The Impact of an SGLT2 Inhibitor versus Ursodeoxycholic Acid on Liver Steatosis in Diabetic Patients.

Non-alcoholic fatty liver disease (NAFLD) is related to metabolic syndrome via insulin resistance, where preventing disease progression is crucial in the management process. The study included 240 NAFLD patients with type 2 diabetes who were randomly allocated into empagliflozin 25 mg (EMPA group), ursodeoxycholic acid 250 mg (UDCA group), or the control group (placebo). The study outcomes included: changes in liver fat content (LFC; %) (utilizing the Dixon-based MRI-PDFF approach), liver enzymes, lipid and glycemic profiles, FIB-4 index, and non-alcoholic fatty liver score (NFS). All endpoints were assessed at baseline and after 6 months. EMPA outperformed UDCA and placebo in decreasing LFC (−8.73% vs. −5.71% vs. −1.99%; p < 0.0001). In post-treatment ultrasound images and MRI-PDFF calculations, more patients had normal fatty liver grade (no steatosis or LFC < 6.5%) with EMPA compared to UDCA. EMPA and UDCA showed significant regression in the FIB-4 index (−0.34 vs. −0.55; p = 0.011) and NFS scores (−1.00 vs. −1.11; p = 0.392), respectively. UDCA achieved higher reductions in insulin resistance than EMPA (p = 0.03); however, only EMPA significantly increased beta-cell function (54.20; p = 0.03). When exploring the differences between the two drugs, EMPA was better in decreasing LFC (%), while UDCA achieved higher reductions in liver fibrosis scores. Both showed a similar safety profile in managing liver steatosis.

Comparison of the Treatment Efficacy of Rosuvastatin versus Atorvastatin Loading Prior to Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction.

The aim of this study was to compare the effect of a single high-dose rosuvastatin versus atorvastatin preloading in ST-elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PCI.) Methods: A total of 99 patients presented with STEMI and were randomly divided into three groups­a control group (n = 33) with no statin treatment, an atorvastatin group (n = 33) with a single 80 mg atorvastatin dose and the rosuvastatin group (n = 33) with a single 40 mg rosuvastatin dose in the emergency room (ER) prior to PCI. Post-interventional thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) were recorded, and ST-segment resolution was measured. Results: CTFC was significantly lower for the atorvastatin group (p-value < 0.01) than in the control group. A final TIMI flow grade 3 was achieved in 32 (97.0%) patients in the rosuvastatin group and 28 (84.8%) patients in the atorvastatin group compared with only 25 (75.8%) patients in the control group (p = 0.014). Peak CK-MB in the rosuvastatin group (263.2 [207.2−315.6]) and the atorvastatin group (208 [151.0−314.1]) was lower compared to that in the control group (398.4 [303.9−459.3]); p < 0.001. Conclusions: A single extensive dose of lipophilic atorvastatin prior to primary PCI in STEMI patients showed better improvement in microvascular myocardial perfusion compared to hydrophilic rosuvastatin.

Perceptions and attitudes of ICU physicians toward antibiotics prescribing and resistance: A cross-sectional study.

BACKGROUND AND AIM: Antibiotic resistance is a major emphasis in intensive care units (ICUs). Better understanding of ICU physicians' perceptions, attitudes, and knowledge about antimicrobial prescribing practices could facilitate more effective interventions in fighting antimicrobial resistance in Egyptian ICUs and establishing a proper Antimicrobial Stewardship Program. METHODS: A cross-sectional questionnaire study was conducted including 92 physicians distributed across the different types of Egyptian healthcare institutions in two cities of Egypt; Cairo and El Monufia. Over a period of three months, started in December 2019 and ended in February 2020. RESULTS: A total of 92 Egyptian physicians were included in the study. Seventy (76.1%) of the surveyed physician strongly agreed and 22 (23.9%) agreed that antibiotic resistance is a worldwide problem. Moreover, 50 (54.3%) strongly agreed and 40 (43.4%) agreed that it is a problem in their hospitals while only 2 (2.1%) disagreed. Poor hand hygiene (67.5%), poor infection control practices by healthcare professionals (63.9%) as well as wrong practices in the management of invasive devices (68.7%), and poor environmental cleaning practices (63.4%) were considered very important causes of AMR by the majority of the surveyed ICU physicians. Almost all of the physicians (95%) rated an advice from a clinical pharmacist as very or moderately helpful intervention, while (52%) declared an advice from a microbiologist or an infectious disease specialist as very helpful. CONCLUSION: The results of the present study showed that the Egyptian ICU physicians have remarkable knowledge regarding antibiotic resistance as a worldwide problem and a high sensibility toward the problem in their hospitals. The study also showed that implementation of proper AMS is an urgent need as physicians answers for the different questions in the survey showed that their attitudes and perceptions regarding antibiotic resistance and their way in prescription could be modified and improved if AMS programs with suitable training programs and local guidelines are provided among different types of Egyptian hospitals.

