Laboratory aid to the diagnosis and therapy of infection in the neonate

Despite the advances in perinatal and neonatal care and use of newer potent antibiotics, the incidence of neonatal sepsis remains high and the outcome is still severe. For years, investigators have sought a test or panel of tests able to identify septic neonates accurately and rapidly in order to obtain an early diagnosis and develop a specific effective treatment for a successful outcome. In addition to the standard procedures (blood, CSF, and urine cultures), such panels have included a combination of haematological investigations (total, differential and immature cell counts), and levels of acute-phase reactants (principally CRP and procalcitonin), and cytokines (such as IL-6 or neutrophil CD64). Furthermore, the science of proteomics and genomics has been applied to the search for bio-markers, production of protein profiles and genetic polymorphisms that can rapidly help the prediction, early diagnosis, and treatment of human diseases, but, for now, data are as yet insufficient to confirm their validity

Cost-utility analysis of palivizumab in Italy: results from a simulation model in the prophylaxis of respiratory syncytial virus infection (RSV) among high-risk preterm infants

Abstract Introduction The aim of this study was to assess the cost-utility of palivizumab versus no prophylaxis in the prevention of respiratory syncytial virus infection among high-risk preterm infants. Methods We used and adapted a pre-existent model in which two cohorts of patients received palivizumab or no prophylaxis. The patients were followed for their expected lifetimes. The economic evaluation was conducted from the perspective of the Italian National Health Service. We considered Life-Years Gained (LYGs), Quality-Adjusted Life-Years (QALYs) and direct medical costs (pharmacological treatment, hospitalization, recurrences for wheezing, etc.). LYGs and QALYs were based on the results of a double blind cohort study with prospective follow-up and direct medical costs were based on Italian treatment patterns. Benefits and costs were discounted at 3%. Costs were assessed in 2007 Euros. Sensitivity and threshold analysis on key clinical and economic parameters were performed. Result For the two cohorts, the expected life-years (per patient) with palivizumab versus no prophylaxis were 29.842 and 29.754 years, respectively. Quality-adjusted life years (per patient) with palivizumab were 29.202, and for no prophylaxis were 29.043. The expected cost (per patient) was € 6,244.20 with palivizumab and € 4,867.70 with no prophylaxis. We calculated for palivizumab versus no prophylaxis the incremental cost per LYG and per QALY gained. It was € 15,568.65 and € 8,676.74, respectively. Conclusion This study suggests that, compared with no prophylaxis, palivizumab is cost-effective in the prevention of respiratory syncytial virus infection among high risk preterm infants.</p

Analysis and modeling of swelling and erosion behavior for pure HPMC tablet

This work is focused on the transport phenomena which take place during immersion in water of pure hydroxypropylmethylcellulose tablets. The water uptake, the swelling and the erosion during immersion were investigated in drug-free systems, as a preliminary task before to undertake the study of drug-loaded ones. The tablets, obtained by powder compression, were confined between glass slabs to allow water uptake only by lateral surface and then immersed in distilled water at 37 °C, with simultaneous video-recording. By image analysis the normalized light intensity profiles were obtained and taken as a measure of the water mass fraction. The time evolutions of the total tablet mass, of the water mass and of the erosion radius were measured, too. Thus a novel method to measure polymer and water masses during hydration was pointed out. Then, a model consisting in the transient mass balance, accounting for water diffusion, diffusivity change due to hydration, swelling and erosion, was found able to reproduce all experimental data. Even if the model was already used in literature, the novelty of our approach is to compare model predictions with a complete set of experimental data, confirming that the main phenomena were correctly identified and described

Swelling of cellulose derivative (HPMC) matrix systems for drug delivery

The water swellable hydrogels are commonly used in the production of solid pharmaceutical dosage systems for oral administration (matrices). Their use allows to obtain the controlled drug release. The key role is played by the transport phenomena which take place: water up-take, gel swelling and erosion, increase in diffusivity due to hydration. Thus, knowledge of these phenomena is fundamental in designing and realizing the pharmaceutical systems. In this work, tablets made of pure hydrogel, HydroxyPropyl-MethylCellulose (HPMC), were produced and immersed in a thermostatic bath filled with stirred distilled water (37 °C). The water up-take was allowed only by radial direction (from the lateral surface) by confining the tablet between two glass slides. Two distinct methods, an optical technique already described in a previous work, and a gravimetric procedure described here, were applied to measure the water concentration profiles along the radial direction in the tablets. The data obtained were used both to clarify the nature of the transport phenomena involved, and to perform a better tuning of a mathematical model previously proposed. doi:10.1016/j.carbpol.2009.05.00

Investigation of Pluronic (c) F127-Water Solutions Phase Transitions by DSC and Dielectric Spectroscopy

The water solutions of the block copolymers PEOn-PPOm-PEOn, known as pluronics, show a complex thermal behavior, since they are liquid at low temperature (5C), and they can give soft gel when heated at body temperature (37C). These properties are of great interest in biomedical applications. To properly design these applications, a prerequisite is the knowledge of the thermodynamics—how much—and of the kinetics—how fast—with which these transformations take place. In this work, solutions of F127 (the copolymer for which n ¼ 100 and m ¼ 65) were studied by varying the concentration and the temperature and analyzing their behavior when heated under several heating rates. The studies were performed by differential scanning calorimetry (DCS) and dielectric spectroscopy. The investigations carried out under equilibrium conditions allowed us to determine the thermodynamics of the phase transitions, whereas the investigations carried out under varying conditions allowed us to quantify the kinetics of the phase transitions. Empirical models were also proposed to describe both the thermodynamics and the kinetics observed

