The effectiveness and pharmacoeconomic study of using different corticosteroids in the treatment of hypersensitivity pneumonitis.

PURPOSE: Interstitial lung diseases (ILDs) are caused by inflammation and/or fibrosis of alveolar walls resulting in impaired gas exchange. Hypersensitivity pneumonitis (HP) is the third most common type of ILDs. Corticosteroids are the mainstay treatment for HP. The use of intramuscular (IM) betamethasone or intravenous (IV) dexamethasone as weekly pulse doses has shown higher benefit than daily oral prednisolone for HP patients. The aim of this study is to directly compare different corticosteroids in terms of effectiveness and in monetary values and perform an economic evaluation. METHODS: One hundred and seven patients were tested for pulmonary function tests (PFTs) and inflammatory markers to assess the treatment effectiveness. A cost-effectiveness analysis (CEA) was performed. ICERs between 3 treatment groups were calculated. RESULTS: Post treatment, Krebs von den Lungen-6 (KL-6) levels significantly improved in betamethasone group from 723.22 ± 218.18 U/ml to 554.48 ± 129.69 U/ml (p = 0.001). A significant improvement in erythrocyte sedimentation rate (ESR) occurred in the dexamethasone group from 56.12 ± 27.97 mm to 30.06 ± 16.04 mm (p = 0.048). A significant improvement in forced expiratory volume (FEV1), forced vital capacity (FVC) and six-minute walk distance (6MWD) was observed within the three treatment groups. A significant improvement in oxygen desaturation percentage (SpO2) occurred within dexamethasone and betamethasone groups. Betamethasone and dexamethasone were found more cost-effective than prednisolone as their ICERs fell in quadrant C. Furthermore, ICER between betamethasone and dexamethasone was performed; a small difference in cost was found compared to the higher benefit of betamethasone. CONCLUSION: Betamethasone and dexamethasone were found to be more effective than prednisolone in improving the inflammatory reaction and the clinical features of HP patients. Betamethasone was found to be the best intervention in terms of cost against the effect.

Knowledge, attitude, and practice of insulin among diabetic patients and pharmacists in Egypt: "cross-sectional observational study".

BACKGROUND: Diabetes recently has been identified as a growing epidemic. Although insulin's vital role in both types of diabetes, it is considered one of the harmful medications if used incorrectly. In Egypt, effective usage of insulin remains a challenge due to insufficient knowledge of insulin and diabetes management, leading to errors in insulin therapy. As pharmacists are experts in pharmacological knowledge, they are uniquely situated to assess adherence to treatment regimens, the effect of drug therapy, or potential alterations in drug therapy to meet patient goals. To provide effective patient education and counseling, community pharmacists in Egypt should be efficiently knowledgeable about diabetes and insulin. OBJECTIVE: To identify the knowledge, attitude, and practice of pharmacists and patients about insulin. To identify pharmacists' educational preparedness and confidence in counseling diabetic patients. METHODS: A descriptive, cross-sectional study was conducted with two knowledge, attitude, and practice surveys. This study was carried out from September 2016 to February 2023. Face-to-face interviews were conducted with patients, and a paper-based questionnaire was administered to pharmacists. The two questionnaires were adapted from previous studies. RESULTS: A total of 492 patients and 465 pharmacists participated in this study. The mean knowledge score of correct answers among patients and pharmacists was 10.67 ± 1.9 and 15 ± 3.6. Most of the patients and pharmacists had a positive attitude regarding insulin's role in improving health and to better control blood glucose. On the negative side, around half of the patients reported that they believe that regular use of insulin leads to addiction, while only 14.5% of the pharmacists believed that insulin could cause addiction. Self-confidence scores for pharmacists differed statistically with sex, years of experience, and pharmacist's direct exposure to diabetic patients. CONCLUSIONS: This study uncovers considerable deficiencies in patients' and pharmacists' knowledge about insulin therapy. This study also strongly recommends higher education and a more structured pharmacist training schedule.

The effect of vitamin K4 supplementation on insulin resistance in individuals with type 2 diabetes: a double-blind randomised placebo-controlled clinical trial.

