The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013.

BACKGROUND: With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS: We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS: Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86-0·94) to 1·45 million (1·38-1·54); YLLs from 31·0 million (29·6-32·6) to 41·6 million (39·1-44·7); YLDs from 0·65 million (0·45-0·89) to 0·87 million (0·61-1·18); and DALYs from 31·7 million (30·2-33·3) to 42·5 million (39·9-45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION: Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING: Bill & Melinda Gates Foundation.

Analysis of patient access to orphan drugs in Turkey.

BACKGROUND: Rare diseases are life-threatening, serious, and chronic conditions that require complex care and have a low prevalence. An estimated one in 15 people worldwide are affected by rare diseases. This study aims to analyze the accessibility, reimbursement status, licensed status, and Anatomical Therapeutic Chemical (ATC) codes of drugs that the European Medicines Agency (EMA) in Turkey considers to be "orphan" pharmaceuticals. METHODS: The drugs included in this analysis were obtained from the list of orphan drugs published by the EMA. Orphan drugs' accessibility and licensing status in Turkey were obtained from the Health Implementation Communiqué published by the Social Security Institution (SGK) and the List of Abroad Active Substance and List of Licensed Products published by the Turkey Pharmaceuticals and Medical Devices Agency (TITCK). Descriptive analysis was applied to determine the accessibility status of orphan drugs identified by the EMA in Turkey. RESULTS: Based on the EMA, 105 pharmaceuticals were approved with "orphan drug" status except for drugs that have lost orphan drug status, decommissioned in the European Union and withdrawn from the European Community Register by January 2020. Of the 105 rare drugs on the EMA list, 34 were inaccessible in Turkey. Of the 71 available drugs, 23 (32%) were licensed and 48 (68%) were unlicensed in Turkey. 17 (74%) of licensed products and 17 (35%) of unlicensed products were covered by reimbursement. When orphan drugs' ATC codes were examined, the most common ATC group was found to be "L-Antineoplastic and Immunomodulatory" agents. CONCLUSION: An orphan drug incentive policy is very important to ensure early access to the drugs used to treat rare diseases. Considering the capacity and prices for orphan drugs in Turkey, it can be said that many patients with rare diseases have difficulty in their treatment. It is obvious that such a policy must prepare for the regulation of orphan drugs in Turkey.

Predictive factors for time to remission and recurrence in patients treated for acute mania: health outcomes of manic episodes (HOME) study.

OBJECTIVE: To determine the time to remission and recurrence in patients treated for acute mania and the predictive factors associated with these outcomes. METHOD: This observational study, conducted in Turkey from April 2003 to January 2005, included patients with a DSM-IV diagnosis of bipolar I disorder, acute manic or mixed episode who were eligible to have an oral medication initiated or changed for the treatment of the episode. The patients were followed-up for 12 months. RESULTS: A total of 584 patients (mean ± SD age = 33.9 ± 11.2, 55.2% outpatients) were enrolled in 53 centers. Eighty-five percent of patients had a manic episode at baseline, with a mean ± SD duration of 21.6 ± 24.4 days. The baseline mean ± SD Clinical Global Impressions scale for use in bipolar disorder and Young Mania Rating Scale (YMRS) scores were 4.9 ± 0.9 (median = 5.0) and 33.2 ± 9.3 (median = 33), respectively. 539 patients achieved remission and, of those, 141 patients had recurrence. One-year remission and recurrence rates were 99.0% and 35.7%, respectively. Mean ± SD times to remission and recurrence in descriptive statistics were 80.9 ± 73.8 (median = 50) and 159.0 ± 95.5 (median = 156) days, respectively. In Cox regression analysis, psychiatric comorbidities (p = .048), a higher YMRS score (p < .001), and a higher number of previous depressive episodes (p = .009) were statistically significant predictors of a longer time to reach remission. Index episodes of longer duration (p = .033) and mixed type (p = 0.49) were significant predictors of a shorter time to recurrence. Confounding factors like concomitant treatment, comorbidities, and lack of blinding and randomization were other limitations. CONCLUSION: Predictors for a longer time to remission were psychiatric comorbidities, a higher YMRS score, and a higher number of previous depressive episodes. Predictors for a shorter time to recurrence were episodes of longer duration and mixed type.

Acute phase results from STORM, a multicountry observational study of bipolar disorder treatment and outcomes.

