Clinical Research Design Research Articles

Novel Definition of Stroke “Good Responders” Predicts 90-Day Outcome after Thrombolysis

IntroductionIdentifying predictors of good response in thrombolytic-treated stroke is important to clinical care, resource allocation, and research design. We developed a simple, novel measure of “Good Responders” to assess if 2 short-term variables could predict 90-day outcomes after thrombolysis in stroke. MethodsIntravenous thrombolysis-treated stroke cases from June 2004 to June 2018 were analyzed from a stroke registry. Intraarterial treatment cases were excluded. Good responders (GR++) were defined as those with length of stay less than or equal to 3 days and discharge to home. Poor responders (GR- -) had length of stay more than 3 days and discharge other than home. Mixed responders (GR+/-) composed the remainder. Baseline characteristics and predictors of 90-day outcome were assessed. ResultsOf 261 patients, there were 101(38.7%) GR++, 67(25.7%) GR- -, and 93(35.6%) GR+/-. For GR++ versus GR- - versus GR+/-, there were differences in mean age (62.7, 71.2, 69.2; P = .0016), and baseline modified Rankin score (mRS) 0-2 (%: 94.9, 74.6, 84.8; P = .008). Younger age, male sex, lower values for systolic BP, glucose, and baseline mRS were associated with good responders. Older age, atrial fibrillation, symptomatic intracerebral hemorrhage, and baseline mRS greater than 2 were associated with poor responders. At 90 days, mortality was reduced in GR++ versus GR- - versus GR+/- (%alive: 92.6, 72, 86; P = .04), and mRS(0-2) (%: 36.8, 0, 11.8; P < .001). ConclusionsGood responders to thrombolysis are younger and have better baseline functional status. Our novel definition of “Good Responders”, using 2 early variables of home disposition and short length of stay, may help predict 90-day post-thrombolytic outcome. Future work should focus on validating this definition.

Estudios de cohortes. 1ª parte. Descripción, metodología y aplicaciones

Los estudios de cohortes (EC), son estudios de carácter longitudinal, observacional y analíticos. Corresponden a uno de los diseños más utilizados en investigación clínica, aportando altos niveles de evidencia, según el tipo de escenario en los que se aplique.Los EC tienen como objetivos, determinar asociación entre un factor de exposición y el desarrollo de alguna enfermedad o evento de interés, a partir de la estimación de riesgos; conocer la historia natural o el curso clínico de una enfermedad o de un evento de interés; determinar supervivencia; estudiar factores protectores y pronósticos.Los EC tienen diversas aplicaciones, por ejemplo: investigación de brotes epidemiológicos, estudios de causalidad, evaluación de intervenciones educacionales, etc.Teóricamente, la mejor aproximación es mediante un estudio de cohortes prospectivas; sin embargo, suelen exigir largos períodos de tiempo de seguimiento para obtener resultados útiles; por lo tanto, se puede recurrir a otras estrategias, como a los estudios retrospectivos y otros, que pueden resultar más factibles respecto de recursos y tiempos de seguimiento.El objetivo de este manuscrito fue generar un documento de estudio referente a descripción, metodología y aplicaciones de los EC en ciencias de la salud.