PURPOSE: The purpose of this study was to assess the possible clinical effects of vitamin K4 supplementation in individuals with type 2 diabetes namely insulin resistance, glycaemic control, and lipid profile. METHODS: This was a prospective randomised double-blind placebo-controlled clinical trial. A total of 106 patients were randomised to receive either 1 mg of vitamin K4 (menadiol diacetate) or placebo for 24 weeks. RESULTS: Ninety patients (n = 45 in each study group) were included in the final analysis. After 24 weeks, homeostatic model assessment of insulin resistance (HOMA-IR) (16.54 ± 7.81 vs. 29.09 ± 36.56, P = 0.027) and fasting serum insulin (FSI) (6.86 ± 3.45 vs. 11.13 ± 12.66 µU/ml, P = 0.032) were significantly lower in the vitamin K group compared to placebo. Additionally, triglycerides (TG) (144.94 ± 50.7 vs. 172.8 ± 101.5 mg/dl, P = 0.031) and very low-density lipoproteins (VLDL) levels (28.9 ± 9.88 vs. 34.6 ± 20.30 mg/dl, P = 0.027) decreased significantly in the vitamin K group after 24 weeks compared to baseline. Moreover, more patients in the vitamin K group (35.6%) had their antidiabetic medication doses reduced after 24 weeks compared to placebo (13.3%, P = 0.029). CONCLUSION: Vitamin K4 supplementation for 24 weeks is capable of improving insulin resistance and TG levels in individuals with type 2 diabetes. In addition, the improvement in insulin resistance was reflected in the decrease in antidiabetic medication doses. However, it did not affect fasting plasma glucose (FPG) or glycated haemoglobin (HbA1c). TRIAL REGISTRATION: The study was registered on clinicaltrials.gov with ID: NCT04285450.

Testing P2Y12 platelet inhibitors generics beyond bioequivalence: a parallel single-blinded randomized trial.

Cardiovascular diseases are the leading cause of death worldwide. Ticagrelor is an oral antiplatelet drug used in acute coronary syndrome. Although generic drugs are approved for their bioequivalence to the original product, they are not necessarily to be therapeutically equivalent. This study was conducted to prove the efficacy and safety of ticagrelor generically named Ticaloguard® compared to its brand Brilique® in healthy volunteers. A loading dose of 180 mg ticagrelor named Brilique® or Ticaloguard® followed by a 90 mg twice daily regimen as maintenance dose was given to 14 and 15 volunteers in Tica and Brili groups, respectively. The platelet aggregation on the ADP agonist was assessed at baseline and repeated 1 h and 3 h after the loading dose, on day 4 (after reaching steady-state), 12 and 24 h after discontinuation of the antiplatelet drug. Adverse effects from trial medications were noted by direct questions. It was shown that generic Ticaloguard® provides a similar therapeutic effect and safety as its branded Brilique® (p > 0.05). This will permit safe and trusted use of the generic Ticaloguard® when treating it in the same manner as Brilique®. Testing generic drug effects rather than simple bioequivalency, especially for drugs that are used in critical life-threatening situations, is crucial. We advocate applying this form of a clinical trial to test surrogate clinical efficacy for generics used in critical indications before having real-world data whenever possible.

A prospective, randomised clinical study comparing triple therapy regimen to hydrocortisone monotherapy in reducing mortality in septic shock patients.

OBJECTIVES: This prospective, comparative and randomised clinical study evaluated the effectiveness of triple therapy regimen (hydrocortisone, thiamine and vitamin C) versus hydrocortisone alone in reducing the mortality rate and preventing progressive organ dysfunction in septic shock patients. METHODS: A total of 94 patients were randomly assigned to one of two groups: the first group received hydrocortisone 50 mg/6-h IV for 7 days or till intensive care unit (ICU) discharge, if sooner, followed by tapering. The second group received hydrocortisone 50 mg/6-h IV for 7 days or ICU discharge followed by tapering, vitamin C 1.5 g/6-h IV for 4 days or till ICU discharge and thiamine 200 mg/12-h IV for 4 days or till ICU discharge. RESULTS: The triple therapy regimen showed a non-significant reduction in 28-day mortality compared to hydrocortisone alone (17 [36.2%] vs. 21 [44.7%]; P = .4005), but it was significantly lower than the control group regarding shock time and the duration of vasopressor use in days (4.000 [3.000-7.000]; 5.000 [4.000-8.000], [P = .0100]). The patients in the control group were likely to get 0.59 more in SCr level than those in the intervention group by a linear regression model which was significant (P < .05). Also, the number of patients who developed a fever after 216 hours was significantly higher in the control group (P value = .0299). CONCLUSION: Vitamin C, thiamine, and hydrocortisone regimen for septic shock management showed non-significant efficacy in decreasing 28-day mortality when compared to hydrocortisone monotherapy. On the other hand, it showed significant efficacy in decreasing the shock time and duration on vasopressors.

