Background: Response surface methodology (RSM) is a cost-effective multivariate technique employed in optimization of pharmaceutical formulations. Central composite experiment design is one of the common designs under RSM used for determining optimum nanoparticle formulation parameters. Objectives: To optimize a formulation for meropenem-loaded chitosan alginate nanoparticles using central composite experimental design. Methodology: Meropenem loaded chitosan-alginate nanoparticles were fabricated using aqueous sodium alginate solution and ionotropic gelation with calcium chloride and chitosan, using an optimized formulation derived from a central composite design. The fabricated Mer-CS/Alg NPs were characterized for their particle size, zeta potential, encapsulation efficiency, and loading capacity. The central composite design has been used to adequately assess the influence of two factors namely meropenem concentration and Alg/CS mass ratio on the responses based on a limited number of 13 triplicate formulation runs. Results: This study successfully formulated meropenem-loaded chitosan/alginate nanoparticles. The optimal formulation of the Mer- CS/Alg NPs was 1.7 mg/mLcurcumin, and a Alg/CS mass ratio of 9.8:1. Based on the predicted values of the response variable, the optimal formulation would have a particle size of 490.64 nm, zeta potential of -28.59 mVand a loading capacity of 76.89%. Conclusion The central composite experimental design successfully optimized the nanoparticle formulation of meropenem and chitosan/alginate polymer solution. The optimum formulation produced nanoparticles with adequate size, high stability, and high drug load.
Meropenem ; Nanoparticles ; Research Design

INTRODUCTION: This scoping review examined the number, types and characteristics of journal publications on ageing in Singapore from 2008 to 2018 to determine how ageing research in medical and social domains in Singapore has transformed over time. METHODS: Using relevant search terms, articles were extracted from multiple databases and then screened and reviewed for eligibility and inclusion by independent reviewers. Data such as article title, authors, year of publication, name of journal, type of journal, study design and the kind of data used were charted from the included articles for evidence synthesis. RESULTS: Since 2008, there has been a steady increase in the number of publications on ageing in medical and social domains in Singapore. In the medical domain, publications on Ophthalmology (22%) made up the largest proportion of the existing medical literature on ageing in Singapore, followed by Physical Functioning (17%), which involved physiological measurements of physical well-being, and Geriatrics (16%). Non-medical publications comprised 38% of all the included publications, with publications on the social aspects of ageing (43%) forming the largest group in this cluster, followed by publications on Prevention (19%) and Healthcare services (18%). The study design was mostly observational (82%), with only 3% of interventional studies. CONCLUSION While ageing research had expanded in Singapore in the last decade, it was predominantly discipline specific and observational in design. As ageing issues are complex, with biology intersecting with psychology and sociology, we call for greater interdisciplinary collaboration, the conduct of more interventional studies, as well as more research in understudied and emerging areas.
Humans ; Singapore ; Aging ; Geriatrics ; Research Design

BACKGROUND

Dengue is a global health concern, particularly in tropical regions such as the Philippines. In 2019,Cebu City reported the highest number of dengue cases in Central Visayas with 3,290 cases and 20 deaths, an 11.8% increase compared to 20181 . To help predict disease outcomes and provide timely management, a scoring system, the Daily Dengue Severity Score (DDSS)² was utilized.

To determine the clinicodemographic profile of dengue patients, determine the accuracy of the DDSS in assessing disease severity, and determine a cut off score that suggests severe dengue.

Patients 1 month to 18 years admitted for dengue at Perpetual Succour Hospital from January 2018 to December 2020 were included. Cases were classified as Dengue without Warning Signs, Dengue with Warning Signs, and Severe Dengue, and scored using the DDSS. Statistical analysis used were Geometric mean and Area Under the Receiver Operating Characteristic (AUROC) curves to analyze the discriminative performance of the DDSS among the different disease severity states.

Out of 327 cases, 34 were classified as Dengue without Warning Signs, 271 Dengue with Warning Signs, and 22 Severe Dengue. The highest mean DDSS was 17.7 ±14.0 at Day -4 among those with Severe Dengue, and the lowest mean DDSS was 1.1 ± 2.0 at Day +3 among those with Dengue without Warning Signs. A cut off point of 10 on Day -1 predicted subsequent Severe Dengue among patients with Dengue with Warning Signs. In 91.39% of cases, there was a significant relationship between the DDSS and dengue classification, and the higher the DDSS, the more severe the disease.

Majority of dengue patients were males, aged 8.1 to 9.2 years. DDSS showed 66.67% sensitivity, 92.86% specificity, a positive likelihood ratio of 9.3, and a cutoff of 10 is predictive of severe dengue among patients with dengue with warning signs.

