On evaluation of consistency in multi-regional clinical trials

In recent years, multi-regional clinical trials (MRCT) that conduct clinical trials simultaneously in Asian Pacific region, Europe, and the United States have become very popular for global pharmaceutical development. The main purpose of multi-regional clinical trials is to shorten the time for pharmaceutical development and regulatory submission, and approval around the world. In practice, however, clinical results observed from some regions (sub-population) may not be consistent with the results from other regions and/or all regions combined (entire population). The inconsistency observed may be due to ethnic differences in different regions, differences in medical practice, time points of assessment, or by random chance due to small sample size for the region. Some regional regulatory agencies require consistency evaluation between local country results and overall results. However, the challenge is there is no detailed guidance on the definition of ‘consistency’ and methodology to evaluate it. Therefore, the questions are: how to evaluate consistency and what statistical methods are appropriate to be used for consistency evaluation? In this article, several statistical tests for consistency (similarity) between clinical results observed from a specific sub-population and the entire population are proposed. These methods are compared through extensive simulation. As most published articles discussed consistency evaluation for superiority situations, we have discussed consistency evaluation for non-inferiority situation in this article through a simulated example concerning consistency in some countries. Recommendations of the statistical methods to be used for consistency evaluation are given. Other aspects that should be considered for consistency evaluation are also provided.     

Two flavonol glycosides from <Emphasis Type="Italic">Liparis bootanensis</Emphasis>

Two new flavonol glycosides, bootanenside I and II (1 and 2), along with ten known compounds (3–12), were isolated from whole plant of Liparis bootanensis Griff. Their structures were elucidated on the basis of extensive spectroscopic analyses, including high-resolution electrospray-ionization mass spectrometry (HR–ESIMS) and one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR). The cytotoxicity of the compounds was investigated against HCT116 human cancer cell line, revealing that none of them possessed considerable cytotoxic activity. Bioassays of the new metabolites showed that compounds 1 and 2 displayed moderate in vitro antiinflammatory activity by inhibiting expression of inducible nitric oxide synthase (iNOS) protein in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells.     

Mechanism of acid production and secretion by osteoclasts]

Osteoclasts are primary cells responsible for bone resorption. The most characteristic feature of osteoclasts is the presence of ruffled borders and clear zones. The resorbing area under the ruffled border of osteoclasts is acidic, which favors dissolution of bone mineral. In bone-resorbing osteoclasts, hydrogen ions are provided by carbonic anhydrase II, which catalyzes the hydration of CO2 to H2CO3. Recently, it has been shown that the proton pump of the vacuolar H(+)-ATPase type exists in the ruffled border membranes of osteoclasts. Secretion of hydrogen ions by osteoclasts generates an equal amount of cytoplasmic base equivalents, principally as HCO3-. Osteoclasts have a chloride/bicarbonate exchanger, which normalizes the intracellular pH when osteoclasts actively resorb bone. In this paper, we review the mechanism of the acid secretion by osteoclasts.     

Trace and evaluation systems for health services quality in rural and remote areas: a systematic review

Aim

To provide a systematic review of the existing theory, framework, systems and instruments for tracing and evaluating quality in rural health services.

Subjects and methods

We searched six electronic databases up to March 2016. Observational studies of quality assessment of rural health services using theoretical models were included. Ekman’s scale was used to evaluate the quality of the included studies.

Results

A total of 18 studies, published between 2001 and 2015, met the inclusion criteria. The corresponding authors for most of them (7, 44%) are from Chinese institutions and three (3, 17%) from Australian institutions. Five studies (28%) focused on township hospitals. Primary health care quality was reported in five studies (28%), followed by clinical service in four (22%). More than half of the studies (61%) were considered of high quality, and the remainder was of moderate quality. These studies applied 16 theoretical systems, including the model/pattern (4, 25%), method/tool (7, 44%) and framework of the theory (5, 31%). Most of the theoretical models (14, 88%) obtained positive observations. In addition, the conceptual model (6, 36%) and TOPSIS method (2, 13%) were more frequently reported.

Conclusion

Although most of the current studies were considered to have high-quality and positive results, there were limitations in the number of publications and research on theoretical systems. The lacks of unified standards and comprehensive evaluation are important issues that need to be pointed out and resolved.

     

Comparative Study of Metal Accumulation in Three Fish Species (<Emphasis Type="Italic">Silurus asotus,Cyprinus carpio</Emphasis>, and <Emphasis Type="Italic">Carassius auratus auratus</Emphasis>) from the Jinsha and Tuo Rivers Located Upstream of the Yangtze River,China

Poland is one of the countries distinguished by a long and colorful past. Undergoing numerous turbulent socio-economic changes forced by the course of history, Poland is now one of the member states of the European Union. Experiencing low water quantity and high contamination levels in surface waters, Poland is following other EU countries in the effort to reach a “good” water status. Herein are presented impacts of changes in Polish history on water legislation, management, and research, as well as explanations for the perceptible split between engineering and scientific approaches to the aquatic issues. Drawbacks caused by unsatisfactory state research funding for the sciences and division of the water related contemporary scientific interests are also discussed.