Subject Of Clinical Research Research Articles

Comparison of Caudal Tramadol with different doses of Midazolam addon for Postoperative analgesia in Children Undergoing Inguinoscrotal Operations

Background: Safe and effective postoperative analgesic modalities have remained a subject of contemporary clinical research, particularly in children. The present study aimed at comparing the effectiveness of pain relief in children undergoing inguinoscrotal surgery with caudal tramadol alone and in combination with different doses of midazolam.
 Methods: Ninety children of either sex, aged one year to fifteen years, undergoing inguinoscrotalsurgical procedures under general anesthesia were recruited in a randomized double blinded fashion to receive one of the three study medications through caudal route. Group T (n= 30) received injectiontramadol 2mg/kg in a volume of 0.5ml/kg up to a maximum volume of 20ml, while group TM (n= 30)and TM/2 (n= 30) received additional midazolam 50mcg/kg and 25mcg/kg respectively. The study medications were administered immediately after induction of anesthesia. Postoperative analgesia was measured using a modified Hannallah 10 points Pediatric Objective Pain Scale described by Hannallah and colleagues. Pain score of ≤ 4 was considered effective analgesia. Duration of analgesia was defined as the time between caudal injection to the first need of analgesia.
 Results: The duration of analgesia in group TM (1145±281.41 min) and TM/2 (1012.67±260.68 min)was significantly longer than that in group T (690.83±215.7 min) (p<0.005). The sedation score was the highest in group TM and the least in group T. Nausea vomiting was the commonest side effect in all the three groups without any significant differences in the incidences between the groups.
 Conclusion: Addition of midazolam to tramadol for caudal administration in children undergoinginguinoscrotal operations produces significantly longer duration of postoperative analgesia than produced by epidural administration of tramadol alone.

3355 The CTSA Institutional website: A higher purpose - Researcher use of institutional Clinical and Translational Science Award (CTSA) website content to assess or promote NCATS CTSA Program Goals.

3355 The CTSA Institutional website: A higher purpose - Researcher use of institutional Clinical and Translational Science Award (CTSA) website content to assess or promote NCATS CTSA Program Goals.

Systematic review and analysis on the appropriate diseases in clinical treatment with Fu's subcutaneous needling therapy

The clinical research articles relevant with Fu's subcutaneous needling therapy (FSN) were retrieved from CNKI, WANFANG, CBM and PubMed databases till January 2018 since the establishment of database. According to the general international criteria of disease classification, the diseases involved in the articles were classified and summarized. In terms of the clinical application and research of FSN, the questions were extracted and commented through expert's consultation. As a result, 412 articles were included. The statistical results of disease spectrum indicated that FSN was adopted in 65 kinds of diseases in 11 systems. Of these diseases, the relevant somatic pain disorders in the musculoskeletal system were the most appropriate. Professor FU Zhong-hua explained that the clinical physicians of FSN should select the muscle-related disorders as the clinical research subject and treat them with normalized manipulation of FSN. The research on FSN is still at the preliminary stage. It needs more high-quality clinical and basic researches to provide the evidences for the therapeutic effects of FSN.