Effect of pressures and type of ventilation on aerosol delivery to chronic obstructive pulmonary disease patients.

Background: Continuous Positive Airway Pressure (CPAP), BiPhasic Positive Airway Pressure (BiPAP), and high flow nasal cannula (HFNC) show some evidence to have efficacy in COVID-19 patients. Delivery during noninvasive mechanical ventilation (NIV) or HFNC gives faster and more enhanced clinical effects than when aerosols are given without assisted breath. The present work aimed to compare the effect of BiPhasic Positive Airway Pressure (BiPAP) mode at two different pressures; low BiPAP (Inspiratory Positive Airway Pressure (IPAP)/Expiratory Positive Airway Pressure (EPAP) of 10/5 cm water) and high BiPAP (IPAP/EPAP of 20/5 cm water), with HFNC system on pulmonary and systemic drug delivery of salbutamol. On the first day of the experiment, all patients received 2500 µg salbutamol using Aerogen Solo vibrating mesh nebulizer. Urine samples 30 min post-dose and cumulative urinary salbutamol during the next 24 h were collected on the next day. On the third day, the ex-vivo filter was inserted before the patient to collect the delivered dose to the patient of the 2500 µg salbutamol. Salbutamol was quantified using high-performance liquid chromatography (HPLC). Results: Low-pressure BiPAP showed the highest amount delivered to the lung after 30 min followed by HFNC then high-pressure BiPAP. But the significant difference was only observed between low and high-pressure BiPAP modes (p = 0.012). Low-pressure BiPAP showed the highest delivered systemic delivery amount followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.017) and high-pressure BiPAP (p = 0.008). No significant difference was reported between HFNC and high-pressure BiPAP. The ex-vivo filter was the greatest in the case of low-pressure BiPAP followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.033) and high-pressure BiPAP (p = 0.008). Also, no significant difference was found between HFNC and high-pressure BiPAP. Conclusions: Our results of pulmonary, systemic, and ex-vivo drug delivery were found to be consistent. The low BiPAP delivered the highest amount followed by the HFNC then the high BiPAP with the least amount. However, no significant difference was found between HFNC and high BiPAP.

Effect of Amlodipine/Nebivolol combination therapy on central BP and PWV compared to Amlodipine/Valsartan combination therapy.

BACKGROUND: Pulse wave velocity (PWV) and central blood pressure (CBP) have been intoduced into managment of hypertensive patients. PWV is positively correlated with arterial wall stiffness while central aortic pressure becomes better predictor of cardiovascular outcome than peripheral pressure. Reduction in CBP provides protective properties against subclinical organ damage. This work aims to investigate the effect of a new combination therapy of Amlodipine/Nebivolol (A/N) on central BP, peripheral BP and PWV. The results of using this combination will be compared to the well-established fixed-dose combination of Amlodipine/Valsartan (A/V). The study conducted between October 2018 and August 2020. One hundred and two hypertensive patients were assigned for Amlodipine 10 mg/Valsartan 160 mg combination therapy (A/V, n = 52) or Amlodipine 10 mg/Nebivolol 5 mg combination therapy (A/N, n = 50) by simple 1:1 randomization. Office, central blood pressure and PWV were measured on first (0 week), second (4-8 weeks) and third visit (10-12). Difference in BP (in each arm and between arms) was calculated along all visits. RESULTS: No statistical significant difference was found between A/V and A/N regarding age, gender, BMI and CV history. OBP, CBP and PWV were significantly reduced in each arm, but no differences were found when comparing both arm results to each other. Recorded side effects were insignificant. CONCLUSIONS: The new combination therapy Amlodipine/Nebivolol (A/N) affords a significant reduction in CBP, PBP and PWV with minor and tolerable side effects. It has provided comparable results to Amlodipine/Valsartan (A/V) combination therapy.

A Battle against COVID-19: Vaccine Hesitancy and Awareness with a Comparative Study between Sinopharm and AstraZeneca.