Qualitative research is a type of research that provides deeper insights into real-world problems. It gathers participants’ experiences, perceptions, and behaviours and answers the how’s and whys instead of how many or how much. It could be structured as a stand-alone study, purely relying on qualitative data or it could be part of mixed-methods research that combines qualitative and quantitative data. Some of the most common methodologies being used in qualitative research include ethnography, grounded theory, phenomenological study, narrative study, historical study and case studies. This article aimed to discuss how to conduct a qualitative study. The steps in conducting a qualitative study include: 1) Create a purpose statement; 2) Formulate the Research Questions; 3) Perform a Literature Review; 4) Choose a qualitative research methodology to use; 5) Identify and Select the Study Population; 6) Develop the data collection procedure; 7) Collect the data and 8) Analyze the data, which if using thematic analysis, can include writing the final report. In writing and appraising qualitative studies, the Consolidated Criteria for Reporting Qualitative Studies (COREQ) can serve as a useful guide. Lastly, like in quantitative studies, researchers doing qualitative studies should be aware of the ethical issues involved in their work, anticipate possible ethical concerns, craft protection strategies, and make the necessary referrals to research ethics committees, appropriate organizations, and other agencies if the need arises.

Humans ; Hypertension/therapy* ; Publications ; Research Design

Conventional wisdom holds that the onset of chronic obstructive pulmonary disease (COPD) is usually in older people. However, with extended follow-up in large cohort studies, the trajectory of lung function development has been gradually delineated, indicating that the decline of lung function may originate early in life. In addition, a large number of studies have shown that people with chronic respiratory symptoms, pulmonary imaging changes and abnormal lung physiology, but not in line with pulmonary function diagnosis of COPD, tend to develop COPD in the future and may have a worse prognosis, suggesting the necessity of early intervention. The GOLD 2022 report proposes a series of terms related to COPD, including COPD in young people and pre-COPD, opening up new opportunities for the prevention, early diagnosis and treatment of COPD. These concepts also guide the study design of the biological mechanism of COPD and the trajectory of disease progression. This article reviews the research progress of COPD in young people and pre-COPD to attract more attention in clinical practice.
Humans ; Aged ; Adolescent ; Pulmonary Disease, Chronic Obstructive ; Lung ; Cohort Studies ; Research Design

Bridging study in vaccine clinical trials means a series of small-scale additional tests on the basis that the original safety and effectiveness of a vaccine have been confirmed in clinical trials, to prove that the characteristics of safety, immunogenicity and effectiveness of a vaccine are similar or consistent after component, population and immunization procedure change to other types which can extrapolate data from existing clinical trials. Compared with traditional vaccine clinical trials, bridging trials can promote the approval of vaccines to the market, accelerate the expansion of vaccine application, and promote the use of vaccines across regions and populations. In recent years, the application of bridge study design in vaccine clinical research has become more and more common. In order to better guide and promote the application of bridging trial design in the field of vaccine clinical research, we reviewed the design characteristics and application examples of bridging study design in vaccine clinical trials, and systematically elaborated the design ideas, key points and statistical evaluation methods of bridging study.
Humans ; Research Design ; Biomedical Research ; Immunization ; Vaccines/therapeutic use*

Bridging study in vaccine clinical trials means a series of small-scale additional tests on the basis that the original safety and effectiveness of a vaccine have been confirmed in clinical trials, to prove that the characteristics of safety, immunogenicity and effectiveness of a vaccine are similar or consistent after component, population and immunization procedure change to other types which can extrapolate data from existing clinical trials. Compared with traditional vaccine clinical trials, bridging trials can promote the approval of vaccines to the market, accelerate the expansion of vaccine application, and promote the use of vaccines across regions and populations. In recent years, the application of bridge study design in vaccine clinical research has become more and more common. In order to better guide and promote the application of bridging trial design in the field of vaccine clinical research, we reviewed the design characteristics and application examples of bridging study design in vaccine clinical trials, and systematically elaborated the design ideas, key points and statistical evaluation methods of bridging study.
Humans ; Research Design ; Biomedical Research ; Immunization ; Vaccines/therapeutic use*

The condition of critically ill patients changes rapidly, involving pathological changes in multiple systems and organs throughout the body. Exploring the causal relationship of mechanisms can further reveal etiology, treatment, and prognosis of diseases. However, traditional prospective studies in the field of critical care are still subject to numerous limitations. As an emerging research method, Mendelian randomization (MR) analysis uses genetic variation to provide causal evidence for instrumental variables, which is expected to provide clues in critical diseases. This article systematically describes the research progresson the application of MR analysis in critical care medicine from four aspects: the principle of MR analysis, the difference between MR analysis and randomized controlled trial (RCT), the use of MR analysis in the field of critical illness, and the possible methods of application, aiming to provide possible directions for the research in this field.
Humans ; Mendelian Randomization Analysis/methods* ; Genetic Variation ; Causality ; Research Design

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.
Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Outcome Assessment, Health Care ; Reference Standards ; Reproducibility of Results ; Research Design ; Clinical Trials as Topic