A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases.

While the preponderance of morbidity and mortality in medulloblastoma patients are due to metastatic disease, most research focuses on the primary tumor due to a dearth of metastatic tissue samples and model systems. Medulloblastoma metastases are found almost exclusively on the leptomeningeal surface of the brain and spinal cord; dissemination is therefore thought to occur through shedding of primary tumor cells into the cerebrospinal fluid followed by distal re-implantation on the leptomeninges. We present evidence for medulloblastoma circulating tumor cells (CTCs) in therapy-naive patients and demonstrate in vivo, through flank xenografting and parabiosis, that medulloblastoma CTCs can spread through the blood to the leptomeningeal space to form leptomeningeal metastases. Medulloblastoma leptomeningeal metastases express high levels of the chemokine CCL2, and expression of CCL2 in medulloblastoma in vivo is sufficient to drive leptomeningeal dissemination. Hematogenous dissemination of medulloblastoma offers a new opportunity to diagnose and treat lethal disseminated medulloblastoma.

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.

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.

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.

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.

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.

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.

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.

Severe DCM phenotype of patient harboring RBM20 mutation S635A can be modeled by patient-specific induced pluripotent stem cell-derived cardiomyocytes.

The ability to generate patient-specific induced pluripotent stem cells (iPSCs) provides a unique opportunity for modeling heart disease in vitro. In this study, we generated iPSCs from a patient with dilated cardiomyopathy (DCM) caused by a missense mutation S635A in RNA-binding motif protein 20 (RBM20) and investigated the functionality and cell biology of cardiomyocytes (CMs) derived from patient-specific iPSCs (RBM20-iPSCs). The RBM20-iPSC-CMs showed abnormal distribution of sarcomeric α-actinin and defective calcium handling compared to control-iPSC-CMs, suggesting disorganized myofilament structure and altered calcium machinery in CMs of the RBM20 patient. Engineered heart muscles (EHMs) from RBM20-iPSC-CMs showed that not only active force generation was impaired in RBM20-EHMs but also passive stress of the tissue was decreased, suggesting a higher visco-elasticity of RBM20-EHMs. Furthermore, we observed a reduced titin (TTN) N2B-isoform expression in RBM20-iPSC-CMs by demonstrating a reduction of exon skipping in the PEVK region of TTN and an inhibition of TTN isoform switch. In contrast, in control-iPSC-CMs both TTN isoforms N2B and N2BA were expressed, indicating that the TTN isoform switch occurs already during early cardiogenesis. Using next generation RNA sequencing, we mapped transcriptome and splicing target profiles of RBM20-iPSC-CMs and identified different cardiac gene networks in response to the analyzed RBM20 mutation in cardiac-specific processes. These findings shed the first light on molecular mechanisms of RBM20-dependent pathological cardiac remodeling leading to DCM. Our data demonstrate that iPSC-CMs coupled with EHMs provide a powerful tool for evaluating disease-relevant functional defects and for a deeper mechanistic understanding of alternative splicing-related cardiac diseases.

Melatonin Receptor 1 Deficiency Affects Feeding Dynamics and Pro-Opiomelanocortin Expression in the Arcuate Nucleus and Pituitary of Mice.

BACKGROUND/METHODS: Melatonin, the neurohormone for darkness, mediates photoperiod-dependent changes in physiology and behavior by targeting specific membrane-bound receptors (MT1 and MT2). In the present study, we investigated the impact of MT1 receptor deficiency on feeding behavior, locomotor activity and mRNA expression levels encoding for the polypeptide pro-opiomelanocortin (Pomc) and neuropeptide Y (Npy) in the hypothalamic arcuate nucleus (ARC) and the adenohypophysis [pars distalis (PD) and pars intermedia (PI)] in a comparison between wild-type (WT) and MT1-deficient (MT1-/-) mice. RESULTS: The MT1-/- mice spent significantly more time feeding than the WT mice, while the general locomotor behavior, body weight and the total amount of food consumed did not differ between both genotypes. The nocturnal expression levels of Pomc in the ARC and PD were significantly higher in WT as compared to MT1-/- mice and exogenous melatonin administered during the light phase stimulated Pomc expression in WT mice only. No differences were found between WT and MT1-/- mice with regard to Pomc expression levels in the PI. CONCLUSION: Thus, the MT1-mediated signaling stimulates Pomc expression in a region-specific pattern. Since the MT1-mediated changes in Pomc expression do not elicit direct orexigenic or anorexigenic effects, such effects are obviously mediated by regulatory systems downstream of the Pomc mRNA (e.g. cleavage and release of POMC derivatives), which are independent of MT1 signaling.