Antimicrobial stewardship solutions with a smart innovative tool.

BACKGROUND: Antimicrobial consumption has been increasing lately. Hence, effective strategies are required to control antimicrobial use and decrease the development of antimicrobial resistance. OBJECTIVE: To evaluate the impact of the use of a mobile app on the implementation of antimicrobial stewardship program (ASP) interventions. METHODS: This was a longitudinal study conducted at El-Nile Badrawi Hospital in Cairo, Egypt, on inpatients receiving antimicrobials from January 2018 to December 2019. The study included 2 phases: the preimplementation phase, which included a paper-based ASP developed according to the Centers for Disease Control and Prevention Core Elements of Hospital Antibiotic Stewardship Programs 2014, and the mobile app phase where the MEDIcare Pro mobile app was developed and used in ASP intervention implementation. The study outcomes were antimicrobial consumption and cost, length of hospital and intensive care unit (ICU) stay, 30-day mortality rate and readmission rate, and detection of drug-related problems (DRPs). RESULTS: The mobile app statistically significantly decreased antimicrobial consumption from 75.1 defined daily dose (DDD)/100 bed-days in the preimplementation phase to 64.65 DDD/100 bed-days in the mobile app phase, with a total cost savings of E£1,237,476. There was a significant reduction in the length of ICU stay, with a mean difference of 1.63 days between the 2 phases, but no significance was detected regarding length of hospital stay or readmission rate. There was a statistically significant decrease in mortality rate from 1.17% in the preimplementation phase to 0.83% in the mobile app phase (P = 0.02). The frequency of DRPs detected by pharmacists statistically significantly increased from 0.54/100 bed-days in the preimplementation phase to 3.23/100 bed-days in the mobile app phase. CONCLUSION: The use of a mobile app was found to be effective, applicable, and usable in guiding health professionals on rational antimicrobial use.

The Effect of Telephone-Based Follow-Up on Adherence, Efficacy, and Toxicity of Oral Capecitabine-Based Chemotherapy.

Background:Adherence and safety challenges aroused with the use of oral chemotherapeutic agents, such as capecitabine, necessitated implementation of a more focused follow-up for patients receiving these agents.Patients and Methods:This prospective, randomized open-label study explored the usefulness of weekly telephone-based follow-up in Egyptian patients with metastatic colorectal or gastric cancer treated with capecitabine-based chemotherapy regimens at the National Cancer Institute, Egypt, compared with a standard care group. Patients' adherence, safety, efficacy, and health service utilization were assessed and compared in 82 eligible patients; control group (n = 38) and intervention group (n = 44).Results:The intervention group showed statistically better tolerability to certain adverse effects in certain cycles with nonsignificantly higher patients' adherence and overall survival (OS), along with statistically higher passive call duration.Conclusion:These results suggested that pharmacist-led telephone follow-up (TFU) could help in building a close trusting rapport between the patient and caregiving pharmacist. They also demonstrated the potential usefulness of the TFU on patients' tolerability, adherence, and OS; however, further trials with a larger sample size should be encouraged to explore more pronounced results. Otherwise, the provided standard care could be considered good enough for these patients.

Nebulized Versus IV Amikacin as Adjunctive Antibiotic for Hospital and Ventilator-Acquired Pneumonia Postcardiac Surgeries: A Randomized Controlled Trial.