JCSE01.02 The Opportunity of Drugs Development on Immunotherapy in China

Immunotherapy gets the breakthrough after almost 100 years of silence. PD1/PD-L1 inhibitors as the representative have been extensively studied in various human malignant tumors and get promising long term response with relatively fewer adverse events. The first PD1 inhibitor indication was approved for melanoma in Japan on July 2014. Up to now, the US Food and Drug Administration had approved several PD-1 pathway blockade treatments including nivolumab, pembrolizumab and atezolizumab using in first line and second line of NSCLC. In China, nivolumab was approved for second line setting for advanced NSCLC and pembrolizumab combined with chemotherapy were approved for first line setting of advanced NSCLC. Two novel PD-1 inhibitors from Chinese pharmaceutical companies were approved for melanoma and lymphoma by National Medical Products Administration (NMPA) of China. And, a lot of clinical trials about domestic novel PD-1 and PD-L1 inhibitors from Chinese pharmaceutical companies are now ongoing. IO arena faces intense in-class competition from both MNC (Multi-National Corporation) and domestic pharmaceutical company in China. Now there are more than 20 IO antibodies from 10 MNCs and 16 pharmaceutical companies in China. Besides PD1/PD-L1 and CTLA4, other hot IO drugs such as IDO or Lag3 et al are also under investigation. Clinical trials about some novel combination, for example, CMET inhibitor plus IO, anti-angiogenesis drugs plus IO, et al, are also ongoing. There are special questions which need to be settled in China. Chinese population has relatively high rates of hepatitis B virus infection and much higher proportion of EGFR mutation. The delightful changing recently is some studies emerging to consider the characteristics of the Chinese or Asian populations. Some clinical trials are trying to answer these questions. Besides clinical trials for advanced NSCLC, Clinical trials focus on local advanced NSCLC, early stage NSCLC and SCLC are also ongoing. New adjuvant and adjuvant IO trials have started in China. Most importantly, some novel combinations overcoming previous IO resistance are now on the way, which will give more interesting results in the near future. Research about Chinese IO treatment remains in their early stage and further efforts are needed to improve the design of future clinical trials and translational research. Meanwhile, the other hot IO drugs and phase I studies need to speed up in China. Immunotherapy, China, Drugs Development

Core Minimal Datasets to Advance Clinical Research for Priority Epidemic Diseases.

The Ebola virus disease outbreak in west Africa has prompted significant progress in responding to the clinical needs of patients affected by emerging infectious disease outbreaks. Among the noteworthy successes of vaccine trials, and the commendable efforts to implement clinical treatment trials during Ebola outbreaks, we should also focus on strengthening the collection and curation of epidemiological and observational data that can improve the conception and design of clinical research.

Defining breakthrough invasive fungal infection-Position paper of the mycoses study group education and research consortium and the European Confederation of Medical Mycology.

Breakthrough invasive fungal infections (IFIs) have emerged as a significant problem in patients receiving systemic antifungals; however, consensus criteria for defining breakthrough IFI are missing. This position paper establishes broadly applicable definitions of breakthrough IFI for clinical research. Representatives of the Mycoses Study Group Education and Research Consortium (MSG-ERC) and the European Confederation of Medical Mycology (ECMM) reviewed the relevant English literature for definitions applied and published through 2018. A draft proposal for definitions was developed and circulated to all members of the two organisations for comment and suggestions. The authors addressed comments received and circulated the updated document for approval. Breakthrough IFI was defined as any IFI occurring during exposure to an antifungal drug, including fungi outside the spectrum of activity of an antifungal. The time of breakthrough IFI was defined as the first attributable clinical sign or symptom, mycological finding or radiological feature. The period defining breakthrough IFI depends on pharmacokinetic properties and extends at least until one dosing interval after drug discontinuation. Persistent IFI describes IFI that is unchanged/stable since treatment initiation with ongoing need for antifungal therapy. It is distinct from refractory IFI, defined as progression of disease and therefore similar to non-response to treatment. Relapsed IFI occurs after treatment and is caused by the same pathogen at the same site, although dissemination can occur. These proposed definitions are intended to support the design of future clinical trials and epidemiological research in clinical mycology, with the ultimate goal of increasing the comparability of clinical trial results.

Report on the ECNP Workshop on Clinical Research Methods, 6–8 November 2019, Barcelona, Spain

This article is a report from a workshop on clinical research methods organised by the European College of Neuropsychopharmacology (ECNP), which took place between 7 and 9 November 2018 in Barcelona. The programme of the workshops and an outline of the content of the speeches were presented here. The author made an effort to synthetically present issues concerning methods used in clinical research design, analysis of published results and creation of scientific publications, which were discussed during the workshop.

