Intact short-term memory and impaired executive functions in obsessive compulsive disorder.

BACKGROUND AND PURPOSE: Previous neuropsychological studies produced inconsistent results with tasks tapping short-term verbal and visual-spatial memory and executive functions in obsessive compulsive disorder (OCD). The aim of this study was to investigate the presence of deficits in these cognitive domains. A further goal was to describe the distribution of patients in different impairment ranges for all functions, and clarify the relationship between symptom severity and cognitive impairments. METHODS: Thirty patients with OCD (DSM-IV) and 30 healthy volunteers were compared using well-known neuropsychological tasks. We assessed short-term verbal memory with the Digit Span Forward and Digit Span Backward Tasks, short-term visual-spatial memory with the Corsi Block Tapping Task, while we measured the level of executive functions with the StroopTask and the Wisconsin Card Sorting Test (WCST). RESULTS: Compared with a matched healthy control group, the performance of OCD patients was in the impaired range only in the two executive tasks. We find a significant positive correlations between the Y-BOCS (Yale-Brown Obsessive Compulsive Scale) total scores and the number of perseverative responses (r(28) = 0.409, p < 0.05) and perseverative errors (r(28) = 0.385, p < 0.05) in the WCST. CONCLUSION: Our results gave evidence that executive functions are impaired while short-term memory is intact in OCD. This is in line with neuropsychological model of OCD that the deficit of cognitive and behavioral inhibition are responsible for the main cognitive findings of this disorder, most prevalently the deficit in set shifting and prepotent response inhibition.

Corrigendum to "Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications".

[This corrects the article DOI: 10.1155/2021/9996193.].

The validation of the Hungarian version of the dimensional Yale-Brown obsessive-compulsive scale.

BACKGROUND: The Obsessive-Compulsive disorder (OCD) has a complex phenotype, which can be summarized by using a few consistent and temporally stable symptom dimensions. The dimensional approach derived from the systematic factor analytic studies of OCD symptoms. In 2006, a new psychometric scale was created by M.C. Rosario-Campos and her colleague, the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS). This scale measures the presence and severity of obsessive-compulsive (OC) symptoms within six distinct dimensions. The Hungarian translation of the test and preliminary results were published in 2009. PURPOSE: The objective of this recent study was two folded: on one hand, our goal was to validate the Hungarian version of the DY-BOCS on a larger sample size. On the other hand, we wanted to publish our results gained by the Hungarian version of the test in English. METHODS: We assessed 30 Hungarian patients diagnosed with OCD by DSM-IV. Reliability and validity of the expert and of the self-report were estimated. RESULTS: Self-report and expert ratings were highly correlated. The global DY-BOCS score was well correlated with the total Yale-Brown Obsessive-Compulsive Scale score. The internal validity of the symptom dimensions and the global severity score were high. Divergent validity was also good. CONCLUSION: These results indicate that the Hungarian version of the DY-BOCS is a reliable and valid clinical tool.

Pricing and Reimbursement of Patent-Protected Medicines: Challenges and Lessons from South-Eastern Europe.