OBJECTIVE: Nebulized antibiotics offer high efficacy due to significant local concentrations and safety with minimal blood levels. This study evaluates the efficacy and nephrotoxicity of nebulized versus IV amikacin in postcardiothoracic surgical patients with nosocomial pneumonia caused by multidrug-resistant Gram- negative bacilli. DESIGN: Prospective, randomized, controlled study on surgical patients divided into two groups. SETTING: Postcardiac surgery ICU. INTERVENTIONS: The first gtroup was administered IV amikacin 20 mg/kg once daily. The second group was prescribed amikacin nebulizer 400 mg twice daily. Both groups were co-administered IV piperacillin/tazobactam empirically. PATIENTS: Recruited patients were diagnosed by either hospital-acquired pneumonia or ventilator-associated pneumonia where 56 (42.1%) patients were diagnosed with hospital-acquired pneumonia, 51 (38.34%) patients were diagnosed with early ventilator-associated pneumonia, and 26 (19.54%) patients with late ventilator-associated pneumonia. MEASUREMENTS AND MAIN RESULTS: Clinical cure in both groups assessed on day 7 of treatment was the primary outcome. Efficacy was additionally evaluated through assessing the length of hospital stay, ICU stay, days on amikacin, days on mechanical ventilator, mechanical ventilator-free days, days to reach clinical cure, and mortality rate. Lower nephrotoxicity in the nebulized group was observed through significant preservation of kidney function (p < 0.001). Although both groups were comparable regarding length of hospital stay, nebulizer group showed shorter ICU stay (p = 0.010), lower number of days to reach complete clinical cure (p = 0.001), fewer days on mechanical ventilator (p = 0.035), and fewer days on amikacin treatment (p = 0.022). CONCLUSION: Nebulized amikacin showed better clinical cure rates, less ICU stay, and fewer days to reach complete recovery compared to IV amikacin for surgical patients with nosocomial pneumonia. It is also a less nephrotoxic option associated with less deterioration in kidney function.

Effect of alfacalcidol on the pulmonary function of adult asthmatic patients: A randomized trial.

BACKGROUND: Despite the use of alfacalcidol in the management of corticosteroid-induced osteoporosis, it has never been considered an adjunct treatment for asthma management. It can target vitamin D deficiency, a possible risk factor for asthma, and, hence, improve pulmonary function of patients with asthma. OBJECTIVE: To explore the effect of alfacalcidol administration on pulmonary function and study the pattern of vitamin D deficiency in adults with asthma in Egypt. METHODS: Serum 25-hydroxyvitamin D was measured in 115 adults: 33 healthy subjects and 82 patients with asthma. Then, patients with asthma were randomized to receive standard asthma treatment only (n = 39) or receive it in addition to 1 µg of alfacalcidol daily for 4 months (n = 43). Randomization was stratified by the stage of asthma severity. Spirometry and measurement of 25-hydroxyvitamin were performed at baseline and end of follow-up. RESULTS: Vitamin D deficiency was more common in patients with asthma (57.3%) than in healthy subjects (21.2%; P < .001). In patients with asthma, alfacalcidol significantly improved forced expiratory volume in the first second and forced vital capacity (P < .001 for the 2 tests). Moreover, more patients in the intervention arm showed improvement in asthma severity stage (P = .04). A nonsignificant difference was observed in improvement of forced expiratory volume in the first second between patients with vitamin D deficiency and those without deficiency in the intervention group (P > .05). CONCLUSION: Alfacalcidol supplementation improved the pulmonary function and severity stage of adult patients with asthma regardless of deficiency. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02747381.

Association Between Combined Presence of Hepatitis C Virus and Polymorphisms in Different Genes With Toxicities of Methotrexate and 6-Mercaptopurine in Children With Acute Lymphoblastic Leukemia.

