Why prudence is needed when interpreting articles reporting clinical trial results in mental health

Background: Clinical trial results' reliability is impacted by reporting bias. This is primarily manifested as publication bias and outcome reporting bias. Mental health trials' specific features: Mental health trials are prone to two methodological deficiencies: (1) using small numbers of participants that facilitates false positive findings and exaggerated size effects, and (2) the obligatory use of psychometric scales that require subjective assessments. These two deficiencies contribute to the publication of unreliable results. Considerable reporting bias has been found in safety and efficacy findings in psychotherapy and pharmacotherapy trials. Reporting bias can be carried forward to meta-analyses, a key source for clinical practice guidelines. The final result is the frequent overestimation of treatment effects that could impact patients and clinician-informed decisions. Mechanisms to prevent outcome reporting bias: Prospective registration of trials and publication of results are the two major methods to reduce reporting bias. Prospective trial registration will allow checking whether they are published (so it will help to prevent publication bias) and, if published, whether those outcomes and analyses that were deemed as appropriate before trial commencement are actually published (hence helping to find out selective reporting of outcomes). Unfortunately, the rate of registered trials in mental health interventions is low and, frequently, of poor quality. Conclusion: Clinicians should be prudent when interpreting the results of published trials and some meta-analyses - such as those conducted by scientists working for the sponsor company or those that only include published trials. Prescribers, however, should be confident when prescribing drugs following the summary of product characteristics, since regulatory agencies have access to all clinical trial results

Impact of a winter upwelling event on the distribution and transport of sardine (Sardina pilchardus) eggs and larvae off western Iberia: a retention mechanism.

A hydrographic and ichthyoplanktonic survey was conducted on the western Iberia Peninsula shelf-slope, with the objective of assessing the influence of wind-driven flow on the transport and survival of sardine early life history stages. Measurements were taken during a 2-week period of an 'upwelling-favourable' wind event. An offshore displacement of the surface low salinity Western Iberia Buoyant Plume (WIBP) was observed well off the shelf break. Below the plume, the current was southward over the mid- and inner-shelf. Offshore, the flow was poleward in the northern part of the survey area and equatorward in the south. A convergence zone was detected along the outer shelf and upper slope where the buoyant plume was apparently trapped and deepened. In general, eggs and larvae were distributed according to the spreading of the low salinity surface waters, and also within the convergent band. Older larvae were retained within the latter feature. The role of wind forcing on the plume and its interaction with the slope flow were analysed. A mechanism of larvae retention was formulated based on simplified models of the observed shelf-slope circulation

Physical–biological interactions in the life history of small pelagic fish in the Western Iberia Upwelling Ecosystem.

This paper reviews relevant investigations conducted in the Western Iberia Upwelling Ecosystem (WIUE) on the dynamics of small pelagic fish (SPF), its relationship to climate changes and processes related to the ‘ocean triad’ (enrichment, concentration, transport/retention). In the last decades, a decline in the productivity of several SPF species (e.g., sardine and horse mackerel) was observed in the WIUE, which is partially explained by environmental variability (e.g., changes in coastal upwelling). The main mechanism proposed to explain this decline is the increased frequency and intensity of upwelling events during the spawning season (winter) of these species, which is typically a period when convergence conditions prevail. Thus, this ‘anomalous’ situation promotes egg and larval dispersal away from the favourable coastal habitat (the shelf) and consequently has a negative impact on their survival and recruitment. However, the variability of local features like the Western Iberia Buoyant Plume (WIBP) and the Iberian Poleward Current (IPC) introduce important fluctuations in the transport patterns of the region, and could modulate the impact of these winter upwelling events in the survival of larvae. The retention on the shelf of larval sardine along convergence zones formed by the interaction of these two features plays an important role in their survival. Furthermore, the WIBP is a suitable environment for the growth of phytoplankton and for larval fish survival. From these findings it is clear that simplified Ekman transport models could not explain larval fish transport/retention patterns in this region and more realistic biophysical models should be used to simulate the local oceanographic conditions to understand larval dynamics and the success of recruitment of SPF in the Western Iberia