BACKGROUND: Awareness about the COVID-19 vaccine's adverse effects is crucial for gaining public trust. As we still lack proof of vaccines' safety, this survey aimed to investigate Egyptians' general awareness of the Sinopharm and AstraZeneca vaccines against COVID-19 and provide considerable evidence on their side effects and complications. METHODS: A cross-sectional questionnaire-based study was conducted in Egypt between 20 September and 10 October in 2021, with multiple-choice questions (MCQs) covering all data on vaccine administration confusion, adverse effects or intensity, and complications. RESULTS: Among the 390 participants, 42.3% reported being hesitant before receiving one of the vaccines. About 40.3% of participants were previously infected before getting vaccinated while only 4.6% reported being infected after vaccination. The AstraZeneca vaccine demonstrated higher side effects and symptoms than the Sinopharm vaccine while the Sinopharm vaccine showed a significantly higher rate of COVID-19 infection after vaccination. CONCLUSIONS: People with higher educational levels and chronic respiratory diseases represent an excellent model for accepting COVID-19 vaccination. A booster shot is recommended for people vaccinated with the Sinopharm vaccine due to a significantly higher rate of COVID-19 infection after vaccination; however, the Sinopharm vaccine shows a more acceptable safety profile.

A New Clinical Utility for Tubular Markers to Identify Kidney Responders to Saxagliptin Treatment in Adults With Diabetic Nephropathy.

OBJECTIVES: In recent clinical studies, saxagliptin exhibited nephroprotective potential by lowering albuminuria. In this study, we aimed to determine whether these kidney effects of saxagliptin were mediated by changes in markers of kidney tubular damage, including urinary neutrophil gelatinase-associated protein (uNGAL) and liver-type fatty acid-binding protein (uL-FABP). METHODS: Our study included 80 patients with type 2 diabetes, hypertension and mild to moderate diabetic kidney disease (DKD) with prevalent albuminuria. Patients were either randomly assigned to saxagliptin as add-on therapy or remained unchanged on their stable antidiabetic therapy as a control arm. RESULTS: Saxagliptin significantly reduced uNGAL with a median change of -25.4% (interquartile range [IQR], -35.6% to -12.2%) compared with the control group (median change, -0.91%; IQR, -12% to 11.88%; p<0.001) after 3 months. Similarly, patients given saxagliptin had a highly significant reduction in uL-FABP (median change, -24.4%; IQR, -30.5% to -15.1%) compared with controls (median change, -3.8%; IQR -10% to 12.5%; p<0.001). Median estimated glomerular filtration rate (eGFR) values after 3 months in the saxagliptin arm were significantly higher (76.5 mL/min per 1.73 m2; IQR, 70 to 92.75 mL/min per 1.73 m2) in the low-risk uNGAL group compared with controls (59.8 mL/min per 1.73 m2; IQR, 51 to 76.2 mL/min per 1.73 m2; p=0.002). Also, higher-although not significantly-posttreatment eGFR levels were observed in patients with low risk of uL-FABP (73 mL/min per 1.73 m2; IQR, 58 to 91.3 mL/min per 1.73 m2) compared with controls (57.3 mL/min per 1.73 m2; IQR, 49.5 to 72.6 mL/min per 1.73 m2; p=0.06). No significant increase was observed in high-risk patients for either marker when compared with controls. CONCLUSIONS: The albuminuria-lowering effect of saxagliptin may be due to inhibition of kidney tubular damage. Use of tubular markers may be a promising approach to identifying kidney responders to gliptins.

Recent therapeutic targets in diabetic nephropathy.

BACKGROUND: The prevalence of diabetes mellitus has been increased dramatically which in turn leads to complications including cardiovascular diseases, diabetic kidney disease, and substantially end-stage renal disease. METHODS: We reviewed articles discussing the pathophysiology of diabetic nephropathy with new agents that may be useful in the management of the disease. We used PubMed, Scopus, Google Scholar and the Open-access searching engines. RESULTS: The recent recommendations primarily depend on glycaemic and blood pressure control and the use of standard renin-angiotensin system blockade. Currently, the use of agents with nephroprotective effects beyond the hyperglycaemic lowering effect has been evidenced clinically. CONCLUSIONS: In his review, the pathophysiology, clinical manifestations, and lines of treatment of diabetic nephropathy are discussed. In addition, a focus on the clinical role and nephroprotective effects of the emerging therapeutic class, dipeptidyl peptidase IV (DPP-4) inhibitors, is addressed in detail.

