The efficacy and safety of itopride in feeding intolerance of critically ill patients receiving enteral nutrition: a randomized, double-blind study.

BACKGROUND: Enteral feeding intolerance (EFI) is a frequent problem in the Intensive care unit (ICU) and is associated with poor clinical outcomes leading to worse prognosis in terms of mortality and ICU stay. Nowadays, prokinetic drugs are the mainstay of therapy in EFI. However, available prokinetics have uncertain efficacy and safety profiles. Itopride, is a prokinetic agent which is different and unique from the available prokinetics because of its dual mode of action as well as its tolerability and safety. The current study compared the efficacy and safety of Itopride against metoclopramide for EFI in critically ill patients. Moreover, it tested the utility and applicability of ultrasonography to measure gastric residual volume (GRV) in this population. METHODS: This randomized, double-blind study included 76 EFI patients who were randomly assigned to either Itopride or metoclopramide group. The primary outcome was to measure GRV by ultrasonography. Secondary outcomes included the percentage ratio of enteral feed volume, energy and protein received by patients over 7 days of treatment, ICU length of stay, safety parameters and occurrence of infectious complications or vomiting. RESULTS: Thirty-five patients of each group completed the study. At day 7, itopride significantly decreased GRV compared with metoclopramide group (p = 0.001). Moreover, there was a significant increase in the ratios of received enteral nutrition feed volume, calories, and protein after the one-week therapy in the itopride group more than the metoclopramide group (p = 0.001), (p = 0.002), (p = 0.01), respectively and there were no differences in any secondary outcomes or adverse events between the two groups. CONCLUSION: In critically ill patients with EFI, itopride was well tolerated with superior efficacy to metoclopramide. In addition, we demonstrated that ultrasonography is a simple, non-invasive, inexpensive, and undemanding method for GRV measurements and can offer reliable assessments in the gastric emptying modality. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov (NCT03698292). Date: October 5, 2018.

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.

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.

Implementation of clinical pharmacy services in a pediatric dialysis unit.

BACKGROUND: End-stage renal disease patients on hemodialysis are on complex drug regimens consisting of multiple medications, many of which are administered in several doses per day. Consequently, such patients are at high risk for developing drug therapy-related problems (DTRPs). The aim of this study was to detect DTRPs in children undergoing hemodialysis and to assess and evaluate the impact of interventions by the clinical pharmacist on the clinical outcome of children undergoing hemodialysis. METHODS: Fifty hemodialysis outpatients were randomly divided into two groups (25 each): the control group and the test group. During the 9-month study period, patients in the control group received the usual medical care, and those in the test group received pharmaceutical care 3 times weekly in addition to the usual medical care. RESULTS: After 9 months of pharmaceutical care implementation, the test group showed a significant decline in systolic and diastolic blood pressure (p = 0.0001), serum phosphorus level (p = 0.006) and parathyroid hormone level (p = 0.001) versus their baseline values and versus the control. The serum Ca*P product level of the test group decreased (p = 0.001) after intervention versus baseline. Serum calcium level significantly increased in test group (p = 0.02) and decreased in the control group (p = 0.001) versus the respective baseline values. Satisfaction with the renal treatment significantly improved in the test group (p = 0.0001) versus the control group after 9 months of pharmaceutical care implementation based on Renal Treatment Satisfaction Questionnaire scores. CONCLUSIONS: Pharmacist-initiated pharmaceutical care improved the satisfaction and biochemical findings of patients on hemodialysis.

The effect of high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients. A randomized placebo controlled trial.

Background and Aim: Non-alcoholic fatty liver (NAFLD) is one of the most common progressive metabolic disorders worldwide. There are increasing scientific interests nowadays for the association between vitamin D status and Non-alcoholic fatty liver. Earlier studies have revealed that vitamin D deficiency is highly prevalent in Non-alcoholic fatty liver patients that contributes to poor outcomes. Hence, the present study aimed to assess the efficacy and safety of oral cholecalciferol on Non-alcoholic fatty liver patients. Subjects and Methods: This study was conducted on 140 patients that were randomized either to group 1 that received the standard conventional therapy in addition to placebo or group 2 that received the standard conventional therapy in addition to cholecalciferol during the 4 months study period. Results: At the end of the study group 2 revealed significant decrease (p < 0.05) in the mean serum level of TG, LDL-C, TC, hsCRP as compared to their baseline results and group 1 results. Additionally, a significant improvement in the serum levels of ALT (p = 0.001) was seen in group 2 at the end of the study when compared to group 1. Whereas group 1 did not show any change in these parameters when compared to group 2 and their baseline results. Conclusion: Cholecalciferol was shown to have beneficial effects on serum ALT levels, hsCRP levels and lipid profile of NAFLD patients. Clinical Trial Registration: https://prsinfo.clinicaltrials.gov/prs-users-guide.html, identifier NCT05613192.

A comparative randomized clinical trial evaluating the efficacy and safety of tacrolimus versus hydrocortisone as a topical treatment of atopic dermatitis in children.

Background: Atopic dermatitis (AD) aetiology is not exactly identified, but it is characterized by pruritic skin reactions with elevation in the levels of inflammatory markers. Despite the fact that Corticosteroids are the mainstay therapy in the management of AD, they have many local and systemic adverse effects. Objective: The aim of this study is to evaluate the efficacy and safety of topical tacrolimus ointment in comparison to topical hydrocortisone cream in the management of the AD of children diagnosed with AD. Patients and Methods: This study was conducted on 200 children with AD. They were simply randomized into two groups, the tacrolimus group treated with 0.03% topical tacrolimus ointment and the hydrocortisone group treated with 1% hydrocortisone cream twice daily during the 3 weeks study period. Results: At the end of the study, both the tacrolimus and hydrocortisone groups showed a significant decline in the mean serum level of IL-10, IL-17, and IL-23 (p < 0.05) when compared to their baseline levels. However, the tacrolimus group showed a more significant decrease (p < 0.05) in the mean serum level of IL-10, IL-17, and IL-23 as compared to the hydrocortisone group [Mean differences = 1.600, 95% CI: 0.9858-2.214; 1.300, 95% CI: 1.086-1.514 and 4.200, 95% CI: 3.321-5.079]. Moreover, the median mEASI decreased similarly from 32 to 21 in the tacrolimus group and from 30 to 22 in the hydrocortisone group (p > 0.05) [Median difference = -2.000, 95% CI: -2.651 to -1.349; Median difference = 1.000, 95% CI: 0.3489-1.651]. Mild to moderate transient stinging and erythema were the main adverse effects that showed higher incidence in the tacrolimus group than in the hydrocortisone group (p < 0.05). In most cases, they resolved within 3-4 days. Besides, tacrolimus ointment did not cause skin atrophy as compared to the hydrocortisone group (p < 0.05). Conclusion: Tacrolimus ointment is more beneficial than hydrocortisone cream in managing AD in children in terms of lowering the inflammatory markers, however, there is no difference on the dermatitis severity scale. Moreover, tacrolimus is safer with a better side effect profile compared to hydrocortisone. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05324618).

The impact of vitamin K2 and native vitamin D supplementation on vascular calcification in pediatric patients on regular hemodialysis. A randomized controlled trial.

BACKGROUND AND AIM: Vascular calcification is one of the most prevalent disorders in pediatric hemodialysis patients that eventually lead to cardiovascular morbidity. Vitamin K2 was investigated in adults in previous studies and showed favorable effects on calcification markers. Our aim in this study was to evaluate the efficacy and safety of vitamin K2 and cholecalciferol on the calcification regulators in pediatric patients. METHODS: A prospective, randomized and controlled trial was conducted on sixty hemodialysis pediatric patients who were divided to four groups; Group 1: administered 100 µg of vitamin K2 (MK-7); Group 2: administered 10 µg of native vitamin D; Group 3: administered 100 µg of vitamin K2 (MK-7) in addition 10 µg of native vitamin D, and Group 4: administered the standard therapy only. The duration of supplementation was 4 months. In addition to a group of healthy normal control of age and sex-matched. RESULTS: At the end of the study period, serum levels of FGF23, dp-uc-MGP, and uc-OC were measured. It was found that serum levels of dp-uc-MGP, uc-OC, and FGF23 were significantly higher (p < 0.05) in the hemodialysis patients as compared to the healthy normal control. After 4 months, group 3 revealed the most significant decrease in dp-uc-MGP, uc-OC as compared to the other groups. However, there was no change in FGF23. CONCLUSION: Vitamin K2 and native vitamin D showed a beneficial effect on calcification regulators in pediatric hemodialysis patients. TRIAL REGISTRATION: clinical trial.gov (NCT04145492).

