There is uncertainty about the incidence of breakthrough psychosis in treatment adherent patients, and the role that factors, such as cumulative antipsychotic exposure, play in this phenomenon.
In a ...nationwide cohort of individuals treated for schizophrenia-spectrum disorders in Finland between 1 January 1996 and 31 December 2015, 'Breakthrough Psychosis on Antipsychotic Maintenance Medication' (BAMM) was defined as hospitalization for psychosis despite ongoing continuous treatment with long-acting injectable antipsychotics (LAIs) or oral antipsychotics (OAPs) for ⩾8 weeks. Incidence rates, survival curves, and risk factors were presented.
In a cohort of 16 031 continuous LAI treatment episodes with virtually assured adherence median duration = 441 days, interquartile range (IQR) = 155-1277, BAMM incidence was 31.5%. For 42 867 OAPs treatment episodes (median duration = 483 days, IQR = 167-1491), for whom adherence was modeled by the PRE2DUP method, BAMM incidence was 31.1%. Factors related to illness instability at treatment onset were associated with BAMM, although median time to BAMM was 291 days (IQR = 121-876) for LAIs and 344 days (IQR = 142-989) for OAPs, and 27.4% (N = 1386) of the BAMM events in the LAI, and 32.9% (N = 4378) in the OAP group occurred despite >1 year since last hospitalization at treatment onset. Cumulative antipsychotic exposure was not a consistent risk factor.
BAMM was relatively common even when adherence was confirmed with LAIs. Illness instability at treatment onset accounted for most cases, but relapse after years of continuous treatment was still prevalent. There was insufficient evidence to support causality between cumulative antipsychotic exposure and BAMM. Future research needs to address the role of symptom severity and neurobiology in BAMM.
Given their large surface area and versatile chemical reactivity, single-walled carbon nanotubes (SWCNTs) are regarded as the basis of new pharmacological complexes. In this study, SWCNTs are ...chemically functionalized with fluorescein, folic acid, and capecitabine, a drug that is commonly used against colorectal cancer. These functionalized SWCNTs are dispersed in water by taking advantage of their synergistic interaction with type-II nanocrystalline cellulose (II-NCC), and the resulting colloidal system is tested in vitro on both normal (differentiated) and cancerous (proliferative) human colon cells (Caco-2). The functionalized SWCNT/II-NCC hybrids show a higher activity than the reference (capecitabine) against the Caco-2 cancer cell line. However, this effect appears to be intrinsically associated with the SWCNT/II-NCC complex, particularly boosted by fluorescein, as the presence of capecitabine is not required. In addition, confocal microscopy fluorescence imaging using cell cultures highlights the enormous potential of this nanohybrid platform for colon cancer theranostics.
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•A nanohybrid material made of comprising carbon nanotubes and nanocellulose has been explored studied.•The sSurface functionalization of nanotubes turns converts it this material into a theranostic platform.•In vitro tests with human colon cells (normal and cancer behaviours types) were conducted.•Only the nanohybrid with type-II nanocellulose selectively kills colon cancer cells.•The sSurface attachment of a chemotherapy drug has no additional therapeutic effects.
A multi-proxy characterization of the uppermost sedimentary infill of an Iberian alpine lake (Cimera, 2140 m a.s.l.) was performed to establish the climatic and environmental conditions for the ...Iberian Central Range (ICR) over the last two millennia. This multi-proxy characterization was used to reconstruct the intense runoff events, lake productivity and soil erosion in the lake catchment and interpret these factors in terms of temperature and precipitation variability. The Roman Period (RP; 200 BCE – 500 CE) beginning was characterized by an alternation between cold and warm periods as indicated by short-lived oscillations of intense runoff conditions and soil erosion, although warm conditions dominated the end of the period and the Early Middle Age (EMA; 500–900 CE) onset in the ICR. A noticeable decrease in intense runoff events and a progressive decrease in soil erosion during the late EMA indicated a shift to colder temperatures. In terms of precipitation, both the RP and EMA climate periods displayed a transition from dry to wet conditions that led to a decrease in lake productivity. The Medieval Climate Anomaly (MCA; 900–1300 CE) was characterized by warm and dry conditions with frequent intense runoff episodes and increases in lake productivity and soil erosion, whereas the Little Ice Age (LIA; 1300–1850 CE) showed the opposite characteristics. The Industrial Era (1850–2012 CE) presented an increase in lake productivity that likely demonstrates the influence of global warming.
