Trends in governmental expenditure on vaccination programmes in the Netherlands, a historical analysis

BACKGROUND: Health economic evaluations are often required before implementing a vaccination programme. Such evaluations rarely consider the historical context of a vaccination programme. We review the financial history of vaccination programmes in the Netherlands, and compare these to demographic and macroeconomic developments as well as avoided mortality burden. METHODS: Previously uncatalogued historical expenditures on the Dutch National Immunisation Programme (NIP) and influenza vaccination were obtained from official reports. Costs were adjusted for inflation using Consumer Price Indices and expressed in Euro of 2016. Estimates on mortality burden averted were obtained from previous research and used to calculate the ratio of expenses to averted mortality burden for vaccinations against diphtheria, tetanus, pertussis, polio, measles, mumps and rubella for birth cohorts 1953-1992. RESULTS: Developments towards a uniform government funded NIP started early 1950s with vaccinations against diphtheria, pertussis and tetanus, culminating in its official launch in 1957 together with polio vaccinations. Since the 1980s, expenditure increased nearly five-fold mostly due to the addition of new vaccines, while spending on already implemented vaccinations tended to decline. Overall, expenditure increased from € 5 million in 1957 to € 93 million in 2014. Relative to total healthcare expenditure, the NIP contributed little, ranging between 0.05% and 0.14%. Spending on influenza vaccination increased from € 37 million in 1996 to € 52 million in 2014, while relative to total healthcare expenditure it decreased from 0.069% to 0.055%. In 2014, 0.15% of healthcare expenditure and € 533 per birth was spent on vaccination programmes. Overall, for birth cohorts 1953-1992, € 5.4 thousand (95% confidence interval: 4.0-7.3) was expended per year-of-life-lost averted. CONCLUSION: The actual costs per year-of-life gained are more favorable than estimated here since averted medical costs were not included. Although expenditure on vaccination programmes increased substantially, the contribution to overall healthcare expenditure remained small

Identification of Nuclear Factor IV/Ku autoantigen in a human 2D-gel protein database Modification of the large subunit depends on cellular proliferation

AbstractNuclear Factor IV (NFIV)is a heterodimeric DNA-binding protein from HeLa cells, recognizing molecular ends and is identical to the autoantigenic target Ku. We have identified the two NFIV/Ku subunits, by comigration, in the 2D-gel database of transformed human amnion cell (AMA) proteins. We observed that the large subunit or NFIV/Ku consists of at least 3 charge variants that correspond to SSP IEFs 5705 (81.2 kDa, pI 5.74), 6707 (81.2 kDa, pI 5.67) and 6706 (81.9 kDa, pI 5.60) in the AMA catalogue. The relative amounts of the 2 major variants (IEFs 5705 and 6707) was dependent on the state of cell proliferation. Inhibition of DNA-synthesis by hydroxyurea also changed the relative levels of the variants, whereas aphidicolin or a thymidine block had no effect. These results suggest a possible role for NFIV/Ku in DNA replication

Phase-based treatment versus immediate trauma-focused treatment for post-traumatic stress disorder due to childhood abuse:Randomised clinical trial

Background It is unclear whether people with post-traumatic stress disorder (PTSD) and symptoms of complex PTSD due to childhood abuse need a treatment approach different from approaches in the PTSD treatment guidelines. Aims To determine whether a phase-based approach is more effective than an immediate trauma-focused approach in people with childhood-trauma related PTSD (Netherlands Trial Registry no.: NTR5991). Method Adults with PTSD following childhood abuse were randomly assigned to either a phase-based treatment condition (8 sessions of Skills Training in Affect and Interpersonal Regulation (STAIR), followed by 16 sessions of eye-movement desensitisation and reprocessing (EMDR) therapy; n = 57) or an immediately trauma-focused treatment condition (16 sessions of EMDR therapy; n = 64). Participants were assessed for symptoms of PTSD and complex PTSD, and other forms of psychopathology before, during and after treatment and at 3- and 6-month follow-ups. Results Data were analysed with linear mixed models. No significant differences between the two treatments on any variable at post-treatment or follow-up were found. Post-treatment, 68.8% no longer met PTSD diagnostic criteria. Self-reported PTSD symptoms significantly decreased for both STAIR–EMDR therapy (d = 0.93) and EMDR therapy (d = 1.54) from pre- to post-treatment assessment, without significant difference between the two conditions. No differences in drop-out rates between the conditions were found (STAIR–EMDR 22.8% v. EMDR 17.2%). No study-related adverse events occurred. Conclusions This study provides compelling support for the use of EMDR therapy alone for the treatment of PTSD due to childhood abuse as opposed to needing any preparatory intervention

Phase-based treatment versus immediate trauma-focused treatment for post-traumatic stress disorder due to childhood abuse:Randomised clinical trial