Investigation of the interrelation between plaque level and tooth decay in children with nephrotic syndrome in the period of mixed dentition

The early onset of carious destruction of hard teeth tissues definitely increases the risk of caries at older age. The insufficient level of oral hygiene around a tooth affected by caries induces the corresponding effect of gingival inflammation. Primary teeth affected by caries carry the potential risk of developmental and structural disturbances of their permanent successors. The aim of this study is characterization of the interrelation between dental plaque levels and tooth decay in children with nephrotic syndrome in the period of mixed dentition. In the investigation are included children with diagnosed nephrotic syndrome and a control group of healthy participants. Implemented clinical methods, epidemiological research and graphics design have been used. In 16.85% of the children with mixed dentition and diagnosed renal disorders the epidemiological index of dft varies in the range between 86% to 100%, at the expense of afflicted by caries and complicated carious lesions primary teeth, as well as, already treated deciduous teeth. Among children suffering from nephrotic syndrome from 6 to 12 years old established a minimum value of PLI=1.32 and maximum level of PLI= 2.68 are established. We have registered a minimum level of the gingival index GI equal to 0.91 and a maximum value of GI=2.05. Concerning children without common health disorders a minimum rate of PLI=0.14 and maximum level of PLI=2.14 are registered. These participants are characterized with fluctuations of the index of GI in the range between 0.00 and 1.68. Optimization of oral hygiene procedures in domestic conditions is related to intensive, thorough and profound training of parents and children by dental medicine doctors. There is a great necessity of performance of motivation programs in the context of oral health promotion.

How Biomedical HIV Prevention Trials Incorporate Behavioral and Social Sciences Research: A Typology of Approaches

In the field of biomedical HIV prevention, researchers have meaningfully incorporated behavioral and social sciences research (BSSR) into numerous clinical trials, though the timing and degree of integration have been highly variable. The literature offers few frameworks that systematically characterize these collaborations. To fill this gap, we developed a typology of BSSR approaches within biomedical HIV prevention research. Focusing on trials that had safety and/or efficacy endpoints, we identified five approaches for combining BSSR and clinical research: formative, embedded, parallel, explanatory, and implications. We describe each approach and provide illustrative examples. By offering a shared vocabulary for distinguishing the timing and design of collaborative BSSR and clinical research, this typology can facilitate greater transparency in collaborators’ expectations and responsibilities, and help collaborators address challenges likely to be associated with such interdisciplinary research.

Trends in Domestic and Foreign Clinical Research on Ultrasound-Guided Acupuncture

Background: The purpose of this study was to analyze domestic and foreign clinical research into ultrasound-guided Oriental medicine acupuncture. Methods: Ultrasound-guided Oriental medicine acupuncture studies were retrieved from PubMed, CNKI, KISS, NDSL, and OASIS. Results: Of 6,260 articles, 17 articles were selected. There was 1 article in 2004, 1 in 2008, 2 in 2011, 1 in 2012, 4 in 2013, 3 in 2016, 2 in 2017, and 3 in 2018. Of the 17 selected articles 6 articles were studies of omalgia, 4 of knee pain and 2 of peroneal nerve palsy. In addition, there was 1 article of occipital headache, 1 of neck pain, 1 of tarsal tunnel syndrome, 1 of angioma and 1 of hiccup. In these 17 studies the ultrasound frequency range where mentioned, was 5-14 MHz. Conclusion: This study provided basic data as reference for the design of more diversified and systematic clinical research in the domestic Oriental medicine community in the future.

Younger age and greater preoperative function predict compliance with 2-year follow-up visits after ACL reconstruction: an analysis of the PIVOT multicentre trial

ObjectivesThe purpose of this investigation was to identify clinical and demographic variables that may predict compliance, defined as patient follow-up at 1-year and 2-year postoperative appointments, after anterior cruciate ligament reconstruction (ACLR).MethodsA total of 107 patients undergoing primary ACLR across four centres were prospectively followed for 2 years. Demographic and clinical data were recorded preoperatively and postoperatively, including patient-reported outcomes such as the Marx Activity Rating Scale, Cincinnati Occupational Rating Scale (CORS), International Knee Documentation Committee Subjective Knee Evaluation Form and Activities of Daily Living Scale (ADLS). Compliance was retrospectively defined using the presence or lack of outcome measures at 1-year and 2-year postoperative visits. Univariate analysis was done to compare demographic and clinical variables between compliant and non-compliant patients at 1-year and 2-year follow-up. Significant variables were entered into a logistic regression model. Significance was set at p<0.05.ResultsThe overall rate of compliance at 1-year and 2-year postoperative appointments was 83.2% (89/107) and 57.0% (61/107), respectively. Regression analysis showed that residence in Kobe, Japan compared with Pittsburgh, USA (OR 10.28; 95% CI 1.0003 to 105.28), and ‘very strenuous’ (OR 16.74; 95% CI 3.21 to 87.43) and ‘strenuous’ (OR 18.78; 95% CI 2.01 to 175.78) preinjury activity level were independent factors associated with compliance at 1-year follow-up. At 2 years follow-up, younger age (OR 0.95; 95% CI 0.91 to 0.997), and greater preoperative score on CORS (OR 1.03; 95% CI 1.01 to 1.06) and on ADLS (OR 1.04; 95% CI 1.01 to 1.07) were independently associated with compliance.ConclusionWhile patients with greater level of strenuous activity were more likely to follow-up after ACL surgery at 1 year, patients who were younger and had higher preoperative function measured by CORS and ADLS were more likely to follow-up at 2 years. Differences in follow-up rates among the USA, Italy, Sweden and Japan may highlight important cultural, socioeconomic and infrastructural differences across international healthcare systems. Orthopaedic surgeons may consider the results of this study during preoperative discussion with their patients and design of future ACL clinical research trials.Level of evidenceLevel III, prospective cohort.

