receiving 30-35 radiotherapy fractions with or without concurrent chemotherapy excluding those intolerant to xanthines, with any bleeding tendency were included. Sixty patients were enrolled; 30 patients received radiotherapy (control group) and 30 patients received radiotherapy with pentoxifylline and vitamin E (intervention group). The incidence, severity, onset and duration of oral mucositis and/or dysphagia were assessed. Locoregional control, quality of life, need for hospitalization, radiotherapy breaks, and adverse events were recorded and compared between groups. Pentoxifylline and vitamin E combination did not affect the incidence or the onset of oral mucositis or dysphagia. After adjusting for age, the combination reduced the incidence of severe oral mucositis (p = 0.01) and dysphagia (p = 0.012). The combination decreased the duration of oral mucositis and dysphagia by 5 weeks (p = 0.002) and 4 weeks (p = 0.003), respectively. The study drugs reduced the need for hospitalization (p = 0.002) and for radiotherapy breaks (p = 0.002) with improvement of FOIS (p = 0.014), EQ-5D index (p = 0.009) and VAS score (p = 0.012). Pentoxifylline and vitamin E decreased the occurrence of dysgeusia (p = 0.026) and fatigue (p = 0.026) without compromising locoregional control. Pentoxifylline/vitamin E combination reduced the severity and duration of acute radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients.Trial registry ClinicalTrials.gov registration number: NCT02397486.

Effect of Nigella Sativa oil versus metformin on glycemic control and biochemical parameters of newly diagnosed type 2 diabetes mellitus patients.

PURPOSE: Nature is a phenomenal treasure of remedies. Numerous previous studies reported that Nigella sativa NS improved glycemic control, reduced insulin resistance, and improved lipid profile. NS was never investigated before as a monotherapy for newly diagnosed type 2 diabetes mellitus T2DM patients. Our aim was to investigate the potential metabolic benefits of NS monotherapy in newly diagnosed T2DM patients. METHOD: Prospective, open-label randomized clinical trial at outpatient endocrinology clinic at Ain-Shams University hospital. Eligible patients were randomly assigned to either metformin tablets or NS oil capsules. Both groups received treatment for 3 months. Glycemic index (FBG, 2 h pp, A1C, insulin sensitivity %S, secretory function %B, insulin resistance IR), lipid profile (TC, LDL, HDL, TG), liver and kidney functions (AST, ALT, Sr cr), total antioxidant capacity TAC, weight, waist circumference WC and body mass index BMI were assessed at baseline and at the end of treatment period. RESULTS: A concentration of 1350 mg/day NS in newly diagnosed T2DM patients was inferior to metformin in terms of lowering FBG, 2 h pp, and A1C or increasing %B. However, NS was comparable to metformin in lowering weight, WC, and BMI significantly. NS was comparable to metformin in regards of their effects on fasting insulin, %S, IR, ALT, TC, LDL, HDL, TG, and TAC. Metformin showed significant increase in AST and creatinine which was reserved in NS group. CONCLUSION: NS administration in newly diagnosed T2DM was tolerable with no side effects as compared to metformin; however, it was inferior to metformin in terms of diabetes management.

Effect of plasma MicroRNA on antihypertensive response to beta blockers in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) studies.

ß-blockers show variable efficacy as antihypertensives. Herein, we evaluated plasma miRNAs as biomarkers for defining antihypertensive response to ß-blockers. Expression of 22 ß-blocker pharmacodynamics-related miRNAs was assessed in baseline plasma samples from 30 responders and 30 non-responders to metoprolol from the PEAR-2 study (Discovery). Logistic regression was performed to identify miRNAs significantly associated with metoprolol response. Those miRNAs were profiled in baseline plasma samples from 25 responders and 25 non-responders to atenolol from the PEAR study (validation). In discovery, miR-101, miR-27a, miR-22, miR-19a, and let-7e were significantly associated with metoprolol response (P = 0.01, 0.017, 0.025, 0.025, and 0.04, respectively). In validation, miR-19a was significantly associated with atenolol response (P = 0.038). Meta-analysis between PEAR-2 and PEAR revealed significant association between miR-19a (P = 0.004), miR-101 (P = 0.006), and let-7e (P = 0.012) and ß-blocker response. Hence, miR-19a, miR-101, and let-7e, which regulate ß1-adrenergic receptor and other ß-blocker pharmacodynamics-related genes, may be biomarkers for antihypertensive response to ß-blockers.

The Effects of Nutrition Awareness and Knowledge on Health Habits and Performance Among Pharmacy Students in Egypt.

A cross-sectional study was conducted on a group of pharmacy students to assess the relation between nutritional knowledge and awareness of university students and their nutrition habits and health related performance and indicators. The students were subjected to a questionnaire designed to approach four health related topics including nutrition literacy, health awareness, nutritional habits and health related performance. Answers on each topic were collected and statistical analysis was performed using GraphPad Prism 5 software including a measure of gender differences and correlative studies. No significant difference between genders in the overall responses but discrepancies in certain questions were observed. Female students showed higher awareness of nutrition concepts and practices but poor implementation from their side was observed. The study revealed that a positive and significant correlation existed between health related performance and nutrition literacy (r = 0.32). Healthier eating habits and lifestyle were associated more with nutrition conscious students (r = 0.73) than knowledgeable students (r = 0.56). It was concluded that knowledge alone is not enough to stimulate individuals to practice healthy habits. Other implementations are required to raise awareness of the issues at hand.

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.

The Use of Glycomacropeptide in Dietary Management of Phenylketonuria.

Dietary therapy is the most common therapy applied in treatment of Phenylketonuria (PKU) with restriction of intake of most natural proteins that are rich in Phenylalanine (Phe). Recently, it has been claimed that caseinoglycomacropeptide (GMP), derived of whey, may be used to replace the amino acid formulae (AAF). The Aim of Work. To study the feasibility of use of GMP for partial replacement of artificial formula in treatment of children with PKU. Methods. Ten patients with PKU were included in the study. They received the recommended daily allowances of protein in the form of AAF or a combination of AAF and GMP. The percent of intake of GMP in phases 1 and 2 was 50% and zero%, respectively. Results. The median and interquartiles of phenyl alanine Phe levels phase were not significantly different in phases I and II, 376 (167-551) µmol/L versus 490 (289-597) µmol/L, respectively. Phenylalanine/tyrosine ratio, amino acids, and other laboratory data showed no significant difference between the two phases. Conclusion. GMP may be used to replace 50% of the protein intake to improve the nutritive value and palatability of diet and to provide a more satisfactory diet. No toxicity or side effects were reported in patients on that regimen.