OBJECTIVES: This prospective observational study examined the outcomes associated with the treatment of bipolar mania in clinical practice settings in a diverse range of countries: Bosnia, Slovenia, Slovakia, Egypt, Saudi Arabia and Turkey. Particular emphasis was placed on investigating outcomes associated with treatment regimens including and excluding the atypical antipsychotic olanzapine. SUBJECTS AND METHODS: In- and outpatients initiating or changing oral medication for the treatment of bipolar mania were grouped into two treatment cohorts: (1) olanzapine (N=569), and (2) non-olanzapine (N=325). Clinical outcome measures included change in Clinical Global Impressions-Bipolar Version Severity of Illness scale (CGI-BP), Young Mania Rating Scale (YMRS) and Hamilton Depression Rating scale- 5 item (HAMD-5) scores, and response and remission rates. Outcomes were analysed by conventional linear or logistic regression, adjusted for potential confounders, using last observation carried forward (LOCF) at endpoint, and a marginal structural model (MSM) approach to account for treatment switching. Results from the 12-week acute phase are presented. RESULTS: Clinical improvements were observed in both cohorts. While no marked differences were apparent between the groups in adjusted mean baseline to LOCF endpoint change, longitudinal analysis of these variables using MSM averaged over all visits indicated greater improvements in the olanzapine versus non-olanzapine cohort in CGI-BP Overall (-0.26, p<0.001), CGI-BP Mania (-0.19, p<0.001), CGI-BP Depression (-0.10, p=0.003), CGI Psychosis (-0.14, p=0.001), YMRS (-1.70, p<0.001), and HAMD-5 (-0.40, p<0.001) scores. CONCLUSIONS: Inclusion of olanzapine after initiating or switching treatment for bipolar mania appeared to be beneficial during treatment in terms of symptom improvement.

Impact of Health Policy Changes on Trends in the Pharmaceutical Market in Turkey.

BACKGROUND: The implementation phase of the Turkish Health Transformation Program (HTP) began in 2003, with the aim of organizing, financing, and delivering health care services effectively, efficiently, and equally. The HTP impacted all clinical and economic outcomes of health, including pharmaceutical sales, by improving access to health services. OBJECTIVES: To understand the impact of five selected major policy changes that made an impact on supply, demand, or price in the pharmaceutical market between 1998 and 2012. METHODS: Monthly sales data (in units and value in US $) of a total of 180 pharmaceuticals covering the period between 1998 and 2012 were used for statistical analysis. Five major policies that could affect health expenditures and the demand and supply of pharmaceuticals were selected and led by the Ministry of Health. A P value of less than 0.05 was considered as the cutoff value for statistical significance. RESULTS: There was a growing trend in pharmaceuticals value and units in years, possibly as a result of the HTP implementation. Supply- and demand-related policies had a negative impact on the trends for value, whereas the pricing policy had a positive impact. CONCLUSIONS: It could be said that the HTP had an impact on units for improved access to health care services. Although this access increased the consumption of pharmaceuticals in units, the policies implemented were successful in controlling pharmaceutical expenditures.

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.

Controlled lithium discontinuation in bipolar patients with good response to long-term lithium prophylaxis.

BACKGROUND: This study aims to investigate whether the risk of recurrence following lithium discontinuation is less than reported in discontinuation of a successful, long-term prophylaxis in bipolar patients. METHODS: A total of 32 bipolar patients discontinued lithium according to the controlled lithium discontinuation (CLD) protocol following a definite good response to lithium maintenance of at least 5 years. Subjects were followed for up to 9 years. RESULTS: The total rate of recurrence was 7% in the first week, 32% in the first month, 62% in the first year, and 81% at the end of the 9th year following discontinuation. Only six of the 32 patients (19%) did not have a recurrence during the follow-up period. CONCLUSIONS: Discontinuation of lithium seems to be followed by a high rate of recurrence in bipolar patients even after good response to a long-duration illness-free period. A controlled discontinuation protocol can reduce the risks of morbidity.

Unipolar mania: a distinct disorder?

BACKGROUND: This study aimed to identify the differences between unipolar mania and classical bipolar disorder. METHODS: Patients with at least four manic episodes and at least 4 years of follow-up without any depressive episodes were classified as unipolar mania. This group was compared to other bipolar-I patients defined according to DSM-IV regarding their clinical and socio-demographic variables. RESULTS: The rate for unipolar mania as defined by the study criteria was found to be 16.3% in the whole group of bipolar-I patients. Unipolar manic patients tended to have more psychotic features and be less responsive to lithium prophylaxis compared to other bipolar-I patients. LIMITATIONS: Because it was a retrospective study, there may be some minor depressive episodes left unrecorded in the unipolar mania group despite careful and thorough investigation. In addition, even with our fairly strict criteria for the diagnosis of unipolar mania, the possibility of a future depressive episode cannot be excluded. CONCLUSIONS: Unipolar mania may be the presentation of a nosologically distinct entity.

Cost-Effectiveness Analysis of Aripiprazole Augmentation Treatment of Patients with Major Depressive Disorder Compared to Olanzapine and Quetiapine Augmentation in Turkey: A Microsimulation Approach.

