Modeling the Health Economic Burden of Hepatitis C Virus Infection in Turkey: Cost-Effectiveness of Targeted Screening.

BACKGROUND/AIMS: In 2016, World Health Organization introduced global goals to eliminate hepatitis C virus by 2030. The aim of this study is to analyze the epidemiologic and economic burden of hepatitis C virus in Turkey and compare current practice (regular care) with a hypothetical active screening and treatment approach (active scenario). MATERIALS AND METHODS: A Markov model was used to analyze and compare regular care with a scenario developed by experts including the screening and treatment of all acute and chronic hepatitis C virus infections between 2020 and 2050. General and targeted populations were focused. The model reflected the natural history of the disease, and the inputs were based on a literature review and expert opinions. Costs were provided by previous studies and national regulations. RESULTS: The active scenario resulted in higher spending for all groups compared with regular care in the first year. Cumulative costs were equalized in the 8th, 12th, 13th, and 16th year and followed by cost-savings of 49.7 million, 1.1 billion, 288.6 million, and 883.4 million Turkish liras in 20 years for prisoners, refugees, people who inject drugs (PWID), and all population, respectively. In all groups, the mortality was found to be lower with the active scenario. In total, 62.8% and 50.6% of expected deaths with regular care in 5 and 20 years, respectively, were prevented with the active scenario. CONCLUSIONS: An active screening and treatment approach for hepatitis C virus infection could be cost-effective for PWID, prisoners, and refugees. Almost two-thirds of deaths in regular care could be prevented in 5 years' time with this approach.

A meta-analysis on the cardiac safety profile of domperidone compared to metoclopramide.

BACKGROUND: This meta-analysis aimed to assess the cardiac safety profile of domperidone treatment for the risk of cardiovascular (CV) event and QT prolongation. METHODS: Data from nine studies involving 101,155 patients were used for the analysis of CV event risk, while data from eight studies involving 390 patients were used for the analysis of QT prolongation risk. RESULTS: Meta-analysis findings suggested a significant increase in CV risk under domperidone as compared to no treatment for domperidone doses of >30 mg/day (OR: 3.14, 95% CI, 1.191 to 8.304, p = 0.021), no significant increase in QT prolongation event rates with domperidone (3.54%, 95% CI, 1.73% to 7.10%) and a significantly lower CV risk for domperidone than for metoclopramide (OR: 0.63, 95% CI, 0.58 to 0.70, p < 0.001). CONCLUSIONS: The present meta-analysis indicates that domperidone treatment may not be associated with an overall CV event risk increase at doses ≤30 mg/day and does not result in QT prolongation.

Renin-angiotensin-aldosterone system blockers and cardiovascular outcomes: a meta-analysis of randomized clinical trials.

OBJECTIVE: Hypertension is the most prevalent modifiable risk factor for cardiovascular (CV) and cerebrovascular morbidity and mortality. This study aimed to assess the effects of renin-angiotensin-aldosterone system (RAAS) blockade on CV outcomes. METHODS: This study was designed according to the Preferred Reporting Items for Systemic reviews and Meta-Analyses statement. Databases were searched for articles published as of December 2014. Two sets of studies were selected. One set included randomized clinical trials comparing RAAS blocker (angiotensin II receptor blocker [ARB] or angiotensin-converting enzyme inhibitor [ACEI]) with placebo or active treatment. Second set included head-to-head randomized clinical trials comparing an ARB with an ACEI. Studies in both sets had reported any CV outcome parameter or death, i.e., all-cause mortality, CV mortality, emergence of CV events, myocardial infarction, cerebrovascular event, stroke, heart failure, and hospitalization for heart failure. RESULTS: Fifty-four pairwise comparisons of 51 trials with 277,609 patients were included. Statistically significant differences in favor of RAAS blockers vs non-RAAS blockers (risk ratio [RR] ranging from 0.805 to 0.967) were observed in terms of most CV outcomes, including all-cause mortality, CV mortality, CV events, myocardial infarction, heart failure and stroke. ARBs and ACEIs were found to be completely comparable (RR ranging from 0.923 to 1.090, all non-significant). CONCLUSION: RAAS blockers are superior to medications other than RAAS blockers with respect to impact on CV outcomes in patients with hypertension. ARBs and ACEIs are comparable in terms of these outcomes.