BACKGROUND: Efficiency and transparency of pricing and reimbursement (P&R) rules and procedures as well as their implementation in South-eastern Europe (SEE) lag substantially behind Western European practice. Nevertheless, P&R systems in SEE are rarely critically assessed, warranting a detailed and wider-encompassing exploration. OBJECTIVE: Our study provides a comparative assessment of P&R processes for patent-protected medicines in ten SEE countries-EU member states: Croatia, Slovenia, Hungary, Romania and Bulgaria; and non-EU countries: Albania, Montenegro, Serbia, North Maceodina, Bosnia and Herzegovina. P&R systems are compared and evaluated through a research framework that focuses on: (1) public financing of patent-protected medicines, (2) definition of benefit packages, (3) requirements for the submission of reimbursement dossiers, (4) assessment and appraisal processes, (5) reimbursement decision making, (6) processes that occur post reimbursement, and (7) pricing. The study aims to contribute to the discussion on improving the efficiency and quality of P&R of patent-protected medicines in the region. METHODS: We conducted a non-systematic literature review of published literature, as well as policy briefs and reports on healthcare systems in the SEE region along with legal documents framing the P&R procedures in local languages. The information gathered from these various sources was then discussed and clarified through structured telephone interviews with relevant national experts from each SEE country, mainly current and former senior officials and/or executives of the funding and assessment/ appraisal bodies (total of 20 interviews conducted in late 2019). RESULTS: Capacity building through sharing knowledge and information on successful reforms across borders is an opportunity for SEE countries to further develop their P&R policies and increase (equitable) access to patent-protected medicines (especially expensive medicines), increasing affordability and containing costs. Simple yet robust and systematic decision-making frameworks that rely on international health technology assessment (HTA) procedures and are based on the pursuit of transparency seem to be the most cost-effective approach to strengthening P&R systems in SEE. CONCLUSIONS: Further reforms aiming to develop transparent and robust national decision-making frameworks (including oversight) and build institutional HTA-related and decision-making capacity are awaited in most of SEE countries, especially the non-EU members. In non-EU SEE countries, these efforts could increase access to patent-protected medicines, which is-at the moment-very limited. The EU-member SEE countries operate more developed P&R systems but could further benefit from developing their procedures, oversight and value-for-money assessment toolbox and capacity, hence further improving the transparency and efficiency of procedures that regulate access to patent-protected medicines.

Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications.

BACKGROUND: Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel. RESULTS: Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups. CONCLUSIONS: There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

Deep brain stimulation for treatment refractory obsessive-compulsive disorder--a case report.

In the past 30 years it has been a great development in the unders-anding and therapy of obsessive-compulsive disorder. Adequate pharmaco- and cognitive-behavior therapies reduce the symptoms in 40-60% of patients, so a remarkable portion of patients still remains refractory to conventional treatment. Neurosurgery--with it's reversible and irreversible techniques--brought a breakthrough in the therapy of treatment refractory patients. In the present case, we represent a 3 months follow-up of an obsessive-compulsive pctient treated by deep brain stimulation. In our case, the stimulation target was the anterior limb of internal capsule. The clinical symptoms were measured by Y-BOCS. In addition various neuropsychological tests were used to monitor patient's executive functions before and 3 months after the deep brain stimulation. We found that obsessive-compu sive symptoms improved after three months of the stimulation. The neuropsychological tests showed improvement in some executive functions (e.g. fluency, set-shifting, decision making). On the other hand our results revealed severe neurocognitive--mainly attention skill--deficits in a treatment refractory obsessive-compulsive patient.

Influence of biosimilar infliximab launch on the utilization pattern of biological medicines: the case of Hungary.

Objectives: Utilization of multisource biological (off-patent originator and its biosimilar) medicines can improve the efficiency of resource allocation by 1) generating savings while maintaining health outcomes or 2) increasing the number of patients treated with more affordable treatments. This study evaluates the efficiency of the Hungarian biosimilar drug policy on the case of biosimilar infliximab. Methods: We analyzed the utilization of biologicals in all reimbursed indications of infliximab including initial therapy of new patients and switching patterns retrospectively based on patient-level payer's data between September 2012 and December 2016. Results: Despite the economic rationale, patent expiry did not manifest in increased utilization of multisource infliximab in an access-restricted environment: 1) Patients previously treated with original biologicals were switched mainly to other original biologicals instead of more affordable biosimilar alternatives. 2) Although some treatment-naive patients started on more affordable multisource infliximab with price competition, the majority of new patients started on other original biologicals with monopolistic price. Conclusion: Policy tools and measures should be developed to facilitate first-line use of multisource biologicals for treatment-naive patients and promoting the use of more affordable multisource biologicals in case of switching.

