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991.
Helmut Schütz 《European journal of clinical pharmacology》2015,71(3):271-281
Purpose
The aim of this study is to assess the current status of non-fixed sample size designs in bioequivalence trials with a focus on two-stage adaptive approaches.Methods
We searched PubMed and Google Scholar from inception to October 2014. Regulatory guidelines were obtained from the public domain. Different methods were compared by Monte Carlo simulations for their impact on the patient’s and producer’s risks.Results
Add-on designs, group sequential designs and adaptive two-stage sequential designs are currently accepted to demonstrate bioequivalence in various regulations. All three approaches may inflate the patient’s risk if applied inconsiderately. Direct transfer of methods developed for superiority testing to bioequivalence is not warranted. Published two-stage frameworks maintain the type I error and generally the desired power. Adaptation based on the observed T/R ratio observed in the first stage should be applied with caution. Monte Carlo simulations are an efficient tool to explore the operating characteristics of methods.Conclusions
Validated two-stage frameworks can be applied without requiring the sponsor to perform own simulations—which could further improve power based on additional assumptions. Two-stage designs are both ethical and economical alternatives to fixed sample designs.992.
Yan Zhou Guoqiang Zhang Zhi Rao Yang Yang Qian Zhou Hongyan Qin Yuhui Wei Xin’an Wu 《Archives of pharmacal research》2015,38(7):1325-1335
Venlafaxine (VLX) could be pumped out of the brain by P-glycoprotein (P-gp). Moreover, the expression of P-gp distributed in blood–brain barrier could be significantly induced by VLX. Thus, P-gp could be considered as the nature barrier for delivering of VLX to the brain. The aim of this study was to investigate whether the efflux function and increased expression of P-gp could be reversed by utilizing solid lipid nanoparticles (SLN). VLX solid lipid nanoparticles (VLX ? SLN) were prepared and evaluated. Pharmacokinetics and brain distribution of VLX in different formulations were conducted after oral or intravenous administration. P-gp efflux function to VLX was evaluated by the brain uptake amount of VLX, while P-gp expression was investigated by Western blotting. Results indicated that the entrapment, mean size and zata potential of VLX ? SLN was 74.9 ± 3.0 %, 186.3 ± 69.26 nm and ?22.8 ± 7.78 mv, respectively. After vein injection of VLX formulations, the brain uptake amount of VLX from VLX ? SLN was significantly higher than that of VLX solution, VLX solution with empty SLN (VLX+ empty SLN) and VLX solution with Verapamil (VLX + Ver), respectively. Furthermore, the protein mass of P-gp in VLX ? SLN treated group was the lowest among all the investigated groups. These results indicated that SLN could overcome P-gp and achieve brain target by intravenous administration. 相似文献
993.
Cilostazol is practically insoluble in water and thus results in poor bioavailability. Only a few approaches have been reported for improving the bioavailability of cilostazol. Solid dispersion technique via solvent evaporation method was applied to improve the solubility and dissolution of cilostazol. Various polymers, mixture of polymer and surfactant, and mixture of polymers were screened as a carrier for the solid dispersion. Solubility of cilostazol was improved significantly when Eudragit® L100 was used as a carrier. However, addition of surfactant to Eudragit® L100 decreased the solubility slightly. Whereas, the mixture of Eudragit® L100 and Eudragit® S100 as a carrier system further increased the solubility. Based on the highest solubility obtained among the carriers screened, 1:1 ratio of Eudragit® L100 and Eudragit® S100 was selected as a carrier, and drug to carrier ratio was optimized to 1:5. Differential scanning calorimetry and X-ray diffraction studies showed that the characteristic peak of cilostazol disappeared in the solid dispersion, indicating that cilostazol existed in amorphous form in this formulation. Spray drying method was superior to vacuum drying method in terms of dissolution rate. Meanwhile, it was observed that the disintegration rate and the concentration of polymer had some effect on the crystallization of cilostazol in dissolution medium. Tablet formulation containing spray dried solid dispersion showed significant improvement in dissolution as compared to the commercial tablet. 相似文献
994.
Emanuel Raschi Elisabetta Poluzzi Ariola Koci Francesco Salvo Antoine Pariente Maurizio Biselli Ugo Moretti Nicholas Moore Fabrizio De Ponti 《British journal of clinical pharmacology》2015,80(2):285-293
Aim
We assessed the hepatic safety of novel oral anticoagulants (NOACs) analyzing the publicly available US-FDA adverse event reporting system (FAERS).Methods
We extracted reports of drug-induced liver injury (DILI) associated with NOACs, including acute liver failure (ALF) events. Based on US marketing authorizations, we performed disproportionality analyses, calculating reporting odds ratios (RORs) with 95% confidence interval (CI), also to test for event- and drug-related competition bias, and case-by-case evaluation for concomitant medications.Results
DILI reports represented 3.7% (n = 146) and 1.7% (n = 222) of all reports for rivaroxaban and dabigatran, respectively. No statistically significant association was found for dabigatran, in primary and secondary analyses. Disproportionality signals emerged for rivaroxaban in primary analysis (ALF: n = 25, ROR = 2.08, 95% CI 1.34, 3.08). In a large proportion of DILI reports concomitant hepatotoxic and/or interacting drugs were recorded: 42% and 37% (rivaroxaban and dabigatran, respectively), especially statins, paracetamol and amiodarone. Among ALF reports, fatal outcome occurred in 49% of cases (44% and 51%, rivaroxaban and dabigatran, respectively), whereas rapid onset of the event (<1 week) was detected in 46% of patients (47% and 44%, respectively).Conclusions
The disproportionality signal for rivaroxaban calls for further comparative population-based studies to characterize and quantify the actual DILI risk of NOACs, taking into account drug- and patient-related risk factors. As DILI is unpredictable, our findings strengthen the role of (a) timely pharmacovigilance to detect post-marketing signals of DILI through FAERS and other data sources, (b) clinicians to assess early, on a case-by-case basis, the potential responsibility of NOACs when they diagnose a liver injury. 相似文献995.
Anna M. de Haan Albert E. Boon Robert R. J. M. Vermeiren Machteld Hoeve Joop T. V. M. de Jong 《Child & youth care forum》2015,44(1):1-16
Background
Dropout from child and adolescent psychotherapy is a common phenomenon which can have negative consequences for the individual later in life. It is therefore important to gain insight on dropout risk factors.Objective
Several potential risk factors [ethnic minority status, a lower socioeconomic status (SES), and higher problem severity] were analyzed in present study. Innovations are that these risk factors were examined for children and adolescents separately, and a distinction was made in termination status between referred patients, dropouts and completers.Methods
For ethnic majority and minority outpatient children (age 5–11, n = 399) and adolescents (age 12–20, n = 352) problem severity, ethnic background, SES, and treatment termination status (completer, dropout, referral) were specified. Multinomial logistic regression models were used as main method of analysis.Results
For children, a Moroccan/Turkish ethnicity and higher externalizing scores were risk factors for being referred. For adolescents, a Surinamese/Antillean ethnicity, being female, being older, and lower parental SES occupation levels were risk factors for dropout.Conclusions
Different dropout risk profiles emerged for children versus adolescents, and for dropouts versus referrals. Also, it depended on the specific ethnic background whether ethnic minority status was a predictor for dropout, and the relationship between SES and termination status differed by whether parental SES occupation or parental SES education were used as SES indicator. Professionals should thus be aware of these potential risk factors for dropout or referral when treating children and adolescents.996.
Akane Anai Kimiyo Ueda Koichi Harada Takahiko Katoh Kumiko Fukumoto Chang-Nian Wei 《Environmental health and preventive medicine》2015,20(6):447-454
Objectives
To assess the difference between self-reported and measured weight values in Japanese men and women and to determine the underlying determinants of the differences between self-reported and measured values.Methods
The data were collected from 363 general Japanese individuals aged 16–88 years living in Kumamoto prefecture. Participants completed a self-administered questionnaire designed for this study with self-reported weight and height values. Measured weight and height were measured immediately after questionnaire completion. Paired t-tests identified differences between self-reported and measured values by sex. Multiple-stepwise regression analysis examined the independent variables’ effects on the differences between self-reported and measured weights.Results
Significant differences were found between self-reported and measured values for both sexes (p < 0.001). There was a significant negative relationship between the difference in an individual’s self-reported and measured weight in each sex, with higher measured weight individuals more likely to underestimate their weight. Multiple-stepwise regression analysis models explained 12.1 % (p < 0.01), 11.3 % (p < 0.01), and 5.6 % (p < 0.01) of the variance in all participants, men, and women, respectively. Significant effects were found for age, weight measurement frequency, and measured weight in total participants, weight measurement frequency, and measured weight for men, and age for women.Conclusions
In this study, the mean absolute value of the weight and height variances proved the unreliability of self-reported weight and height values. This study’s findings suggest self-reported weight inaccuracy especially for obese populations. This should be adjusted when using it in epidemiological studies and healthcare planning.997.
