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.

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.

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.

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.

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 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.

Efficacy and safety of nicotinamide in the management of hyperphosphatemia in pediatric patients on regular hemodialysis.

BACKGROUND: Hyperphosphatemia is a common problem in patients with end-stage renal disease (ESRD) who are on maintenance hemodialysis (HD) and contributes to the development of secondary hyperparathyroidism and cardiovascular complications. Nicotinamide (NAM) has been shown in some studies to inhibit intestinal and renal sodium/phosphorus co-transporters and reduce serum phosphorus levels. We have therefore evaluated the efficacy and safety of NAM as adjunctive therapy to calcium-based phosphate binders to control hyperphosphatemia in hemodialysis patients. METHODS: Sixty pediatric HD outpatients were randomly divided into two equally sized groups (30 children each). One group received calcium-based phosphate binder (control group), and the other received both the calcium-based phosphate binder + NAM at a dose of 100 mg twice or three times daily (nicotinamide group). Both groups were followed for a 6-month period. RESULTS: Over the 6-month treatment period, children in the NAM group showed a significant decline in the levels of serum phosphorus (p = 0.0001), serum calcium-phosphorus (Ca × P; p = 0.0001) product and parathyroid hormone (p = 0.02) versus baseline values and those of the control group. After 6 months of NAM treatment, the mean serum high-density lipoprotein cholesterol levels had increased significantly (p = 0.01), and the median serum triglyceride levels had decreased (p = 0.009). There was no significant change in any of these parameters among the children of the control group. The major adverse events associated with the NAM therapy were diarrhea, flushing and nausea. CONCLUSION: The addition of NAM to therapy with phosphate binders is effective in lowering phosphorus levels and has a beneficial effect on the lipid profile with only mild side effects.

Effects of Nigella sativa on outcome of hepatitis C in Egypt.

AIM: To evaluate the safety, efficacy and tolerability of Nigella sativa (N. sativa) in patients with hepatitis C not eligible for interferon (IFN)-α. METHODS: Thirty patients with hepatitis C virus (HCV) infection, who were not eligible for IFN/ribavirin therapy, were included in the present study. Inclusion criteria included: patients with HCV with or without cirrhosis, who had a contraindication to IFN-α therapy, or had refused or had a financial constraint to IFN-α therapy. Exclusion criteria included: patients on IFN-α therapy, infection with hepatitis B or hepatitis I virus, hepatocellular carcinoma, other malignancies, major severe illness, or treatment non-compliance. Various parameters, including clinical parameters, complete blood count, liver function, renal function, plasma glucose, total antioxidant capacity (TAC), and polymerase chain reaction, were all assessed at baseline and at the end of the study. Clinical assessment included: hepato and/or splenomegaly, jaundice, palmar erythema, flapping tremors, spider naevi, lower-limb edema, and ascites. N. sativa was administered for three successive months at a dose of (450 mg three times daily). Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study. RESULTS: N. sativa administration significantly improved HCV viral load (380808.7 ± 610937 vs 147028.2 ± 475225.6, P = 0.001) and TAC (1.35 ± 0.5 vs 1.612 ± 0.56, P = 0.001). After N. sativa administration, the following laboratory parameters improved: total protein (7.1 ± 0.7 vs 7.5 ± 0.8, P = 0.001), albumin (3.5 ± 0.87 vs 3.69 ± 0.91, P = 0.008), red blood cell count (4.13 ± 0.9 vs 4.3 ± 0.9, P = 0.001), and platelet count (167.7 ± 91.2 vs 198.5 ± 103, P = 0.004). Fasting blood glucose (104.03 ± 43.42 vs 92.1 ± 31.34, P = 0.001) and postprandial blood glucose (143.67 ± 72.56 vs 112.1 ± 42.9, P = 0.001) were significantly decreased in both diabetic and non-diabetic HCV patients. Patients with lower-limb edema decreased significantly from baseline compared with after treatment [16 (53.30%) vs 7 (23.30%), P = 0.004]. Adverse drug reactions were unremarkable except for a few cases of epigastric pain and hypoglycemia that did not affect patient compliance. CONCLUSION: N. sativa administration in patients with HCV was tolerable, safe, decreased viral load, and improved oxidative stress, clinical condition and glycemic control in diabetic patients.

An open-label phase I pilot study of continuous intrapleural infusion of escalated doses of methotrexate in malignant pleural mesothelioma.

OBJECTIVES: The aim of this study was to evaluate the toxicity from escalated methotrexate (MTX) doses infused intrapleural over 5 days and to determine pleural and systemic drug levels with this chemotherapeutic approach. PATIENTS AND METHODS: Five patients with malignant pleural mesothelioma were treated with 3 cycles of intrapleural MTX infused through a pigtail catheter inserted in the pleural space. MTX levels were estimated in the pleural fluid and serum once daily throughout the treatment cycles. Fourteen days between cycles were calculated from the last day of the previous one. The total dose for each cycle was infused over 5 days with simultaneous intravenous calcium folinate. The total cycle dose for the first, second, and third cycles were: 300, 501, and 750.5 mg/m, respectively. RESULTS: The mean serum MTX level was 1.72 µmole/L, whereas that of the pleural fluid was 503.224 µmole/L. The mean serum/pleural ratio was 0.00396, whereas the pleural/serum ratio was 396.21. No remarkable toxicity was observed in the 5 patients except for patient 1 who developed fluid leakage around the puncture site. Patient 2 developed grade I hepatotoxicity and both patients developed grade I pleuritic chest pain and dry irritative cough. CONCLUSIONS: This study demonstrates no grade II toxicity from 750.5 mg/m of MTX infused intrapleural over 5 days. This approach allows attaining MTX pleural levels that are 95 to 3000 times higher than systemic serum levels, with minimal toxicity. The results mandate performing this trial on a wider scale as a preliminary step for a formal phase II study.