Aerosol delivery aspects within a high-flow therapy system in COPD patients.

There is a lack of information about the influence of patient interfaces such as facemasks or mouthpieces on the effective dose of aerosolised drugs while using high-flow therapy in a clinical setting. These interfaces can improve pulmonary drug delivery over nasal cannulas but patient preference and comfort should also be considered. The present work was to determine the effect of three different interfaces (nasal cannula, valved face mask, and mouthpiece) when combined with titrated oxygen flow on aerosol delivery in patients with COPD hospitalised due to acute exacerbation. The variations between these interfaces were addressed in terms of change in lung function measurements pre-and post-inhalation, the delivered salbutamol dose, and patient tolerance to each interface. A high-flow nasal cannula was the most comfortable interface used. However, its pulmonary drug delivery was significantly lower than both the valved face mask and mouthpiece (p<0.05). Although drug delivery was different with the three tested interfaces, the lung function improvements were similar.

Effect of ciprofloxacin vs levofloxacin on QTc-interval and dysglycemia in diabetic and non-diabetic patients.

BACKGROUND: Levofloxacin and ciprofloxacin are more commonly used amongst fluoroquinolone class and the question of cardiac safety and glucose hemostasis of this class has been raised. OBJECTIVE: To compare intravenous levofloxacin and ciprofloxacin regarding their risk on QTc prolongation and dysglycemia in diabetic and non-diabetic patients. METHODS: A randomised prospective study at Beni-Suef university hospital was conducted on 200 adult patients over 6 months. The patients received intravenous levofloxacin 750mg once daily or ciprofloxacin 400mg twice daily. Electrocardiogram and fasting blood glucose were obtained from each patient before starting the antibiotic, 24 hours, 72 hours after the first dose, and 72 hours after antibiotics cessation. RESULTS: The results of the current study showed the relative risk for QTc prolongation with levofloxacin was more than ciprofloxacin by about 4 and 1.5 times in diabetic and non-diabetic patients, respectively. The relative risk for dysglycemia with levofloxacin was 2.28 and 1.39 times more than ciprofloxacin in diabetic and non-diabetic patients, respectively. CONCLUSION: The present study showed that the risk for QTc prolongation and hyperglycemia was greater with levofloxacin than ciprofloxacin in diabetic and non-diabetic patients. In addition, the risk for hypoglycemia was greater with levofloxacin than ciprofloxacin in non-diabetic patients.

A randomized trial to compare procalcitonin and C-reactive protein in assessing severity of sepsis and in guiding antibacterial therapy in Egyptian critically ill patients.

BACKGROUND: Procalcitonin (PCT) and C-reactive protein (CRP) are the main used biomarkers for sepsis and in guiding antibiotic therapy, although PCT high cost limits its use in developing countries. OBJECTIVE: Comparing between PCT and CRP in assessing severity of sepsis and in guiding antibacterial therapy in critically ill patients. METHODS: In a prospective randomized study, 60 patients were included from an Egyptian Intensive Care Unit. Patients were divided into CRP and PCT groups. CRP and PCT were measured at baseline and on days 4 and 7. Validity, sensitivity, and specificity of both biomarkers and their correlation with sepsis scores (Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sepsis-related Organ Failure Assessment (SOFA)) were evaluated. Antibacterial continuation at days 4 and 7 was assessed. RESULTS: The diagnostic accuracy, specificity, and sensitivity of PCT were higher than CRP (80.79% vs 69.45%, 36% vs 28.7%, 87.6% vs 72.4%, respectively). PCT levels were significantly correlated with APACHE II score (P ≤ 0.0001) and SOFA score (P = 0.005), while CRP levels were not correlated with APACHEII and SOFA scores,(P > 0.05). PCT was associated with less antibacterial exposure (33% stopped their antibiotics on day 4 versus 6% in CRP, P = 0.009). Only 33% continued their antibacterial regimen in PCT group after 7 days versus 83% in CRP group (*P ≤ 0.0001). CONCLUSION: PCT is a more accurate diagnostic and prognostic biomarker than CRP in patients with sepsis. PCT significantly shortened patients' exposure to antibacterial therapy and hospital length of stay.

In vitro and in vivo performance modelling and optimisation of different dry powder inhalers: A complementary study of neural networks, genetic algorithms and decision trees.

