Are Dutch homeowners willing to invest in sustainable heating systems?:Comparing intentions and determinants in four scenarios

The energy transition, replacing fossil fuels with renewable energy, requires everyone's efforts to succeed. In the Netherlands, homeowners are expected to invest in sustainable heating. This article describes a cross-sectional survey among Dutch homeowners (N = 302) investigating determinants of their intentions to make such investments. Unlike earlier research, this study problematized the concept of investment intentions, assuming that intentions and determinants might vary between different investment scenarios. Four scenarios were distinguished: (1) long-term status quo intentions, (2) short-term status quo intentions, (3) intentions in the case of higher natural gas prices, and (4) intentions in the case of government support. The results show that homeowners' investment intentions differed significantly between the four scenarios: Government support led to the highest intentions, followed by, respectively, long-term status quo intentions, intentions in the case of higher gas prices, and short-term status quo intentions. Furthermore, the behavioral determinants differed considerably between the scenarios. The overall conclusion is that strategies to promote homeowners' investments in sustainable heating must be aligned with the scenarios foreseen. For each scenario, our study lists determinants that could be emphasized.</p

Improved detection of artifactual viral minority variants in high-throughput sequencing data

textabstractHigh-throughput sequencing (HTS) of viral samples provides important information on the presence of viral minority variants. However, detection and accurate quantification is limited by the capacity to distinguish biological from artificial variation. In this study, errors related to the Illumina HiSeq2000 library generation and HTS process were investigated by determining minority variant frequencies in an influenza A/WSN/1933(H1N1) virus reverse-genetics plasmid pool. Errors related to amplification and sequencing were determined using the same plasmid pool, by generation of infectious virus using reverse genetics followed by in duplo reverse-transcriptase PCR (RT-PCR) amplification and HTS in the same sequence run. Results showed that after "best practice" quality control (QC), within the plasmid pool, one minority variant with a frequency >0.5% was identified, while 84 and 139 were identified in the RT-PCR amplified samples, indicating RT-PCR amplification artificially increased variation. Detailed analysis showed that artifactual minority variants could be identified by two major technical characteristics: their predominant presence in a single read orientation and uneven distribution of mismatches over the length of the reads. We demonstrate that by addition of two QC steps 95% of the artifactual minority variants could be identified. When our analysis approach was applied to three clinical samples 68% of the initially identified minority variants were identified as artifacts. Our study clearly demonstrated that, without additional QC steps, overestimation of viral minority variants is very likely to occur, mainly as a consequence of the required RT-PCR amplification step. The improved ability to detect and correct for artifactual minority variants, increases data resolution and could aid both past and future studies incorporating HTS. The source code has been made available through Sourceforge (https://sourceforge.net/projects/mva-ngs)

Network Meta-analysis for the Diagnostic Approach to Pathologic Nipple Discharge

Pathologic nipple discharge (PND) is one of the most common breast-related complaints for referral because of its supposed association with breast cancer. The aim of this network meta-analysis (NMA) was to compare the diagnostic efficacy of ultrasound, mammogram, cytology, magnetic resonance imaging (MRI), and ductoscopy in patients with PND, as well as to determine the best diagnostic strategy to assess the risk of malignancy as cause for PND. Cochrane Library, PubMed, and Embase were searched to collect relevant literature from the inception of each of the diagnostic methods until January 27, 2020. The search yielded 1472 original citations, of which 36 studies with 3764 patients were finally included for analysis. Direct and indirect comparisons were performed using an NMA approach to evaluate the combined odd ratios and to determine the surface under the cumulative ranking curves (SUCRA) of the diagnostic value of different imaging methods for the detection of breast cancer in patients with PND. Additionally, a subgroup meta-analysis comparing ductoscopy to MRI when conventional imaging was negative was also performed. According to this NMA, sensitivity for detection of malignancy in patients with PND was highest for MRI (83%), followed by ductoscopy (58%), ultrasound (50%), cytology (38%), and mammogram (22%). Specificity was highest for mammogram (93%) followed by ductoscopy (92%), cytology (90%), MRI (76%), and ultrasound (69%). Diagnostic accuracy was the highest for ductoscopy (88%), followed by cytology (82%), MRI (77%), mammogram (76%), and ultrasound (65%). Subgroup meta-analysis (comparing ductoscopy to MRI when ultrasound and mammogram were negative) showed no significant difference in sensitivity, but ductoscopy was statistically significantly better with regard to specificity and diagnostic accuracy. The results from this NMA indicate that although ultrasound and mammogram may remain low-cost useful first choices for the detection of malignancy in patients with PND, ductoscopy outperforms most imaging techniques (especially MRI) and cytology

A trial like ALIC4E: why design a platform, response-adaptive, open, randomised controlled trial of antivirals for influenza-like illness?

