Algorithms for optimizing drug therapy

BACKGROUND: Drug therapy has become increasingly efficient, with more drugs available for treatment of an ever-growing number of conditions. Yet, drug use is reported to be sub optimal in several aspects, such as dosage, patient's adherence and outcome of therapy. The aim of the current study was to investigate the possibility to optimize drug therapy using computer programs, available on the Internet. METHODS: One hundred and ten officially endorsed text documents, published between 1996 and 2004, containing guidelines for drug therapy in 246 disorders, were analyzed with regard to information about patient-, disease- and drug-related factors and relationships between these factors. This information was used to construct algorithms for identifying optimum treatment in each of the studied disorders. These algorithms were categorized in order to define as few models as possible that still could accommodate the identified factors and the relationships between them. The resulting program prototypes were implemented in HTML (user interface) and JavaScript (program logic). RESULTS: Three types of algorithms were sufficient for the intended purpose. The simplest type is a list of factors, each of which implies that the particular patient should or should not receive treatment. This is adequate in situations where only one treatment exists. The second type, a more elaborate model, is required when treatment can by provided using drugs from different pharmacological classes and the selection of drug class is dependent on patient characteristics. An easily implemented set of if-then statements was able to manage the identified information in such instances. The third type was needed in the few situations where the selection and dosage of drugs were depending on the degree to which one or more patient-specific factors were present. In these cases the implementation of an established decision model based on fuzzy sets was required. Computer programs based on one of these three models could be constructed regarding all but one of the studied disorders. The single exception was depression, where reliable relationships between patient characteristics, drug classes and outcome of therapy remain to be defined. CONCLUSION: Algorithms for optimizing drug therapy can, with presumably rare exceptions, be developed for any disorder, using standard Internet programming methods

Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes

BACKGROUND: Mouse and human skeletal muscle transcriptome profiles vary by muscle type, raising the question of which mouse muscle groups have the greatest molecular similarities to human skeletal muscle. METHODS: Orthologous (whole, sub-) transcriptome profiles were compared among four mouse-human transcriptome datasets: (M) six muscle groups obtained from three mouse strains (wildtype, mdx, mdx(5cv)); (H1) biopsied human quadriceps from controls and Duchenne muscular dystrophy patients; (H2) four different control human muscle types obtained at autopsy; and (H3) 12 different control human tissues (ten non-muscle). RESULTS: Of the six mouse muscles examined, mouse soleus bore the greatest molecular similarities to human skeletal muscles, independent of the latters' anatomic location/muscle type, disease state, age and sampling method (autopsy versus biopsy). Significant similarity to any one mouse muscle group was not observed for non-muscle human tissues (dataset H3), indicating this finding to be muscle specific. CONCLUSION: This observation may be partly explained by the higher type I fiber content of soleus relative to the other mouse muscles sampled

The experience of international nursing students studying for a PhD in the U.K: A qualitative study

<p>Abstract</p> <p>Background</p> <p>Educating nurses to doctoral level is an important means of developing nursing capacity globally. There is an international shortage of doctoral nursing programmes, hence many nurses seek their doctorates overseas. The UK is a key provider of doctoral education for international nursing students, however, very little is known about international doctoral nursing students' learning experiences during their doctoral study. This paper reports on a national study that sought to investigate the learning expectations and experiences of overseas doctoral nursing students in the UK.</p> <p>Methods</p> <p>Semi-structured qualitative interviews were conducted in 2008/09 with 17 international doctoral nursing students representing 9 different countries from 6 different UK universities. Data were analysed thematically. All 17 interviewees were enrolled on 'traditional' 3 year PhD programmes and the majority (15/17) planned to work in higher education institutions back in their home country upon graduation.</p> <p>Results</p> <p>Studying for a UK PhD involved a number of significant transitions, including adjusting to a new country/culture, to new pedagogical approaches and, in some cases, to learning in a second language. Many students had expected a more structured programme of study, with a stronger emphasis on professional nursing issues as well as research - akin to the professional doctorate. Students did not always feel well integrated into their department's wider research environment, and wanted more opportunities to network with their UK peers. A good supervision relationship was perceived as the most critical element of support in a doctoral programme, but good relationships were sometimes difficult to attain due to differences in student/supervisor expectations and in approaches to supervision. The PhD was perceived as a difficult and stressful journey, but those nearing the end reflected positively on it as a life changing experience in which they had developed key professional and personal skills.</p> <p>Conclusions</p> <p>Doctoral programmes need to ensure that structures are in place to support international students at different stages of their doctoral journey, and to support greater local-international student networking. Further research is needed to investigate good supervision practice and the suitability of the PhD vis a vis other doctoral models (e.g. the professional doctorate) for international nursing students.</p

Модернизация технологического процесса механической обработки детали ступица КЗК 12-0602605 с разработкой проекта участка цеха, средств технологического оснащения и исследованием электрохимического шлифования