INTRODUCTION: Aerosol delivery from DPIs could be affected by different factors. This study aimed to evaluate and predict the effects of different factors on drug delivery from DPIs. METHODS: Modelling and optimisation for both in vitro and in vivo data of different DPIs (Diskus, Turbohaler and Aerolizer) were carried out using neural networks associated with genetic algorithms and the results are confirmed using a decision tree (DT) and random forest regressor (RFR). All variables (the type of DPI, inhalation flow, inhalation volume, number of inhalations and type of subject) were coded as numbers before using them in the modelling study. RESULTS: The analysis of the in vitro model showed that Turbohaler had the highest emitted dose compared with the Diskus and the Aerolizer. Increasing flow resulted in a gradual increase in the emitted dose. Little differences between the inhalation volumes 2 and 4 litres were shown at fast inhalation flow, and interestingly two inhalations showed somewhat higher emitted doses than one-inhalation mode with Turbohaler and Diskus at slow inhalation flow. Regarding the in vivo model, the percent of drug delivered to the lung was highly increased with Turbohaler and Diskus in healthy subjects where continuous contour lines were observed. The Turbohaler showed increased lung bioavailability with the two-inhalation modes, the Diskus showed a nearly constant level at both one and two inhalations at slow inhalation. The Turbohaler and Aerolizer showed little increasing effect moving from one to two inhalations at slow inhalation. CONCLUSIONS: Modelling of the input data showed a good differentiating and prediction power for both in vitro and in vivo models. The results of the modelling refer to the high efficacy of Diskus followed by Turbohaler for delivering aerosol. With two inhalations, the three DPIs showed an increase in the percent of drug excreted at slow inhalations.

Saxagliptin and vildagliptin lowered albuminuria in patients with diabetes and hypertension independent on glycaemic control.

BACKGROUND: Preclinical data illustrated that the dipeptidyl peptidase-4(DPP-4) inhibitors did lower urinary albumin excretion in diabetes-induced rats. We evaluated the effects of saxagliptin and vildagliptin on albuminuria in patients with diabetic nephropathy on top of the renin-angiotensin-aldosterone system (RAAS) blockade therapy. METHODS: This study included 120 patients with type 2 diabetes (T2D), hypertension, and prevalent albuminuria [defined as urine albumin-to-creatinine ratio (UACR) 30-3000mg/g creatinine] on a stable dose of olmesartan as a standard RAAS blocker for diabetic nephropathy. Patients were assigned to receive either of saxagliptin 5mg/day (n = 40), vildagliptin 100mg/day (n = 40), or traditional antidiabetic therapy as control patients (n = 40) for 12 weeks. RESULTS: Each of saxagliptin and vildagliptin significantly reduced albuminuria after 12 weeks, with mean percentage changes (%) of -57.9% [95% confidence interval (CI) -66.1 to -49.8], and -55.2% (95% CI -64.9 to -45.4); P < .001, respectively, compared with the control group. Significantly, saxagliptin shifted higher proportions of patients towards lower albuminuria categories (P < .001) compared with vildagliptin despite a similar UACR rate of changes. Results of binary logistic models confirmed that the change in UACR because saxagliptin was independent of changes in systolic blood pressure (SBP), glycated hemoglobin (HbA1c ), estimated glomerular filtration rate (eGFR), or body weight (overall regression: P = .002, R2  = 0.398) vs control. Likewise, vildagliptin reduced UACR independently on other confounders (overall regression: P = .002, R2  = 0.388). Furthermore, no significant correlation was observed between the change in UACR and changes in HbA1c, SBP or eGFR with either saxagliptin or vildagliptin (Pearson coefficients: 0.203, 0.143, -0.190; P > .05, and 0.003, 0.241, 0.019; P > .05, respectively). CONCLUSIONS: DPP-4 inhibitors, saxagliptin, and vildagliptin, resulted in substantial reductions in albuminuria in patients with T2D and hypertension on top of RAAS blockade after short term therapy independently on glycaemic or hemodynamic changes. Saxagliptin was superior to vildagliptin in albuminuria-categorical shifting.

Safety and Efficacy of Pharmaco-invasive Approach Using Streptokinase Compared With Primary Percutaneous Coronary Angiography.

