Efficacy and safety of azithromycin in Covid-19 patients: A systematic review and meta-analysis of randomized clinical trials.

Azithromycin (AZM) is commonly used in Covid-19 patients based on low-quality evidence, increasing the risk of developing adverse events and antimicrobial resistance. The current systematic review and meta-analysis investigated the safety and efficacy of AZM in treating Covid-19 patients using published randomized controlled trials. Google Scholar, PubMed, Scopus, Cochrane Library, Clinical Trials.gov, MEDLINE, bioRxiv and medRxiv were searched for relevant studies. The random-effects model was used to pool estimates using the Paule-Mandel estimate for heterogeneity. The odds ratio and raw difference in medians were used for dichotomous and continuous outcomes, respectively. The analysis included seven studies with 8822 patients (median age, 55.8 years; 61% males). The risk of bias was assessed as 'low' for five of the seven mortality results and as 'some concerns' and 'high' in one trial each. There were 657/3100 (21.2%) and 1244/5654 (22%) deaths among patients randomized to AZM and standard of care, respectively. The use of AZM was not associated with mortality in Covid-19 patients (OR = 0.96, 95% CI 0.88-1.05, p = 0.317 based on the random-effect meta-analysis). The use of AZM was not associated with need for invasive mechanical ventilation (OR = 0.96, 95% CI 0.49-1.87, p = 0.85) and length of stay (Δ = 1.11, 95% CI -2.08 to 4.31, p = 0.49). The results show that using AZM as routine therapy in Covid-19 patients is not justified due to lack of efficacy and potential risk of bacterial resistance that is not met by an increased clinical benefit.

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.

The potential hepatoprotective effect of metformin in hepatitis C virus-infected adolescent patients with beta thalassemia major: Randomised clinical trial.

BACKGROUND: Iron overload-induced oxidative stress and transfusion-acquired hepatitis C virus (HCV) infection are the main reasons of liver damage in beta thalassemia major (ß-TM). OBJECTIVES: Based on metformin's hepatic benefits in nondiabetic populations, the study aims to investigate the safety and the potential hepatoprotective effect of metformin in HCV-infected ß-TM adolescent patients. METHODS: This was a prospective, randomised, parallel, controlled, open-label study in which 60 HCV-infected ß-TM adolescent patients aged 11 to 18 years and receiving no antiviral therapy were selected and randomly assigned to treatment or control group in 1:1 allocation. Both groups were receiving ß-TM standard-of-care regimen, whereas metformin (500 mg, twice daily) was added to the treatment group's regimen only. Patients were prospectively followed up for 6 months with assessment of liver biochemical profile, oxidative stress markers, liver fibrosis, clinical symptom improvement and metformin's adverse effects. RESULTS: Aspartate aminotransferase serum level decreased significantly over time in the treatment group only (P = .013). However, improvement was not clinically significant and did not attain normality. Change in total antioxidant capacity and malondialdehyde serum levels indicated significantly improved oxidative stress status in the treatment group versus significant deterioration in the control group (P < .001). Fibrosis grade improvement was observed in 14 patients in the treatment group versus one improved case in the control group. CONCLUSION: The use of metformin in HCV-infected ß-TM adolescent patients as an adjuvant antioxidant hepatoprotective agent is promising and can improve liver damage.

Ledipasvir/Sofosbuvir in Hepatitis C Virus-Infected Children With Hematological Malignancies: A Pharmacokinetic Study.

PURPOSE: Children with hematological malignancies and chronic hepatitis C virus (HCV) infection are at a higher risk for rapid progression of liver disease and malignancy relapse due to multiple hepatitis flares and chemotherapy interruption. They are therefore potential candidates for microelimination of HCV infection. This study aimed to assess the effect of acute lymphoblastic leukemia (ALL) on the pharmacokinetic (PK) profile of direct-acting antivirals, namely ledipasvir/sofosbuvir (LDV/SOF) and the SOF major metabolite GS-331007. METHODS: This was a 24-week, prospective, controlled, open-label, 2-arm PK study of patients receiving 45/200 mg once-daily LDV/SOF orally for 12 weeks. Eligible patients were HCV-RNA-positive, treatment-naive children aged 6 to <12 years and/or weighing 17 to <35 kg with genotype 4 chronic HCV infection without cirrhosis. The primary efficacy and safety end points were the achievement of sustained virologic response for all patients with absence of any adverse events leading to permanent discontinuation of the study drug. Steady-state noncompartmental analysis was performed to determine the PK parameters of SOF, GS-331007, and LDV as the primary PK outcome. Dose suitability was based on the 90% CI of exposure geometric mean ratio percentage within 50% to 200% compared with adults. FINDINGS: Ten HCV-infected children with ALL (chemotherapy treatment group) and 12 eligible children with no malignancy (control group) were enrolled and completed the study period. All 22 patients achieved the sustained virologic response with no adverse events leading to interruption or permanent discontinuation of the study drug. Compared with the control group, the ALL group patients had similar SOF, GS-331007, and LDV exposure. Compared with adults, the AUCτ of GS-331007 was lower and the AUCτ and Cmax,ss of SOF and the Cmax,ss of LDV were modestly higher in the ALL group (acceptance limit, 50%-200%). However, the observed efficacy and favorable safety profile made these changes not clinically significant. IMPLICATIONS: Weight-based dosing of LDV/SOF (45/200 mg) is highly effective and safe among genotype 4 HCV-infected children weighing 17 to <35 kg and diagnosed with ALL undergoing maintenance chemotherapy. The similarity in the drug exposure, efficacy, and safety clinical end points between patients with and without hematological malignancy support their therapeutic equivalence. Further studies with a larger sample size may be required to confirm the safety of LDV/SOF in patients with ALL and to recommend appropriate dosing in children with hematological malignancies, if needed. CLINICALTRIALS: gov identifier: NCT03903185.

Comparison between topical cetirizine with minoxidil versus topical placebo with minoxidil in female androgenetic alopecia: a randomized, double-blind, placebo-controlled study.

Androgenetic alopecia (AGA) is the most common cause of hair loss in both genders with a higher psychological impact on females. Currently, topical minoxidil is the only FDA-approved treatment for female AGA and it needs life-long application and causes side effects. Cetirizine is an antihistamine that may be effective in hair loss treatment. This study aimed to compare the efficacy and safety of topical cetirizine with minoxidil (group 1) versus topical minoxidil with placebo (group 2) in female patients with AGA. This was a double-blind, randomized, controlled, parallel study conducted at Dermatology Clinic, Cairo University Teaching Hospital (Kasr- Al- Ainy), Egypt. Sixty-six patients with female AGA, aged 20-50 years, Sinclair (II-IV), were randomly assigned to one of the 2 groups for 24 weeks. The trichoscopic parameters, patients' self-assessment, side effects and global photographic assessment were evaluated. There was a statistically significant change from baseline in frontal and vertex terminal and vellus hair density (P < 0.0005) with a significant increase in vertex hair shaft thickness and average number of hairs per follicular unit in group 1 (P < 0.05). Patients reported significantly better scores in patient self-assessment in group 1 (P < 0.05). Side effects were not significantly different between groups (P > 0.05). Topical cetirizine increases hair shaft thickness and results in a higher clinical improvement from patients' perspective with a good safety profile (NCT04481412, study start date: July 2020).

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.

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.

The EQ-5D-5L Valuation Study in Egypt.

INTRODUCTION: No value sets exist for either the EQ-5D-3L or the EQ-5D-5L in Egypt, despite local pharmacoeconomic guidelines recommending the use of the EQ-5D to derive utility. Most published Egyptian economic evaluation studies have used utility values from other published studies and systematic reviews. OBJECTIVE: Our objective was to develop an Egyptian EQ-5D-5L value set using the international EuroQol standardized protocol (EQ-VT-2.1). METHODS: Adult Egyptian participants were recruited from public places using multi-stratified quota sampling based on age, sex, and geographical distribution. Two elicitation techniques were applied: the composite time trade-off (cTTO) and discrete-choice experiments (DCEs). Before actual data collection, interviewers' performance was assessed in a pilot phase. Data were modelled using generalized least square, Tobit, heteroskedastic, logit, and hybrid models, and the best fitting model was selected based on the value range between observed and predicted values, logical consistency of the parameters, significance level, and prediction accuracy. RESULTS: A total of 1378 interviews were conducted, of which 188 were excluded because they were incomplete or did not comply with protocol, 216 were pilot interviews, and 974 were included in the final analysis. The heteroskedastic model (model 4) based on the cTTO data was selected as the preferred model to generate the value set. Values ranged from - 0.93 for the worst health state (55555) to 1 for full health (11111), with 1136 (36.3%) of all predicted health states being worse than dead. Mobility had the largest impact on health state preference values. CONCLUSION: This is the first value set for the EQ-5D-5L based on social preferences obtained from a nationally representative sample in Egypt or any Arabic-speaking country. The value set can be used as a scoring system for economic evaluations and to improve the quality of health technology assessment in the Egyptian healthcare system.

Pharmacokinetics of daclatasvir in Egyptian adolescents with genotype-4 HCV infection.

BACKGROUND: Daclatasvir has potent antiviral activity against HCV infection when used in combination with sofosbuvir, however, its pharmacokinetics have not been described in adolescents. The aim is to determine the pharmacokinetic parameters of daclatasvir in adolescents, and to develop a population pharmacokinetic (PopPK) model. METHODS: Seventeen adolescent patients with genotype-4 chronic HCV infection received once daily oral daclatasvir 60 mg in combination with 400 mg sofosbuvir for 12 weeks. Steady state concentrations were determined. Non-compartmental and population PK were determined. RESULTS: The average PK parameters calculated by non-compartmental analysis (NCA): maximum plasma concentration (Cmax), area under the curve (AUC), apparent oral volume of distribution (V/F), apparent oral clearance (CL/F) and half-life (T1/2) were 1,092 ng/ml, 11,178 ng/ml•h, 55 l, 4.5 l/h and 8.5 h, respectively. Daclatasvir was best described by one compartment structural PK model with zero order absorption and first-order elimination. The absorption rate constant (K0), V/F, and CL/F of the final PopPK model of daclatasvir were 1.5/h, 52 l and 4.7 l/h, respectively. Body weight and serum albumin had significant effect on the V/F parameter. CONCLUSIONS: Body weight and serum albumin were the major determinants of daclatasvir V/F in this population. PK parameters were comparable to those reported in adult HCV patients, demonstrating that 60 mg daclatasvir is an appropriate dose for adolescents. ClinicalTrials.gov NCT03540212.

Conceptual Framework of the Impact of Health Technology on Healthcare System.

The World Health Organization (WHO) promotes health systems strengthening as a means of improving population health, especially in low- and middle-income countries. The United Nations Sustainable Development Goals highlight the importance of investing in workforce development to improve population health and economic well-being. In relation to pharmaceuticals, health systems face challenges in terms of i) guaranteeing access to needed drugs, ii) rationalizing medicines use, and iii) avoiding harm from adverse events. There is a pressing need to better understand the relationships between technology and pharmacy practice when strengthening pharmaceutical care systems. In response, this paper examines ways in which harnessing new technologies can change pharmacy practice and strengthen pharmaceutical systems for the benefit of patients. The paper will present a conceptual framework as well as exploring case studies.

Randomized comparative efficacy and safety study of intermittent simvastatin versus fenofibrate in hemodialysis.

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.

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.

The impact of a 600-mg loading dose of clopidogrel in diabetic and non-diabetic patients undergoing elective PCI.

BACKGROUND: High platelet reactivity (HPR) and suboptimal response to dual antiplatelet therapy (DAPT) may explain high recurrent rates of ischemic events in type 1 and 2 diabetes mellitus (DM) patients undergoing percutaneous coronary intervention (PCI). The aim of this study was to determine the effect of diabetes mellitus on clopidogrel activity in cardiac patients undergoing PCI. METHODS: This is an observational study. Patients were categorized according to DM status into diabetic group (N.=30) and non-diabetic group (N.=33). All patients received clopidogrel in a loading dose of 600 mg before PCI. Platelet function was assessed using light transmittance aggregometry (LTA) technique at baseline (before clopidogrel administration), 24 hour after clopidogrel loading dose administration and 7-10 days after PCI. All patients were followed up for at least one year after PCI for recurrence of acute cardiac events. RESULTS: There was no statistically significant difference between the two groups with respect to 10 µm adenosine diphosphate (ADP)-induced platelet aggregation measured at baseline (P=0.64), 24 hours after PCI (P=0.874), and 7-10 days after PCI (0.643). Diabetics were not significantly different from non-diabetics in terms of post-PCI acute stent thrombosis (P=0.945), sub-acute stent thrombosis (P=0.945), unstable angina (P=0.29) and cardiac death (P=0.64). There was a statistically significant difference between patients with and without post-PCI acute events regarding ADP aggregation measured 24 hours and 7-10 days after PCI. CONCLUSIONS: The use of a high loading dose of clopidogrel (600 mg) in patients undergoing elective PCI can overcome the significant increase in post-PCI platelet aggregation and rate of acute cardiac events induced by diabetes mellitus as co-morbidity in those patients.