Cost of heart failure management in Turkey: results of a Delphi Panel.

OBJECTIVE: To analyze health-related cost of heart failure (HF) and to evaluate health-related source utilization aiming to provide data on the economic burden of HF in actual clinical practice in Turkey. METHODS: The study used the Delphi process of seeking expert consensus of opinion including 11 cardiologists who are experienced in HF. The standardized questionnaire comprised items to reflect the opinion of the expert panelists on the distribution of the HF patients in terms of demographic and clinical characteristics and background disease states. Costs related to out-patient follow-up, in-patient follow-up, medications, and other therapies were also evaluated. RESULTS: 34.1% of the HF patients were in the age range of 60-69 years, and 62.3% were males. Coronary heart disease was the leading cause of HF (59.6%); 63.6% of the HF patients had reduced ejection fraction (rEF) and 42.3% were in New York Heart Association (NYHA)-II class. Approximately 75 % of the patients were followed up by a cardiology unit. The total annual visit number was estimated as 3.41. Approximately 32% of HF patients were hospitalized 1.64 times a year, for an average of 6.77 days each time. The total annual costs of all HF patients and HF-rEF patients were estimated as 1.537 TL and as 2.141 TL, respectively. CONCLUSION: The analysis demonstrating the magnitude of the economic impact of HF management on Turkey's healthcare system may help facilitate health and social policy interventions to improve the prevention and treatment of HF.

Cost-effectiveness analysis of oral anti-viral drugs used for treatment of chronic hepatitis B in Turkey.

BACKGROUND: All international guidelines suggested that Tenofovir and Entecavir are the primary drugs at the first line therapy for the treatment of chronic hepatitis B (CHB). However, in Turkey these medications reimbursed at the second line therapy according to the Healthcare Implementation Notification. The aim of this study is to compare the cost effectiveness of oral antiviral treatment strategies in CHB for Turkey using lamuvidine, telbuvidine, entecavir, and tenofovir as medications. METHODS: The analysis was conducted using Markov models. The analysis scenarios based on first line treatment options with Lamuvidine, Telbuvidine, Entecavir, and Tenofovir as the medications. In the analysis, inadequate response or resistance after receiving 12 months of the treatment with Entecavir and Telbivudine were compared to the results found from switching from Entecavir to Tenofovir or from switching from Telbuvidine to Tenofovir. In additional, inadequate response or resistance after receiving 6 months of the treatment for Lamivudine was compared to the results found from switching from Lamivudine to Tenofovir. The study population included men and women, who were 40 years of age. The patients` compliance was estimated 100 % for all of the therapy options. The model duration was constructed to evaluate, treatment strategy duration of 40 years. The cost of medications, examinations/follow-ups and complications were included in the model. Years of Potential Life Lost was used as the health outcome. An incremental cost-effectiveness ratio analysis has been conducted. RESULTS AND DISCUSSION: While the minimum years of life lost was found as 0.22 with tenofovir treatment in 5 years, treatment cost was calculated as 12,169 TL. These values were detected as 0.56 years and 7727 TL, 0.37 years and 12,770 TL, respectively for lamuvidine and telbuvidine treatments. The maximum years of life lost and treatment cost was with lamuvidine treatment were detected as 1.60 years and 18,813 TL and, secondly 0.89 years and 24,007 TL for lamuvidine-tenofovir treatment during 10 years. The minimum years of life lost and cost are 0.54 year and 35,821 TL for tenofovir treatment during 10 years. The minimum years of life lost and cost were determined as 1.21 years and 52,839 TL for tenofovir treatment strategy during 20 years. During 30 years period, tenofovir treatment was found to have the minimum years of life lost (1.73 years) and minimum cost (84,149 TL). When the results of 40 years period were analyzed, years of life lost and costs are 2.06 years and 119,604 TL, 2.13 years and 162,115 TL, 2.13 years and 161,642 TL, 6.52 years and 147,245 TL, 3.20 years and 132,157 TL, 4.10 years and 151,059 TL and 3.05 years and 138,182 TL for tenofovir, entecavir, entecavir-tenofovir, lamuvidine, lamuvidine-tenofovir, telbivudine and telbivudine-tenofovir. CONCLUSIONS: In the model presented in this study, in cost effectiveness analysis about CHB treatments, Tenofovir was found to be one of the cost effective methods in comparison with other treatment strategies different time intervals. Beyond this achievement Tenofovir has shown to reduce cumulative treatment cost in first line CHB treatment when compared with regard to 40 year cumulative treatment cost.