BACKGROUND: Fibrin-specific fibrinolytics are preferred when they used in STEMI patients (pharmaco-invasive approach). However, streptokinase is still the most common used thrombolytic agent in Egypt because of its cheaper cost. METHODS: 266 STEMI patients were randomly assigned to undergo PPCI or pharmacoinvasive (using streptokinase). Primary end point (death, shock, congestive heart failure, or reinfarction up to 30 d) and secondary end point (ischemic stroke, intracranial hemorrhage, or nonintracranial bleeding) were followed for 30 days after reperfusion. In pharmaco-invasive arm, urgent coronary angiography was performed in case of failed reperfusion. Based on the reperfusion time from symptoms onset, patients in both arms were divided into; early (≤3 hrs) and late reperfusion (>3 hrs). RESULTS: No statistical significant difference regarding left ventricular ejection fraction, end diastolic and end systolic diameter in both arms. Early PPCI (≤3 hrs) had highest ejection fraction values (56.9 ± 7.5). Myocardial wall preservation was best achieved in early pharmaco-invasive (≤3 hrs).There was no statistical significant difference in TIMI flow results between all subgroups (early and late of both arms) (P = 0.750). Suction devices and IV Eptifibatide were less frequently used in the pharmaco-invasive comparing to PPCI arm; (P = 0.000 and P = 0.006) subsequently. No statistical significant difference regarding complication incidence in both arms (P = 0.518). Radial access was more commonly used in the pharmaco-invasive arm (P = 0.015). CONCLUSION: Utilizing streptokinase in early re-perfused patients by PI approach (≤3 hrs) seems safe and efficient when PPCI delay (>120 min from symptom onset) is the other option.

The impact of changing patient interfaces on delivering aerosol with titrated oxygen in the high flow system.

INTRODUCTION: Despite the widespread oxygen-culture as more is better in prehospital and hospital settings, the use of titrated oxygen-flow within a high-flow system can be beneficial especially when combined with aerosol-delivery and also save the patient from unnecessary-hyperoxia. METHODS: Forty-five COPD patients were included in this study where they allocated in three-groups (nasal-delivery, oral-delivery, and oronasal-delivery groups). All patients were received their inhaled-salbutamol dose using Aerogen Solo nebuliser by one of the three interfaces, eg, nasal-cannula, mouthpiece, and facemask in two conditions; with oxygen-flow and without any oxygen-flow. Pulmonary and systemic salbutamol deposition was estimated by collecting two urine-samples from the patient; 30 min post-inhalation and cumulatively 24 hr post-inhalation. The quantity of salbutamol in these collected samples was measured by high-performance liquid chromatography. Lung function measurement was performed pre-bronchodilator inhalation and 30 min post-bronchodilator to estimate the change in pulmonary functions post-inhalation regarding all tested interfaces. RESULTS: COPD patients showed the highest salbutamol percentage excreted 30 min post-inhalation of 5.7% (1.4) with mouthpiece interface when combined with oxygen at P < .002. While with the same condition using oxygen, valved-facemask showed the highest salbutamol percentage excreted in 24 hr post inhalation samples but the difference is only significantly compared with nasal cannula (P < .006). Moreover, without oxygen delivery, mouthpiece and valved facemask showed approximately the same salbutamol percentage excreted in 30 min post-inhalation samples, higher than that delivered by nasal cannula (P < .001). Of note, salbutamol delivery is significantly increased with oxygen flow for all interfaces (P < .05) except with nasal cannula. CONCLUSIONS: The nasal cannula is a more comfortable and tolerable interface despite the lower fraction of the delivered drug compared with other tested interfaces. The use of oxygen-flow with aerosol delivery within a high flow system positively affects the delivered drug fraction and the pulmonary deposition of the drug.

Applicability of American College of Clinical Pharmacy (ACCP) competencies to clinical pharmacy practice in Egypt.

BACKGROUND: The American College of Clinical Pharmacy (ACCP) prepared clinical pharmacist competencies that have specific recommendations. Recently, many efforts to advance clinical pharmacy services in Egypt exist. The literature revealed that no country has assessed the extent of applicability of ACCP competencies in its current pharmacy practice setting. Egyptian pharmacists can provide feedback about applicability of such competencies in clinical pharmacy settings in Egypt. OBJECTIVE: The objective of this study was to investigate the extent to which ACCP competencies were implemented by Egyptian clinical pharmacists and therefore evaluate development of clinical pharmacy practice in Egypt. The study also investigated factors affecting the applicability of such competencies in the current clinical pharmacy practice setting in Egypt. METHODS: Four hundred and ninety-five randomly selected clinical pharmacists from several hospitals were invited to participate in a cross sectional survey using a self-administered validated questionnaire composed of 31 questions classified into six domains. This questionnaire was designed to determine the pharmacists' perception about applicability of ACCP competencies to clinical pharmacy practice in Egypt. RESULTS: The response rate was 64% as 317 out of 495 pharmacists completed the questionnaire. These pharmacists were categorized according to age; gender; qualifications; years of previous work experience, years since BSc. and type of hospitals they are currently working at. Analysis of data revealed the professionalism domain to have the highest percentage of acceptance among pharmacists, while the system-based care & population health domain had the lowest percentage of acceptance. Results also showed that qualifications of participants did not affect their response in three domains; "Direct Patient Care", "Systems-based Care & Population Health" and "Continuing Professional Development" (p=0.082, 0.081, 0.060), respectively. Nevertheless, qualifications of participants did affect their response in the other three domains; "Pharmacotherapy Knowledge", "Communication" and "Professionalism" (p<0.05). The age of pharmacists, gender, years of previous work experience, and graduation year did not affect their responses in all six domains. The type of hospital they are currently working at, though, affected their responses where, there was a highly statistically significant increase of the mean score of all domains among participants working at the NGOs/private hospitals compared to governmental hospitals (p<0.001). CONCLUSIONS: Egyptian pharmacists generally apply high percentage of ACCP competencies but the provided clinical pharmacy services need to be improved through applying the standards of best practice.

Corrigendum to "Protective Effects of Simvastatin, a Lipid Lowering Agent, Against Oxidative Damage in Experimental Diabetic Rats".

[This corrects the article DOI: 10.1155/2011/167958.].

Effects of enalapril and paricalcitol treatment on diabetic nephropathy and renal expressions of TNF-α, p53, caspase-3 and Bcl-2 in STZ-induced diabetic rats.

This study aimed to assess the renopreventive effect of enalapril and/or paricalcitol on streptozotocin (STZ) diabetes-induced nephropathy and to elucidate their mechanisms of action through investigation of the effects on renal oxidative stress, antioxidant defense system and expressions of TNF-α, p53, caspase-3, and Bcl-2. Diabetes mellitus was induced in fasting male Wistar rats by single intraperitoneal injection of STZ (45 mg /kg b.w.) dissolved in citrate buffer (pH 4.5). Ten days after STZ injection, the diabetic rats were treated with enalapril (25 mg/l of drinking water) and/or paricalcitol (8 µg/kg b.w. per os) dissolved in 5% DMSO daily for 4 weeks. The obtained data revealed that the treatment of diabetic Wistar rats with enalapril and/or paricalcitol led to significant decreases in the elevated serum urea, uric acid, creatinine, sodium and potassium levels; thereby reflecting the improvement of the impaired kidney function. The deteriorated kidney lipid peroxidation, GSH content and GST and catalase activities in diabetic rats were significantly ameliorated as a result of treatment with enalapril and/or paricalcitol. The elevated fasting and post-prandial serum glucose levels and the lowered serum insulin and C-peptide levels were also improved. The treatment with enalapril and paricalcitol in combination was the most potent in decreasing the elevated serum glucose levels. Moreover, the treatment of diabetic rats successfully prevented the diabetes-induced histopathological deleterious changes of kidney and islets of Langerhans of pancreas. In association, the immunohistochemically detected pro-inflammatory cytokine, TNF-α, and apoptotic mediators, p53 and caspase-3, were remarkably decreased in kidney of diabetic rats as a result of treatment while the expression of anti-apoptotic protein Bcl-2 was increased. Based on these findings, it can be concluded that enalapril and paricalcitol alone or in combination can prevent STZ diabetes-induced nephropathy through amelioration of the glycemic state and antioxidant defense system together with the suppression of oxidative stress, inflammation and apoptosis. However, the treatment of diabetic rats with enalapril and paricalcitol in combination has no further significant improvement effects on renal function and damage when compared with enalapril or paclitaxel treated diabetic groups.

Effect of Oxygen Flow on Aerosol Delivery From a Nebulizer With a Holding Chamber.