Preparation and evaluation of chitosan-hydrophobic silica composite microspheres: Role of hydrophobic silica in modifying their properties

International audienceBiodegradable microspheres used as controlled release systems are important in pharmaceutics. Chitosan biopolymer represents an attractive alternative to other biomaterials because of its significant physicochemical and biological behaviors. Chitosan microspheres are expected to become promising carrier systems for drug and vaccine delivery, especially via oral, mucosal and transdermal routes. Controlling the swelling rate and swelling capacity of the hydrogel and improving the fragile nature of microspheres under acidic conditions are the key challenges that need to be overcome to allow the use of chitosan microspheres for controlled or sustained release specially via these non-invasive administration routes. There have been many studies on the modification of chitosan microsphere structures with cross-linkers, blends with various kinds of polymers and new organic-inorganic hybrid systems in order to obtain some improved properties. In this work, microspheres composed of chitosan and nanosized hydrophobic silica commercialized under the name Aerosil R972 were generated by a method consisting of two steps: first, preparation of a macroscopically homogeneous chitosan-hydrophobic silica dispersion by an optimized procedure, and then drying. Spray drying was the technique used here. FTIR spectroscopy, X-ray powder diffraction, differential scanning calorimetry, thermal gravimetric analysis, Scanning Electron Microscopy (SEM) and high resolution Transmission Electron Microscopy (TEM) were used to characterize the microspheres, besides acid stability, moisture sorption capacity, release properties and biological assays. The chitosan-hydrophobic silica composite microspheres showed improved thermal degradation, lower water affinity, better acid stability and ability to retard rifampicin (drug model) release under simulated gastric conditions. In vitro biocompatibility studies indicated low cytotoxicity and low capacity to activate cell production of the pro-inflammatory mediator nitric oxide, encouraging further studies on the use of the new chitosan-hydrophobic silica composite microspheres as drug carrier systems via oral or nasal routes

Diabetes primary prevention program: new insights from data analysis of recruitment period

Primary Prevention of Diabetes Program in Buenos Aires Province evaluates the effectiveness of adopting healthy lifestyle to prevent type 2 diabetes (T2D) in people at high risk of developing it. We aimed to present preliminary data analysis of FINDRISC and laboratory measurements taken during recruitment of people for the Primary Prevention of Diabetes Program in Buenos Aires Province in the cities of La Plata, Berisso, and Ensenada, Argentina.Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Elgart, Jorge Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Bourgeois, Marcelo Javier. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro Interdisc.universitario Para la Salud; ArgentinaFil: Etchegoyen, Graciela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Fantuzzi, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Ré, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Ricart, Juan P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: García, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Giampieri, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Gonzalez, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Suárez Crivaro, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Kronsbein, Peter. Niederrhein University of Applied Sciences Mönchengladbach; AlemaniaFil: Angelini, Julieta M.. Universidad Nacional de La Plata; ArgentinaFil: Martinez, Camilo. Universidad Nacional de La Plata; ArgentinaFil: Martinez, Jorge. Universidad Nacional de La Plata; ArgentinaFil: Ricart, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Humanidades y Ciencias Sociales. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales; ArgentinaFil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; Argentin

Direct powder extrusion 3d printing of praziquantel to overcome neglected disease formulation challenges in paediatric populations

For the last 40 years, praziquantel has been the standard treatment for schistosomiasis, a neglected parasitic disease affecting more than 250 million people worldwide. However, there is no suitable paediatric formulation on the market, leading to off-label use and the splitting of commercial tablets for adults. In this study, we use a recently available technology, direct powder extrusion (DPE) three-dimensional printing (3DP), to prepare paediatric Printlets™ (3D printed tablets) of amorphous solid dispersions of praziquantel with Kollidon® VA 64 and surfactants (Span™ 20 or Kolliphor® SLS). Printlets were successfully printed from both pellets and powders obtained from extrudates by hot melt extrusion (HME). In vitro dissolution studies showed a greater than four-fold increase in praziquantel release, due to the formation of amorphous solid dispersions. In vitro palatability data indicated that the printlets were in the range of praziquantel tolerability, highlighting the taste masking capabilities of this technology without the need for additional taste masking excipients. This work has demonstrated the possibility of 3D printing tablets using pellets or powder forms obtained by HME, avoiding the use of filaments in fused deposition modelling 3DP. Moreover, the main formulation hurdles of praziquantel, such as low drug solubility, inadequate taste, and high and variable dose requirements, can be overcome using this technology

Evaluating semi-supervision methods for medical image segmentation: applications in cardiac magnetic resonance imaging

PURPOSE: Purpose Neural networks have potential to automate medical image segmentation but require expensive labeling efforts. While methods have been proposed to reduce the labeling burden, most have not been thoroughly evaluated on large, clinical datasets or clinical tasks. We propose a method to train segmentation networks with limited labeled data and focus on thorough network evaluation. APPROACH: We propose a semi-supervised method that leverages data augmentation, consistency regularization, and pseudolabeling and train four cardiac magnetic resonance (MR) segmentation networks. We evaluate the models on multiinstitutional, multiscanner, multidisease cardiac MR datasets using five cardiac functional biomarkers, which are compared to an expert’s measurements using Lin’s concordance correlation coefficient (CCC), the within-subject coefficient of variation (CV), and the Dice coefficient. RESULTS: The semi-supervised networks achieve strong agreement using Lin’s CCC (>0.8), CV similar to an expert, and strong generalization performance. We compare the error modes of the semi-supervised networks against fully supervised networks. We evaluate semi-supervised model performance as a function of labeled training data and with different types of model supervision, showing that a model trained with 100 labeled image slices can achieve a Dice coefficient within 1.10% of a network trained with 16,000+ labeled image slices. CONCLUSION: We evaluate semi-supervision for medical image segmentation using heterogeneous datasets and clinical metrics. As methods for training models with little labeled data become more common, knowledge about how they perform on clinical tasks, how they fail, and how they perform with different amounts of labeled data is useful to model developers and users

Phylodynamics of Hepatitis C Virus Subtype 2c in the Province of Córdoba, Argentina

The Hepatitis C Virus Genotype 2 subtype 2c (HCV-2c) is detected as a low prevalence subtype in many countries, except in Southern Europe and Western Africa. The current epidemiology of HCV in Argentina, a low-prevalence country, shows the expected low prevalence for this subtype. However, this subtype is the most prevalent in the central province of Córdoba. Cruz del Eje (CdE), a small rural city of this province, shows a prevalence for HCV infections of 5%, being 90% of the samples classified as HCV-2c. In other locations of Córdoba Province (OLC) with lower prevalence for HCV, HCV-2c was recorded in about 50% of the samples. The phylogenetic analysis of samples from Córdoba Province consistently conformed a monophyletic group with HCV-2c sequences from all the countries where HCV-2c has been sequenced. The phylogeographic analysis showed an overall association between geographical traits and phylogeny, being these associations significant (α = 0.05) for Italy, France, Argentina (places other than Córdoba), Martinique, CdE and OLC. The coalescence analysis for samples from CdE, OLC and France yielded a Time for the Most Common Recent Ancestor of about 140 years, whereas its demographic reconstruction showed a “lag” phase in the viral population until 1880 and then an exponential growth until 1940. These results were also obtained when each geographical area was analyzed separately, suggesting that HCV-2c came into Córdoba province during the migration process, mainly from Europe, which is compatible with the history of Argentina of the early 20th century. This also suggests that the spread of HCV-2c occurred in Europe and South America almost simultaneously, possibly as a result of the advances in medicine technology of the first half of the 20th century