Melatonin receptor deficiency decreases and temporally shifts ecto-5'-nucleotidase mRNA levels in mouse prosencephalon.

Ecto-5'-nucleotidase (eN) is the major extracellular adenosine-producing ecto-enzyme in mouse brain. Via the production of adenosine, eN participates in many physiological and pathological processes, such as wakefulness, inflammation, nociception and neuroprotection. The mechanisms regulating the expression of eN are therefore of considerable neurobiological and clinical interest. Having previously described a modulatory effect of melatonin in the regulation of eN mRNA levels, we decided to analyze the melatonin receptor subtype involved in the regulation of eN mRNA levels by comparing eN mRNA patterns in melatonin-proficient transgenic mice lacking either the melatonin receptor subtype 1 (MT1 KO) or both melatonin receptor subtypes (MT1 and MT2; MT1/2 KO) with the corresponding melatonin-proficient wild-type (WT) controls. By means of radioactive in situ hybridization, eN mRNA levels were found to be diminished in both MT1 and MT1/2 KO mice compared with WT controls suggesting stimulatory impacts of melatonin receptors on eN mRNA levels. Whereas eN mRNA levels increased during the day and peaked at night in WT and MT1 KO mice, eN mRNA levels at night were reduced and the peak was shifted toward day-time in double MT1/2 KO mice. These data suggest that the MT2 receptor subtype may play a role in the temporal regulation of eN mRNA availability. Notably, day-time locomotor activity was significantly higher in MT1/2 KO compared with WT mice. Our results suggest melatoninergic signaling as an interface between the purinergic system and the circadian system.

Testing the construct validity of hospital care quality indicators: a case study on hip replacement.

BACKGROUND: Quality indicators are increasingly used to measure the quality of care and compare quality across hospitals. In the Netherlands over the past few years numerous hospital quality indicators have been developed and reported. Dutch indicators are mainly based on expert consensus and face validity and little is known about their construct validity. Therefore, we aim to study the construct validity of a set of national hospital quality indicators for hip replacements. METHODS: We used the scores of 100 Dutch hospitals on national hospital quality indicators looking at care delivered over a two year period. We assessed construct validity by relating structure, process and outcome indicators using chi-square statistics, bootstrapped Spearman correlations, and independent sample t-tests. We studied indicators that are expected to associate as they measure the same clinical construct. RESULT: Among the 28 hypothesized correlations, three associations were significant in the direction hypothesized. Hospitals with low scores on wound infections had high scores on scheduling postoperative appointments (p-value = 0.001) and high scores on not transfusing homologous blood (correlation coefficient = -0.28; p-value = 0.05). Hospitals with high scores on scheduling complication meetings, also had high scores on providing thrombosis prophylaxis (correlation coefficient = 0.21; p-value = 0.04). CONCLUSION: Despite the face validity of hospital quality indicators for hip replacement, construct validity seems to be limited. Although the individual indicators might be valid and actionable, drawing overall conclusions based on the whole indicator set should be done carefully, as construct validity could not be established. The factors that may explain the lack of construct validity are poor data quality, no adjustment for case-mix and statistical uncertainty.

Are performance indicators used for hospital quality management: a qualitative interview study amongst health professionals and quality managers in The Netherlands.

BACKGROUND: Hospitals are under increasing pressure to share indicator-based performance information. These indicators can also serve as a means to promote quality improvement and boost hospital performance. Our aim was to explore hospitals' use of performance indicators for internal quality management activities. METHODS: We conducted a qualitative interview study among 72 health professionals and quality managers in 14 acute care hospitals in The Netherlands. Concentrating on orthopaedic and oncology departments, our goal was to gain insight into data collection and use of performance indicators for two conditions: knee and hip replacement surgery and breast cancer surgery. The semi-structured interviews were recorded and summarised. Based on the data, themes were synthesised and the analyses were executed systematically by two analysts independently. The findings were validated through comparison. RESULTS: The hospitals we investigated collect data for performance indicators in different ways. Similarly, these hospitals have different ways of using such data to support their quality management, while some do not seem to use the data for this purpose at all. Factors like 'linking pin champions', pro-active quality managers and engaged medical specialists seem to make a difference. In addition, a comprehensive hospital data infrastructure with electronic patient records and robust data collection software appears to be a prerequisite to produce reliable external performance indicators for internal quality improvement. CONCLUSIONS: Hospitals often fail to use performance indicators as a means to support internal quality management. Such data, then, are not used to its full potential. Hospitals are recommended to focus their human resource policy on 'linking pin champions', the engagement of professionals and a pro-active quality manager, and to invest in a comprehensive data infrastructure. Furthermore, the differences in data collection processes between Dutch hospitals make it difficult to draw comparisons between outcomes of performance indicators.