Systematic review of acupuncture placebo devices with a focus on the credibility of blinding of healthy participants and/or acupuncturists.

An ideal placebo design in clinical research should resemble the intervention under investigation to facilitate blinding, yet remain clinically inert. With regard to physical interventions such as acupuncture, a true placebo device has not been developed and validated. Since 1998, researchers have designed several placebo acupuncture devices (PADs). The three most widely used PADs are the Streitberger, the Park and the Takakura device. This review focuses on evaluating studies of these devices, in the context of credibility of blinding (COB), assessment of penetrating pain or sensation, and de qi sensation. Electronic database searches were conducted in four English and two Chinese databases from their inception until November 2016. All studies included in the review were conducted on healthy participants and compared verum manual acupuncture with any of the aforementioned PADs with respect to one or more of the above three outcomes related to blinding effect. The synthesised analyses of the 15 included studies showed that the Streitberger and Park placebo devices may not blind participants successfully when tested at a sensitive acupuncture point (LI4). In terms of penetrating sensation, there were significant differences between these two placebo devices and verum acupuncture when applied at this point. The Takakura device was the only PAD that had the potential to blind the acupuncturist. However, the blinding analyses of all outcome measures were inconsistent. Overall, there were insufficient data to confirm the blinding effects of these skin-contact PADs as each device was associated with limitations that warrant further design improvements.

National Institute of Neurological Disorders and Stroke and Department of Defense Sport-Related Concussion Common Data Elements Version 1.0 Recommendations.

Through a partnership with the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, and Department of Defense, the development of Sport-Related Concussion (SRC) Common Data Elements (CDEs) was initiated. The aim of this collaboration was to increase the efficiency and effectiveness of clinical research studies and clinical treatment outcomes, increase data quality, facilitate data sharing across studies, reduce study start-up time, more effectively aggregate information into metadata results, and educate new clinical investigators. The SRC CDE Working Group consisted of 32 worldwide experts in concussion from varied fields of related expertise divided into three Subgroups: Acute (<72 h post-concussion), Subacute (3 days-3 months post-concussion) and Persistent/Chronic (>3 months post-concussion). To develop CDEs, the Subgroups reviewed various domains, then selected from, refined, and added to existing CDEs, case report forms and field-tested data elements from national registries and funded research studies. Recommendations were posted to the NINDS CDE Website for Public Review from February 2017 to April 2017. Following an internal Working Group review of recommendations, along with consideration of comments received from the Public Review period, the first iteration (Version 1.0) of the NINDS SRC CDEs was completed in June 2017. The recommendations include Core and Supplemental-Highly Recommended CDEs for cognitive data elements and symptom checklists, as well as other outcomes and end-points (e.g., vestibular, oculomotor, balance, anxiety, depression), and sample case report forms (e.g., injury reporting, demographics, concussion history) for domains typically included in clinical research studies. The NINDS SRC CDEs and supporting documents are publicly available on the NINDS CDE website www.commondataelements.ninds.nih.gov . Widespread use of CDEs by researchers and clinicians will facilitate consistent SRC clinical research and trial design, data sharing, and metadata retrospective analysis.