BACKGROUND: The aim of the present study is to determine the correlation of hepatitis C virus (HCV) infection and polymorphisms in different genes with toxicity of either methotrexate (MTX) or 6-mercaptopurine (6-MP) administered to children with acute lymphoblastic leukemia (ALL). PROCEDURE: One hundred children with low-risk ALL, who were treated according to the St. Jude Total therapy XV, were recruited. The recruited children were receiving MTX and 6-MP during maintenance phase. Patients were excluded from the study if they had other types of leukemia. Genotyping analyses for the thiopurine methyltransferase (TPMT), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferase (GST) genes were performed using a combination of polymerase chain reaction (PCR) and PCR-RFLP (where RFLP is restriction fragment length polymorphism) protocols. Relevant clinical data on adverse drug reactions were collected objectively (blinded to genotypes) from the patient medical records. RESULTS: There was a significant correlation between the combined presence of HCV and TPMT*3B G460A gene polymorphisms and grades 2-4 hepatotoxicity as aspartate aminotransferase (AST) elevation (P < 0.04). The same observation was seen when comparing either the presence of HCV alone or the presence of the gene polymorphism alone. A significant association between the combined presence of HCV and MTHFR C677T polymorphism and grades 2-4 hepatotoxicity as alanine aminotransferase (ALT), AST, and alkaline phosphatase (ALP) elevation was observed (P values <0.001, 0.02, and 0.001, respectively). The presence of HCV infection had a significant negative effect on hepatic transaminases. CONCLUSIONS: The present data support a role for combining analysis of genetic variation in drug-metabolizing enzymes and the presence of HCV in the assessment of specific drugs toxicities in multiagent chemotherapeutic treatment regimens.

Obesity Does Not Affect Propofol Pharmacokinetics During Hypothermic Cardiopulmonary Bypass.

OBJECTIVE: Because of the lack of data regarding the impact of obesity on propofol pharmacokinetics in patients undergoing cardiac surgery using hypothermic cardiopulmonary bypass (CPB), the authors sought to explore propofol pharmacokinetics and develop a predictive pharmacokinetic model that characterizes and predicts propofol pharmacokinetics in this population. DESIGN: A prospective, observational study. SETTING: A teaching hospital. PARTICIPANTS: The study comprised 17 obese and 17 control (nonobese) patients undergoing hypothermic CPB. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patients mainly underwent valve surgery. On initiation of hypothermic CPB (28°C-32°C), patients received a propofol (1%) bolus (1 mg/kg) immediately followed by a 2 mg/kg/h infusion. Blood samples were withdrawn at the following times: before dosing; 1, 3, 5, and 7 minutes after the propofol bolus dose; every 20 minutes during infusion; just before discontinuation of the infusion; and at 1, 3, 5, 7, 10, 20, 30, and 60 minutes after discontinuation of the infusion. The plasma propofol concentration was determined using high-performance liquid chromatography, and then data were imported into Monolix (Lixoft, Antony, France) for population pharmacokinetic modeling and pharmacokinetic parameters estimation. A 2-compartment pharmacokinetic model with age as a covariate on the peripheral volume of distribution (V2) best described the pooled data. The pooled data was internally evaluated successfully to describe and predict propofol pharmacokinetics in the addressed population. Propofol clearance, intercompartmental clearance, and central volume of distribution were 805 mL/min, 1140 mL/min and 18.8 L, respectively. V2 was calculated as 9.86×exp.(1.88×[age/40]) L. CONCLUSION: Propofol pharmacokinetic parameters were similar in obese and nonobese patients undergoing hypothermic CPB. Age was the major determinant of propofol V2 in the obese population.

Efficacy of Different Perioperative Statin Regimens on Protection Against Post-Coronary Artery Bypass Grafting Major Adverse Cardiac and Cerebral Events.

OBJECTIVES: Comparing different perioperative statin regimens for the prevention of post-coronary artery bypass grafting adverse events. DESIGN: A randomized, prospective study. SETTING: Cardiothoracic surgical units in a government hospital. PARTICIPANTS: The study comprised 94 patients scheduled for elective, isolated on- or off- pump coronary artery bypass grafting. INTERVENTIONS: Patients were assigned randomly to 1 of the following 3 treatment groups: group I (80 mg of atorvastatin/day for 2 days preoperatively), group II (40 mg of atorvastatin/day for 5-9 days preoperatively), or group III (80 mg of atorvastatin/day for 5-9 days preoperatively). The same preoperative doses were restarted postoperatively and continued for 1 month. MEASUREMENTS AND MAIN RESULTS: Cardiac troponin I, creatine kinase, and C-reactive protein (CRP) levels were assayed preoperatively; at 8, 24, and 48 hours postoperatively; and at discharge. CRP levels at 24 hours (p = 0.045) and 48 hours (p = 0.009) were significantly lower in group III compared with the other 2 groups. However, troponin I levels at 8 hours (p = 0.011) and 48 hours (p = 0.025) after surgery were significantly lower in group II compared with group III. The incidence of postoperative major adverse cardiac and cerebrovascular events was assessed, and there was no significant difference among the 3 groups. CONCLUSION: The 3 regimens did not result in any significant difference in outcomes, but only simple trends. The higher-dose regimen resulted in a significant reduction in the CRP level. Thus, more studies are needed to confirm the benefit of higher-dose statins for the protection from post-coronary artery bypass grafting adverse events.