[Hungarian translation of the Dimensional Yale-Brown Obsessive-Compulsive Scale and our first experiences with the test]. / A dimenzionális Yale-Brown obszesszív-kompulzív teszt (DY-BOCS) magyar fordítása, és a teszttel szerzett elsö tapasztalataink.

According to the dimensional approach of the obsessive-compulsive disorder (OCD), it is possible to identify phenotypic subtypes--so called dimensions--within the heterogeneous clinical manifestations of OCD by statistical techniques (principal component analysis). The Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS) measures the presence of the obsessive-compulsive symptoms within the phenotype. The scale is a semi-structured instrument, which includes a symptom list divided into six dimensions for the patients and a part reserved for the clinician. The authors gave their written permission for the translation of the DY-BOCS test into Hungarian, revised the back-translation of the Hungarian version and the final, revised version is published for the first time, in Hungary. The Hungarian DY-BOCS was administered to seventeen OCD patients at 2nd Department of Psychiatry, Nyírô Gyula Hospital. The reliability analysis produced strong correlation coefficients. The internal consistency (Cronbach alpha) scores were high, ranging from 0.97 to 0.99. The scores of the validity scales were also good. There was a strong convergent validity between the gold standard, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) global severity scores and the DY-BOCS global severity scores (p=0.001 / r=0.744). The examination of the internal validity showed that the DY-BOCS global score and the aggressive and miscellaneous dimension severity rating scores are strongly correlated. We also experienced strong correlation between the DY-BOCS global score and the component scores of the global severity ratings (time, distress, interference, and impairment), the Pearson's r ranged from 0.815 to 0.960. There was no significant inter-correlation between the dimensions, which supports the assumption that these dimensions are independent constructs. In the divergent validity measures, we used the Hamilton Depression Scale (HAM-D) to compare OCD dimensions with the most common comorbid disorder (depression) symptoms. The severity scores of the HAM-D were correlated with the severity scores of the DY-BOCS dimensions. In this latter validity test, we found only one significant correlation between the aggressive dimension and the severity of the depression. In the case of the remaining dimensions, there was no significant correlation between the dimensions and the severity of depression; thus, it seems that the two tests examine widely different psychological phenomena . The evaluating scores of the Hungarian version of the DY-BOCS are very close to the original published scores. These results indicate that the Hungarian version of the DY-BOCS is a reliable and a valid clinical tool and we hope that by using the test, Hungarian professionals will become familiar with and accept the dimensional approach of OCD.

When health technology assessment is confidential and experts have no power: the case of Hungary.

Health technology assessment (HTA) is not simply a mechanistic technical exercise as it takes place within a specific institutional context. Yet, we know little about how this context influences the operation of HTA and its ability to influence policy and practice. We seek to demonstrate the importance of considering institutional context, using a case study of Hungary, a country that has pioneered HTA in Central and Eastern Europe. We conducted 26 in-depth, semi-structured interviews with public- and private-sector stakeholders. We found that while the HTA Department, the Hungarian HTA organisation, fulfilled its formal role envisaged in the legislation, its potential for supporting evidence-based decision-making was not fully realised given the low levels of transparency and stakeholder engagement. Further, the Department's practical influence throughout the reimbursement process was perceived as being constrained by the payer and policy-makers, as well as its own limited organisational capacity. There was also scepticism as to whether the current operational form of the HTA process delivered 'good value for money'. Nevertheless, it still had a positive impact on the development of a broader institutional HTA infrastructure in Hungary. Our findings highlight the importance of considering institutional context in analysing the HTA function within health systems.

[Impaired executive functions in obsessive compulsive (OCD). Review]. / A végrehajtó funkciók sérülése obszesszív-kompulzív zavarban. Attekinto tanulmány.