The Past Need Not Be Prologue: Recommendations for Testing and Positioning the Most-Promising Medical Countermeasures for the Next Outbreak of Ebola Virus Infection.

The 2013-2016 outbreak of Ebola virus disease (EVD) in West Africa led to unprecedented morbidity and mortality. Although different classes of putative antiviral agents with supportive preclinical data were available for testing, and although several attempts to perform meaningful evaluation of these agents were undertaken during the epidemic, different research methods, a lack of appropriate controls in most studies, and formidable logistical challenges to completion of studies under field conditions hampered the success of these efforts. Ultimately only 1 randomized, placebo-controlled clinical trial (PREVAIL II) was performed in this setting, and, owing to a decrease in the number of new cases available for study, it, too, ended prior to reaching definitive results. Retrospective review of the lessons learned from this outbreak argues strongly for the need for much better preparedness in terms of selecting the trial design and drug(s) for use during the next outbreak. Using recent data provided by representatives from the pharmaceutical industry, clinical and laboratory subject matter experts from the National Institute of Allergy and Infectious Diseases, other US government agencies, and academic partners were consulted regarding the current state of knowledge about several lead compounds with putative activity against EVD. Consensus was sought on recommendations concerning the most promising treatment strategies against EVD that should be studied in the context of a randomized clinical trial during the next outbreak. Four compounds from 2 different classes (monoclonal antibody [mAb] cocktails and direct-acting antiviral agents [DAAs]) were highlighted as lead candidates, limitations in the current knowledge base about these drug classes were reviewed, and recommendations about the optimal clinical research design for studying combinations of these different agents were made. Although achieving the desired sample size could be challenging, a randomized, controlled clinical trial based on a combination strategy of a mAb with a DAA was recommended as the most appropriate clinical trial design to be undertaken during the next outbreak of EVD.

Strategies for recruiting a sample of adults with type 2 diabetes from primary care clinics in rural Appalachia: Incorporating cultural competence

BackgroundRecruiting research participants from primary care in rural Appalachia is a major challenge and can be influenced by cultural characteristics, making it critically important to incorporate strategies of cultural competence in the overall design of clinical research. ObjectivesThe purpose of this paper is to describe culturally competent strategies used for recruitment and data collection with a sample of adults with type 2 diabetes from primary care settings in Appalachia. DesignThe Purnell model of cultural competence and relevant literature served as a framework for study design. Four overarching approaches informed the organization of recruitment strategies and development of the data collection plan. ProceduresThe approaches included selection of research sites, establishing collaborations, sustaining collaborative relationships, and enhancing understanding of benefits of participation. Four recruitment sites were selected based on potential to enhance diversification of participants; multiple steps were included in each of the three remaining approaches to build relationships and gain participation. A study log was maintained to provide evaluation data. ResultsRecruitment took 14 months and a sample of 102 subjects provided consent with 101 participants providing complete data. Demographics were representative of the region except that African American participation was higher (6.9%) compared to current north central Appalachia (3%). Over 72% of participants indicated they would be interested in participating in future studies. ConclusionsThese findings emphasize the importance of employing strategies for cultural competence in study design. Use of concepts from the Purnell model led to enhanced representativeness and potential for subsequent generalizability.

Involving children and young people in clinical research through the forum of a European Young Persons' Advisory Group: needs and challenges.

Children and young people are seen as fundamental to the design and delivery of clinical research as active and reflective participants. In Europe, involvement of children and young people in clinical research is promoted extensively in order to engage young people in research as partners and to give them a voice to raise their own issues or opinions and for their involvement in planning and decision making in addition to learning research skills. Children and young people can be trained in clinical research through participation in young person advisory groups (YPAGs). Members of YPAGs assist other children and young people to learn about clinical research and share their experience and point of view with researchers, thereby possibly influencing all phases of research including the development and prioritization of research questions, design and methods, recruitment plans, and strategies for results dissemination. In the long term, the expansion of YPAGs in Europe will serve as a driving force for refining pediatric clinical research. It will help in a better definition of research projects according to the patients' needs. Furthermore, direct engagement of children and young people in research will be favorable to both researchers and young people.

