Comparing Medical Training Costs Internationally: A Systematic Review.

Background: Acquiring a thorough understanding of the expenses linked to the education of health sciences students is crucial for effective university planning, budgeting, and overall preparedness. This systematic review aimed to identify and compare the per capita costs associated with educating medical and other health science students internationally-particularly emphasizing the context of Iran. Methods: A systematic review was conducted in 2023 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search covered the period from January 1, 2000, to November 11, 2022, using MeSH and EMTREE terms. Databases such as PubMed, Scopus, Web of Science, Embase, and Iranian databases were searched. Manual searches were performed using Google and Google Scholar. Results: The study retrieved 1336 publications from bibliometric databases and, following thorough screening, included 8 relevant articles from 5 countries (Australia, Iran, United States, Thailand, and Vietnam). An additional 17 relevant articles from Iranian databases were also included. Based on USD purchasing power parity (PPP) 2019, the results show that the mean per capita cost of training a medical student for 1 academic year in Iran is $61,493.86 (range, $28,102-$133,603; standard deviation, $35,476.03). In comparison, the cost of training a medical student for 1 year is $263,305 in the United States and $44,674 in Australia. In Thailand and Vietnam, a 6-year medical program costs is $284,058 and $69,323, respectively. Moreover, according to most studies, training students in other health sciences in Iran for 1 academic year generally costs ˂$20,000 (PPP 2019). Conclusion: The study reveals that the costs associated with medical student education in Iran exceed that of most countries, second only to the United States. These findings highlight the importance of such data in improving the efficiency, sustainability, and informed resource allocation of global medical education programs for future planning and budgeting.

The Development of a New Approach for the Harmonized Multi-Sectoral and Multi-Country Cost Valuation of Services: The PECUNIA Reference Unit Cost (RUC) Templates.

BACKGROUND: Increasing healthcare costs require evidence-based resource use allocation for which assessing costs rigorously and comparably is crucial. Harmonized cross-country costing methods for evaluating interventions from a societal perspective are lacking. This study presents the development process and content of the service costing templates developed as part of the European project PECUNIA. METHODS: The six developmental steps towards technological readiness of the templates included (1) a common conceptual costing framework and review of methodological costing issues, (2) harmonization strategy formulation, (3) proof-of-concept with expert feedback, (4) piloting, (5) validation, and (6) demonstration in six European countries. RESULTS: The PECUNIA Reference Unit Cost (RUC) Templates for service costing are three new self-completion tools to be used with secondary or primary data for top-down micro-costing or top-down gross-costing approaches. Complementary data collection and unit cost aggregation/weighting templates are available. The applications leading to the final versions including (4) piloting through calculation of 15-unit costs, (5) validation within a Health Technology Assessment framework, and (6) RUC calculations mostly based on secondary data demonstrated the templates' general feasibility, with feedback for improved usability incorporated and a supplementary user guide developed. CONCLUSION: The validated PECUNIA RUC Templates for multi-sectoral and multi-country service costing allow for harmonized RUC development while incorporating flexibility and transparency in the choice of costing approaches, data sources and magnitude of remaining heterogeneity. The templates are expected to significantly improve the quality, comparability and availability of unit costs for economic evaluations, and promote the transferability of service cost information across Europe.

Examining Variability in Intra-Hospital Patient Referrals to Specialized Palliative Care: A Comprehensive Analysis of Disciplines and Mortality.

