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

Consumption of alcohol, cigarettes and illegal substances among physicians and medical students in Brandenburg and Saxony (Germany)

<p>Abstract</p> <p>Background</p> <p>Patients regard health care professionals as role models for leading a healthy lifestyle. Health care professionals' own behaviour and attitudes concerning healthy lifestyle have an influence in counselling patients. The aim of this study was to assess consumption of alcohol, cigarettes and illegal substances among physicians and medical students in two German states: Brandenburg and Saxony.</p> <p>Methods</p> <p>Socio-demographic data and individual risk behaviour was collected by an anonymous self-administered questionnaire. Physicians were approached via mail and students were recruited during tutorials or lectures.</p> <p>Results</p> <p>41.6% of physicians and 60.9% of medical students responded to the questionnaire; more than 50% of the respondents in both groups were females. The majority of respondents consumed alcohol at least once per week; median daily alcohol consumption ranged from 3.88 g/d (female medical students) to 12.6 g/d (male physicians). A significantly higher percentage of men (p < 0.05) reported hazardous or harmful drinking compared to women. A quarter of all participating physicians and one third of all students indicated unhealthy alcohol-drinking behaviour. The majority of physicians (85.7%) and medical students (78.5%) were non-smokers. Both groups contained significantly more female non-smokers (p < 0.05). Use of illegal substances was considerably lower in physicians (5.1%) than medical students (33.0%). Male students indicated a significantly (p < 0.001) higher level of illegal drug-use compared to female students.</p> <p>Conclusion</p> <p>More than one third of the medical students and health care professionals showed problematic alcohol-drinking behaviour. Although the proportion of non-smokers in the investigated sample was higher than in the general population, when compared to the general population, medical students between 18-24 reported higher consumption of illegal substances.</p> <p>These results indicate that methods for educating and promoting healthy lifestyle, particularly with respect to excessive alcohol consumption, tobacco use and abuse of illegal drugs should be considered.</p

Year in review in Intensive Care Medicine 2009: I. Pneumonia and infections, sepsis, outcome, acute renal failure and acid base, nutrition and glycaemic control

Journal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). METHODS/DESIGN: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure 6430 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. DISCUSSION: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration metho

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Margem de papel ou corpo despedaçado do texto On the margins of the paper, or the text's shattered body

O artigo propõe-se a refletir a travessia dos signos do universo socioeconômico do Estado do Mato Grosso do Sul e a constituição da identidade e representação em textos diversos da literatura e da crítica cultural que tematizam a questão. Adotando uma perspectiva baseada na crítica cultural e/ou nos estudos culturais, o artigo analisa a complexidade da relação entre narração e representação, elaborando uma síntese da noção de região num espaço que compreende o entorno do pantanal sul-mato-grossense. As conclusões do trabalho indicam que a travessia e circulação dos signos culturais se dão enquanto agenciamento discursivo, que ora reflete o objeto da representação, ora o mascara, pois a natureza desse objeto se demonstra enquanto tecido emblemático de um corpo despedaçado.<br>This article reflects on the passage of signs through the socioeconomic universe of the State of Mato Grosso do Sul, Brazil, and the establishment of identity and representation in various texts from both the literature and cultural critique dealing with the issue. Adopting a perspective based on cultural critique and/or cultural studies, the article analyzes the complexity of the relationship between narration and representation, elaborating a synthesis of the notion of region in the area around what is known as the Pantanal (Swampland) in Mato Grosso do Sul. The study concludes that the passage and circulation of cultural signs occur as a discursive agency which alternately reflects both the object of representation and the mask, since the nature of this object appears as the emblematic fabric of a shattered body