MALAT1 as a Regulator of the Androgen-Dependent Choline Kinase A Gene in the Metabolic Rewiring of Prostate Cancer

Simple Summary Despite the rapid advance in cancer therapies, treatment-resistant relapse remains a significant challenge in cancer treatment. Acquired resistance arises during or after treatment administration, and is usually the main contributor to relapse. For example, prostate cancer, the most frequent type of cancer in the elderly male population, frequently develops into aggressive forms resistant to chemical and hormonal therapies. In this condition, the so-called "cholinic phenotype" that is characterized by the overexpression of choline kinase alpha (CHKA) and increased phosphocholine levels leads to aberrant lipid metabolism. Our work demonstrates that CHKA, which is necessary for membrane phospholipid synthesis, is a target of the long non-coding RNA MALAT1. This study helps to further decipher how MALAT1 affects the regulation of crucial phospholipid/sphingolipid metabolic enzymes, as well as how the androgen receptor pathway is involved in MALAT1-dependent transcriptional regulation. Background. Choline kinase alpha (CHKA), an essential gene in phospholipid metabolism, is among the modulated MALAT1-targeted transcripts in advanced and metastatic prostate cancer (PCa). Methods. We analyzed CHKA mRNA by qPCR upon MALAT1 targeting in PCa cells, which is characterized by high dose-responsiveness to the androgen receptor (AR) and its variants. Metabolome analysis of MALAT1-depleted cells was performed by quantitative High-resolution 1 H-Nuclear Magnetic Resonance (NMR) spectroscopy. In addition, CHKA genomic regions were evaluated by chromatin immunoprecipitation (ChIP) in order to assess MALAT1-dependent histone-tail modifications and AR recruitment. Results. In MALAT1-depleted cells, the decrease of CHKA gene expression was associated with reduced total choline-containing metabolites compared to controls, particularly phosphocholine (PCho). Upon MALAT1 targeting a significant increase in repressive histone modifications was observed at the CHKA intron-2, encompassing relevant AR binding sites. Combining of MALAT1 targeting with androgen treatment prevented MALAT1-dependent CHKA silencing in androgen-responsive (LNCaP) cells, while it did not in hormone-refractory cells (22RV1 cells). Moreover, AR nuclear translocation and its activation were detected by confocal microscopy analysis and ChIP upon MALAT1 targeting or androgen treatment. Conclusions. These findings support the role of MALAT1 as a CHKA activator through putative association with the liganded or unliganded AR, unveiling its targeting as a therapeutic option from a metabolic rewiring perspective

Modeling the drug release from hydrogel-based matrices

In this work the behavior of hydrogel-based matrices, the most widespread systems for oral controlled release of pharmaceuticals, has been mathematically described. In addition, the calculations of the model have been validated against a rich set of experimental data obtained working with tablets made of hydroxypropyl methylcellulose (a hydrogel) and theophylline (a model drug). The model takes into account water uptake, hydrogel swelling, drug release, and polymer erosion. The model was obtained as an improvement of a previous code, describing the diffusion in concentrated systems, and obtaining the erosion front (which is a moving boundary) from the polymer mass balance (in this way, the number of fitting parameters was also reduced by one). The proposed model was found able to describe all the observed phenomena, and then it can be considered a tool with predictive capabilities, useful in design and testing of new dosage systems based on hydrogels

The clinical effectiveness of an integrated multidisciplinary evidence-based program to prevent intraoperative pressure injuries in high-risk children undergoing long-duration surgical procedures: a quality improvement study

The prevention of hospital-acquired pressure injuries (HAPIs) in children undergoing long-duration surgical procedures is of critical importance due to the potential for catastrophic sequelae of these generally preventable injuries for the child and their family. Long-duration surgical procedures in children have the potential to result in high rates of HAPI due to physiological factors and the difficulty or impossibility of repositioning these patients intraoperatively. We developed and implemented a multi-modal, multi-disciplinary translational HAPI prevention quality improvement program at a large European Paediatric University Teaching Hospital. The intervention comprised the establishment of wound prevention teams, modified HAPI risk assessment tools, specific education, and the use of prophylactic dressings and fluidized positioners during long-duration surgical procedures. As part of the evaluation of the effectiveness of the program in reducing intraoperative HAPI, we conducted a prospective cohort study of 200 children undergoing long-duration surgical procedures and compared their outcomes with a matched historical cohort of 200 children who had undergone similar surgery the previous year. The findings demonstrated a reduction in HAPI in the intervention cohort of 80% (p &lt; 0.01) compared to the comparator group when controlling for age, pathology, comorbidity, and surgical duration. We believe that the findings demonstrate that it is possible to significantly decrease HAPI incidence in these highly vulnerable children by using an evidence-based, multi-modal, multidisciplinary HAPI prevention strategy

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS &lt; 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders