Hakkı Gürsöz’s research while affiliated with Apollo Medical Devices and other places

We described the significance of systematic monitoring nationwide antimicrobial stewardship programs (ASPs) in primary care. All the prescriptions given by family physicians were recorded in Prescription Information System established by the Turkish Medicines and Medical Devices Agency of Ministry of Health. We calculated, for each prescription, “antibiotics amount” as number of boxes times number of items per box for medicines that belong to antiinfectives for systemic use (i.e., J01 block in the Anatomical Therapeutic Chemical Classification System). We compared the antibiotics amount before (2015) and after (2016) the extensive training programs for the family physicians. We included 266,389,209 prescriptions from state-operated family healthcare units (FHUs) between January 1, 2015 and December 31, 2016. These prescriptions were given by 26,313 individual family physicians in 22,518 FHUs for 50,713,181 individual patients. At least one antimicrobial was given in 37,024,232 (28.31%) prescriptions in 2015 and 36,154,684 (26.66%) prescriptions in 2016. The most common diagnosis was “acute upper respiratory infections (AURI)” (i.e., J00-J06 block in the 10th revision of the International Statistical Classification of Diseases and Related Health Problems) with 28.05%. The average antibiotics amount over prescriptions with AURI decreased in 79 out of 81 provinces, and overall rate of decrease in average antibiotics amount was 8.33%, where 28 and 53 provinces experienced decreases (range is between 28.63% and −3.05%) above and below this value, respectively. In the most successful province, the highest decrease in average amount of “other beta-lactam antibacterials” per prescription for AURI was 49.63% in January. Computational analyses on a big data set collected from a nationwide healthcare system brought a significant contribution in improving ASPs.

Objective The use of biological agents in the treatment of ocular Behçet’s disease has recently become more frequent. The use of two agents, infliximab (IFX) and adalimumab (ADA), for the treatment of Behçet’s disease requires prior approval by the Turkish Medicines and Medical Devices Agency. We report on a review of such applications with a view to informing on how such agents are used off-label in Turkey. Methods Prescriptions for off-label use of IFX or ADA sent from hospitals in Turkey to the Turkish Medicines and Medical Devices Agency in 2018 were evaluated. Demographic data, previous treatment regimens and reasons for referral were extracted from the files of the cases. Results A total of 662 patients were considered for off-label use of IFX or ADA for the treatment of ocular Behçet’s disease. The mean age of the patients was 35.7±10.8 years (range 12–76); 61.5% of patients were men and 38.5% were women. Of the applications, 345 (52.1%) were for IFX and 317 (47.9%) for ADA. Among the referring hospitals, the public university hospitals ranked first, accounting for 77.9% of IFX and 88.6% of ADA prescriptions. Most applications were made after the failure of conventional therapy, which included steroids and immunosuppressive agents. Conclusion IFX and ADA are rarely used as initial therapy. Stepwise treatment is still preferred in the treatment of ocular Behçet’s disease in Turkey. Our report informs on the management of this difficult-to-treat condition.

INTRODUCTION: To assess demographic characteristics in patients with ocular Behçet's disease who use off-label drugs in Turkey. METHODS: The applications for off-label drug use (infliximab, adalimumab, mycophenolat mofetil) from hospitals in Turkey to the Turkish Medicines and Medical Devices Agency from January to December 2013 were evaluated retrospectively. The files of the cases were evaluated in terms of demographic data, previous treatment regimens and reasons for referral. RESULTS: The study included 124 patients who were admitted for off-label drug use. The mean age of the patients was 32.1 +- 7.9 years. While 72.6% of all applications were male, 27.4% were female. Seventy-eight percent of the applicants were from Marmara and Central Anatolia. Infliximab was the most applied off-label drug in ocular Behçet's disease at a rate of 75% in Turkey. When the hospitals that applied were taken, the state universities took the first place with a ratio of 88% and the education and research hospitals came to the fore with a 6.5% rate. DISCUSSION AND CONCLUSION: Examination of demographic data on off-label drug use can be a guide in terms of providing the necessary convenience in legislation in line with drug preferences.

Purpose: To evaluate the demographic characteristics of patients who use off-label drugs for retinal vein occlusion (RVO) in Turkey. Material and Method: The applications for off-label drug use in patients with RVO (dexamethasone implant, ranibizumab, bevacizumab, aflibercept) from hospitals in Turkey to the Turkish Medicines and Medical Devices Agency from January to December 2013 were examined retrospectively. The files of the cases were evaluated in terms of demographic data, previous treatment regimens, reasons for application, dosage and usage of the drug. Results: This study was enrolled 30 patients who were admitted for off-label drug use for retinal vein occlusion. The mean age of all patients was 64.43±9.48 years and 56.7% of patients were male, 43.3% were female. Of these applications, 70% was dexamethasone implant, 30% was ranibizumab. The first two places in the distribution of the applications were Central Anatolia (66.6%), Ege (23.3%). In the distribution of the referring hospitals, the state universities were seen first rank with a rate of 80% , the education and research hospitals were second rank with a ratio of 13.3% and the foundation universities were third rank with a rate of 6.7% of patients, five (16.7%) were naïve patients with no previous treatment regimen and eleven patients (36.7%) were previously treated with ranibizumab. Conclusion: The evaluation of off-label drug use in the treatment of retinal vein occlusion will guide us in determining the treatment options in such a challenging treatment process in Turkey as well as its contribution to the literature.