The most critical question when reading a meta-analysis report: Is it comparing apples with apples or apples with oranges?

OBJECTIVE: While the number of meta-analyses published has increased recently, most of them have problems in the design, analysis, and/or presentation. An example of meta-analyses with a study selection bias is a meta-analysis of over 160,000 patients in 20 clinical trials, published in Eur Heart J in 2012 by van Vark, which concluded that the significant effect of renin-angiotensin-aldosterone system (RAAS) inhibition on all-cause mortality was limited to the class of angiotensin-converting enzyme inhibitors (ACEIs), whereas no mortality reduction could be demonstrated with angiotensin receptor blockers (ARBs). Here, we aimed to discuss how to select studies for a meta-analysis and to present our results of a re-analysis of the van Vark data. METHODS: The data were re-analyzed in three steps: firstly, only ACEI/ARB-based studies (4 ACEI and 12 ARB studies) were included; secondly, placebo-controlled studies were excluded, and 10 studies left were analyzed; and thirdly, 2 studies that were retracted after the manuscript of van Vark had been published were excluded. The final analysis included 8 studies with ~65,000 patients (3 ACEI and 5 ARB studies). RESULTS: The hazard ratios for all-cause mortality and cardiovascular mortality were 0.992 (95% CI 0.899-1.095; p=0.875) and 1.017 (0.932-1.110; p=0.703) for the ACEI versus control group and 1.007 (0.958-1.059; p=0.778) and 0.967 (0.911-1.025; p=0.258) for the ARB versus control group in the first step. The results were similar in the second and third steps. CONCLUSION: The studies to be included in meta-analyses, particularly comparing ACEIs and ARBs, should be chosen carefully.

Oral systemic administration of Ankaferd blood stopper has no short-term toxicity in an in vivo rabbit experimental model.

BACKGROUND: Ankaferd blood stopper (ABS) is a standardized herbal extract obtained from 5 different plants. In Turkey, it has been approved for local topical applications in external postsurgical and postdental surgery bleedings. Ankaferd blood stopper, besides its hemostatic activity, has in vitro anti-infectious and antineoplastic actions. OBJECTIVE: The aim of this study was to assess short-term hematological and biochemical safety following the oral systemic administration of ABS to rabbits. METHODS: Twelve rabbits (aged 6-12 months) were included to test the safety of oral ABS. Animals were divided into 4 groups, which had ABS administered orally at doses of 1, 3, 6, and 9 mL, irrespective of their weight. The general well-being and feeding patterns of the animals were observed for a period of 7 days. Blood samples (5.5 mL) were obtained just before oral administration, on days 1 and 4. RESULTS: During the observation period of 7 days, none of the animals showed any abnormal behavior or deviation from the normal. Acute mucosal toxicity, hematotoxicity, hepatotoxicity, nephrotoxicity, and biochemical toxicity were not observed during the short-term follow-up of the animals. CONCLUSIONS: No signs of toxicity were observed in rabbits during short-term study with oral ABS administration.

Ultrastructural and morphological analyses of the in vitro and in vivo hemostatic effects of Ankaferd Blood Stopper.

Ultrastructural and morphological analyses of a novel hemostatic agent, Ankaferd Blood Stopper (ABS), in comparison to its in vitro and in vivo hemostatic effects were investigated. High-resolution scanning electron microscopy (SEM) images accompanied with morphological analysis after topical application of ABS revealed a very rapid (<1 second) protein network formation within concurrent vital erythroid aggregation covering the classical coagulation cascade. Histopathological examination revealed similar in vivo ABS-induced hemostatic network at the porcine hepatic tissue injury model. Instantaneous control of bleeding was achieved in human surgery-induced dental tissue injury associated with primary and secondary hemostatic abnormalities. Ankaferd Blood Stopper could hold a great premise for clinical management of surgery bleedings as well as immediate cessation of bleeding on external injuries based on upcoming clinical trials.