Virtual clinical pharmacy training in the era of COVID-19: A report on undergraduate students' perceptions and academic performance.

INTRODUCTION: The study objective was to explore the impact of the complete virtual transition of in-hospital clinical training on students' academic performance and to assess students' perceptions of the overall experience. METHODS: In-hospital clinical training was delivered via distance learning using daily synchronous videoconferences for two successive weeks to 350 final-year pharmacy students. The Virtual Faculty of Pharmacy Cairo University (VFOPCU) platform allowed trainees to virtually browse patient files interactively with their clinical instructors to simulate a typical rounding experience. Academic performance was evaluated through identical 20-question tests before and after training. Perceptions were assessed through an online survey. RESULTS: Response rates were 79% pretest and 64% posttest. The median score was significantly higher after receiving the virtual training (7/20 [6-9] out of 20 pretest vs. 18/20 [11-20] posttest, P < .001]. Training evaluations revealed high levels of satisfaction (average rating > 3.5/5). Around 27% of respondents were completely satisfied with the overall experience, providing no suggestions for improvement. However, inappropriate timing of the training (27.4%) and describing training as being condensed and tiring (16.2%) were the main disadvantages reported. CONCLUSIONS: Implementing a distance learning method with the aid of the VFOPCU platform to deliver clinical experiences instead of physical presence in hospitals appeared to be feasible and helpful during the COVID-19 crisis. Consideration of student suggestions and better utilization of available resources will open the door for new and better ideas to deliver clinical skills virtually even after resolution of the pandemic.

Hepatoprotective efficacy of ursodeoxycholic acid in pediatrics acute lymphoblastic leukemia.

Ursodeoxycholic acid (UDCA) possesses a hepatoprotective effect in drug-induced hepatotoxicity. In a prospective randomized parallel study, 39 children with acute lymphoblastic leukemia (ALL) were randomized to receive UDCA with chemotherapy for 6 months, then discontinued UDCA and were followed up for 3 months, (UDCA group) (N = 19) or receive chemotherapy without UDCA and followed up for 9 months (control group) (N = 20). In this pilot study, UDCA treatment was associated with a trend toward decreased levels of hepatic transaminases when concomitantly administered with chemotherapy and, therefore, safer outcome in children with ALL. Future studies with a larger sample size are needed to confirm the efficacy and safety of UDCA in this setting.

Combined effect of high-dose vitamin A, vitamin E supplementation, and zinc on adult patients with diabetes: A randomized trial.

In type 2 diabetes mellitus (T2DM), hyperglycemia leads to oxidative insult. Vitamins A and E have antioxidant potentials and may help in managing diabetes. The combined effect of high-dose vitamin A plus E supplementation with and without zinc on T2DM, has never been examined. Thus, this study aimed to evaluate and compare the effect of high-dose vitamin A plus E supplementation (AE) versus high-dose vitamin A plus E with zinc (AEZ), on different diabetic parameters. Ninety-eight patients with T2DM were randomized to receive either: 50,000 IU vitamin A and 100 mg vitamin E (AE group, N = 36), an equivalent dose of vitamin A and E combined with 25 mg zinc (AEZ group, N = 35), or no supplements (control group, N = 27) for three months. Compared to control, AEZ group showed significant reductions in fasting blood glucose, 2 h postprandial blood glucose, and glycated hemoglobin (HbA1c) with significant increases in homeostasis model assessment of beta-cell function and difference value of fasting insulin. Two hair loss cases were recorded in both treated groups. Although vitamin A needs dose moderation, these results suggest that, high-dose vitamin A plus E supplementation combined with zinc may improve glycemic control, ß-cell function, and insulin secretion in adults with T2DM.