ALIC4E is the first publicly funded, multicountry, pragmatic study determining whether antivirals should be routinely prescribed for influenza-like illness in primary care. The trial aims to go beyond determining the average treatment effect in a population to determining effects in patients with combinations of participant characteristics (age, symptom duration, illness severity, and comorbidities). It is one of the first platform, response-adaptive, open trial designs implemented in primary care, and this article aims to provide an accessible description of key aspects of the study design. 1) The platform design allows the study to remain relevant to evolving circumstances, with the ability to add treatment arms. 2) Response adaptation allows the proportion of participants with key characteristics allocated to study arms to be altered during the course of the trial according to emerging outcome data, so that participants' information will be most useful, and increasing their chances of receiving the trial intervention that will be most effective for them. 3) Because the possibility of taking placebos influences participant expectations about their treatment, and determining effects of the interventions on patient help seeking and adherence behaviour in real-world care is critical to estimates of cost-effectiveness, ALIC4E is an open-label trial

Determinants of the Use of a Diabetes Risk-Screening Test

A study was designed to investigate why people do or do not make use of a diabetes risk test developed to facilitate the timely diagnosis of diabetes. Data were collected using a web-based questionnaire, which was based on the Health Belief Model, the Theory of Planned Behavior, and the Threatening Medical Situations Inventory. People who had and had not used the risk test were recruited to complete the survey. The sample consisted of 205 respondents: 44% who had used the test and 56% who had not. The hypothesized relationships between the dependent variable (diabetes risk test use) and the determinants used in this study were tested using logistic regression analysis. Only two significant predictors of diabetes risk test use were found: gender and barriers. More women than men use the test. Furthermore, people who experience more barriers will be less inclined to use the test. The contribution of diabetes screening tests fully depends on people’s willingness to use them. To optimize the usage of such test, it is especially important to address the barriers as perceived by the public. Two types of barriers must be addressed: practical barriers (time to take the test, fear of complexity of the test), and consequential barriers (fear of the disease and treatment, uncertainties about where to go in the case of an increased risk of diabetes)

A real-time RT-PCR for detection of clade 1 and 2 H5N1 Influenza A virus using Locked Nucleic Acid (LNA) TaqMan probes

<p>Abstract</p> <p>Background</p> <p>The emergence and co-circulation of two different clades (clade 1 and 2) of H5N1 influenza viruses in Vietnam necessitates the availability of a diagnostic assay that can detect both variants.</p> <p>Results</p> <p>We developed a single real-time RT-PCR assay for detection of both clades of H5N1 viruses, directly from clinical specimens, using locked nucleic acid TaqMan probes. Primers and probe used in this assay were designed based on a highly conserved region in the <it>HA </it>gene of H5N1 viruses. The analytical sensitivity of the assay was < 0.5 PFU and 10 - 100 ssDNA plasmid copies. A total of 106 clinical samples (58 from patients infected with clade 1, 2.1 or 2.3 H5N1 viruses and 48 from uninfected or seasonal influenza A virus-infected individuals) were tested by the assay. The assay showed 97% concordance with initial diagnostics for H5 influenza virus infection with a specificity of 100%.</p> <p>Conclusions</p> <p>This assay is a useful tool for diagnosis of H5N1 virus infections in regions where different genetic clades are co-circulating.</p

Import and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study

BACKGROUND: International travel contributes to the dissemination of antimicrobial resistance. We investigated the acquisition of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) during international travel, with a focus on predictive factors for acquisition, duration of colonisation, and probability of onward transmission. METHODS: Within the prospective, multicentre COMBAT study, 2001 Dutch travellers and 215 non-travelling household members were enrolled. Faecal samples and questionnaires on demographics, illnesses, and behaviour were collected before travel and immediately and 1, 3, 6, and 12 months after return. Samples were screened for the presence of ESBL-E. In post-travel samples, ESBL genes were sequenced and PCR with specific primers for plasmid-encoded β-lactamase enzymes TEM, SHV, and CTX-M group 1, 2, 8, 9, and 25 was used to confirm the presence of ESBL genes in follow-up samples. Multivariable regression analyses and mathematical modelling were used to identify predictors for acquisition and sustained carriage, and to determine household transmission rates. This study is registered with ClinicalTrials.gov, number NCT01676974. FINDINGS: 633 (34·3%) of 1847 travellers who were ESBL negative before travel and had available samples after return had acquired ESBL-E during international travel (95% CI 32·1-36·5), with the highest number of acquisitions being among those who travelled to southern Asia in 136 of 181 (75·1%, 95% CI 68·4-80·9). Important predictors for acquisition of ESBL-E were antibiotic use during travel (adjusted odds ratio 2·69, 95% CI 1·79-4·05), traveller's diarrhoea that persisted after return (2·31, 1·42-3·76), and pre-existing chronic bowel disease (2·10, 1·13-3·90). The median duration of colonisation after travel was 30 days (95% CI 29-33). 65 (11·3%) of 577 remained colonised at 12 months. CTX-M enzyme group 9 ESBLs were associated with a significantly increased risk of sustained carriage (median duration 75 days, 95% CI 48-102, p=0·0001). Onward transmission was found in 13 (7·7%) of 168 household members. The probability of transmitting ESBL-E to another household member was 12% (95% CI 5-18). INTERPRETATION: Acquisition and spread of ESBL-E during and after international travel was substantial and worrisome. Travellers to areas with a high risk of ESBL-E acquisition should be viewed as potential carriers of ESBL-E for up to 12 months after return. FUNDING: Netherlands Organisation for Health Research and Development (ZonMw)

Oseltamivir Is Adequately Absorbed Following Nasogastric Administration to Adult Patients with Severe H5N1 Influenza

In the absence of a parenteral drug, oral oseltamivir is currently recommended by the WHO for treating H5N1 influenza. Whether oseltamivir absorption is adequate in severe influenza is unknown. We measured the steady state, plasma concentrations of nasogastrically administered oseltamivir 150 mg bid and its active metabolite, oseltamivir carboxylate (OC), in three, mechanically ventilated patients with severe H5N1 (male, 30 yrs; pregnant female, 22 yrs) and severe H3N2 (female, 76 yrs). Treatments were started 6, 7 and 8 days after illness onset, respectively. Both females were sampled while on continuous venovenous haemofiltration. Admission and follow up specimens (trachea, nose, throat, rectum, blood) were tested for RNA viral load by reverse transcriptase PCR. In vitro virus susceptibility to OC was measured by a neuraminidase inhibition assay. Admission creatinine clearances were 66 (male, H5N1), 82 (female, H5N1) and 6 (H3N2) ml/min. Corresponding AUC0–12 values (5932, 10,951 and 34,670 ng.h/ml) and trough OC concentrations (376, 575 and 2730 ng/ml) were higher than previously reported in healthy volunteers; the latter exceeded 545 to 3956 fold the H5N1 IC50 (0.69 ng/ml) isolated from the H5N1 infected female. Two patients with follow-up respiratory specimens cleared their viruses after 5 (H5N1 male) and 5 (H3N2 female) days of oseltamivir. Both female patients died of respiratory failure; the male survived. 150 mg bid of oseltamivir was well absorbed and converted extensively to OC. Virus was cleared in two patients but two patients died, suggesting viral efficacy but poor clinical efficacy

Las políticas de reequilibro territorial e innovación institucional en Madrid, 2015-2019