BACKGROUND: A new holding chamber was designed to be used with a vibrating mesh nebulizer to increase the total inhalable dose for patients. It facilitates intermittent and continuous nebulization as well as the optional supply of supplemental oxygen via a T-piece with a mouthpiece adapter. This study aimed to evaluate the effect of oxygen introduction in the new holding chamber on aerosol delivery using a vibrating mesh nebulizer. METHODS: The study was divided into 2 parts. First, the total inhalable dose of 1 mL of a respirable solution (nominal dose of 5,000 µg-salbutamol) was determined using a breathing simulator set to provide a tidal volume of 500 mL, a breathing frequency of 15 breaths/min, and an inspiratory:expiratory ratio of 1:1 for adults as a quiet-breathing pattern. Three experimental nebulizer setups were used: a vibrating mesh nebulizer with the holding chamber and oxygen set at 6 L/min, a vibrating mesh nebulizer with the holding chamber and no oxygen, and a vibrating mesh nebulizer with the T-piece. Aerodynamic particle size characterizations were determined using cooled Andersen cascade impaction at an inhalation flow of 15 L/min. Second, we performed an in vivo study involving 12 healthy non-smoking subjects (6 female) who were > 18 y old with an average FEV1 > 90% of predicted. Using normal tidal breathing, subjects inhaled 1 mL of nebulized salbutamol (5,000 µg) through the vibrating mesh nebulizer with the holding chamber with and without oxygen and through the vibrating mesh nebulizer with a T-piece. To analyze salbutamol content, urine samples were obtained 30 min after dosing as an index of lung deposition, and their urine was cumulatively collected for 24 h as an index of systemic absorption. RESULTS: The holding chamber significantly increased the total inhalable dose or amount of salbutamol excreted in the first 30 min, as well as the amount of salbutamol excreted over a 24-h period compared to the dose received with the vibrating mesh nebulizer with a T-piece (P = .005, P = .034, and P = .02, respectively), and relatively decreased the mass median aerodynamic diameter, although the difference was not significant. However, when oxygen was introduced in the holding chamber, the total inhalable dose, or amount of salbutamol excreted in the first 30 min, significantly decreased compared to use without oxygen (P = .003, P = .03 respectively). No significant difference was found between the vibrating mesh nebulizer with the holding chamber with oxygen and the vibrating mesh nebulizer with a T-piece. CONCLUSIONS: The vibrating mesh nebulizer with a holding chamber and without oxygen resulted in much better aerosol delivery compared to vibrating mesh nebulizer with a holding chamber and with oxygen delivery and to the vibrating mesh nebulizer with a T-piece. The use of oxygen with the holding chamber significantly decreased aerosol delivery and its benefit, and recommended flow should be reevaluated.

Inhaled salbutamol from aerolizer and diskus at different inhalation flows, inhalation volume and number of inhalations in both healthy subjects and COPD patients.

The aim of the present study was to demonstrate the effect of inhalation-flow, inhalation-volume and number of inhalations on aerosol-delivery of inhaled-salbutamol from two different dry powder inhalers (DPIs) in both healthy-subjects and chronic obstructive pulmonary disease (COPD) patients. Relative pulmonary-bioavailability and systemic-bioavailability of inhaled-salbutamol, delivered by Diskus and Aerolizer, was determined in 24-COPD patients and 24-healthy subjects. The healthy-subjects and the COPD-patients participated in the study for 7 days in which they received 4 study doses of 200 µg salbutamol (one slow-inhalation, two slow-inhalations, one fast-inhalation, and two fast-inhalations) in four alternative days with 24 hr washout period after each dose. Two urine-samples were collected from each study subjects. The first was provided 30 min post inhalation (USAL0.5), as an index of relative pulmonary-bioavailability, and the second was pooled to 24 hr post inhalation (USAL24), as an index of systemic-bioavailability. Fast-inhalation resulted in significantly higher USAL0.5 and USAL24 than slow-inhalation (p˂0.05) after one-inhalation in both healthy-subjects and COPD-patients but there was no significant difference between slow and fast-inhalation after two-inhalations. One-inhalation resulted in significantly higher USAL0.5 and USAL24 in healthy-subjects compared to COPD-patient at both slow and fast-inhalation (p˂0.05) except USAL0.5 with Diskus at slow-inhalation there was no significant difference. Also, two-inhalations resulted in significantly higher USAL0.5 and USAL24 compared to one-inhalation at slow-inhalation only (p˂0.05). No significant difference was found between Aerolizer and Diskus except in USAL0.5 of one slow-inhalation in both health-subjects and COPD-patients (p = 0.048 and 0.047, respectively). Device-formula relation is present at low inhalation-flow since Diskus resulted in significantly higher USAL0.5 and USAL24 in healthy-subjects compared to COPD-patient at slow inhalation than Aerolizer. It is essential to inhale-twice and as hard and deep as possible from each dose when using DPI especially with COPD-patients having poor inspiratory efforts such as elderly patients and children.