Updated Rules for Human Research Become Effective in January

Back to table of contents Previous article Next article Professional NewsFull AccessUpdated Rules for Human Research Become Effective in JanuaryNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:26 Oct 2018https://doi.org/10.1176/appi.pn.2018.11a15AbstractForthcoming changes to the Federal Policy for the Protection of Human Subjects are hoped to reduce the administrative burdens facing clinical trial designers while also simplifying the consent forms given to participants.After more than six years of extensive deliberation and review, the Department of Health and Human Services (HHS) will finally implement a host of changes to the rules governing the use of human subjects in clinical research. The updated Federal Policy for the Protection of Human Subjects, popularly known as the Common Rule, will go into effect on January 21, 2019.Robert K. Chin/Alamy These are the first revisions made to the Common Rule since it was officially codified by HHS in 1991. Many of the regulations involving human research subjects, however, had been in place since the mid-1970s.“The intent of these changes is to streamline the administrative requirements involved in the oversight of clinical trials, while also providing more clarity to participants and researchers about how information and biological specimens can be used,” said Philip Wang, M.D., Ph.D., director of APA’s Division of Research.The updates were a needed response to the increase in size and complexity of clinical trials over the past three decades. Today, multisite clinical trials and the use of digital tools to create and store large amounts of data are the norm in clinical research. Many researchers believed that the Common Rule requirements have not kept up with these changes, making the administrative portion of clinical trials costly and cumbersome.The most significant change overall is that multisite clinical studies will no longer require an Institutional Review Board (IRB) at every trial site. IRBs are independent entities that oversee every clinical trial, with the power to stop a trial if deemed necessary. Researchers conducting large, multisite studies will now be able to use a single IRB, which will make coordination much easier. However, since it may take a while for some researchers to select a central IRB and determine how to coordinate information, HHS has pushed back this requirement until January 2020.For mental health researchers, perhaps the most significant change involves reducing the IRB requirements for studies with minimal risk. Currently, all clinical trials must undergo an annual review. However, starting next year, studies considered “minimal risk” will no longer have this requirement.One class of studies that falls under this low-risk category is “benign behavioral interventions,” which includes any cognitive or behavioral trial that is not overly long or potentially causing emotional distress in participants.Research studies that conduct secondary analyses of existing clinical trial data are also exempt from IRB reviews, so long as patient information remains protected.Another important change is that researchers conducting clinical trials that collect identifiable biospecimens—samples such as DNA that could be traced back to an individual—can ask participants to give “broad consent” on how the biospecimen is used. That way, future trials can use that specimen rather than having to reacquire patient consent or seek a waiver through the IRB.“This is a sensible change that will greatly benefit research,” Wang told Psychiatric News. “We don’t know what the important research questions in mental health will be five or 10 years from now. Broad consent provides the flexibility to address unexpected changes, while still ensuring that individuals who give samples are protected.”While researchers will benefit from many of these changes, so will participants. One example concerns today’s overly complex consent forms that can perplex even seasoned lawyers. The updated rule requires consent forms to contain a simple and concise explanation at the beginning of the document about the key elements of the clinical trial. These elements include the purpose of the research, its risks and benefits, and alternative treatments that might be beneficial to the prospective subject. Consent forms must also clearly state the circumstances when clinically relevant research findings (for example, a genetic analysis reveals a strong risk of some disease) will be shared with the subject. ■ More information on the Common Rule, including the new updates, can be accessed here. ISSUES NewArchived

“We are just numbers”: Gaps in Ethical Research Conduct revealed by clinical research subjects

“We are just numbers”: Gaps in Ethical Research Conduct revealed by clinical research subjects

“We are just numbers”: Gaps in Ethical Research Conduct revealed by clinical research subjects

“We are just numbers”: Gaps in Ethical Research Conduct revealed by clinical research subjects

Privacy of Clinical Research Subjects: An Integrative Literature Review.

With changes in clinical research practice, the importance of a study-subject's privacy and the confidentiality of their personal data is growing. However, the body of research is fragmented, and a synthesis of work in this area is lacking. Accordingly, an integrative review was performed, guided by Whittemore and Knafl's work. Data from PubMed, Scopus, and CINAHL searches from January 2012 to February 2017 were analyzed via the constant comparison method. From 16 empirical and theoretical studies, six topical aspects were identified: the evolving nature of health data in clinical research, sharing of health data, the challenges of anonymizing data, collaboration among stakeholders, the complexity of regulation, and ethics-related tension between social benefits and privacy. Study subjects' privacy is an increasingly important ethics principle for clinical research, and privacy protection is rendered even more challenging by changing research practice.

A clinical practice guideline for temporomandibular disorders in traditional Korean medicine: An evidence-based approach

IntroductionIn overseas reports, temporomandibular disorders (TMDs) are said to affect 5–12% of the population, and the number of TMD patients seeking treatment in Korea is on the rise. Even though Korean medicine (KM) treatments are commonly used for TMDs in clinical practice, clinical practice guidelines (CPGs) for TMDs in traditional KM have not yet been established. This evidence-based KM CPG on TMDs was therefore established. MethodsThe key questions of the KM CPG on TMDs were determined based on clinical practice surveys on the use of KM for TMDs and expert opinion from the relevant academic societies by the CPG development committee. Then, a systematic literature review of KM treatments for TMDs was conducted for each key question, and the guideline draft was created in accordance with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) levels of evidence and grades of recommendation. Official consensus was achieved using the Delphi method on the draft, and the draft was further revised through external review to produce the final guideline, which was certified by the relevant academic societies. ResultsA total of 15 recommendations are established to address the 13 key clinical questions about the clinical efficacy of 9 types of KM treatments for TMD, including grades and levels of evidence. ConclusionsThe present guideline is expected to aid in the decision-making process of physicians and TMD patients, improve the overall quality of KM practice, and suggest subjects for future clinical research.

Long-term preservation of biomedical research data

Genomics and molecular imaging, along with clinical and translational research have transformed biomedical science into a data-intensive scientific endeavor. For researchers to benefit from Big Data sets, developing long-term biomedical digital data preservation strategy is very important. In this opinion article, we discuss specific actions that researchers and institutions can take to make research data a continued resource even after research projects have reached the end of their lifecycle. The actions involve utilizing an Open Archival Information System model comprised of six functional entities: Ingest, Access, Data Management, Archival Storage, Administration and Preservation Planning. We believe that involvement of data stewards early in the digital data life-cycle management process can significantly contribute towards long term preservation of biomedical data. Developing data collection strategies consistent with institutional policies, and encouraging the use of common data elements in clinical research, patient registries and other human subject research can be advantageous for data sharing and integration purposes. Specifically, data stewards at the onset of research program should engage with established repositories and curators to develop data sustainability plans for research data. Placing equal importance on the requirements for initial activities (e.g., collection, processing, storage) with subsequent activities (data analysis, sharing) can improve data quality, provide traceability and support reproducibility. Preparing and tracking data provenance, using common data elements and biomedical ontologies are important for standardizing the data description, making the interpretation and reuse of data easier. The Big Data biomedical community requires scalable platform that can support the diversity and complexity of data ingest modes (e.g. machine, software or human entry modes). Secure virtual workspaces to integrate and manipulate data, with shared software programs (e.g., bioinformatics tools), can facilitate the FAIR (Findable, Accessible, Interoperable and Reusable) use of data for near- and long-term research needs.

Long-term preservation of biomedical research data

Genomics and molecular imaging, along with clinical and translational research have transformed biomedical science into a data-intensive scientific endeavor. For researchers to benefit from Big Data sets, developing long-term biomedical digital data preservation strategy is very important. In this opinion article, we discuss specific actions that researchers and institutions can take to make research data a continued resource even after research projects have reached the end of their lifecycle. The actions involve utilizing an Open Archival Information System model comprised of six functional entities: Ingest, Access, Data Management, Archival Storage, Administration and Preservation Planning. We believe that involvement of data stewards early in the digital data life-cycle management process can significantly contribute towards long term preservation of biomedical data. Developing data collection strategies consistent with institutional policies, and encouraging the use of common data elements in clinical research, patient registries and other human subject research can be advantageous for data sharing and integration purposes. Specifically, data stewards at the onset of research program should engage with established repositories and curators to develop data sustainability plans for research data. Placing equal importance on the requirements for initial activities (e.g., collection, processing, storage) with subsequent activities (data analysis, sharing) can improve data quality, provide traceability and support reproducibility. Preparing and tracking data provenance, using common data elements and biomedical ontologies are important for standardizing the data description, making the interpretation and reuse of data easier. The Big Data biomedical community requires scalable platform that can support the diversity and complexity of data ingest modes (e.g. machine, software or human entry modes). Secure virtual workspaces to integrate and manipulate data, with shared software programs (e.g., bioinformatics tools), can facilitate the FAIR (Findable, Accessible, Interoperable and Reusable) use of data for near- and long-term research needs.

Reversal of Resistance in Targeted Therapy of Metastatic Melanoma: Lessons Learned from Vemurafenib (BRAFV600E-Specific Inhibitor).

Malignant melanoma is the most aggressive form of skin cancer and has a very low survival rate. Over 50% of melanomas harbor various BRAF mutations with the most common being the V600E. BRAFV600E mutation that causes constitutive activation of the MAPK pathway leading to drug-, immune-resistance, apoptosis evasion, proliferation, survival, and metastasis of melanomas. The ATP competitive BRAFV600E selective inhibitor, vemurafenib, has shown dramatic success in clinical trials; promoting tumor regression and an increase in overall survival of patients with metastatic melanoma. Regrettably, vemurafenib-resistance develops over an average of six months, which renders melanomas resistant to other therapeutic strategies. Elucidation of the underlying mechanism(s) of acquisition of vemurafenib-resistance and design of novel approaches to override resistance is the subject of intense clinical and basic research. In this review, we summarize recent developments in therapeutic approaches and clinical investigations on melanomas with BRAFV600E mutation to establish a new platform for the treatment of melanoma.