Evaluation of the combination effect of rutin and vitamin C supplementation on the oxidative stress and inflammation in hemodialysis patients.

Background: Hemodialysis (HD) patients are at risk of malnutrition, cardiovascular complications, and all-cause mortality due to oxidative stress and inflammation. Some studies have demonstrated that rutin attenuates oxidative stress and inflammation in CKD rats, but its effects in HD patients are unknown to date. Aim: The aim of this study was to evaluate the effect of rutin and vitamin C versus vitamin C alone on oxidative stress and inflammation in HD patients. Methods: A prospective randomized, open-label, controlled trial enrolled on hundred and five HD patients divided into three groups as follows: patients in group 1 were given a rutin/vitamin C combination (Ruta C group as the combination trade name is known as Ruta C 60 tablets), patients in group 2 were given vitamin C (1 g) (vitamin C group), and group 3 was the control group; the study period was 16 weeks. The following were assessed at baseline and at the end of the study: serum malondialdehyde (MDA), glutathione peroxidase (GPx), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), lipid profile levels, and erythrocyte sedimentation rate. Results: It was found that vitamin C significantly increased serum GPx in group 2 (p = 0.001) compared to a non-significant result in both group 1 and 3; in addition, serum MDA and TNF-α values had decreased significantly in the three groups compared to their baselines; however, a non-significant difference was seen among the studied groups at the end of the study. On the other hand, MDA levels were reduced by 50% in interventional groups compared to 28% in the control group, while the Ruta C group showed an 80% reduction in the level of TNF α compared to the 78% reduction observed in the vitamin C group, and finally, the interventional drugs showed a significant improvement in the lipid profile. Conclusion: Vitamin C supplementation alone for 16 weeks had a potential effect on the antioxidant's GPx activity. Moreover, it was reported that both vitamin C alone or the rutin/vitamin C combination (Ruta C) showed a protective role against lipid peroxidation, evidenced by the reduced levels of MDA. Finally, rutin had a favorable synergistic effect with vitamin C in reducing TG and TNF-α levels and increasing HDL-C level.

Effect of zinc versus vitamin A supplementation on pediatric patients with community-acquired pneumonia.

Background: Community-acquired pneumonia (CAP) is one of the most common infectious diseases affecting the respiratory tract and is responsible for a high mortality rate in children less than 5 years of age. The mortality rate due to CAP is much higher in low/middle-income countries than in high-income countries due to malnutrition and different micronutrient deficiencies that weaken the immune system. Aim: The aim of this study was to compare the effects of zinc and vitamin A, as two elements of micronutrient agents, on the recovery rate of children suffering from CAP aged from 6 months to 5 years. The length of hospital stays was also investigated. Method: A comparative, randomized, open-label, controlled, interventional study was carried out among children less than 5 years of age in the pediatric intensive care unit (PICU) diagnosed with CAP who were randomly divided into three groups. In addition to the standard therapy, group 1 was given zinc, group 2 was given vitamin A, and group 3 was the control group, given the standard therapy only. We compared the three groups in terms of recovery rate and hospital stay. Result: The duration of hospitalization following zinc and vitamin A supplementation was reduced by an average of 3.21 days (95% CI: 5.01-1.41, p = 0.01) and 2.43 days (95% CI: 4.29-0.57, p = 0.01), respectively, compared to the control group. In addition, the two groups of vitamin A and zinc supplementation were associated with a shorter duration of pneumonic effusion (p < 0.001) in comparison to the control group. Additionally, there was no significant difference between the effects of zinc and vitamin A when compared to each other in terms of duration of hospital stay and pneumatic effusion. Conclusion: The administration of zinc or vitamin A supplementation proved to be useful as an add-on therapy in community-acquired pneumonia, where it reduced the length of hospital stay and the duration of pneumonic effusion in pneumonic children less than 5 years of age.

Effects of Ramipril on Biomarkers of Endothelial Dysfunction and Inflammation in Hypertensive Children on Maintenance Hemodialysis: the SEARCH Randomized Placebo-Controlled Trial.