Background It is unclear whether people with post-traumatic stress disorder (PTSD) and symptoms of complex PTSD due to childhood abuse need a treatment approach different from approaches in the PTSD treatment guidelines. Aims To determine whether a phase-based approach is more effective than an immediate trauma-focused approach in people with childhood-trauma related PTSD (Netherlands Trial Registry no.: NTR5991). Method Adults with PTSD following childhood abuse were randomly assigned to either a phase-based treatment condition (8 sessions of Skills Training in Affect and Interpersonal Regulation (STAIR), followed by 16 sessions of eye-movement desensitisation and reprocessing (EMDR) therapy; n = 57) or an immediately trauma-focused treatment condition (16 sessions of EMDR therapy; n = 64). Participants were assessed for symptoms of PTSD and complex PTSD, and other forms of psychopathology before, during and after treatment and at 3- and 6-month follow-ups. Results Data were analysed with linear mixed models. No significant differences between the two treatments on any variable at post-treatment or follow-up were found. Post-treatment, 68.8% no longer met PTSD diagnostic criteria. Self-reported PTSD symptoms significantly decreased for both STAIR-EMDR therapy (d = 0.93) and EMDR therapy (d = 1.54) from pre- to post-treatment assessment, without significant difference between the two conditions. No differences in drop-out rates between the conditions were found (STAIR-EMDR 22.8% v. EMDR 17.2%). No study-related adverse events occurred. Conclusions This study provides compelling support for the use of EMDR therapy alone for the treatment of PTSD due to childhood abuse as opposed to needing any preparatory intervention.</p

Series: Public engagement with research. Part 1: The fundamentals of public engagement with research

BACKGROUND: In the first of a four-part series, we describe the fundamentals of public engagement in primary care research. OBJECTIVES: The article's purpose is to encourage, inform and improve the researcher's awareness about public engagement in research. For a growing number of researchers, funders and patient organisations in Europe, public engagement is a moral and ethical imperative for conducting high-quality research. DISCUSSION: Starting with an explanation of the role of public engagement in research, we highlight its diversity and benefits to research, researchers and the public members involved. We summarise principles of good practice and provide valuable resources for researchers to use in their public engagement activities. Finally, we discuss some of the issues encountered when researchers collaborate with members of the public and provide practical steps to address them. Case studies of real-life situations are used to illustrate and aid understanding. CONCLUSION: We hope this article and the other papers in this series will encourage researchers to better consider the role and practice of public engagement and the potential added value to research that collaborating with the public could provide

Василь Васильович Тарновський: духовні витоки українського патріотизму та благодійності

Context: Climate change can directly affect habitats within ecological networks, but may also have indirect effects on network quality by inducing land use change. The relative impact of indirect effects of climate change on the quality of ecological networks currently remains largely unknown. Objectives: The objective of this study was to determine the relative impact of direct and indirect effects of climate change on a network of breeding habitat of four meadow bird species (Black-tailed godwit, Common redshank, Eurasian oystercatcher and Northern lapwing) in the Netherlands. Methods: Habitat models were developed that link meadow bird breeding densities to three habitat characteristics that are sensitive to environmental change (landscape openness, land use and groundwater level). These models were used to assess the impact of scenarios of landscape change with and without climate change on meadow bird breeding habitat quality for a case study area in the peat meadow district of the Netherlands. Results: All scenarios led to significantly reduced habitat quality for all species, mainly as a result of conversion of grassland to bioenergy crops, which reduces landscape openness. Direct effects of climate change on habitat quality were largely absent, indicating that especially human adaptation to climate change rather than direct effects of climate change was decisive for the degradation of ecological network quality for breeding meadow birds. Conclusions: We conclude that scenario studies exploring impacts of climate change on ecological networks should incorporate both land use change resulting from human responses to climate change and direct effects of climate change on landscapes

Cerebellar Cathodal Transcranial Direct Stimulation and Performance on a Verb Generation Task: A Replication Study

The role of the cerebellum in cognitive processing is increasingly recognized but still poorly understood. A recent study in this field applied cerebellar Transcranial Direct Current Stimulation (c-tDCS) to the right cerebellum to investigate the role of prefrontal-cerebellar loops in language aspects of cognition. Results showed that the improvement in participants' verbal response times on a verb generation task was facilitated immediately after cathodal c-tDCS, compared to anodal or sham c-tDCS. The primary aim of the present study is to replicate these findings and additionally to investigate possible longer term effects. A crossover within-subject design was used, comparing cathodal and sham c-tDCS. The experiment consisted of two visits with an interval of one week. Our results show no direct contribution of cathodal c-tDCS over the cerebellum to language task performance. However, one week later, the group receiving cathodal c-tDCS in the first visit show less improvement and increased variability in their verbal response times during the second visit, compared to the group receiving sham c-tDCS in the first visit. These findings suggest a potential negative effect of c-tDCS and warrant further investigation into long term effects of c-tDCS before undertaking clinical studies with poststroke patients with aphasia