Attractivité de la France pour la recherche clinique internationale : résultats de la 8e enquête du Leem

TheLeem (French association of pharmaceutical companies)hasconducted the eighth survey on attractiveness of France for clinical research. It serves to measure France's global competitiveness for international clinical trials and assess its strengths and areas of excellence. It also highlights the potential for progress and emerging trends at a time when the regulatory environment in France and Europe is undergoing change. This survey has been updated every two years since 2002 using the same methodology. It assesses the current status of research undertaken in France by the pharmaceutical industry between January 1st 2014 and December 31st 2015. Thirty companies (62% of the French market) have participated in this 8thsurvey which involved 3474 centers (versus 2860 in 2014) and 16,622 patients (versus 14,634 in 2014) enrolled in France across 586 clinical trials (versus 613 in 2014). This survey shows a reduction in the number of phase I and phase II trials. It also confirms that the studies conducted in France are primarily concerned with oncology (45%). Despite improvements across hospital contracts times (due to the adoption of the sole agreement) and performance indicators in trials (such as the number of patients enrolled by center), trial setup times in France are still overly lengthy (with stable times by French authorities). Ensuring that clinical research remains a priority issue for country is crucial for patients because of rapid access to innovation but also for the vitality of the French economy. Constructive dialogue with stakeholders on the subject of clinical research is essential to enhance the attractiveness of France and to improve the continuum between research, innovation and care.

The research progress of relationship between body mass index and esophagus cancer

The effect of body mass index (BMI) on the incidence rate and prognosis of esophageal cancer is one of the significant subjects of clinical research about esophageal cancer in recent years.Researchers have attempted to use BMI to predict the risk and prognosis of esophageal cancer.However, no consensus has yet been reached.In this article, the author reviewed related articles published at home and abroad during the last decade to explore the correlation between BMI and esophageal cancer. Key words: Body mass index; Esophagus cancer; Incidence; Prognosis

%JM: A SAS Macro to Fit Jointly Generalized Mixed Models for Longitudinal Data and Time-to-Event Responses

In clinical research subjects are usually observed during a period of time. Primary and secondary endpoints are often either responses measured longitudinally over time or the time at which an event of interest occurs. Joint modeling is increasingly being used for multiple purposes such as to adjust the analysis of the longitudinal response for informative dropout mechanisms. In this paper we present %JM, a SAS macro that fits jointly generalized mixed models for longitudinal data and proportional hazards models for time-to-event responses. The macro fits normal, binary, binomial and Poisson longitudinal responses and allows choosing among a range of options to fit the trajectories of the longitudinal response over time: a linear function, splines, natural cubic splines and B-splines. For the time-to-event response, that might be right-censored, the macro fits parametric, stratified or not, proportional hazards models with the following baseline risk functions: exponential, Weibull, piecewise exponential and the generalizations of the Weibull and the Gompertz models based on splines. %JM offers several options to connect the longitudinal model and the time-to-event model: current-value-dependent and slope-dependent shared parameters, lagging effects, cumulative effects, random effects coefficients as shared parameters and interaction effects.

Chloride in intensive care units: a key electrolyte.

Over the past few years, chloride has joined the league of essential electrolytes for critically ill patients. Dyschloremia can occur secondary to various etiologic factors before and during patient admission in the intensive care unit. Some cases are disease-related; others, treatment-related. Chloride abnormalities were shown in animal models to have adverse effects on arterial blood pressure, renal blood flow, and inflammatory markers, which have led to several clinical investigations. Hyperchloremia was studied in several settings and correlated to different outcomes, including death and acute kidney injury. Baseline hypochloremia, to a much lesser extent, has been studied and associated with similar outcomes. The chloride content of resuscitation fluids was also a subject of clinical research. In this review, we describe the effect of dyschloremia on outcomes in critically ill patients. We review the major studies assessing the chloride content of resuscitation fluids in the critically ill patient.