Background: In Austria, specialized palliative care (SPC) access is limited, with unclear referral criteria, making it challenging to identify hospitalized patients requiring SPC and determine referral timing and mortality at the palliative care unit (PCU). Methods: This retrospective cohort study analyzed patients who underwent a palliative care (PC) needs assessment between March 2016 and November 2021 and were subsequently admitted to the PCU of Austria's largest academic hospital. Demographic, clinical, and standardized referral form data were used for analysis, employing descriptive statistics and logistic regression. Results: Out of the 903 assessed patients, 19% were admitted to the PCU, primarily cancer patients (94.7%), with lung (19%) and breast cancer (13%) being most prevalent. Common referral reasons included pain (61%) and nutritional problems (46%). Despite no significant differences in referral times, most patients (78.4%) died in the PCU, with varying outcomes based on cancer type. Referral reasons like pain (OR = 2.3), nutritional problems (OR = 2.4), and end-of-life care (OR = 6.5) were significantly associated with the outcome PCU mortality. Conclusions: This study underscores Austria's SPC access imbalance and emphasizes timely PC integration across disciplines for effective advance care planning and dignified end-of-life experiences in PCUs.

Facilitators and barriers of implementing end-of-life care volunteering in a hospital in five European countries: the iLIVE study.

BACKGROUND: End-of-life (EoL) care volunteers in hospitals are a novel approach to support patients and their close ones. The iLIVE Volunteer Study supported hospital volunteer coordinators from five European countries to design and implement an EoL care volunteer service on general wards in their hospitals. This study aimed to identify and explore barriers and facilitators to the implementation of EoL care volunteer services in the five hospitals. METHODS: Volunteer coordinators (VCs) from the Netherlands (NL), Norway (NO), Slovenia (SI), Spain (ES) and United Kingdom (UK) participated in a focus group interview and subsequent in-depth one-to-one interviews. A theory-inspired framework based on the five domains of the Consolidated Framework for Implementation Research (CFIR) was used for data collection and analysis. Results from the focus group were depicted in radar charts per hospital. RESULTS: Barriers across all hospitals were the COVID-19 pandemic delaying the implementation process, and the lack of recognition of the added value of EoL care volunteers by hospital staff. Site-specific barriers were struggles with promoting the service in a highly structured setting with many stakeholders (NL), negative views among nurses on hospital volunteering (NL, NO), a lack of support from healthcare professionals and the management (SI, ES), and uncertainty about their role in implementation among VCs (ES). Site-specific facilitators were training of volunteers (NO, SI, NL), involving volunteers in promoting the service (NO), and education and awareness for healthcare professionals about the role and boundaries of volunteers (UK). CONCLUSION: Establishing a comprehensive EoL care volunteer service for patients in non-specialist palliative care wards involves multiple considerations including training, creating awareness and ensuring management support. Implementation requires involvement of stakeholders in a way that enables medical EoL care and volunteering to co-exist. Further research is needed to explore how trust and equal partnerships between volunteers and professional staff can be built and sustained. TRIAL REGISTRATION: NCT04678310. Registered 21/12/2020.

SARS-CoV-2 vaccination may mitigate dysregulation of IL-1/IL-18 and gastrointestinal symptoms of the post-COVID-19 condition.

The rapid development of safe and effective vaccines helped to prevent severe disease courses after SARS-CoV-2 infection and to mitigate the progression of the COVID-19 pandemic. While there is evidence that vaccination may reduce the risk of developing post-COVID-19 conditions (PCC), this effect may depend on the viral variant. Therapeutic effects of post-infection vaccination have been discussed but the data for individuals with PCC remains inconclusive. In addition, extremely rare side effects after SARS-CoV-2 vaccination may resemble the heterogeneous PCC phenotype. Here, we analyze the plasma levels of 25 cytokines and SARS-CoV-2 directed antibodies in 540 individuals with or without PCC relative to one or two mRNA-based COVID-19 vaccinations as well as in 20 uninfected individuals one month after their initial mRNA-based COVID-19 vaccination. While none of the SARS-CoV-2 naïve individuals reported any persisting sequelae or exhibited PCC-like dysregulation of plasma cytokines, we detected lower levels of IL-1ß and IL-18 in patients with ongoing PCC who received one or two vaccinations at a median of six months after infection as compared to unvaccinated PCC patients. This reduction correlated with less frequent reporting of persisting gastrointestinal symptoms. These data suggest that post-infection vaccination in patients with PCC might be beneficial in a subgroup of individuals displaying gastrointestinal symptoms.

