A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice

This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same drug

Emergence of 3D Printed Dosage Forms: Opportunities and Challenges

The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such as extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, including design flexibility and control and manufacture which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry

Variation in outcomes among 24/7 percutaneous coronary intervention centres for patients resuscitated from out-of-hospital cardiac arrest.

BackgroundPatients treated at 24/7 percutaneous coronary intervention (PCI) centres following out-of-hospital cardiac arrest (OHCA) have better outcomes than those treated at non-24/7 PCI centres. However, variation in outcomes between 24/7 PCI centres is not well studied.ObjectivesTo evaluate variation in outcomes among 24/7 PCI centres and to assess stability of 24/7 PCI centre performance.MethodsAdult patients in the California Office of Statewide Health Planning and Development Patient Discharge Database with a "present on admission" diagnosis of cardiac arrest admitted to a 24/7 PCI centre from 2011 to 2015 were included. Primary outcome was good neurologic recovery at hospital discharge. Secondary outcomes were survival to hospital discharge, cardiac catheterisation, and DNR orders within 24 h. Data were analysed using mixed effects logistic regression models. Hospitals were ranked each year and overall.ResultsOf 27,122 patients admitted to 128 24/7 PCI centres, 41% (11,184) survived and 27% (7188) had good neurologic recovery. Adjusted rates of good neurologic recovery (18%-39%; p,0.001), survival (32%-51%; p < 0.0001), cardiac catheterisation (11%-49%; p < 0.0001) and DNR orders within 24 h (4.8%-49%; p < 0.0001) varied between 24/7 PCI centres. For the 26 hospitals with mean good neurologic rankings in the top or bottom tenth during 2011-2013, 14 (54%) remained in their respective tenth for 2014-2015.ConclusionSignificant variation exists between 24/7 PCI centres in good neurologic recovery following OHCA and persists over time. Future studies should evaluate hospital-level factors that contribute to these differences in outcomes between 24/7 PCI centres

Variation in outcomes among 24/7 percutaneous coronary intervention centres for patients resuscitated from out-of-hospital cardiac arrest.

BackgroundPatients treated at 24/7 percutaneous coronary intervention (PCI) centres following out-of-hospital cardiac arrest (OHCA) have better outcomes than those treated at non-24/7 PCI centres. However, variation in outcomes between 24/7 PCI centres is not well studied.ObjectivesTo evaluate variation in outcomes among 24/7 PCI centres and to assess stability of 24/7 PCI centre performance.MethodsAdult patients in the California Office of Statewide Health Planning and Development Patient Discharge Database with a "present on admission" diagnosis of cardiac arrest admitted to a 24/7 PCI centre from 2011 to 2015 were included. Primary outcome was good neurologic recovery at hospital discharge. Secondary outcomes were survival to hospital discharge, cardiac catheterisation, and DNR orders within 24 h. Data were analysed using mixed effects logistic regression models. Hospitals were ranked each year and overall.ResultsOf 27,122 patients admitted to 128 24/7 PCI centres, 41% (11,184) survived and 27% (7188) had good neurologic recovery. Adjusted rates of good neurologic recovery (18%-39%; p,0.001), survival (32%-51%; p < 0.0001), cardiac catheterisation (11%-49%; p < 0.0001) and DNR orders within 24 h (4.8%-49%; p < 0.0001) varied between 24/7 PCI centres. For the 26 hospitals with mean good neurologic rankings in the top or bottom tenth during 2011-2013, 14 (54%) remained in their respective tenth for 2014-2015.ConclusionSignificant variation exists between 24/7 PCI centres in good neurologic recovery following OHCA and persists over time. Future studies should evaluate hospital-level factors that contribute to these differences in outcomes between 24/7 PCI centres

Hemoglobin Interlaken in combination with beta thalassemia trait

We report a rare a1 globin gene variant (Hb Interlaken) found in a 63-year-old woman of Italian ancestry living in Buenos Aires Province, Argentina. The variant, a missense mutation at cd15 (GGT &rarr; GAT) causing a Gly &rarr;Asp amino acid substitution and also known as Hb J Oxford, was found in combination with the common thalassemia trait cd 39 (C&rarr;T). The clinical picture of the patient was that of a b-thalassemia trait.&nbsp;我们曾报道在阿根廷布宜诺斯艾利斯一名63岁意大利血统的妇女体内发现罕有的1珠蛋白基因（因特拉肯血红蛋白）变体。研究发现该变体是导致Gly &rarr; Asp氨基酸置的错义突变，也称为Hb J Oxford，与常见的地中海贫血性症cd 39 （C &rarr; T）有关。该患者临床症状与乙型地中海贫血特征相同。</p

Ancient Hunting Strategies of Wild Camelids Through the Study of Multiple Lines of Archaeological Evidences at Southern Argentine Puna

In recent decades, wild camelids hunting strategies have been a topic ofinterest for several research groups in Argentina?s southern Puna in NorthwesternArgentina. In this chapter, we present a synthesis of hunting strategies models thatwould have been implemented at Antofagasta de la Sierra (Catamarca, Argentina)in a long-lasting account that covers the entire Holocene. The models we will treatwere defined for two discrete areas within this Puna environment: Quebrada Seca andthe Antofalla ravine. For both areas, different hunting models were postulated basedon the combination of a series of variables such as landscape features and weaponsystems. They varied in time and space for both areas, although vicuñas were acommon factor as hunting prey. Our interest here lies, then, in reflexively evaluatingthese models in order to form a theoretical, methodological, and technical basis forthe study of pre-Hispanic hunting practices in the higher Andes environment.Fil: Moreno, Enrique Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Catamarca. Universidad Nacional de Catamarca. Centro de Investigaciones y Transferencia de Catamarca; ArgentinaFil: Martinez, Jorge Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucumán. Instituto Superior de Estudios Sociales; ArgentinaFil: Aschero, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucumán. Instituto Superior de Estudios Sociales; Argentin

Application of xylitol in food formulations and benefits for health

Sugar substitution by any sweetener in the food industry is usually made taking into account the calories of the sweetener, the possibility of using it in diets for weight reduction or control, and the degree of similarity between its flavor and the traditional sugar. Among the existent alternative sweeteners, xylitol has attracted the attention of food manufacturers since it has sweetening power similar to sucrose but with lower caloric value, and can be consumed by diabetics. Nowadays, a variety of products containing xylitol in the formulation can be found in the market. Most of them are especially formulated for people with insulin-deficiency. Another important advantage of xylitol ingestion when compared to the traditional sugar is that it promotes several benefits for human health, acting both on the prevention and/or treatment of diseases. Due to these important properties, the use of xylitol in food products is a market in great expansion. The current applications of xylitol in food formulations are summarized in this chapter. The benefits to health promoted by its ingestion are also presented and discussed.(undefined