Inspirations of Rome Ⅳ on clinical evaluation of traditional Chinese medicine for functional gastrointestinal disease

The Rome Foundation released the Rome Ⅳ for functional gastrointestinal diseases (FGIDs) in 2016, which fully presented the latest advances and views on the disease origin, definition, diagnosis, classification, pathology, mechanism, clinical features, influential factors, interventions, clinical evaluation, clinical research design and so on, showing high positive effects on global researches. Traditional Chinese medicines (TCM) have cognitive advantages and well-recognized and-demonstrated efficacy in the prevention and treatment for FGIDs. However, the monotonous presentation ways and weak interpretation on clinical evaluation have also hindered the inherent advantages explanation, characteristics quantization, evidence and communication accumulation. This study first analyzed the background and key points on clinical evaluation of Rome Ⅳ and corresponding inspirations, believed that its concept and viewpoints were assimilated with systematic medicine, and emphasized the important influence of subjective factors such as mental psychology and social culture on the disease and its importance in clinical evaluation. Its views on several aspects such as the theoretical model, internal and external causes, and transfer process were highly consistent with TCM. Therefore, TCM researchers should devote more dedication and courage on the innovation and collaboration with global researches to advance related studies. Then, based on 59 TCM clinical researches for FGIDs funded by national projects upon searching in CNKI with strict search strategy, the clinical evaluation methods and indexes and their correlations were summarized and analyzed, and it was found that more attention was paid to the disease symptoms and impact, symptom/syndrome score, patient report outcome, et al. However, many limitations were also founded, such as disordered relationships among different indexes, ambiguous explanation of research results, and extremely few domestic evaluation instruments in Chinese culture. Therefore, it is suggested that future research should regress and highlight the subjective features of patients and diseases, standardize the elemental structure and management mode of clinical evaluation, enhance the values and status of reported outcomes. It is highly recommended that the domestic disease-specific instruments developed in Chinese culture should be adopted as primary outcome for clinical evaluation, assisted with symptoms/signs assessment tools and doctors reporting outcome scale, et al. The common used TCM syndrome scores in current researches are not recommended as the primary outcome. However, there are some limitations in the above suggestions. We hope that more relevant researches will explore and establish a unified outcome assessment system for FGIDs and improve the quality of TCM clinical research.

Lightheadedness After Concussion: Not All Dizziness is Vertigo.

To characterize the presence and degree of postconcussion lightheadedness in relation to postconcussion vertigo and dizziness, and to determine whether lightheadedness influences overall symptom duration. Prospective, cohort design. Nationwide Children's Hospital, Sports Concussion Clinic. Five hundred ten patients (9-19 years of age) within 30 days of concussion injury. Patient ratings (scale 0-6) of multiple postconcussion symptoms including lightheadedness, vertigo, and dizziness, reported from the day of clinic evaluation and recalled from the day of concussion. Postconcussion lightheadedness occurred commonly relative to vertigo. Lightheadedness was recalled more than vertigo (70.8% vs 48.6%, P < 0.001) on concussion day and reported more than vertigo (47.1% vs 24.1%, P < 0.001) on the day of clinic evaluation. Principal component analysis demonstrated strong correlations among lightheadedness, vertigo, balance difficulties, difficulty concentrating, mental fogginess, and difficulty remembering, relative to other postconcussion symptoms. When present on the day of clinic evaluation, these highly correlated symptoms predicted prolonged concussion recovery [P = 0.028; Hazard Ratio (HR) = 1.2]. Female sex (P = 0.04; HR = 1.23), emotional symptoms recalled from the day of concussion (P = 0.007; HR = 1.23), and cephalalgic symptoms (P < 0.001; HR = 1.34) reported on the day of clinic evaluation also predicted prolonged concussion recovery. Not all postconcussion dizziness is vertigo. Postconcussion lightheadedness is common and, when present at the time of clinic evaluation, can influence concussion recovery. Distinguishing postconcussion lightheadedness from vertigo may help to inform clinical treatment and concussion research design. This study adds to the growing body of evidence that supports an association between concussion and autonomic dysfunction.

NINDS Common Data Elements for Congenital Muscular Dystrophy Clinical Research: A National Institute for Neurological Disorders and Stroke Project.