The efficacy of Ankaferd Blood Stopper in antithrombotic drug-induced primary and secondary hemostatic abnormalities of a rat-bleeding model.

Ankaferd comprises a standardized mixture of plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum and Urtica dioica. Ankaferd Blood Stopper (ABS) as a medicinal product has been approved in the management of external hemorrhage and dental surgery bleedings in Turkey. This study aimed to evaluate the in-vivo hemostatic effect of ABS in rats pretreated with acetylsalicylic acid or enoxaparin. Wistar rats (210-270 g) of both sexes were used in this study. The animals were pretreated with acetylsalicylic acid (10 mg/kg) orally for 4 days or enoxaparin sodium (8 mg/kg) subcutaneously for 3 days or did not receive any anticoagulant before tail cut at 4th day. ABS was administered topically [a total of 4 ml (1 ml/puff x 4)] to the cut tail in the studied animals. The duration of bleeding and the amount of bleeding were measured in order to evaluate the hemostatic effect of ABS. In acetylsalicylic acid-treated animals, topical ABS reduced both the duration and also the amount of bleeding volume by 68.4 and 54.6%, respectively. It was also effective in shortening the duration of bleeding (30.6%) and decreasing the amount of bleeding (32.8%) in enoxaparin-treated animals. ABS, a traditional folkloric medicinal plant extract, has in-vivo hemostatic actions, which may provide a therapeutic potential for the management of patients with deficient hemostasis in the clinical medicine.

In vivo hemostatic effect of the medicinal plant extract Ankaferd Blood Stopper in rats pretreated with warfarin.

AIM: Ankaferd comprises a mixture of Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum and Urtica dioica. Ankaferd Blood Stopper (ABS) has been approved in the management of bleedings. This study aimed to evaluate in vivo hemostatic effect of ABS in rats pretreated with warfarin. MATERIALS AND METHODS: Wistar rats (210-270 g) were treated either with warfarin (2 mg/kg) or vehicle (0.9% NaCl) orally before bilateral hind leg amputation. ABS was administered topically to one of the amputed legs. The duration of bleeding and the amount of bleeding were measured to evaluate the hemostatic effect of ABS. RESULTS: Topical ABS administration to amputed leg shortened the duration of bleeding markedly in both untreated and warfarin-treated rats by 31.9% [1.42 min (95% CI: 0.35-2.49)] and 43.5% [5.12 min (95% CI: 2.16-8.07)] respectively. The amount of bleeding in ABS-administered amputed leg showed a decrease by 53.8% in warfarin-treated group. CONCLUSIONS: ABS has in vivo hemostatic actions that may provide a therapeutic potential for the management of patients with deficient primary hemostasis in clinical medicine.

Atherosclerosis in Behçet's Syndrome.

OBJECTIVES: We had the impression and preliminary evidence that atherosclerosis was not much increased in Behçet's syndrome (BS). Thus, we evaluated the presence of subclinical atherosclerosis in a sizeable group of patients with BS both with major organ involvement and mucocutaneous disease along with diseased and healthy controls. METHODS: We studied 239 (162 M/ 77 F; mean age: 40.7+/-7.0) patients with BS. Seventy-two (32 M/ 40 F) had only mucocutaneous and/or joint disease and 167 (130 M/ 37 F) had major organ involvement. Also 100 (24 M/ 76 F; mean age: 44.7+/-7.1) patients with rheumatoid arthritis (RA), 74 (58 M/ 16 F; mean age: 39.4+/-7.0) patients with ankylosing spondylitis (AS) and 156 (83 M/ 73 F; mean age: 39.2+/-6.6) healthy controls (HC) were studied as the control groups. We used B-mode USG to assess the frequency of plaques and intima-media thickness (IMT) in the carotid and femoral arteries. Traditional atherosclerotic risk factors were also evaluated. Men and women were analyzed separately. RESULTS: The frequency of plaques and the mean IMT in the carotid and femoral arteries were similar between patients with BS, AS and HC and also between the 2 subgroups of BS, among both men and women. Only men with RA were found to have significantly increased frequency of carotid artery plaques after adjustment for atherosclerotic risk factors. CONCLUSION: Increased atherosclerosis is not a prominent feature of BS, even among those patients with major organ involvement.