Short-term Effects of Alfacalcidol on Hospital Length of Stay in Patients Undergoing Valve Replacement Surgery: A Randomized Clinical Trial.

PURPOSE: Vitamin D deficiency is highly prevalent in critically ill patients, and has been associated with more prolonged length of hospital stay and poor prognosis. Patients undergoing open-heart surgery are at higher risk due to the associated life-threatening postoperative complications. This study investigated the effect of alfacalcidol treatment on the length of hospital stay in patients undergoing valve-replacement surgery. METHODS: This single-center, randomized, open-label, controlled trial was conducted at El-Demerdash Cardiac Academy Hospital (Cairo, Egypt), from April 2017 to January 2018. This study included adult patients undergoing valve-replacement surgery who were randomized to the intervention group (n = 47; alfacalcidol 2 µg/d started 48 h before surgery and continued throughout the hospital stay) or to the control group (n = 42). The primary end points were lengths of stay (LOS) in the intensive care unit (ICU) and in the hospital. Secondary end points were the prevalence of postoperative hospital-acquired infections, cardiac complications, and in-hospital mortality. FINDINGS: A total of 86 patients were included in the final analysis, with 51 (59.3%) being vitamin D deficient on hospital admission. Treatment with alfacalcidol was associated with a statistically significant decrease in ICU LOS (hazard ratio = 1.61; 95% CI, 1.77-2.81; P = 0.041) and hospital LOS (hazard ratio = 1.63; 95% CI, 1.04-2.55; P = 0.034). Treated patients had a significantly lower postoperative infection rate than did the control group (35.5% vs 56.1%; P = 0.017). The median epinephrine dose was lower in the intervention group compared to that in the control group (5.9 vs 8.2 mg; P = 0.019). The rate of in-hospital mortality was not significantly different between the 2 groups. IMPLICATIONS: Early treatment with 2 µg of alfacalcidol in patients undergoing valve-replacement surgery is promising and well tolerated. This effect may be attributed to its immunomodulatory and cardioprotective mechanisms. ClinicalTrials.gov identifier: NCT04085770.

Beta-thalassemia major alters sofosbuvir/ledipasvir exposure in Hepatitis C virus infected adolescent patients.

BACKGROUND: Hepatitis C virus (HCV) infected adolescents with beta-thalassemia major (BTM) are considered a potential population for HCV micro-elimination model development where BTM may negatively impact the pharmacokinetic exposure parameters of sofosbuvir/ledipasvir (SOF/LED). OBJECTIVES: The study aimed at studying the effect of BTM on SOF/LED and SOF metabolite (GS-331007) pharmacokinetics. METHODS: A prospective, controlled study recruiting BTM and control HCV infected adolescents (Clinicaltrials.gov identifier-NCT04353986). Pharmacokinetic exposure to GS-331007 and LED was the primary pharmacokinetic outcome. No-effect boundaries were set to 90% confidence interval (CI) of exposure geometric mean ratio (GMR) within 70-143%. Dose suitability was based on the 90% CI of exposure GMR within 50-200% compared to adults. The percentage of patients achieving sustained virologic response 12 weeks post-treatment (SVR12) was the primary efficacy endpoint. RESULTS: Thirteen patients were enrolled per study group. All patients were included in the pharmacokinetic analysis (n=26). BTM patients showed lower GS-331007 and LED exposure that could, respectively, be as low as 45.4% and 36.1% compared to their control group. GS-331007 exposure in BTM patients was nearly half (56.8%, 90% CI 45.3-71.2%) that observed in adults. Despite that low drug exposure in 46.2% of BTM patients may alert dose unsuitability, they achieved SVR12. Moreover, patients with total bilirubin ≥1.93 mg/dL were predicted to have low GS-331007 exposure (0.913 receiver operating characteristic area under the curve with sensitivity and specificity >80%). CONCLUSION AND RELEVANCE: The identified systematically lower drug exposure in BTM patients might partially explain relapses or treatment failures among BTM patients reported in other studies. BTM may be a hurdle towards implementing HCV micro-elimination model that may necessitate dose-adjustment.