A Congenital Muscular Dystrophy (CMD) Working Group (WG) consisting of international experts reviewed common data elements (CDEs) previously developed for other neuromuscular diseases (NMDs) and made recommendations for all types of studies on CMD. To develop a comprehensive set of CDEs, data definitions, case report forms and guidelines for use in CMD clinical research to facilitate interoperability of data collection, as part of the CDE project at the National Institute of Neurological Disorders and Stroke (NINDS). One working group composed of ten experts reviewed existing NINDS CDEs and outcome measures, evaluated the need for new elements, and provided recommendations for CMD clinical research. The recommendations were compiled, internally reviewed by the CMD working group, and posted online for external public comment. The CMD working group and the NIH CDE team reviewed the final version before release. The NINDS CMD CDEs and supporting documents are publicly available on the NINDS CDE website (https://www.commondataelements.ninds.nih.gov/CMD.aspx#tab=Data_Standards). Content areas include demographics, social status, health history, physical examination, diagnostic tests, and guidelines for a variety of specific outcomes and endpoints. The CMD CDE WG selected these documents from existing versions that were generated by other disease area working groups. Some documents were tailored to maximize their suitability for the CMD field. Widespread use of CDEs can facilitate CMD clinical research and trial design, data sharing and retrospective analyses. The CDEs that are most relevant to CMD research are like those generated for other NMDs, and CDE documents tailored to CMD are now available to the public. The existence of a single source for these documents facilitates their use in research studies and offers a clear mechanism for the discussion and update of the information as knowledge is gained.

Risk Factors of Hyperemesis Gravidarum: Review Article

Hyperemesis gravidarum (HG) is the most severe form of nausea and vomiting during pregnancy (NVP). It is diagnosed clinically by its typical clinical picture and exclusion of other causes of nausea and vomiting in the pregnant woman. Nausea and vomiting are a common experience affecting 50% to 90% of all women. It is the most common indication for hospitalization during the first half of pregnancy. HG occurs in only about 0.5 to 2% of cases but when it occurs, it may be associated with morbidity of both mother and fetus. There are many risk factors related to HG, but we are still in need of adequate clinical research methodology and design for reporting these associations. In this article, we will discuss them and review epidemiological studies and statistics that support them. HG is found to be common in young aged mothers. There is a debate between studies regarding ethnicity as a risk factor. Low socio-economic level is found to be associated with HG. Dietary factors are considered in Indians who are mostly vegan and Asians who are mostly lactose intolerant. Deficiencies of trace elements are associated with more progression of the disease. Women affected by NVP are mostly nonsmoker. Molar pregnancy, multiple pregnancies, fetus with Down syndrome and primi-gravidity are common obstetric risk factors. Studies theorize relation between hyperthyroidism and HG based on structural similarity between hCG and TSH but more studies are needed to highlight this relation. Mood and anxiety disorders are associated with the disease but causal relation has not been established yet. GERD, peptic ulcer disease and specifically H. pylori infection are among common risk factors. Asthma is associated with prolonged duration of hospitalization. Strong positive family history of HG in patients highlights genetic predisposition of this disease.

THE EFFECT OF THE POP-UP BOOK AKU DAN GIGIKU ON PULSE RATE IN CHILDREN AGED 4–6 YEARS

Objective: Anxiety is regarded as a major problem in children undergoing dental treatment. One of the physiological responses to anxiety is an increased pulse rate. Young children respond aggressively to anxiety and are in need of psychological intervention. Pop-up books can be used as an instrument to improve their interest and to help them understand the substance of dental health education.The objective of this study was to utilize pulse rate measurements to investigate the intervention of a pop-up book in reducing anxiety. A total of 78 children aged 4–6 years were divided into two groups: An intervention group with the pop-up book Aku dan Gigiku and a control group without intervention. The pulse rates of both groups were measured. This study comprised an experimental clinical research design. The independent t-test was used to measure comparisons of decreased pulse rate between the two groups.Result: The result showed that there was a statistically significant difference in decreased pulse rate with and without the intervention of the pop-up book Aku dan Gigiku. Pop-up books are often used as an educational medium for children because they present interesting illustrations and are easy to understand.Conclusion: As a medium of dental health education, pop-up books can contribute significantly to reducing anxiety in children.