The neurocognitive deficits that underlie major symptoms in obsessive compulsive disorder (OCD) are not yet completely clarified. Hereby we present a review of the most important recent results in the field and also provide an overview of the main open questions and challenges. The primary cognitive deficit which contributes to the neuropsychology profile of the OCD is the dysfunction of the executive system. In our theoretical thinking and analysis we applied the psychometric model of the executive system proposed by Miyake et al (2000). According to this concept there are three main executive components: shifting-monitoring, updating and inhibition. Shifting is the ability of the individual to shift from the irrelevant set to the relevant one according to the task, updating refers to the dynamic manipulation and updating of contents of working memory, while inhibition consists in output monitoring and inhibition of the dominant, prepotent responses. In our research we grouped together neuropsychological tests according to the above components in order to find a coherent interpretation frame. OCD patients show higher latency scores, commit more perseverative errors and have difficulties in feed-back use in executive tasks. We propose that defining different patterns of executive functions may represent a fundamental step in the process to properly characterize the endophenotype of OCD, which may contribute to the development of a goal directed and more efficient rehabilitation therapy program.

[Surgical treatment of patients with therapy-resistant obsessive-compulsive disorder. Review]. / Terápiarezisztens kényszerbetegek mûtéti kezelése. Attekintô tanulmány.

In spite of adequate pharmaco- and psychotherapy, only 60-80 percent of the patients with obsessive compulsive disorder (OCD) respond to treatment and the symptoms of OCD will persist in 20-40 percent of the cases. These patients are considered therapy resistant. Neurosurgical procedures may bring a breakthrough for patients with OCD, especially in therapy resistant OCD and the burden of the illness can be reduced. The theoretical background of these procedures is based on the new biological theories of OCD. Here we summarise the loop theories and describe the four different types of irreversible neurosurgical techniques used in OCD (cingulotomy, subcaudate tractotomy, limbic leucotomy and anterior capsulotomy). We will review the reversible neurosurgical techniques (deep brain stimulation), as well. Two techniques, namely anterior capsulotomy and deep brain stimulation will be discussed in greater detail. Finally, we review the results of neuropsychological and personality changes associated with anterior capsulotomy.

Eveningness is associated with poor sleep quality and negative affect in obsessive-compulsive disorder.

Background Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive behaviors that severely encumber daily functioning. OCD patients seem to exhibit sleep disturbances, especially delayed bedtimes that reflect disrupted circadian rhythmicity. Morningness-eveningness is a fundamental factor reflecting individual variations in diurnal preferences related to sleep and waking activities. Eveningness reflecting a delayed sleep-wake timing has repeatedly been associated with sleep problems and negative affect (NA). Therefore, the aim of this study was to examine the associations between morningness-eveningness, sleep complaints, and symptom severity in OCD patients and compared with a mixed psychiatric control group. Materials and methods The data of 49 OCD and 49 mixed psychiatric inpatients (with unipolar depression and anxiety disorders) were analyzed. Patients completed questionnaires regarding morningness-eveningness, sleep quality, nightmare frequency, depression, anxiety, and affective states. Obsessive and compulsive symptom severity was also assessed within the OCD group by clinician-rated scales. Results Eveningness preference was associated with impaired sleep quality and higher NA in OCD patients. In addition, impaired sleep quality showed a moderate correlation with anxiety and strong correlations with depressive symptoms and NA. Interestingly, in the mixed psychiatric group, eveningness was not linked to NA, and sleep quality also showed weaker associations with depressive symptoms and NA. Within the OCD group, eveningness preference was predictive of poorer sleep quality regardless the influence of depressive symptoms. Conclusion Our findings suggest that eveningness and sleep complaints are predictive of affective dysfunctions, and should be carefully considered in the evaluation and treatment of OCD patients.

Comparative Analysis of Legislative Requirements About Patients' Access to Biotechnological Drugs for Rare Diseases in Central and Eastern European Countries.