Marianne Eisinger-Watzl Andrea Straßburg Josa Ramünke Carolin Krems Thorsten Heuer Ingrid Hoffmann 《European journal of nutrition》2015,54(3):343-354
Purpose
To further characterise the performance of the diet history method and the 24-h recalls method, both in an updated version, a comparison was conducted.Methods
The National Nutrition Survey II, representative for Germany, assessed food consumption with both methods. The comparison was conducted in a sample of 9,968 participants aged 14–80. Besides calculating mean differences, statistical agreement measurements encompass Spearman and intraclass correlation coefficients, ranking participants in quartiles and the Bland–Altman method.Results
Mean consumption of 12 out of 18 food groups was higher assessed with the diet history method. Three of these 12 food groups had a medium to large effect size (e.g. raw vegetables) and seven showed at least a small strength while there was basically no difference for coffee/tea or ice cream. Intraclass correlations were strong only for beverages (>0.50) and revealed the least correlation for vegetables (<0.20). Quartile classification of participants exhibited more than two-thirds being ranked in the same or adjacent quartile assessed by both methods. For every food group, Bland–Altman plots showed that the agreement of both methods weakened with increasing consumption.Conclusions
The cognitive effort essential for the diet history method to remember consumption of the past 4 weeks may be a source of inaccurateness, especially for inhomogeneous food groups. Additionally, social desirability gains significance. There is no assessment method without errors and attention to specific food groups is a critical issue with every method. Altogether, the 24-h recalls method applied in the presented study, offers advantages approximating food consumption as compared to the diet history method.998.
Zulfiqar A. Bhutta Assad Hafeez 《Health research policy and systems / BioMed Central》2015,13(Z1):S49
Pakistan faces huge challenges in meeting its international obligations and agreed Millennium Development Goal targets for reducing maternal and child mortality. While there have been reductions in maternal and under-5 child mortality, overall rates are barely above secular trends and neonatal mortality has not reduced much. Progress in addressing basic determinants, such as poverty, undernutrition, safe water, and sound sanitary conditions as well as female education, is unsatisfactory and, not surprisingly, population growth hampers economic growth and development across the country. The devolution of health to the provinces has created challenges as well as opportunities for action. This paper presents a range of actions needed for change within the health and social sectors, including primary care, social determinants, strategies to reach the unreached, and accountability. 相似文献
999.
Zahida Sarwar Andrea Cutherell Arif Noor Farah Naureen Jennifer Norman 《Health research policy and systems / BioMed Central》2015,13(Z1):S50
While Pakistan has made progress toward achieving Millennium Development Goal 5 for maternal health, it is unlikely to achieve the target; further, it is also not on track for Millennium Development Goal 4 regarding child health. Two low-cost, temperature stable and life-saving drugs, misoprostol and chlorhexidine, can respectively avert maternal and newborn deaths, and are particularly pertinent for poor and marginalized areas which bear the brunt of maternal and newborn deaths in Pakistan. In response, Mercy Corps led focused advocacy efforts to promote changes in policies, protocols, and regulatory environments for misoprostol (2012–2014) and for chlorhexidine (2014). These short-duration advocacy projects facilitated significant policy gains, such as inclusion of misoprostol and chlorhexidine into province-specific essential drug lists, development and endorsement of clinical protocols for the two drugs by provincial health departments, inclusion of misoprostol into pre-service training curriculum for several health cadres, and application for registration of chlorhexidine (at the concentration required for newborn care) by two pharmaceutical companies. These results were achieved by a consultative and evidence-based process which generated feedback from community members, program implementers, and policymakers, and ultimately put the government in the driver’s seat to facilitate change. Community Action Dialogue forums were linked with provincial-level Technical Working Groups and Provincial Steering Committees, who passed on endorsed recommendations to the Health Secretary. The key factors which facilitated change were the identification of champions within the provincial health departments, prioritization of relationship building and follow-up, focus on concrete advocacy aims rather than broad objectives, and the use of multi-stakeholder forums to secure an enabling environment for the policy changes to take root. While these advocacy initiatives resulted in significant policy changes in Pakistan’s devolved health system, to ensure these policy changes have an impact on health outcomes, Pakistan should focus on the scale-up of appropriate use of chlorhexidine and misoprostol. Further, future policy initiatives in Pakistan should make use of similar multi-stakeholder policy forums, while ensuring a third party to facilitate the process so that civil society and community voices are not lost in the policy development discussion. 相似文献
1000.
Zubia Mumtaz Adrienne V. Levay Gian S. Jhangri Afshan Bhatti 《Health research policy and systems / BioMed Central》2015,13(Z1):S51