Methodological challenges and potential solutions for economic evaluations of palliative and end-of-life care: A systematic review.

BACKGROUND: Given the increasing demand for palliative and end-of-life care, along with the introduction of costly new treatments, there is a pressing need for robust evidence on value. However, comprehensive guidance is missing on methods for conducting economic evaluations in this field. AIM: To identify and summarise existing information on methodological challenges and potential solutions/recommendations for economic evaluations of palliative and end-of-life care. DESIGN: We conducted a systematic review of publications on methodological considerations for economic evaluations of adult palliative and end-of-life care as per our PROSPERO protocol CRD42020148160. Following initial searches, we conducted a two-stage screening process and quality appraisal. Information was thematically synthesised, coded, categorised into common themes and aligned with the items specified in the Consolidated Health Economic Evaluation Reporting Standards statement. DATA SOURCES: The databases Medline, Embase, HTADatabase, NHSEED and grey literature were searched between 1 January 1999 and 5 June 2023. RESULTS: Out of the initial 6502 studies, 81 were deemed eligible. Identified challenges could be grouped into nine themes: ambiguous and inaccurate patient identification, restricted generalisability due to poor geographic transferability of evidence, narrow costing perspective applied, difficulties defining comparators, consequences of applied time horizon, ambiguity in the selection of outcomes, challenged outcome measurement, non-standardised measurement and valuation of costs as well as challenges regarding a reliable preference-based outcome valuation. CONCLUSION: Our review offers a comprehensive context-specific overview of methodological considerations for economic evaluations of palliative and end-of-life care. It also identifies the main knowledge gaps to help prioritise future methodological research specifically for this field.

The identification of economically relevant health and social care services for mental disorders in the PECUNIA project.

BACKGROUND: Health economic research is still facing significant problems regarding the standardization and international comparability of health care services. As a result, comparative effectiveness studies and cost-effectiveness analyses are often not comparable. This study is part of the PECUNIA project, which aimed to improve the comparability of economic evaluations by developing instruments for the internationally standardized measurement and valuation of health care services for mental disorders. The aim of this study was to identify internationally relevant services in the health and social care sectors relevant for health economic studies for mental disorders. METHODS: A systematic literature review on cost-of-illness studies and economic evaluations was conducted to identify relevant services, complemented by an additional grey literature search and a search of resource use measurement (RUM) questionnaires. A preliminary long-list of identified services was explored and reduced to a short-list by multiple consolidation rounds within the international research team and an external international expert survey in six European countries. RESULTS: After duplicate removal, the systematic search yielded 15,218 hits. From these 295 potential services could be identified. The grey literature search led to 368 and the RUM search to 36 additional potential services. The consolidation process resulted in a preliminary list of 186 health and social care services which underwent an external expert survey. A final consolidation step led to a basic list of 56 services grouped into residential care, daycare, outpatient care, information for care, accessibility to care, and self-help and voluntary care. CONCLUSIONS: The initial literature searches led to an extensive number of potential service items for health and social care. Many of these items turned out to be procedures, interventions or providing professionals rather than services and were removed from further analysis. The resulting list was used as a basis for typological coding, the development of RUM questionnaires and corresponding unit costs for international mental health economic studies in the PECUNIA project.

The relationship of hospital and surgeon volume indicators and post-operative outcomes in pancreatic surgery: a systematic literature review, meta-analysis and guidance for valid outcome assessment.

BACKGROUND: Available evidence on the volume-outcome relationship after pancreatic surgery is limited due to the narrow focus of interventions, volume indicators and outcomes considered as well as due to methodological differences of the included studies. Therefore, we aim to evaluate the volume-outcome relationship following pancreatic surgery following strict study selection and quality criteria, to identify aspects of methodological variation and to define a set of key methodological indicators to consider when aiming for comparable and valid outcome assessment. METHODS: Four electronic databases were searched to identify studies on the volume-outcome relationship in pancreatic surgery published between the years 2000-2018. Following a double-screening process, data extraction, quality appraisal, and subgroup analysis, results of included studies were stratified and pooled using random effects meta-analysis. RESULTS: Consistent associations were found between high hospital volume and both postoperative mortality (OR 0.35, 95% CI: 0.29-0.44) and major complications (OR 0.87, 95% CI: 0.80-0.94). A significant decrease in the odds ratio was also found for high surgeon volume and postoperative mortality (OR 0.29, 95%CI: 0.22-0.37). DISCUSSION: Our meta-analysis confirms a positive effect for both hospital and surgeon volume indicators for pancreatic surgery. Further harmonization (e.g. surgery types, volume cut-offs/definition, case-mix adjustment, reported outcomes) are recommended for future empirical studies.

Development of an Instrument for the Assessment of Health-Related Multi-sectoral Resource Use in Europe: The PECUNIA RUM.

BACKGROUND: Measuring objective resource-use quantities is important for generating valid cost estimates in economic evaluations. In the absence of acknowledged guidelines, measurement methods are often chosen based on practicality rather than methodological evidence. Furthermore, few resource-use measurement (RUM) instruments focus on the measurement of resource use in multiple societal sectors and their development process is rarely described. Thorn and colleagues proposed a stepwise approach to the development of RUM instruments, which has been used for developing cost questionnaires for specific trials. However, it remains unclear how this approach can be translated into practice and whether it is applicable to the development of generic self-reported RUM instruments and instruments measuring resource use in multiple sectors. This study provides a detailed description of the practical application of this stepwise approach to the development of a multi-sectoral RUM instrument developed within the ProgrammE in Costing, resource use measurement and outcome valuation for Use in multi-sectoral National and International health economic evaluAtions (PECUNIA) project. METHODS: For the development of the PECUNIA RUM, the methodological approach was based on best practice guidelines. The process included six steps, including the definition of the instrument attributes, identification of cost-driving elements in each sector, review of methodological literature and development of a harmonized cross-sectorial approach, development of questionnaire modules and their subsequent harmonization. RESULTS: The selected development approach was, overall, applicable to the development of the PECUNIA RUM. However, due to the complexity of the development of a multi-sectoral RUM instrument, additional steps such as establishing a uniform methodological basis, harmonization of questionnaire modules and involvement of a broader range of stakeholders (healthcare professionals, sector-specific experts, health economists) were needed. CONCLUSION: This is the first study that transparently describes the development process of a generic multi-sectoral RUM instrument in health economics and provides insights into the methodological aspects and overall validity of its development process.

Harmonization issues in unit costing of service use for multi-country, multi-sectoral health economic evaluations: a scoping review.

BACKGROUND: Valuation is a critical part of the costing process in health economic evaluations. However, an overview of specific issues relevant to the European context on harmonizing methodological requirements for the valuation of costs to be used in health economic evaluation is lacking. We aimed to inform the development of an international, harmonized and multi-sectoral costing framework, as sought in the European PECUNIA (ProgrammE in Costing, resource use measurement and outcome valuation for Use in multi-sectoral National and International health economic evaluAtions) project. METHODS: We conducted a scoping review (information extraction 2008-2021) to a) to demonstrate the degree of heterogeneity that currently exists in the literature regarding central terminology, b) to generate an overview of the most relevant areas for harmonization in multi-sectoral and multi-national costing processes for health economic evaluations, and c) to provide insights into country level variation regarding economic evaluation guidance. A complex search strategy was applied covering key publications on costing methods, glossaries, and international costing recommendations augmented by a targeted author and reference search as well as snowballing. Six European countries served as case studies to describe country-specific harmonization issues. Identified information was qualitatively synthesized and cross-checked using a newly developed, pilot-tested data extraction form. RESULTS: Costing methods for services were found to be heterogeneous between sectors and country guidelines and may, in practice, be often driven by data availability and reimbursement systems in place. The lack of detailed guidance regarding specific costing methods, recommended data sources, double-counting of costs between sectors, adjustment of unit costs for inflation, transparent handling of overhead costs as well as the unavailability of standardized unit costing estimates in most countries were identified as main drivers of country specific differences in costing methods with a major impact on valuation and cost-effectiveness evidence. CONCLUSION: This review provides a basic summary of existing costing practices for evaluative purposes across sectors and countries and highlights several common methodological factors influencing divergence in cost valuation methods that would need to be systematically incorporated and addressed in future costing practices to achieve more comparable, harmonized health economic evaluation evidence.