Objectives: The aim of the study was to compare the access of patients with rare diseases (RDs) to biotechnological drugs in several Central and Eastern European countries (CEECs). We focused on the legislative pricing and reimbursement requirements, availability of biotechnological orphan medicinal products (BOMPs) for RDs, and reimbursement expenditures. Methods: A questionnaire-based survey was conducted among experts from 10 CEECs: Bulgaria, Croatia, Estonia, Greece, Hungary, Poland, Romania, Slovakia, Serbia, and Macedonia. The legal requirements for reimbursement and pricing of BOMPs were collected. All BOMPs and medicines without prior orphan designations were extracted from the European list of orphan medicinal products, 2017. The reimbursement status of these medicinal products in 2017 in the public coverage of the included CEECs as well as the share of their costs in relation to the total public pharmaceutical spending for the period from 2014 to 2016 were defined. Results: Our survey revealed that some differences in the legal requirements for pricing and reimbursement of BOMPs amongst the countries included in the study. All European Union countries have developed and implemented pharmacoeconomic guidelines with or without some specific reimbursement requirements for orphan medicinal products. Cost-effectiveness analysis, cost-utility analysis, Markov models, meta-analysis, and discount levels of costs and results were required only in Bulgaria, Poland and Hungary. The number of reimbursed BOMPs and biotechnological medicinal products for RDs without prior orphan designation was the highest in Hungary (17 and 40, respectively). Patient-based reimbursement schemes were available only in Hungary for 11 out of 17 BOMPs. Poland and Greece have the highest pharmaceutical expenditure of reimbursed BOMPs with are ~214 million and 180 million EUR, respectively in the observed period from 2014 to 2016. High proportion of the pharmaceutical expenditure on the reimbursed biotechnological medicinal products for RDs for the observed period 2014-2016 is presented in Bulgaria and Slovakia. Conclusions: The non-European Union CEECs face a significant delay in the legal implementation of pharmacoeconomic guideline for assessment of BOMPs. The access to BOMPs is similar among the observed CEECs and the countries with the best access are Hungary and Greece. The influence of BOMP expenditures on the budget in the individual countries is significant.

[New approach to obsessive-compulsive disorder: dopaminergic theories]. / A kényszerbetegség új megközelítése: a dopaminerg teóriák.

In patients with obsessive-compulsive disorder (OCD), structural and volumetric abnormalities have been identified by up-to-date neuroimaging techniques both in the prefrontal region and in the basal ganglia (striatum, thalamus, amygdala). The dysfunction of these regions also has been proved by neuroimaging techniques. These alterations can be described as dopaminergic hyperfunction in the prefrontal cortex and serotonergic hypofunction in the basal ganglia. The dysfunction of the so-called 'cortico-striato-thalamic' loops is strongly linked to the symptoms of OCD, where the dopamine is the most dominant neurotransmitter. The ascending serotonergic projections from the raphe nuclei restrain and control the function of these loops. Thus, when serotonergic hypofunction is present, the predominantly dopaminergic loops became overactive, which has been confirmed by neuroimaging techniques and by neurocognitive tests as well. The linkage of the two predominant neurotransmitter systems affected in OCD can be the reason for the fact that SSRIs have limited success in the treatment of OCD symptoms. In recent international, multicentric studies, the treatment of SSRI non-responder subgroup of OCD patients were supplemented by antipsychotics with dopaminergic activity. Many studies have confirmed the beneficial effect of these antidopaminergic substances on the hyperactive cortico-striato-thalamic loops in OCD. The investigation of these dysfunctional loops is also connected to the genetic background of OCD, because some of the candidate gene regions of OCD are coding proteins of the dopamine synthesis (for example: COMT). In this paper, we present a detailed overview of these relationships based on recent findings of OCD research.