Bimetallic Pd/Cu and Pd/Ag catalytic systems were used for borylation of propargylic alcohol derivatives. The substrate scope includes even terminal alkynes. The reactions proceed stererospecifically with formal S(N)2' pathways to give allenyl boronates. Opening of propargyl epoxides leads to 1,2-diborylated butadienes probably via en allenylboronate intermediate.AuthorCount:4;</p

Chemical synthesis, characterisation and in vitro and in vivo metabolism of the synthetic opioid MT-45 and its newly identified fluorinated analogue 2F-MT-45 with metabolite confirmation in urine samples from known drug users

© 2018 The Author(s) Purpose: The detection of a novel psychoactive substance, 2F-MT-45, a fluorinated analogue of the synthetic opioid MT-45, was reported in a single seized tablet. MT-45, 2F-, 3F- and 4F-MT-45 were synthesised and reference analytical data were reported. The in vitro and in vivo metabolisms of MT-45 and 2F-MT-45 were investigated. Method: The reference standards and seized sample were characterised using nuclear magnetic resonance spectroscopy, ultra-performance liquid chromatography–quadrupole time of flight mass spectrometry, gas chromatography–mass spectrometry, attenuated total reflectance-Fourier transform infrared spectroscopy and Raman spectroscopy. Presumptive tests were performed and physicochemical properties of the compounds determined. Metabolite identification studies using human liver microsomes, human hepatocytes, mouse hepatocytes and in vivo testing using mice were performed and identified MT-45 metabolites were confirmed in authentic human urine samples. Results: Metabolic pathways identified for MT-45 and 2F-MT-45 were N-dealkylation, hydroxylation and subsequent glucuronidation. The major MT-45 metabolites identified in human in vitro studies and in authenticated human urine were phase I metabolites and should be incorporated as analytical targets to existing toxicological screening methods. Phase II glucuronidated metabolites were present in much lower proportions. Conclusions: 2F-MT-45 has been detected in a seized tablet for the first time. The metabolite identification data provide useful urinary metabolite targets for forensic and clinical testing for MT-45 and allows screening of urine for 2F-MT-45 and its major metabolites to determine its prevalence in case work

Enabling overweight children to improve their food and exercise habits -school nurses counselling in multilingual settings Enabling overweight children to improve their food and exercise habits -school nurses counselling in multilingual settings Enabling

Abstract Aims and objectives The study aimed at analysing school nurses&apos; counselling of overweight and obese children in settings with many immigrants, focusing on content concerning food and physical activity and how this was communicated. Background For people with a predisposition for overweight, the weight control process requires cognitive skills. School nurses&apos; counselling of overweight children has the potential to support this process by enabling personal resources in the children and their families. However, there is uncertainty among nurses about how to conduct supportive counselling. Design An explorative design was used when collecting and analysing data. Method Twenty-two counselling sessions between eight school nurses and 20 overweight children were audio-recorded and analysed using qualitative content analysis. Most of the participating schools represented areas with low socioeconomic status and a high proportion of immigrants and refugees. Results Less adequate skills in enabling resources in the children and their parents were observed. Concurrently, school nurses provided inadequate explanations about food and physical activity. Topics related to general nutrition models were frequently communicated as general advice instead of individually tailored counselling. Counselling families with other languages and food cultures than the traditional Swedish created additional difficulties. Conclusions Improved nutritional knowledge for nurses may enhance their skills in enabling children&apos;s and families&apos; resources. School nurses should be provided with opportunities to cooperate with other professions in counteracting overweight. Relevance to clinical practice Our findings demonstrate a relationship between content skills and person-centeredness in the counselling. This highlights the importance of interprofessional collaboration to ensure a high quality of lifestyle counselling. School health authorities should give high priority to facilitating school nurses&apos; evidence-based continuing education

Childhood obesity and prevention in different socio-economic contexts

Objective To assess recent trends in obesity, health beliefs, and lifestyles in Swedish schoolchildren, with focus on socioeconomic disparities. Method The study was conducted in two areas with high and low socioeconomic status (SES). 340 11–12 year olds participated in three cross-sectional surveys assessing food-related behaviours, physical activity and health beliefs, together with anthropometric examinations. Comparisons were made before and after a community-based intervention (2003 versus 2008) within the low-SES school, and between the low and high-SES school (2008 only). Results In the low-SES school BMI z-score decreased over 5 years (0.80 vs 0.46) as did the percentage of children frequently consuming sweet drinks (43.5 vs 26.8%), statistically significant in girls only (p &lt; 0.05). Children increasingly perceived benefits of healthy life-styles (37 vs 55%). In 2008, consumption of breakfast, vegetables, sweets and sweet drinks differed between schools, as did screen-time and physical activity, all in favour of the high SES-school where the obesity-prevalence was significantly lower (0.8 vs 6.7%). Conclusion Positive changes in diet and weight status were observed, especially in girls, within a low-income multi-ethnic community undergoing a health promotion intervention. Our results underscore the multifactorial etiology of childhood obesity and the importance of continuing tailored, gender-sensitive prevention efforts.Funding agencies|Region Vastra Gotaland, Sweden||Swedish Council of Working Life and Social Research (FAS)|