Variability of cost trajectories over the last year of life in patients with advanced breast cancer in the Netherlands

Objective In breast cancer patients, treatment at the end of life accounts for a major share of medical spending. However, little is known about the variability of cost trajectories between patients. This study aims to identify underlying latent groups of advanced breast cancer patients with similar cost trajectories over the last year before death. Methods Data from deceased advanced breast cancer patients, diagnosed between 2010 and 2017, were retrieved from the Southeast Netherlands Advanced Breast Cancer (SONABRE) Registry. Costs of hospital care over the last twelve months before death were analyzed, and the variability of longitudinal patterns between patients were explored using group-based trajectory modeling. Descriptive statistics and multinomial logistic regression were applied to investigate differences between the identified latent groups. Results We included 558 patients. Over the last twelve months before death, mean hospital costs were €2,255 (SD = €492) per month. Costs increased over the last five months and reached a maximum of €3,614 in the last month of life, driven by hospital admissions, while spending for medication declined over the last three months of life. Based on patients’ individual cost trajectories, we identified six latent groups with distinct longitudinal patterns, of which only two showed a marked increase in costs over the last twelve months before death. Latent groups were constituted of heterogeneous patients, and clinical characteristics explained membership only to a limited extent. Conclusions The average costs of advanced breast cancer patients increased towards the end of life. However, we uncovered several latent groups of patients with divergent cost trajectories, which did not reflect the overall increasing trend. The mechanisms underlying the variability in cost trajectories warrants further research

Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study

Background: The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions. Methods: In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission. Results: One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment. Conclusion: The definition persistent postpartum haemo

Primary prevention of major cardiovascular and cerebrovascular events with statins in diabetic patients: a meta-analysis

BACKGROUND: Patients with diabetes mellitus are at increased risk of developing cardiovascular disease. Controlling lipid levels has a preventive effect on the occurrence of major cardiovascular and cerebrovascular events. Individual trials have shown varying data on the efficacy of treatment with lipid-lowering statin therapy in the primary prevention of such events in diabetes. OBJECTIVE: The objective of this study was to assess the efficacy of statins in the primary prevention of the first-time occurrence of a major cardiovascular or cerebrovascular event in diabetic patients. Secondary endpoints were fatal/non-fatal stroke, fatal/non-fatal myocardial infarction and all-cause mortality. METHODS: A systematic search for trial reports was conducted in PubMed, EMBASE, The Cochrane library and clinicaltrials.gov for the years 1966-2011. Reference lists of reviews and meta-analyses of related subjects were searched. High-quality, randomized, double-blinded clinical trials comparing a statin with placebo for the primary prevention of major cardiovascular and cerebrovascular events in diabetic patients were selected. Only large studies with a minimum of 500 diabetic participants followed-up for at least 2 years were included. Endpoints were major cardiovascular and cerebrovascular events. Trial and patient characteristics were extracted by three researchers. The quality of the included studies was tested with the Jadad score. The combined effect on primary as well as secondary endpoints was measured with a fixed-effect model. Publication bias was examined with a funnel plot. RESULTS: Four trials were included, for a total of 10,187 participants. Treatment with statins in the primary prevention of major cardiovascular and cerebrovascular events in diabetic patients resulted in a significant relative risk (RR) reduction in the first-time occurrence of major cardiovascular or cerebrovascular events (RR 0.75, 95% CI 0.67-0.85), fatal/non-fatal stroke (RR 0.69, 95% CI 0.51-0.92) and fatal/non-fatal myocardial infarction (RR 0.70, 95% CI 0.54-0.90) and a non-significant RR reduction in all-cause mortality (RR 0.84, 95% CI 0.65-1.09). Among the studies there was non-significant heterogeneity in the individual effect estimates and no publication bias. LIMITATIONS: Exclusion criteria and endpoints varied slightly between studies. The type and dosing of statin therapy differed between studies. Non-compliance in the statin treatment group and the use of statin treatment in the placebo group could have led to lower risk reductions. CONCLUSION: Treatment with statins in primary prevention among diabetic patients has a significant beneficial effect on event rates of the first-time occurrence of a major cardiovascular or cerebrovascular event, fatal/non-fatal stroke and fatal/non-fatal myocardial infarction. There was a non-significant RR reduction in all-cause mortality