Turkish patients with osteoarthritis: their awareness of the side effects of NSAIDs.

BACKGROUND/AIMS: The study aim was to determine the awareness of Turkish osteoarthritis patients of the side effects of non-steroidal anti-inflammatory drugs. METHODS: The patients were interviewed by 138 doctors regarding the level of their knowledge of the side effects of non-steroidal anti-inflammatory drugs. RESULTS: A total of 3,755 patients (female/male: 3/1, 35% > 65 years) were included in the study. 35.5% of the patients were aware of side effects of non-steroidal anti-inflammatory drugs. 85.4% and 11.5% were aware of the gastrointestinal and other system-related side effects, respectively. 51% had learned of the side effects from doctors, 19.8% received information from the package inserts, 21.3% had experienced side effects, and 10.0% and 0.8% had learned from their friends and pharmacist, respectively. CONCLUSIONS: Turkish osteoarthritis patients have a moderate level of knowledge of side effects of non-steroidal anti-inflammatory drugs. Defining factors for knowledge of side effects of non-steroidal anti-inflammatory drugs were geographical region, socio-economic level and gender. This study reveals the physician's responsibility to educate patients about the side effects of non-steroidal anti-inflammatory drugs.

The use and safety profile of non-steroidal antiinflammatory drugs among Turkish patients with osteoarthritis.

BACKGROUND/AIMS: To determine the use and safety profile of non-steroidal anti-inflammatory drugs (NSAIDs) among Turkish osteoarthritis patients. METHODS: Osteoarthritis patients were interviewed by 138 doctors from clinics in nine different cities. Doctors completed a questionnaire regarding non-steroidal anti-inflammatory drugs use and safety profile while interviewing the patients. RESULTS: Totally 3,755 patients (female/male: 3/1, mean age 59.0 +/- 12.2 years), 3,442 under non-steroidal anti-inflammatory drugs treatment, were included in the study. The use of meloxicam (5.5% vs. 14.4%) and specific cyclooxygenase-2 (COX-2) inhibitors (for celecoxib 3.3% vs. 12.2%; for rofecoxib 3.0% vs. 11.2%) increased more than that of other non-selective non-steroidal anti-inflammatory drugs. The most common side effects were epigastric burning (37%), other dyspeptic symptoms (25.3%), abdominal pain (17.0%), constipation (12.7%), nausea (10.6%) and diarrhea (3.0%). COX-2 selective and specific inhibitors had significantly lower incidence of dyspeptic complaints compared to non-selective non-steroidal anti-inflammatory drugs. No difference was found between the different non-steroidal anti-inflammatory drugs regarding the ratio of discontinuation of therapy due to inefficacy. The ratios of discontinuation due to side effects were lower in patients using COX-2 specific inhibitors compared to non-selective and selective non-steroidal anti-inflammatory drugs: celecoxib (7.7%), rofecoxib (10.3%), etodolac (12.4%), meloxicam (12.6%), tenoxicam (16.5%), diclofenac (16.8%), ibuprofen (19.4%), and naproxen (27.4%). Discontinuation of the non-steroidal anti-inflammatory drugs due to dyspeptic complaint was significantly less for specific COX-2 inhibitors than for non-selective and selective non-steroidal anti-inflammatory drugs: celecoxib (2.5%), rofecoxib (8.4%), meloxicam (9.5%), etodolac (13.4%), tenoxicam (14.0%), diclofenac (14.1%), ibuprofen (17.2%), and naproxen (24.4%). CONCLUSIONS: The use of meloxicam and specific COX-2 inhibitors seems to have increased more than that of other non-selective non-steroidal anti-inflammatory drugs, if previously used non-steroidal anti-inflammatory drugs are considered. Fewer dyspeptic complaints have been reported with specific COX-2 inhibitors.