The spatio-temporal integration of the Cimera record with other Iberian reconstructions has been used to identify the main climate drivers over this region. During the RP and EMA, N–S and E–W humidity gradients were dominant, whereas during the MCA and LIA, these gradients were not evident. These differences could be ascribed to interactions between the North Atlantic Oscillation (NAO) and East Atlantic (EA) phases. During the RP, the general warm conditions and the E–W humidity gradient indicate a dominant interplay between a negative NAO phase and a positive EA phase (NAO−–EA+), whereas the opposite conditions during the EMA indicate a NAO+–EA− interaction. The dominant warm and arid conditions during the MCA and the cold and wet conditions during the LIA indicate the interplay of the NAO+–EA+ and NAO−–EA−, respectively. Furthermore, the higher solar irradiance during the RP and MCA may support the predominance of the EA+ phase, whereas the opposite scenario during the EMA and LIA may support the predominance of the EA− phase, which would favour the occurrence of frequent and persistent blocking events in the Atlantic region during these periods.
•We perform a high-resolution multiproxy study from Iberian alpine lake sediments.•Climatic conditions for Iberian Central Range over the last two millennia.•Climate gradients distinguished the Iberian Roman Period and the Early Middle Ages.•Spatial homogeneous climate conditions depicted MCA and LIA in the Iberian region.•The NAO and EA interactions drive climate patterns over Iberian Peninsula.
Summary Background Our objective was to assess therapeutic non-inferiority of dual treatment with lopinavir–ritonavir and lamivudine to triple treatment with lopinavir–ritonavir plus two ...nucleos(t)ides for maintenance of HIV-1 viral suppression. Methods In this randomised, open-label, non-inferiority trial, we recruited patients from 32 HIV units in hospitals in Spain and France. Eligible patients were HIV-infected adults (aged ≥18 years) with HIV-1 RNA of less than 50 copies per mL, for at least 6 months on triple treatment with lopinavir–ritonavir (twice daily) plus lamivudine or emtricitabine and a second nucleos(t)ide, with no resistance or virological failure to these drugs, and no positive hepatitis B serum surface antigen. Investigators at each centre randomly assigned patients (1:1; block size of four; stratified by time to suppression <1 year or >1 year and nadir CD4 cell count <100 cells per μL or >100 cells per μL; computer-generated random sequence) to continue triple treatment or switch to dual treatment (oral lopinavir 400 mg and oral ritonavir 100 mg twice daily plus oral lamivudine 300 mg once daily). The primary endpoint was response to treatment in the intention-to-treat population (all randomised patients) at 48 weeks. The non-inferiority margin was 12%. This study is registered with ClinicalTrials.gov , number NCT01471821. Findings Between Oct 1, 2011, and April 1, 2013, we randomly assigned 250 participants to continue triple treatment (127 51% patients) or switch to dual treatment (123 49% patients). In the intention-to-treat population, 110 (86·6%) of 127 patients in the triple-treatment group responded to treatment versus 108 (87·8%) of 123 in the dual-treatment group (difference −1·2% 95% CI −9·6 to 7·3; p=0·92), meeting the criteria for non-inferiority. Serious adverse events occurred in eight (7%) patients in the triple-treatment group and five (4%) in the dual-treatment group (p=0·515), and study drug discontinuations due to adverse events occurred in four (3%) in the triple-treatment group and one (1%) in the dual-treatment group (p=0·223). Interpretation Dual treatment with lopinavir–ritonavir plus lamivudine has non-inferior therapeutic efficacy and is similarly tolerated to triple treatment. Funding AbbVie and Red Temática Cooperativa de Investigación en Sida.