Realisatie landelijke doelen Vogel- en Habitatrichtlijn : een onderzoek naar de noodzaak voor aanvullende beleidsmaatregelen ter realisatie van de landelijke doelen van de Vogel- en Habitatrichtlijn

Nederland heeft voor de soorten en habitattypen van de VHR landelijke doelstellingen geformuleerd. Dit onderzoek analyseert voor welke soorten en habitattypen de realisatie van de landelijke doelen afdoende geborgd is via het bestaand natuurbeleid (Natura 2000, EHS, Programma Beheer, soortenbeleid, gedragscodes, leefgebiedenbenadering) en voor welke niet. Onderzoek in samenwerking met Particulier Gegevensbeherende Organisaties (PGO), namelijk EIS, FLORON, SOVON, VZZ, BLWG, RAVON en Vlinderstichtin

Evaluation of subunit vaccines against feline immunodeficiency virus infection

Subunit vaccines prepared against feline immunodeficiency virus (FIV) infection were evaluated in two trials. First, cats were immunized with bacterial expression products of an envelope fragment that contained the V3 neutralization domain of the FIV surface protein fused to either galactokinase (K-SU3) or glutathione-S-transferase (G-SU3). Quantitative and qualitative differences in the humoral immune response were observed with three adjuvants of which Quil A was the best in terms of total and virus neutralizing antibody. Notwithstanding the responses induced, 19 of 20 immunized cats did not resist challenge and became infected. To determine whether priming with a live viral vector would confer protection, cats were inoculated oronasally and subcutaneously with a feline herpesvirus (FHV) mutant expressing the FIV env gene; two booster immunizations followed using the K-SU3 product in either Quil A or a mineral oilAl(OH)3 adjuvant. FIV-specific antibody responses were only weak, and the vaccinates did not withstand challenge with a low dose of homologous virus

Realisatie landelijke doelen Vogel- en Habitatrichtlijn : een onderzoek naar de noodzaak voor aanvullende beleidsmaatregelen ter realisatie van de landelijke doelen van de Vogel- en Habitatrichtlijn

Nederland heeft voor de soorten en habitattypen van de VHR landelijke doelstellingen geformuleerd. Dit onderzoek analyseert voor welke soorten en habitattypen de realisatie van de landelijke doelen afdoende geborgd is via het bestaand natuurbeleid (Natura 2000, EHS, Programma Beheer, soortenbeleid, gedragscodes, leefgebiedenbenadering) en voor welke niet. Onderzoek in samenwerking met Particulier Gegevensbeherende Organisaties (PGO), namelijk EIS, FLORON, SOVON, VZZ, BLWG, RAVON en Vlinderstichtin

Instruments for oral disease-intervention strategies : recombinant Lactobacillus casei expressing tetanus toxin fragment C for vaccination or myelin proteins for oral tolerance induction in multiple sclerosis

Lactobacillus strains possess properties that make them attractive candidates as vehicles for oral administration of therapeutics. In this report we describe the construction and analysis of recombinant Lactobacillus casei applicable in oral vaccination against an infectious disease (tetanus) and in oral tolerance induction for intervention in an autoimmune disease, multiple sclerosis. Recombinant L. casei which express surface-anchored tetanus toxin fragment C (TTFC) were generated. Quantitative analysis by flow cytometry demonstrated a high level of cell wall-bound expression of TTFC and immunogenicity was demonstrated by parenteral immunization with whole cell extracts of the recombinants. A series of expression vectors was constructed to secrete human myelin basic protein (hMBP) or hMBP as a fusion protein with β-glucuronidase from Escherichia coli. These heterologous products produced by L. casei were detected in the growth medium and parenteral immunization with this medium evoked antibodies against hMBP, confirming that secretion indeed had occurred. Based on the different localization of the heterologous proteins, lactobacilli expressing surface-anchored TTFC are ideally suited for the induction of antibody responses, whereas lactobacilli that secrete myelin proteins can be used for the induction of peripheral T-cell tolerance. In conclusion, the specific technology described here allows the construction of a wide array of safe live recombinant lactobacilli which may prove to be useful in oral intervention strategies for the prevention of infectious diseases or treatment of autoimmune diseases