Familial colloid cysts: not a chance occurrence.

PURPOSE: Colloid cysts are rare, benign brain tumors of the third ventricle with an estimated population prevalence of 1 in 5800. Sudden deterioration and death secondary to obstructive hydrocephalus are well-described presentations in patients with a colloid cyst. Although historically conceptualized as driven by sporadic genetic events, a growing body of literature supports the possibility of an inherited predisposition. METHODS: A prospective registry of patients with colloid cysts was maintained between 1996 and 2021. Data pertaining to a family history of colloid cyst was collected retrospectively; self-reporting was validated in each case by medical record or imaging review. Frequency of patients with a documented first-degree family member with a colloid cyst based on self-reporting was calculated. The rate of familial co-occurrence within our series was then compared to a systematic literature review and aggregation of familial case studies, as well as population-based prevalence rates of sporadic colloid cysts. RESULTS: Thirteen cases with affected first-degree relatives were identified in our series. Of the entire cohort, 19/26 were symptomatic from the lesion (73%), 12/26 (46.2%) underwent resection, and 2/26 (7.7%) had sudden death from presumed obstructive hydrocephalus. The majority of transmission patterns were between mother and child (9/13). Compared with the estimated prevalence of colloid cysts, our FCC rate of 13 cases in 383 (3.4%) estimates a greater-than-chance rate of co-occurrence. CONCLUSION: Systematic screening for FCCs may facilitate early recognition and treatment of indolent cysts, thereby preventing the rapid deterioration that can occur with an unrecognized third ventricular tumor. Furthermore, identifying a transmission pattern may yield more insight into the molecular and genetic underpinnings of colloid cysts.

Establishing a comprehensive list of mental health-related services and resource use items in Austria: A national-level, cross-sectoral country report for the PECUNIA project.

BACKGROUND: A comprehensive, comparable assessment of the economic disease burden and the value of relevant care forms a major challenge in the case of mental diseases. This study aimed to inform the development of a resource use measurement (RUM) instrument and harmonized reference unit costs valid for multi-sectoral and multi-national cost assessments for mental health diseases as part of the European PECUNIA project. METHODS: An iterative, multi-methods approach was applied. Systematic literature reviews appended with national grey literature searches in six European countries were conducted to generate preliminary, literature-based, international, mental health-related service and resource use lists for all investigated sectors in 2018. As part of a multi-national expert survey, these lists were reviewed by 18 Austrian sector-specific experts regarding the clarity, relevance, comprehensiveness and availability in the Austrian context. RESULTS: Out of 295 items included in the preliminary, international, sector-specific lists (health and social care-201 items, criminal justice-35 items, education-39 items; patient, family and informal care-20 items), a total of 261 items and descriptions (88%) were considered clear by all experts. 42 items (14%) were considered not existing in Austria, and 111 items (38%) were prioritized regarding their relevance in the national context. Thirteen additional items (4%) were suggested to be added to accommodate for Austria-specific features of the individual sectors. Major typological difficulties based on item names were observed. CONCLUSIONS: The identified country-specific variations and general typological bias and their potential contributions to service and resource use cost variations across countries and sectors call for further systematic investigation. Next, PECUNIA will develop internationally harmonized and comparable definitions of the listed items and their units of analysis based on a new conceptual multi-sectoral costing framework. The developed lists will require consolidation and further prioritization for the development of a patient-reported RUM instrument and consequent reference unit cost valuation.

Ventral Windowed Total Contact Casts Safely Offload Diabetic Feet and Allow Access to the Foot.

BACKGROUND: Irremovable total contact casts (TCCs) are the gold standard to offload diabetic foot ulcers (DFUs) and to immobilize feet with active Charcot neuro-osteoarthropathy (CN). They do not allow checks of the foot and are contraindicated in people with peripheral arterial disease (PAD). Frequently, removable TCCs and other removable devices are used because they allow wound care, modifications of the inner surface of the cast, and checks of the foot. The authors propose TCCs with ventral windows (VW-TCCs) whenever patients with high-risk conditions show poor adherence to wearing a removable cast all the time and access to the foot is necessary. METHODS: This retrospective study compares treatments with bivalved, removable TCCs applied prior to the introduction of the novel design (from 1 January 2016 to 1 July 2017, "c") to treatments in the following period (t) with both bivalved removable TCCs and VW-TCCs in use. RESULTS: Forty-five treatments after introduction (17 with the VW-TCC) showed a 52.8% lower median time to reach remission of the DFS than 41 controls (128/267 days, log-rank test P = .013). Reasons given for not using the novel design were: sufficient offloading with a removable TCC (16), patient preference (six), anatomical conditions (two), casts applied as a service for other facilities (three), and calf ulcers (one). Adverse effects from both designs were uncommon and not severe. CONCLUSIONS: VW-TCCs combine advantages of both removable and irremovable TCCs. Complications do not limit the use, even in patients with PAD.

A critical analysis of surgery for occult tethered cord syndrome.

INTRODUCTION: Tethered cord syndrome (TCS) is an amalgamation of neurological, urological, orthopedic, and dermatologic signs and symptoms with radiographic evidence of a thickened filum and low-lying conus. Surgical sectioning of the filum and disconnection of any tethering entities such as dermal sinus tracts or lipomas has been shown to improve outcomes. The manifestation of TCS symptoms in the absence of a low-lying conus has been referred to as occult tethered cord syndrome (OTCS) and is much less well reviewed in the literature. To date, there has only been one randomized controlled trial examining the effect of intervention in OTCS; therefore, contemporary data is often elicited from limited cohorts. OBJECTIVE: To perform a comprehensive literature review of management in OTCS and evaluate treatment response rates to sectioning of the filum terminale. RESULTS: Seventeen papers met inclusion criteria for our review. Sample sizes ranged from 8 to 60 children, and results were mixed, often dependent on study design, definition of typical OTCS symptoms, and follow-up intervals. Symptomatic improvement was observed in > 50% of patients for all but one study; however, the recurrence rates were highly variable. CONCLUSION: The data regarding the efficacy of surgical treatment in OTCS is mixed and merits more rigorous scientific examination with strict and clear parameters regarding symptomatic operationalization and follow-up time points to monitor for TCS recurrence.

Mass Spectrometry Imaging Reveals a Gradient of Cancer-like Metabolic States in the Vicinity of Cancer Not Seen in Morphometric Margins from Microscopy.