Development and validation of LC-MS/MS assay for the determination of the prodrug Midodrine and its active metabolite Desglymidodrine in plasma of ascitic patients: Application to individualized therapy and comparative pharmacokinetics.

Midodrine (MD) is a prodrug that is converted after oral administration to Desglymidodrine (DMD). In this study, an LC-MS/MS assay was developed and validated for investigation of the pharmacokinetics of MD and DMD in non azotemic patients with liver cirrhosis and tense ascites. Results were compared to those noted with healthy volunteers following the adminstration of a single oral dose of MD. Sample preparation was performed by liquid-liquid extraction using t-butyl methyl ether. HPLC separation was carried out using RP C18 column (4.6mm×50mm, 5µm). Isocratic elution was performed using methanol:0.2% formic acid (70:30, v/v) as the mobile phase, at a flow rate of 0.7mL/min. Tandem mass spectrometric detection was employed at positive electrospray ionization in MRM mode for the determination of MD and DMD. Analysis was carried out within 1.0min over a concentration range of 0.50-40.00ng/mL for the prodrug and its active metabolite. The assay was validated according to FDA guidelines for bioanalytical method validation and satisfactory results were obtained. The applicability of the assay for the determination of the pharmacokinetic parameters of MD and DMD and personalized therapy was demonstrated in healthy volunteers and ascitic patients. Results revealed significant differences in pharmacokinetic parameters among the studied groups. Such differences were explained on the basis of the medical condition and co-adminstered medications exerting possible drug-drug interaction. Results confirmed the need for implementation of reliable analysis tools for therapeutic dose adjustment.

The role of clinical pharmacists as perceived by Egyptian physicians.

OBJECTIVES: Clinical pharmacists play an important role in ensuring the safe and rational use of medicines; however, physicians in developing countries may not always recognize the wide scope of services that a pharmacist can provide to improve patient safety and achieve clinical outcomes. The aim of this study was to investigate the perceptions and experience of physicians regarding the role of the pharmacists, the pharmacists' ability to perform clinical services, their acceptance of new pharmacist roles and the extent of collaboration that can occur between the two disciplines. METHODS: In this cross-sectional survey, 583 randomly selected physicians from the Grand Cairo area were invited to complete a survey composed of 25 questions designed to determine their perceptions of the role of clinical pharmacists. KEY FINDINGS: The response rate was 53%. Of the 312 physicians who completed the questionnaire, 50.5% reported direct contact with the pharmacists using the pharmacist as a source of information about the name of the medication, side effects, drug interactions or efficacy as the main role. About one-third believed that pharmacists could be a reliable source of clinical information, identify clinically related problems or advise the physicians about medication's cost effectiveness. More than 80% agreed that physicians and clinical pharmacists should have daily cooperation, and face-to-face contact was selected to be the best method of communication. CONCLUSION: Although a wide proportion of the physicians were aware of the clinical pharmacy principle, the service itself is not well promoted or applied. Greater effort needs to be directed towards increasing physicians' awareness and knowledge of the importance of clinical pharmacist and promote the benefit of the clinical pharmacy service.

Antibiotic dispensing in Egyptian community pharmacies: an observational study.