Aim: To evaluate the demographic characteristics of patients who use off-label drugs for Age-related Macular Degeneration (AMD) in Turkey. Materials and Methods: The applications for off-label drug use in patients with AMD (bevacizumab, ranibizumab, aflibercept, verteporfin) from hospitals in Turkey to the Turkish Medicines and Medical Devices Agency from January to December 2013 were evaluated retrospectively. The files of the cases were evaluated in terms of demographic data, previous treatment regimens, reasons for application, dosage and usage of the drug. Results: This study included 64 patients who applied for off-label drug use under the diagnosis of AMD. The mean age of all patients was 70.12 ± 11.01 years and 46.9 % were male, 53.1 % were female. Of these, 39.1 % was ranibizumab, 29.7 % was verteporfin, 18.8 % was aflibercept, and 12.5 % was bevacizumab. Applications belonged to Ege (48.4%), Central Anatolia (23.4%), Marmara (25.0%) and East Anatolia (3.1%) regions. In the distribution of the referring hospitals, the first three hospitals were the state universities (48.4 %), the education and research hospitals (40.6%) and the foundation universities (7.8%) Of patients, twelve (18.8%) were naïve patients with no previous treatment regimen. Resistance to other anti-vascular endothelial growth factors as the cause of admission was in the 1st rank with 64.1%. Conclusion: In the treatment of AMD, determining the off-label drug application information and the actual records related to this subject will give us instructive information about our treatment options as well as its contribution to the literature.

Objective: To evaluate the demographic characteristics of the applications for off-label drug usage in patients with diabetic retinopathy (DRP) in Turkey. Materials and Methods: The applications for off-label drug use in patients with DRP (bevacizumab, ranibizumab, dexamethasone implant, aflibercept) from hospitals in Turkey to the Turkish Medicines and Medical Devices Agency from January to December 2013 were examined retrospectively. The files of the cases were evaluated in terms of demographic data, previous treatment regimens, reasons for application, dosage and usage of the drug. Results This study was enrolled 320 patients who were admitted for off-label drug use for DRP. The mean age of all patients was 63.05 ± 9.32 years and % 51.9 of patients was male, % 48.1 was female. Of these applications, 95.31% was dexamethasone implant, 4.06% was ranibizumab, 0.63% was bevacizumab. There appeared no applications for aflibercept. The first three places in the distribution of the applications were Central Anatolia (26.69%), Ege (28.75%) and Marmara Regions (21.56%). In the distribution of the referring hospitals, the state universities were seen first rank with a rate of 55.9%, the foundation universities were second rank with a rate of 22.2%, and the education and research hospitals were third rank with a ratio of 21.3%. Of patients, thirty nine (9.7%) were naïve patients with no previous treatment regimen. Conclusion In our country, the evaluation of off-label drug use in the treatment of DRP will guide us in determining the treatment options in Turkey as well as its contribution to the literature.

Aim: The top 100 medicines having the highest annual average sales between the years 2006 and 2015, had exceeded one-fourth of the total pharmaceutical market’s value in these years. We aimed to study the status of biotechnological medicines among these medicines and evaluate the effects of policy interventions on their sales. Methods: Sales of all medicines on an annual average value basis were calculated. The top 100 medicines with the highest annual average sales were included in the study. Time series analysis has been used for prospective estimations. Results: Up to 2007 biotechnological medicines had not been in the top ten medicines; it increased dramatically after 2007 and in 2016, the sales of biotechnological medicines reached to 82% in top 10 sales in Turkey. On the other hand the number of biotechnological medicines among the top 100 medicines was 4 in 2003; it reached to 27 in 2016. However the number of biotechnological medicines in the top 10 medicines was 1 in 2003 and it reached to 8 in 2016. Conclusion: The shares of biotechnological medicines in both the total pharmaceutical market and in the group of medicines with high sales are increasing every year. New policies should be developed to ensure the stability of the reimbursement system. © 2019 by The Medical Bulletin of İstanbul Haseki Training and Research Hospital.

Objective: The use of drugs outside the purpose for which they are approved, e.g. different indications, doses, administration forms, age groups, or special populations etc. is called "off-label drug use" (OLDU). This study aimed to investigate OLDU at provincial and territorial levels in Turkey. Methods: A total of 5681 applications submitted to the Turkish Medicines and Medical Devices Agency in 2011 were investigated. These applications were examined at provincial and NUTS-1 (Nomenclature of Territorial Units for Statistics-1) levels based on age, sex, time and place of application, etc. and top five most common drugs for each region. Results: OLDU applications were submitted mainly during Quarter 2 and 81.6% of them were from university hospitals. Except for "Southeastern Anatolia", the average age was 30-year in all regions and majority of patients (55.1%) were female. Applications were mostly submitted from "Western Anatolia" (34.9%), followed by "Istanbul" (26,5%) and "Aegean" (10,3%) regions at institutional level. The highest and lowest number of applications per 1000 specialist physician at provincial level were Cankiri (778.8) and Istanbul (20.0), respectively. While varying by rank among NUTS-1 regions, most commonly applied drugs were rituximab, mycophenolate mofetil, and iloprost trometamol. Conclusion: Rational OLDU practice depends on some critical factors including regional characteristics. This study is the first to show variations of OLDU applications at provincial and regional level, which need to be considered to improve functionality of OLDU. These findings are expected to shed light on new regulations and studies that will elucidate the causes of differences.