A systematic review and meta-analysis on the association between quality of hospital care and readmission rates in patients with heart failure.

UNLABELLED: In recent years, readmission rates have been increasingly used as a measure of quality of hospital care for patients with heart failure. The aim of this systematic review is to assess the scientific evidence regarding the relation between hospital readmission rates and quality of hospital care for patients with heart failure. METHODS: We defined quality of hospital care for patients with heart failure by adhering to the performance measures developed by the American College of Cardiology (ACC)/American Heart Association (AHA). Relevant articles published in English and indexed in the bibliographic databases Embase, Medline OvidSP, Web of Science, Cochrane Central, and PubMed were reviewed. RESULTS: Of the 2,638 studies identified, 18 were included. They varied widely in their methodology, data sources used, and study populations. We found mixed but rather limited evidence that there is a relationship between the ACC/AHA process measures and the rate of readmission. Four of 10 studies showed a significant correlation of readmission rate with "angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use." Three of 9 studies showed a significant correlation between readmission rates and "evaluation of left ventricular systolic function." One of 7 studies showed a significant correlation with "smoking cessation counseling," and 2 of 8 showed a significant correlation with "providing discharge instructions." No evidence was found for a relationship between readmission rates and the performance measure "warfarin for atrial fibrillation." CONCLUSIONS: Readmission rates after heart failure are mostly not related to the evidence-based ACC/AHA in-hospital process indicators for heart failure. It is unclear whether in-hospital quality of care is the key determinate of the readmission rate or whether readmissions are likely influenced more by postdischarge care. Further research is needed to clarify whether the readmission rate is a reflection of hospital care or quality of care on a larger level, especially when it is used for a pay-for-performance scheme to measure quality of hospital care.

Expression of ectonucleotidases in the prosencephalon of melatonin-proficient C3H and melatonin-deficient C57Bl mice: spatial distribution and time-dependent changes.

Extracellular purines (ATP, ADP, AMP and adenosine) are important signaling molecules in the CNS. Levels of extracellular purines are regulated by enzymes located at the cell surface referred to as ectonucleotidases. Time-dependent changes in their expression could profoundly influence the availability of extracellular purines and thereby purinergic signaling. Using radioactive in situ hybridization, we analyzed the mRNA distribution of the enzymes NTPDase1, -2 and -3 and ecto-5'-nucleotidase in the prosencephalon of two mouse strains: melatonin-proficient C3H and melatonin-deficient C57Bl. The mRNAs of these enzymes were localized to specific brain regions, such as hippocampus, striatum, medial habenula and ventromedial hypothalamus. NTPDase3 expression was more widely distributed than previously thought. All ectonucleotidases investigated revealed a prominent time-dependent expression pattern. In C3H, the mRNA expression of all four enzymes gradually increased during the day and peaked during the night. In contrast, in C57Bl, ecto-5'-nucleotidase expression peaked at the beginning of the day and gradually decreased to trough levels at night. Recording of locomotor activity revealed higher daytime activity of C57Bl than of C3H. Our results indicate that the expression of ectonucleotidases varies according to time and genotype and suggest that melatonin exerts modulatory effects associated with different regulations of purinergic signaling in the brain. These findings provide an important basis for further examination of the complexity of the purinergic system in the brain.

Influences of definition ambiguity on hospital performance indicator scores: examples from The Netherlands.

RESEARCH OBJECTIVE: Reliable and unambiguously defined performance indicators are fundamental to objective and comparable measurements of hospitals' quality of care. In two separate case studies (intensive care and breast cancer care), we investigated if differences in definition interpretation of performance indicators affected the indicator scores. DESIGN: Information about possible definition interpretations was obtained by a short telephone survey and a Web survey. We quantified the interpretation differences using a patient-level dataset from a national clinical registry (Case I) and a hospital's local database (Case II). In Case II, there was additional textual information available about the patients' status, which was reviewed to get more insight into the origin of the differences. PARTICIPANTS: For Case I, we investigated 15 596 admissions of 33 intensive care units in 2009. Case II consisted of 144 admitted patients with a breast tumour surgically treated in one hospital in 2009. RESULTS: In both cases, hospitals reported different interpretations of the indicators, which lead to significant differences in the indicator values. Case II revealed that these differences could be explained by patient-related factors such as severe comorbidity and patients' individual preference in surgery date. CONCLUSIONS: With this article, we hope to increase the awareness on pitfalls regarding the indicator definitions and the quality of the underlying data. To enable objective and comparable measurements of hospitals' quality of care, organizations that request performance information should formalize the indicators they use, including standardization of all data elements of which the indicator is composed (procedures, diagnoses).

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.