Methylmalonic acidemia (MMA) and propionic acidemia (PA) are inborn errors of metabolism. While survival of MMA and PA patients has improved in recent decades, long-term outcome is still ...unsatisfactory. A protein restricted diet is the mainstay for treatment. Additional amino acid mixtures (AAM) can be prescribed if natural protein is insufficient. It is unknown if dietary treatment can have an impact on outcome.
We performed a nationwide retrospective cohort study and evaluated both longitudinal dietary treatment and clinical course of Dutch MMA and PA patients. Protein prescription was compared to the recommended daily allowances (RDA); the safe level of protein intake as provided by the World Health Organization. The association of longitudinal dietary treatment with long-term outcome was evaluated.
The cohort included 76 patients with a median retrospective follow-up period of 15 years (min–max: 0–48 years) and a total of 1063 patient years on a protein restricted diet. Natural protein prescription exceeded the RDA in 37% (470/1287) of all prescriptions and due to AAM prescription, the total protein prescription exceeded RDA in 84% (1070/1277). Higher protein prescriptions were associated with adverse outcomes in severely affected patients. In PA early onset patients a higher natural protein prescription was associated with more frequent AMD. In MMA vitamin B12 unresponsive patients, both a higher total protein prescription and AAM protein prescription were associated with more mitochondrial complications. A higher AAM protein prescription was associated with an increased frequency of cognitive impairment in the entire.
Protein intake in excess of recommendations is frequent and is associated with poor outcome.
We investigate the emergence of magnetic flux in the quiet Sun at very small spatial scales, focusing on the magnetic connection between the photosphere and chromosphere. The observational data ...consist of spectropolarimetric measurements and filtergrams taken with the Hinode satellite and the Dutch Open Telescope. We find that a significant fraction of the magnetic flux present in internetwork regions appears in the form of Omega-shaped loops. The emergence rate is 0.02 loops per hour and arcsec-2, which brings 1.1 × 1012 Mx s-1 arcsec-2 of new flux to the solar surface. Initially, the loops are observed as small patches of linear polarization above a granular cell. Shortly afterward, two footpoints of opposite polarity become visible in circular polarization within or at the edges of the granule and start moving toward the adjacent intergranular space. The orientation of the footpoints does not seem to obey Hale's polarity rules. The loops are continuously buffeted by convective motions, but they always retain a high degree of coherence. Interestingly, 23% of the loops that emerge in the photosphere reach the chromosphere (16 cases out of 69). They are first detected in Fe I 630 nm magnetograms and 5 minutes later in Mg I b 517.3 nm magnetograms. After about 8 minutes, some of them are also observed in Ca II H line-core images, where the footpoints produce small brightness enhancements.
Since the United Nations approved the eight Millennium Development Goals in 2000 and, 15 years later, the 2030 Agenda for Sustainable Development and its 17 Sustainable Development Goals (SDGs), the ...highest political institutions in the world have not stopped worrying about achieving the sustainability of the planet. Also in 2015, the European Commission prepared the European Union Action Plan for the Circular Economy, seeking a transition towards a less linear economy, in which products, materials, and resources are kept in the system for as long as possible and in which the generation of waste is minimized.
Since then, the European Union has continued issuing reports and communications to accelerate this process in search of a circular economy, making continuous references to the fact that, through circular economy initiatives, the SDGs would be fulfilled. In this context, the objectives of this paper are 1) to determine, through exploratory factor analysis and correlation analysis, whether there is a statistically significant relationship between circular economy initiatives undertaken in the EU and compliance with the SDGs; 2) to check, through a cluster analysis, if there are homogeneous groups of countries worldwide in terms of compliance with the SDGs; and 3) using this same technique, to check whether the countries that make up the EU achieve similar results in terms of compliance with the SDGs.