BACKGROUND: Hypertension, endothelial dysfunction, and inflammation are associated with increased cardiovascular mortality in end-stage kidney disease. We evaluated the effects of ACE (angiotensin-converting enzyme) inhibition on biomarkers of endothelial dysfunction and inflammation in hypertensive children with end-stage kidney disease on maintenance hemodialysis. METHODS: In a randomized, double-blind, placebo-controlled trial, 135 (72 males/63 females) children and adolescents (age 7-15 years) were randomly assigned to treatment with either 2.5 mg once daily ramipril (n=68) or placebo (n=67) for 16 weeks. Primary outcome were the serum concentrations of asymmetrical dimethylarginine, a marker of endothelial dysfunction and hs-CRP (high-sensitivity C-reactive protein), a marker of inflammation. Changes in IL-6 (interleukin-6), TNF-α (tumor necrosis factor-alpha), systolic (S), and diastolic (D) blood pressure were secondary outcomes. Change in potassium levels and incidence of hyperkalemia were among the safety parameters. RESULTS: Ramipril, but not placebo, significantly reduced serum levels of asymmetrical dimethylarginine (-79.6%; P<0.001), hs-CRP (-46.5%; P<0.001), IL-6 (-27.1%; P<0.001), and TNF-α (-51.7%; P<0.001). Systolic blood pressure and diastolic blood pressure were significantly lowered in both groups with a greater reduction in children receiving ramipril (median between-group differences -12.0 [95% CI -18.0 to -9.5] and -9.0 [95% CI -12.0 to -4.5]; P<0.001, respectively). Changes in asymmetrical dimethylarginine, hs-CRP, IL-6, or TNF-α in the ramipril group did not significantly correlate with blood pressure reductions. No severe cases of hyperkalemia or other serious treatment-associated adverse events were observed. CONCLUSIONS: Ramipril improves biomarkers of endothelial dysfunction and inflammation in hypertensive children on maintenance hemodialysis in addition to its efficacious and safe potential to lower blood pressure. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04582097.

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.

Efficacy and safety of active vitamin D supplementation in chronic spontaneous urticaria patients.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disorder affecting negatively patients' lives. Vitamin D deficiency has been reported to be associated to many allergic skin disorders. OBJECTIVE: This study aimed to evaluate the association between the serum level of 25 hydroxy vitamin D and CSU and to assess the efficacy and safety of active vitamin D in management of CSU. METHODS: The study was conducted on 77 patients with CSU and 67 healthy controls, then the 77 CSU patients were randomized to either the study group that received 0.25 µg alfacalcidol daily or the placebo group that received oral placebo for 12 weeks. RESULTS: Serum 25(OH) D was significantly lower in CSU as compared to healthy controls and was negatively correlated to the urticarial severity. After alfacalcidol administration, the study group showed significant higher level of 25(OH) D compared to the placebo group. In addition, the mean serum level of IL6, hsCRP and TNFα significantly decreased in the study group in comparison to the placebo group and as compared to their baseline results. CONCLUSION: Vitamin D deficiency is more common in CSU patients as compared to healthy people and hence, alfacalcidol might have a beneficial role as add on therapy in CSU management with no reported side effects.

The impact of active vitamin D administration on the clinical outcomes of acne vulgaris.

Acne vulgaris is one of the most common chronic inflammatory skin disorder affecting millions of people worldwide. Vitamin D deficiency has a role in various inflammatory skin diseases as acne. This study aimed to investigate the serum level of 25 hydroxy vitamin D in acne patients and to assess the efficacy and safety of active vitamin D in management of acne. This study was conducted on 100 patients with acne and 100 healthy controls, then the 100 acne patients were randomized to either the study group that received 0.25ug alfacalcidol daily or the placebo group that received oral placebo during the 3 months study period. Serum levels of 25-hydroxy-vitamin D were significantly lower in acne patients than in healthy control and were inversely correlated to the severity of acne. After alfacalcidol administration, the study group showed significant higher level of 25(OH) D levels (p < .05) compared to placebo group. In addition, median serum level of IL6 and TNFα significantly decreased (p < .05) in the study group in comparison to placebo group and as compared to their baseline results. Acne patients are more commonly to have vitamin D deficiency as compared to healthy people and hence, alfacalcidol might have a beneficial role in the acne management with no reported side effects.