Spatially resolved ambient mass spectrometry imaging methods have gained popularity to characterize cancer sites and their borders using molecular changes in the lipidome. This utility, however, is predicated on metabolic homogeneity at the border, which would create a sharp molecular transition at the morphometric borders. We subjected murine models of human medulloblastoma brain cancer to mass spectrometry imaging, a technique that provides a direct readout of tissue molecular content in a spatially resolved manner. We discovered a distance-dependent gradient of cancer-like lipid molecule profiles in the brain tissue within 1.2 mm of the cancer border, suggesting that a cancer-like state progresses beyond the histologic border, into the healthy tissue. The results were further corroborated using orthogonal liquid chromatography and mass spectrometry (LC-MS) analysis of selected tissue regions subjected to laser capture microdissection. LC-MS/MS analysis for robust identification of the affected molecules implied changes in a number of different lipid classes, some of which are metabolized from the essential docosahexaenoic fatty acid (DHA) present in the interstitial fluid. Metabolic molecular borders are thus not as sharp as morphometric borders, and mass spectrometry imaging can reveal molecular nuances not observed with microscopy. Caution must be exercised in interpreting multimodal imaging results stipulated on a coincidental relationship between metabolic and morphometric borders of cancer, at least within animal models used in preclinical research.

n-Propyl 6-amino-2,6-dideoxy-2,2-difluoro-ß-d-glucopyranoside is a good inhibitor for the ß-galactosidase from E. coli.

A convenient route has been developed for the synthesis of novel 6-amino-2,2-(or 3,3-difluoro)-2-(or 3),6-dideoxy-hexopyranoses. Biological screening showed these compounds as good inhibitors for several glycosidases. Especially n-propyl 6-amino-2,6-dideoxy-2,2-difluoro-ß-d-glucopyranoside (8) was an excellent competitive inhibitor for the ß-galactosidase from E. coli holding a K i of 0.50 µM.

Are Unit Costs the Same? A Case Study Comparing Different Valuation Methods for Unit Cost Calculation of General Practitioner Consultations.

OBJECTIVES: To inform allocation decisions in any healthcare system, robust cost data are indispensable. Nevertheless, recommendations on the most appropriate valuation approaches vary or are nonexistent, and no internationally accepted gold standard exists. This costing analysis exercise aims to assess the impact and implications of different calculation methods and sources based on the unit cost of general practitioner (GP) consultations in Austria. METHODS: Six costing methods for unit cost calculation were explored, following 3 Austrian methodological approaches (AT-1, AT-2, AT-3) and 3 approaches applied in 3 other European countries (Germany, The Netherlands, United Kingdom). Drawing on Austrian data, mean unit costs per GP consultation were calculated in euros for 2015. RESULTS: Mean unit costs ranged from €15.6 to €42.6 based on the German top-down costing approach (DE) and the Austrian Physicians' Chamber's price recommendations (AT-3), respectively. The mean unit cost was estimated at €18.9 based on Austrian economic evaluations (AT-1) and €17.9 based on health insurance payment tariffs (AT-2). The Dutch top-down (NL) and the UK bottom-up approaches (UK) yielded higher estimates (NL: €25.3, UK: €29.8). Overall variation reached 173%. CONCLUSIONS: Our study is the first to systematically investigate the impact of differing calculation methods on unit cost estimates. It shows large variations with potential impact on the conclusions in an economic evaluation. Although different methodological choices may be justified by the adopted study perspective, different costing approaches introduce variation in cross-study/cross-country cost estimates, leading to decreased confidence in data quality in economic evaluations.

Challenges of Epilepsy Surgery.

Though frequently effective in the management of medically refractory seizures, epilepsy surgery presents numerous challenges. Selection of the appropriate candidate patients who are likely to benefit from surgery is critical to achieving seizure freedom and avoiding neurocognitive morbidity. Identifying the seizure focus and mapping epileptogenic networks involves an interdisciplinary team dedicated to formulating a safe and effective surgical plan. Various strategies can be employed either to eliminate the epileptic focus or to modulate network activity, including resection of the focus with open surgery or laser interstitial thermal therapy; modulation of epileptogenic firing patterns with responsive neurostimulation, deep brain stimulation, or vagus nerve stimulation; or non-invasive disconnection of epileptic circuits with focused ultrasound, which is also discussed in greater detail in the subsequent chapter in our series. We review several challenges of epilepsy surgery that must be thoughtfully addressed in order to ensure its success.