Introduction
The SARS-CoV-2 pandemic has produced an unprecedented clinical situation, causing a direct and indirect impact on the physical and mental health of the population. In Spain, between ...March 15 and June 21 of 2020, it was decreed a home confinement that caused the interruption of the daily life of millions of people. However, there are few studies that analyze the changes produced in psychiatric care in the Emergency Department (ED).
Objectives
To analyze the changes produced in psychiatric emergencies, subanalysing paediatric population, during the first year of the pandemic (COV1/Y-COV1) compared to the previous year (NOCOV/Y-NOCOV1). To analyze the clinical features of patients attended during the lockdown period of the pandemic (LOCK) and compare it to the period of the pandemic after the lockdown (NOLOCK).
Methods
Through the registry of computerized medical records, patients who attended the psychiatric hospital emergency department between 03/01/2019 and 02/28/2021 were identified. We also identified all attendances from 15/03 to 21/06 in 2019 and in 2020 to obtain variables from the lockdown period.
Results
During period of this study, 2694 psychiatric visits made in the ED (1744 patients - 54.3% women, and 69.5% were between 25 and 64 years-), 1537 in NOCOV and 1157 in COV1. Significant differences were found between COV1 and NOCOV in sociodemographic variables, such as employment status and number of offspring. At a clinical level, in COV1, we observed an increase in attendance due to heteroaggressive behaviors, mania, insomnia and problems due to substance use. An increase in the prescription and/or modification of treatment was observed (59.3% vs 54.3%). During COV1, in terms of discharge follow-up in the month following the ED visit, telematic assistance increased (11.4% vs. 5.3%). During the period of study, 282 ED attendances were performed, 153 in Y-NOCOV and 129 in Y-COV1. At a clinical level, during Y-COV1, a decrease in attendances related to substance use was found significant. The sub-analysis carried out for LOCK and NOLOCK yields similar data to those obtained in the COV1 vs. NOCOV1 comparison. During lockdown, the face-to-face follow-up in the month following the ED was significantly lower (39,5% vs 57,1%) regarding telematic follow-up (24,4% vs 5,8%) In this period, an increase of adolescents without previous mental health follow-up was observed (44% LOCK vs. 22% NOLOCK).
Conclusions
Our work supports the hypothesis that the COVID-19 pandemic caused a change in psychiatric care in the ED. It also shows how lockdown changed the attendance in psychiatric emergencies, and also in the later community care attendance. Changes are detected in emergency care for adolescents during the pandemic compared to the previous year. Strikingly, our study does not reflect a quantitative increase in the demand. It would be of interest to continue collecting data after the time of the present project.
Disclosure of Interest
None Declared
Skin rash is an adverse event which might be associated with longer survival in patients treated with epidermal growth factor receptor tyrosine kinase inhibitors. The aim of this nonrandomised phase ...II clinical trial is to prospectively evaluate the relationship between skin rash and overall survival (OS) in advanced/metastatic pancreatic cancer treated with erlotinib plus gemcitabine.
Patients were given gemcitabine (1000 mg/m2/week, 3 weeks every 4 weeks) plus erlotinib (100 mg/day orally continuously) until disease progression/unacceptable toxicity. The primary end point was OS.
A total of 153 eligible patients were enrolled (grade ≥ 2 rash, 25%; grade < 2 rash, 75%). OS was longer in patients with grade ≥2 rash versus grade <2 (11 versus 5 months; P < 0.001). Progression-free survival was longer in patients with grade ≥2 rash versus grade <2 (6 versus 3 months; P < 0.001) and shorter in those without rash versus grade 1 (2 versus 4 months; P = 0.005) or grade ≥2 (2 versus 6 months; P < 0.001). Patients with grade ≥2 rash showed higher rates of overall response (21% versus 7%; P < 0.05) and disease control (84% versus 43%; P < 0.05) versus grade <2.
This study prospectively confirms the relationship between rash and longer OS in unresectable locally advanced/metastatic pancreatic cancer treated with erlotinib plus gemcitabine.
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