OBJECTIVES: Major depressive disorder (MDD) is a chronic illness associated with a major burden on quality of life (QOL) and health care resources. Aripiprazole augmentation to antidepressant treatment was recently approved for patients with MDD responding insufficiently to antidepressant treatment in Turkey. The objective was to estimate the cost-effectiveness of aripiprazole augmentation in this indication compared with olanzapine and quetiapine augmentation from a payer perspective. METHODS: A lifetime economic model was built simulating transitions of patients with MDD between major depressive episodes (MDEs) and remission. During MDEs, patients were treated with adjunctive aripiprazole, quetiapine, or olanzapine. Patients who did not respond switched to subsequent treatment lines. Comparative effectiveness between adjunctive aripiprazole, quetiapine, and olanzapine was estimated by using an indirect comparison. Resource utilization and costs were obtained from Turkish studies. RESULTS: Over a lifetime horizon, patients treated with aripiprazole spent less time in MDEs than did patients treated with quetiapine (-11 weeks) and olanzapine (-7 weeks). On average, patients treated with aripiprazole showed improvement in QOL compared with patients treated with quetiapine (+0.054 quality-adjusted life-years [QALYs]) and olanzapine (+0.039 QALYs) combined with cost saving of 593 Turkish lira (TL) versus quetiapine and 485 TL versus olanzapine. The probability that adjunctive aripiprazole would be cost-effective among the three strategies ranged between 74% and 75% for willingness-to-pay values between 0 TL and 100,000 TL per QALY gained. CONCLUSIONS: This is the first lifetime health-economic model in Turkey that takes patient heterogeneity into account when assessing QOL and costs of different adjunctive strategies in MDD. The results indicate that adjunctive treatment with aripiprazole provides health benefits at lower costs in patients with MDD when compared with quetiapine and olanzapine augmentation.

Olanzapine versus chlorpromazine in the treatment of schizophrenia: a pooled analysis of four 6-week, randomized, open-label studies in the Middle East and North Africa.

This pooled analysis of four 6-week, randomized, open-label, parallel trials of patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) compared the efficacy and tolerability of olanzapine (5-20 mg/d) with those of chlorpromazine (200-800 mg/d). Of the 123 patients randomly allocated to olanzapine (n = 83) or chlorpromazine (n = 40), 109 completed the study (olanzapine, n = 77; chlorpromazine, n = 32). Olanzapine-treated patients showed significantly greater baseline-to-end point mean improvements in the primary efficacy measure, Brief Psychiatric Rating Scale total, compared with chlorpromazine-treated patients (least-squares means: olanzapine, -21.1; chlorpromazine, -10.4; P < 0.001). Response rate was significantly higher in the olanzapine group (66.3% vs. 32.4%; P = 0.001). Baseline-to-maximum changes in the UKU scores for akathisia were significantly different between the groups (P = 0.018). A decrease (improvement) in these scores was observed in 6/74 (8.1%) of olanzapine- and 1/36 (2.8%) chlorpromazine-treated patients. Weight gain was the only common (> or =10%) adverse event that occurred more frequently, although not significantly differently, in the olanzapine group (27.7%) than the chlorpromazine group (12.5%), whereas postural hypotension was the only common adverse event whose occurrence was significantly different between the groups (olanzapine, 0.0%; chlorpromazine, 10.0%; P = 0.010). Both the incidence of > or =7% weight gain from baseline (olanzapine, 26.3%; chlorpromazine, 24.3%) and baseline-to-end point changes in weight (mean +/- SD, kg: olanzapine, 3.41 +/- 3.14; chlorpromazine, 2.81 +/- 2.65) were not significantly different between the treatment groups. Baseline-to- end point changes in nonfasting glucose differed significantly between the groups (mean +/- SD, mmol/L: olanzapine, 0.09 +/- 1.11; chlorpromazine, 0.72 +/- 2.04; P = 0.042). This analysis suggests that, compared with chlorpromazine, olanzapine may be more efficacious and have a more favorable tolerability profile in treating patients with schizophrenia.

Obsessive-compulsive disorder secondary to bilateral frontal damage due to a closed head injury.

OBJECTIVE: To describe a patient who exhibited obsessive-compulsive disorder and frontal lobe dysfunction signs after a closed head trauma. BACKGROUND: Recent evidence indicates that frontal-subcortical circuits are involved in the pathogenesis of primary obsessive-compulsive disorder. There are a number of case reports of secondary obsessive-compulsive disorder after lesions involving certain parts of these circuits. METHOD: Clinical examinations, cognitive and behavioral assessments, and-lesion analysis based on magnetic resonance imaging were conducted. RESULTS: The patient displayed marked obsessive-compulsive behavior along with hyperorality and apathy. Magnetic resonance imaging showed symmetrical frontal-polar abnormal signal intensity. Topographic lesion analysis revealed involvement of Brodmann areas 11, 10, 24, 25, and 32. CONCLUSIONS: The patient presented in this report had both frontal lobe dysfunction signs and obsessive-compulsive disorder secondary to bilateral frontal damage due to a closed head injury. The etiological significance of head injury and frontal lobe involvement in obsessive-compulsive disorder is discussed in the context of the clinical and neuroimaging findings and of previous series of brain injured patients.