BACKGROUND: Antibiotics are commonly dispensed medications from community pharmacies, and they are frequently prescribed for inappropriate indications. In many countries, they are easily accessible without prescriptions. The inappropriate use of antibiotics results in the emergence of resistant bacterial strains, which represents a considerable public health problem, particularly in developing countries. OBJECTIVE: This study aimed to describe the pattern of antibiotics dispensing from Egyptian community pharmacies and to collect baseline descriptive data on the antibiotics dispensed and their appropriateness. METHODS: A cross-sectional, observational study of antibiotic dispensing encounters was conducted at 36 randomly selected pharmacies in Greater Cairo, Egypt. Data were collected during one shift at each pharmacy. Structured questionnaires recording patient demographics, antibiotics dispensed and reasons for dispensing were completed for each antibiotic dispensing encounter. The data were descriptively analysed. RESULTS: Overall, 1158 antibiotics were dispensed during the study period with a total cost of L.E. 24,487 (approximately 3,673 $USD). While self-medication and purchasing without medical prescriptions were common, representing around 23.3% of the antibiotics (n = 270), most antibiotics were prescribed by a doctor or dentist (n = 736, 63.6%). Pharmacist recommendations accounted for the remainder (n = 152, 13.1%). The main reasons for antibiotic use were respiratory tract ailments and gastroenteritis symptoms. The antibiotics most commonly dispensed were: penicillins, erythromycin, metronidazole, neomycin, clotrimoxazole and tetracyclines. Approximately 70% of the antibiotics dispensed on prescriptions were judged to be appropriate for the indications while this percentage was around 61% for antibiotics dispensed on pharmacist recommendation and patient's request. CONCLUSIONS: The results of this study show that antibiotics are frequently dispensed from community pharmacies in Egypt without appropriate prescriptions and for inappropriate indications. These findings support the need for strict enforcement of pharmacy laws through improved inspection processes. They highlight the need for evidence-based guidelines and educational interventions to improve antibiotic prescribing and dispensing practices.

Subconjunctival bevacizumab for corneal neovascularization.

PURPOSE: This work aimed to study and evaluate the effect of subconjunctival bevacizumab injection in patients with corneal neovascularization (CNV) resulting from different ocular surface disorders. METHODS: Ten eyes with CNV caused by different ocular surface disorders were studied. All eyes had both major and minor vessel CNV caused by factors such as healed corneal ulcers, long-standing chronic inflammatory diseases and corneal ischaemia (caused by contact lenses). All eyes received a single subconjunctival injection of 2.5mg (0.1ml) bevacizumab. Morphological changes in the major and minor vessels were evaluated using slit-lamp biomicroscopy and corneal photography. RESULTS: Conspicuous recession of the minor vessels of CNV was observed in all eyes at 2 weeks post-injection. The extent of CNV of the major vessels was significantly decreased at 2 weeks post-injection. The level of CNV continued to decrease noticeably for 3 months and then stabilized for the remainder of the 6-month follow-up period. Parameters used for evaluation included the total area of CNV, which amounted to 14.0 ± 5.4% of the corneal surface pre-injection, compared with 9.4 ± 3.9% post-injection (p < 0.01), reflecting a mean decrease in CNV of 33 ± 8%, and the extent of neovascularization, which decreased from 4.3 ± 1.5 clock hours pre-injection to 2.4 ± 1.1 clock hours post-injection (p <0.01). During the 6-month follow-up, none of the 10 eyes showed any complication that could be related to subconjunctival bevacizumab injection. CONCLUSIONS: Bevacizumab can be used safely and effectively for CNV resulting from different ocular surface disorders. It represents an effective treatment for minor vessel neovascularization caused by long-standing chronic inflammation (e.g. trachoma) or long-standing corneal ischaemia (e.g. contact lenses), as well as for major vessel neovascularization resulting from different causes. Bevacizumab was well tolerated over the 6-month follow-up period.

Management of intraepithelial and invasive neoplasia of the cornea and conjunctiva: a long-term follow up.

PURPOSE: The aim of this work is to report the long-term results of using immunotherapy for the management of cornea and conjunctiva intraepithelial neoplasia and squamous cell carcinoma after surgical excision of the neoplasm. METHODS: Ten eyes of 10 patients with cornea and conjunctiva intraepithelial neoplasia or squamous cell carcinoma had wide surgical excisions of the neoplasm after evaluation of the level of corneal involvement using ultrasound biomicroscopy. All eyes received topical cyclosporine A (0.05%) and topical mitomycin C (0.01%) 4 times daily for 12 weeks after surgery. All eyes were followed up every month for 6 months and then every 6 months for another 18 months. RESULTS: All eyes showed total cure with no recurrence during the 2-year follow-up period. Epithelial toxicity (punctate keratopathy) occurred in 3 eyes, ocular irritation and mild conjunctival hyperemia in 5 eyes, and lid toxicity in 2 cases during the treatment with mitomycin C. There were no serious complications that necessitated stopping the treatment. CONCLUSION: During a 2-year follow-up period, the use of topical cyclosporine A (0.05%) combined with mitomycin C (0.01%) as an adjunctive treatment after surgical excision in cornea and conjunctiva intraepithelial neoplasia and squamous cell carcinoma was found to prevent tumor recurrence, especially in extensive lesions, when surgical excision cannot ensure a tumor-free margin.