Maggie Abbassi

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.

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.

Untreated invasive aspergillosis results in high mortality rate in pediatric cancer patients. Voriconazole (VORI), the first line of treatment, requires strict dose monitoring because of its narrow therapeutic index and individual variation in plasma concentration levels. Commonly co-administered drugs; either Esomeprazole (ESO) or Ondansetron (OND) have reported drug-drug interaction with VORI that should adversely alter therapeutic outcomes of the latter. Although VORI, ESO and OND are co-administered to pediatric cancer patients, the combined effect of ESO and OND on the plasma concentration levels of VORI has not been fully explored. In this study, an accurate, reliable and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed and validated for simultaneous determination of VORI, ESO, and OND in ultra-low sample volumes (25 μL) of plasma of pediatric cancer patients. Based on the physicochemical properties of the studied drugs and internal standard, liquid-liquid extraction was successfully adopted with methyl t-butyl ether. Consistent and reproducible recovery of the three drugs and the internal standard were calculated using plasma and matrix matched samples (RE% > 72.97%, RSD < 8.29%). Chromatographic separation was carried out using UPLC with C18 column and a mobile phase of acetonitrile:water:methanol (70:25:5 V/V/V) at 0.3 mL/min. Mass spectrometric determination at positive electrospray ionization in the MRM mode was employed. The analysis was achieved within 4 min over a linear concentration range of 1.00-200.00 ng/mL for the three drugs. The assay validity was assessed as per the Food and Drug Administration guidelines for bioanalytical method validation, and satisfactory results were obtained. The accuracy and precision were within the acceptable limits for the three drugs in both quality control and incurred plasma samples. Matrix effect and process efficiency were investigated in neat solvent, post-extraction matrix, and plasma. Correlation of the plasma concentration levels of the three drugs revealed differences from the reported drug-drug interactions. This confirmed the need for simultaneous determination of VORI and co-administered drugs in order to achieve optimal therapeutic outcomes. To achieve this, analysis results of this study, genetic polymorphisms in CYP2C19 and clinical data will be used to establish one model incorporating all possible factors that might lead to variation in therapeutic outcomes.

AIM: Compare the safety and efficacy of intermittent fenofibrate versus simvastatin in chronic hemodialysis patients.

PATIENTS & METHODS: Sixty patients received either fenofibrate 100 mg or simvastatin 20 mg after their dialysis session (parallel study). The safety and efficacy of drugs on lipid profile, oxidized low-density lipoprotein (Ox-LDL), glutathione peroxidase and C-reactive protein were compared before and after 16-week treatment.

RESULTS: After treatment, significant increase in glutathione peroxidase, significant decrease in total cholesterol, triglycerides, low density lipoprotein (LDL) and ox-LDL (p < 0.05) and no significant changes in C-reactive protein (p > 0.05) were observed in both groups. Both drugs were well tolerated with no serious side effects reported by the patients.

CONCLUSION: Both drugs have comparable efficacy and safety when used as intermittent low dose regimen in hemodialysis. Larger studies with longer follow-up periods are needed to confirm our new findings.

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.

BACKGROUND: Using fluoroquinolone prophylaxis in pediatric neutropenic patients is a controversial issue due to the concern about emergence of resistant strains in addition to the lack of pediatric studies. This study was performed to assess the effectiveness of levofloxacin prophylaxis in pediatric patients during autologous stem cell transplantation.

METHODS: This was an observational study of pediatric patients who underwent autologous stem cell transplantation, comparing patients who received levofloxacin prophylaxis to historical controls.

RESULTS: A total of 96 patients were included (46 patients in the control group and 50 patients received levofloxacin). The median duration till onset of first fever was 11 d in the control group as compared to 15 d in patients who received levofloxacin (p ≤ 0.001). The incidence of infectious complications was higher in patients without levofloxacin (4/46) than those with levofloxacin (1/50). The median duration of empirical antibiotic use was 10 d in the levofloxacin group compared with 14 d in the control group (p < 0.001).

CONCLUSION: Levofloxacin prophylaxis delayed first spike of fever, decreased the incidence of septic complications, and shortened the duration of empiric antibiotic use, but its impact on emergence of resistant organisms should be closely monitored.