Serum trace element levels in COPD patient: the relation between trace element supplementation and period of mechanical ventilation in a randomized controlled trial.

BACKGROUND AND OBJECTIVE: Many trace elements play important roles in activating or inhibiting enzymatic reactions, by competing with other elements and metalloproteins for binding sites, by affecting the permeability of cell membranes and by other mechanisms. They play important roles in the oxidant/antioxidant balance. As such, trace elements are thought to be involved directly or indirectly in the pathogenesis of several diseases. The aim of the present study is to investigate the effect trace elements (Se, Mn and Zn) intravenously administered on the period the COPD patients spend on mechanical ventilation. METHODS: In a randomized double-blinded controlled trial a set of 120 subjects (40 normal volunteers and 80 COPD) were recruited. Serum concentration levels of Se, Mn and Zn were determined for all enrolled subjects with Inductively Coupled Plasma spectroscopy. COPD patients received intravenous supplementation of the above trace elements and the period the patients spent on mechanical ventilation was determined. RESULTS: There was a significant reduction (P = 0.013) in the period the patients with COPD spent on the mechanical ventilation when received intravenous supplementation (9.4 +/- 7.3 days) compared with the COPD patients who received placebo (17.8 +/- 7.6 days). CONCLUSIONS: Trace element (Se, Mn and Zn) status is altered in critically ill patients with COPD. The supplementation achieved a reduction in the period those patients spent on the mechanical ventilation. A larger multi-centre trial is required to confirm this preventive effect and to explore its applicability to other critical care conditions.

Transdermal delivery of salbutamol sulphate: formulation and evaluation.

Salbutamol patches were prepared and evaluated. The effect of different Eudragits and various plasticizers on the properties of the patches were studied. Patches were prepared by casting method employing different plasticizers. These patches were evaluated for weight, thickness uniformity, swelling index, tensile strength, elongation percent and moisture absorption capacity. Release was studied. Tensile strength of the patches using Eudragit RS 100 as well as RS100 + L100 and triacetin was the lowest. Formulae containing 10% oleic acid and 5% dimethyl formamide, respectively, showed the highest permeability. These two formulae were studied clinically, the first formula only showed a significant improvement.

Adverse drug reactions reporting: a questionnaire-based study on Egyptian pharmacists' attitudes following an awareness workshop.

RATIONALE, AIMS AND OBJECTIVES: Hospital pharmacists can promote medication safety through spontaneous reporting of adverse drug reactions (ADRs). However, different educational interventions and different factors (socio-demographic and professional) have been implicated to influence the reporting process. The aims of this study were to assess the impact of pharmacovigilance awareness workshop on knowledge of hospital pharmacists; and to identify the main factors and barriers that influence ADRs reporting. METHODS: Two validated self-administered questionnaires were distributed to pharmacists attending an awareness workshop (pre and post); and a telephone survey was completed three months after the workshop. ADR reports (yellow cards) received from participating pharmacists were monitored for six months, and analysed for quality (validity and seriousness) and reporter demographic and professional factors. RESULTS: Two hundred and eighty-one pharmacists (95.25%) and 270 pharmacists (91.52%) completed pre- and post-workshop questionnaires respectively. A comparison of their knowledge of ADRs to report before and after the workshop showed significant difference (Wilcoxon test P < 0.05). Two hundred and four pharmacists (72.6%) completed the follow-up questionnaire, with lack of time, administrative barriers and inability to complete patient details being the most frequent reasons for not reporting. A total of 163 yellow cards were received from 49 pharmacists (17.44%) over 6 months, of which 126 reports (77.3%) were serious ADRs. Demographics of reporting pharmacists showed significance for completion of post-graduate studies, ministry of health hospitals and pharmacist post in hospital. CONCLUSION: Despite pharmacists' adequate knowledge after the workshop, they failed to maintain consistent reporting. Addressing the barriers to reporting and the personal factors influencing the process may be needed.