Demographics and Functional Outcome of Toe Fractures

Toe fractures are common; however, there are few data on demographics and functional outcome. We studied outcomes in 339 consecutive patients with toe fractures treated between January 2006 and September 2008. Two hundred and sixty-four patients, aged 16 to 75, were mailed an outcome questionnaire, and overall subjective satisfaction with the outcome of treatment was measured using a visual analog scale (VAS). Most frequently affected were the first (38%) and fifth (30%) toes, and most (75.6%) of the fractures were caused by stubbing or crush injury. More than 95% of the fractures were displaced less than 2 mm, and all of the fractures were treated conservatively. The questionnaire was returned by 141 (53%) patients with a median follow-up of 27 months. Respondents were female in 57.4% of cases and had a median age of 45 years. The median AOFAS score was 100 (P25, P75= 93,100) points; the median VAS was 10 (P25, P75= 8, 10) points. Univariate regression analysis revealed no statistically significant associations between outcome and the particular toe or phalanx involved, number of fractured toes, fracture type and location, articular involvement, gender, age, body mass index, smoking habits, and the presence of diabetes mellitus. Satisfaction VAS was dependent on age (P = .047) and gender (P = .049) in the multivariate analysis. The AOFAS midfoot score was not influenced by any of the covariates. This is the first epidemiological investigation using 2 outcome-scoring systems to determine function and satisfaction following treatment of toe fractures

Levodopa-loaded nanoparticles for the treatment of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) resulting in dopamine (DA) deficiency, which manifests itself in motor symptoms including tremors, rigidity and bradykinesia. Current PD treatments aim at symptom reduction through oral delivery of levodopa (L-DOPA), a precursor of DA. However, L-DOPA delivery to the brain is inefficient and increased dosages are required as the disease progresses, resulting in serious side effects like dyskinesias. To improve PD treatment efficacy and to reduce side effects, recent research focuses on the encapsulation of L-DOPA into polymeric- and lipid-based nanoparticles (NPs). These formulations can protect L-DOPA from systemic decarboxylation into DA and improve L-DOPA delivery to the central nervous system. Additionally, NPs can be modified with proteins, peptides and antibodies specifically targeting the blood-brain barrier (BBB), thereby reducing required dosages and free systemic DA. Alternative delivery approaches for NP-encapsulated L-DOPA include intravenous (IV) administration, transdermal delivery using adhesive patches and direct intranasal administration, facilitating increased therapeutic DA concentrations in the brain. This review provides an overview of the recent advances for NP-mediated L-DOPA delivery to the brain, and debates challenges and future perspectives on the field

Predicting Upper Limb Motor Impairment Recovery after Stroke: A Mixture Model

Objective: Spontaneous recovery is an important determinant of upper extremity recovery after stroke and has been described by the 70% proportional recovery rule for the Fugl–Meyer motor upper extremity (FM-UE) scale. However, this rule is criticized for overestimating the predictability of FM-UE recovery. Our objectives were to develop a longitudinal mixture model of FM-UE recovery, identify FM-UE recovery subgroups, and internally validate the model predictions. Methods: We developed an exponential recovery function with the following parameters: subgroup assignment probability, proportional recovery coefficient rk, time constant in weeks τk, and distribution of the initial FM-UE scores. We fitted the model to FM-UE measurements of 412 first-ever ischemic stroke patients and cross-validated endpoint predictions and FM-UE recovery cluster assignment. Results: The model distinguished 5 subgroups with different recovery parameters (r1 = 0.09, τ1 = 5.3, r2 = 0.46, τ2 = 10.1, r3 = 0.86, τ3 = 9.8, r4 = 0.89, τ4 = 2.7, r5 = 0.93, τ5 = 1.2). Endpoint FM-UE was predicted with a median absolute error of 4.8 (interquartile range [IQR] = 1.3–12.8) at 1 week poststroke and 4.2 (IQR = 1.3–9.8) at 2 weeks. Overall accuracy of assignment to the poor (subgroup 1), moderate (subgroups 2 and 3), and good (subgroups 4 and 5) FM-UE recovery clusters was 0.79 (95% equal-tailed interval [ETI] = 0.78–0.80) at 1 week poststroke and 0.81 (95% ETI = 0.80–0.82) at 2 weeks. Interpretation: FM-UE recovery reflects different subgroups, each with its own recovery profile. Cross-validation indicates that FM-UE endpoints and FM-UE recovery clusters can be well predicted. Results will contribute to the understanding of upper limb recovery patterns in the first 6 months after stroke. ANN NEUROL 2020