[Dimensionality and neurocognitive symptoms in OCD]. / Dimenzionalitás és neurokognitív eltérések OCD-ben

Obsessive-compulsive disorder (OCD) is composed of heterogenous phenomenological symptoms. The genetic background is proved but not described in detail; thus it seems to advantageous clustering the symptoms into groups, also called dimensions. The 71 items of the Y-BOCS symptom list have been subdivided in several ways. A subdivision system of 5 different factors in OCD has been proposed recently for the DSM-V instead of the 3 factor model of the DSM-IV used today (I. predominantly obsessive/ II. predominantly compulsive/ III. mixed subgroup). These factors as endophenotypes are supposed to be transmitted by common genetical pathways. Subdivision of the OCD by factors helps us to reveal the relation between subgroups of gender, age of onset of the disease, comorbid illnesses, and the responsivity to treatment. This approach of dimensionality is also useful in understanding the neurocognitive differences experienced in OCD. This is why we summarised up-to-date findings of the neurocognitive deficits connected to the affected brain areas in OCD: OFC, DLPFC, ACC, striatum, amygdala, thalamus. Finally the cognitive domains affected in OCD are summarised, such as: memory, planning, decision making, response inhibition, set-shifting, and attention deficits.

Drug Policy in Hungary.

We present a brief overview of the health care system in Hungary, focusing particularly on the pricing and reimbursement procedures of medicines. The National Institute of Health Insurance Fund Management is responsible for the administration of the health insurance system and public reimbursement of health technologies. There are two major types of reimbursement techniques in the outpatient care: the normative reimbursement is applied to all physicians and may be used for all indications listed in the Summary of Product Characteristics, and the indication-linked reimbursement is applied only to specialists who are authorized to prescribe the drug. Pharmaceuticals used in the inpatient care are fully reimbursed and are financed through diagnosis-related groups. Several cost-containment measures such as external price referencing and internal price referencing with blind bidding are applied. Proposing managed entry agreements is a mandatory condition for reimbursing innovative pharmaceuticals. Compared with other countries in the region, the implementation of health technology assessment has a relatively long history in Hungary. The health technology assessment body critically evaluates reimbursement submissions of pharmaceuticals, simple medical devices, and complex medical devices such as hospital technologies.

Policy objective of generic medicines from the investment perspective: The case of clopidogrel.

The objective of generic drug policies in most countries is defined from a disinvestment perspective: reduction in expenditures without compromising health outcomes. However, in countries with restricted access of patients to original patented drugs, the objective of generic drug policies can also be defined from an investment perspective: health gain by improved patient access without need for additional health budget. This study examines the investment aspect of generic medicines by analyzing clopidogrel utilization in European countries between 2004 and 2014 using multilevel panel data models. We find that clopidogrel consumption was strongly affected by affordability constraints before the generic entry around 2009, but this effect decayed by 2014. After controlling for other variables, utilization had a substantially larger trend increase in lower-income European countries than in the higher-income ones. Generic entry increased clopidogrel consumption only in lower- and average-income countries but not in the highest-income ones. An earlier generic entry was associated with a larger effect. The case of clopidogrel indicates that the entrance of generics may increase patient access to effective medicines, most notably in lower-income countries, thereby reducing inequalities between European patients. Policymakers should also consider this investment aspect of generic medicines when designing pharmaceutical policies.

Pricing and Reimbursement of Biosimilars in Central and Eastern European Countries.