Lograr un mejor reparto de los recursos materiales es una tarea inseparable de una transformación institucional dirigida a un mejor reparto del poder y de la capacidad de decisión. Es preciso reconfigurar las instituciones para redefinir la relación entre estas y la ciudadanía. El espacio de cooperación entre las instituciones públicas y la sociedad civil organizada es un terreno privilegiado para lograr esa reconfiguración institucional. El Fondo de Reequilibrio Territorial se concibe como un primer paso en ese complejo camino y se relaciona con el proceso de descentralización y con el concepto de cooperación público-social. Debe entenderse en relación con otros desarrollos institucionales, como el Consejo Coordinador de los Distritos o los Foros Locales. Una tarea de estas características no puede realizarse desde un solo espacio institucional y en un solo mandato, pero en todo caso debe hacerse contando con la firme voluntad y dirección política del equipo de gobierno que quiera desempeñarla. El gobierno es una herramienta formidable para emprender un proceso de reequilibrio territorial, pero aun cuando no hay en el mismo voluntad política en este sentido existen posibilidades para estimular o condicionar la voluntad del equipo de gobierno: articular un amplio pacto entre los actores políticos, sociales, económicos, académicos, etc. que ponga la cuestión en el centro de la agenda política y eleve hasta lo impagable el coste político de seguir dando la espalda a una cuestión crucial para el futuro de la democracia.Lograr un mejor reparto de los recursos materiales es una tarea inseparable de una transformación institucional dirigida a un mejor reparto del poder y de la capacidad de decisión. Es preciso reconfigurar las instituciones para redefinir la relación entre estas y la ciudadanía. El espacio de cooperación entre las instituciones públicas y la sociedad civil organizada es un terreno privilegiado para lograr esa reconfiguración institucional.El Fondo de Reequilibrio Territorial se concibe como un primer paso en ese complejo camino y se relaciona con el proceso de descentralización y con el concepto de cooperación público-social. Debe entenderse en relación con otros desarrollos institucionales, como el Consejo Coordinador de los Distritos o los Foros Locales. Una tarea de estas características no puede realizarse desde un solo espacio institucional y en un solo mandato, pero en todo caso debe hacerse contando con la firme voluntad y dirección política del equipo de gobierno que quiera desempeñarla. El gobierno es una herramienta formidable para emprender un proceso de reequilibrio territorial, pero aun cuando no hay en el mismo voluntad política en este sentido existen posibilidades para estimular o condicionar la voluntad del equipo de gobierno: articular un amplio pacto entre los actores políticos, sociales, económicos, académicos, etc. que ponga la cuestión en el centro de la agenda política y eleve hasta lo impagable el coste político de seguir dando la espalda a una cuestión crucial para el futuro de la democracia

Design and rationale of DUTCH-AF:a prospective nationwide registry programme and observational study on long-term oral antithrombotic treatment in patients with atrial fibrillation

Introduction Anticoagulation therapy is pivotal in the management of stroke prevention in atrial fibrillation (AF). Prospective registries, containing longitudinal data are lacking with detailed information on anticoagulant therapy, treatment adherence and AF-related adverse events in practice-based patient cohorts, in particular for non-vitamin K oral anticoagulants (NOAC). With the creation of DUTCH-AF, a nationwide longitudinal AF registry, we aim to provide clinical data and answer questions on the (anticoagulant) management over time and of the clinical course of patients with newly diagnosed AF in routine clinical care. Within DUTCH-AF, our current aim is to assess the effect of non-adherence and non-persistence of anticoagulation therapy on clinical adverse events (eg, bleeding and stroke), to determine predictors for such inadequate anticoagulant treatment, and to validate and refine bleeding prediction models. With DUTCH-AF, we provide the basis for a continuing nationwide AF registry, which will facilitate subsequent research, including future registry-based clinical trials. Methods and analysis The DUTCH-AF registry is a nationwide, prospective registry of patients with newly diagnosed 'non-valvular' AF. Patients will be enrolled from primary, secondary and tertiary care practices across the Netherlands. A target of 6000 patients for this initial cohort will be followed for at least 2 years. Data on thromboembolic and bleeding events, changes in antithrombotic therapy and hospital admissions will be registered. Pharmacy-dispensing data will be obtained to calculate parameters of adherence and persistence to anticoagulant treatment, which will be linked to AF-related outcomes such as ischaemic stroke and major bleeding. In a subset of patients, anticoagulation adherence and beliefs about drugs will be assessed by questionnaire. Ethics and dissemination This study protocol was approved as exempt for formal review according to Dutch law by the Medical Ethics Committee of the Leiden University Medical Centre, Leiden, the Netherlands. Results will be disseminated by publications in peer-reviewed journals and presentations at scientific congresses