Objectives: The aim of this study was to review the requirements for the reimbursement of biosimilars and to compare the reimbursement status, market share, and reimbursement costs of biosimilars in selected Central and Eastern European (CEE) countries. Methods: A questionnaire-based survey was conducted between November 2016 and January 2017 among experts from the following CEE countries: Bulgaria, Czech Republic, Croatia, Estonia, Hungary, Latvia, Lithuania, Poland, Slovakia, and Romania. The requirements for the pricing and reimbursement of biosimilars were reviewed for each country. Data on the extent of reimbursement of biologic drugs (separately for original products and biosimilars) in the years 2014 and 2015 were also collected for each country, along with data on the total pharmaceutical and total public health care budgets. Results: Our survey revealed that no specific criteria were applied for the pricing and reimbursement of biosimilars in the selected CEE countries; the price of biosimilars was usually reduced compared with original drugs and specific price discounts were common. Substitution and interchangeability were generally allowed, although in most countries they were at the discretion of the physician after a clinical assessment. Original biologic drugs and the corresponding biosimilars were usually in the same homogeneous group, and internal reference pricing was usually employed. The reimbursement rate of biosimilars in the majority of the countries was the same and amounted to 100%. Generally, the higher shares of expenditures were shown for the reimbursement of original drugs than for biosimilars, except for filgrastim, somatropin, and epoetin (alfa and zeta). The shares of expenditures on the reimbursement of biosimilar products ranged from 8.0% in Estonia in 2014 to 32.4% in Lithuania in 2015, and generally increased in 2015. The share of expenditures on reimbursement of biosimilars in the total pharmaceutical budget differed between the countries, with the highest observed value for Slovakia and Hungary and the lowest-for Croatia. Conclusions: The requirements for the pricing and reimbursement of biosimilar products as well as the access of patients to biologic treatment do not differ significantly between the considered CEE countries. Biosimilar drugs significantly influence the reimbursement systems of these countries, and the expenditure on the reimbursement of biosimilars is increasing as they are becoming more accessible to patients.

Pharmaceutical Regulation in Central and Eastern European Countries: A Current Review.

Objectives: The aim of this study was to review reimbursement environment as well as pricing and reimbursement requirements for drugs in selected Central and Eastern Europe (CEE) countries. Methods: A questionnaire-based survey was performed in the period from November 2016 to March 2017 among experts involved in reimbursement matters from CEE countries: Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Slovakia, and Romania. A review of requirements for reimbursement and implications of Health Technology Assessment (HTA) was performed to compare the issues in above-mentioned countries. For each specified country, data for reimbursement costs, total pharmaceutical budget, and total public health care budget in the years 2014 and 2015 were also collected. Questionnaires were distributed via emails and feedback data were obtained in the same way. Additional questions, if any, were also submitted to respondents by email. Pricing and reimbursement data were valid for March 2017. Results: The survey revealed that the relation of drug reimbursement costs to total public healthcare spending ranged from 0.12 to 0.21 in the year 2014 and 2015 (median value). It also revealed that pricing criteria for drugs, employed in the CEE countries, were quite similar. External reference pricing as well as internal reference pricing were common in mentioned countries. Positive reimbursement lists were valid in all countries of the CEE region, negative ones were rarely used; reimbursement decisions were regularly revised and updated in the majority of countries. Copayment was common and available levels of reimbursement differed within and between the countries and ranged from 20 to 100%. Risk-sharing schemes were often in use, especially in the case of innovative, expensive drugs. Generic substitution was also possible in all analyzed CEE countries, while some made it mandatory. HTA was carried out in almost all of the considered CEE countries and HTA dossier was obligatory for submitting a pricing and reimbursement application. Conclusions: Pricing and reimbursement requirements are quite similar in the CEE region although some differences were identified. HTA evaluations are commonly used in considered countries.

Obsessed not to forget: lack of retrieval-induced suppression effect in obsessive-compulsive disorder.

The aim of the present study was to investigate the role of executive functions in resolving memory interference in a clinical sample of patients with obsessive-compulsive disorder (OCD). Retrieval of memories has been shown to involve some form of executive act that diminishes the accessibility of rival memory traces, leading to retrieval-induced forgetting (RIF). These executive control processes might suppress unwanted thoughts and irrelevant memories during competitive retrieval. We assessed RIF with the retrieval practice paradigm among 25 OCD patients and 25 healthy controls matched for age and education. Retrieval of target memories led to enhancement of target memory recall in both groups, but suppression of related memories (RIF) occurred only among controls. Our results suggest that suppression of irrelevant, interfering memories during competitive recall is impaired in OCD.