Novel Therapeutics for Ovarian Cancer: The 11th Biennial Rivkin Center Ovarian Cancer Research Symposium.

The aim of this study was to summarize developments in novel therapeutics for ovarian cancer presented at the Ovarian Cancer Research Symposium held at the University of Washington. A symposium of the leaders in ovarian cancer research was convened to present and discuss current advances and future directions in ovarian cancer research. The fourth session was held on September 13, 2016, and focused on Novel Therapeutics for Ovarian Cancer. The session featured a keynote presentation on Novel Immunotherapeutics for Ovarian Cancer from Nora Disis and an invited oral presentation from Scott Kaufmann that discussed poly (ADP-ribose) polymerase (PARP) Inhibitor Combinations for the Treatment of Ovarian Cancer. Eight additional oral presentations were selected from abstract submissions. Thirty-eight abstracts were presented as posters highlighting recent advances in tumor immunology, PARP inhibition, chemoresistance, and novel targets for ovarian cancer therapy. PARP inhibitors, immunotherapies, and targeted therapies are but some of the expanding number of treatment options for ovarian cancer patients. Identification of the subsets of patients who will benefit most from these treatments remains the subject of intense preclinical and clinical research. Evidence presented at this symposium suggests that non-BRCA patients also benefit from PARP inhibitor therapies. Improved understanding of the mechanisms of chemoresistance and encouraging preclinical data presented for combinatorial approaches may soon yield new therapies for ovarian cancers that are resistant and refractory to standard treatments.

Closed-loop Administration of General Anaesthesia: From Sensor to Medical Device

AbstractClosed-loop administration devices for general anaesthesia have become a common subject of clinical research over the last decade and appear more and more acceptable in clinical practice. They encompass various therapeutic needs of the anesthetized patient, e. g. fluid administration, hypnotic and analgesic drug administration, myorelaxation. Multiple clinical trials involving closed-loop devices have underscored their safety, but data concerning their clinical benefit to the patient are still lacking. As the marketing of various devices increases, clinicians need to understand how comparisons between these devices can be made: the measure of performance error and wobble are technical but have also a clinical meaning, to which clinical outcomes can be added, such as drug consumption and maintenance of hemodynamic parameters (e. g. heart rate and blood pressure) within predefined ranges. Clinicians using closed-loop devices need especially to understand how various physiological signals lead to specific drug adaptations, which means that they switch from decision making to supervision of general anaesthesia.

AN INNOVATIVE APPROACH TO ENHANCE THE INFORMED CONSENT PROCESS FOR PEOPLE WITH DEMENTIA: THE ENSURE PROJECT

People with dementia have the right to decide whether or not they want to participate in clinical research and to give their free, prior and informed consent. However, as dementia progresses, they can lose their ability to give informed consent to complex medical research because of an increasing loss of cognitive functions. At first sight, it seems ethically problematic to involve dementia patients in research, as people with impaired mental capacity must be protected against the risks of research participation. In contrast to informed consent to medical treatment, an individual benefit from participation in research can rarely be taken for granted. However, people with dementia also have a right to benefit from medical research in particular, so their categorical exclusion would appear to be ethically problematic too. The international, interdisciplinary ENSURE project (Enhancing the informed consent process: Supported decision-making and capacity assessment in clinical dementia research) aims to provide interdisciplinary recommendations to support the development of an action model of an informed consent process in clinical dementia research that 1) enhances the capacity to consent of people with dementia, 2) improves the assessment of decision-making capacity, 3) protects those who do not have the capacity to consent, and 4) guarantees the ethically justified inclusion of research subjects in clinical dementia research. To achieve this, four international project partners cooperate on four interdisciplinary interlinked subprojects. The disciplines involved are gerontology, ethics and law. A flow-chart of ENSURE and an overview of the first results of the subprojects will be presented. Implications for practical use in informed consent procedures will be discussed.

Abstract 190: Risk Factors and Outcomes of Hyperbilirubinemia Following Transcatheter Aortic Valve Replacement

Background: It has been established that postoperative hyperbilirubinemia is associated with increased mortality and morbidity after cardiac surgery. However, hyperbilirubinemia after transcatheter aortic valve replacement (TAVR) has not yet been a subject of clinical research. We evaluated the incidence and risk factors of post-TAVR hyperbilirubinemia, and aimed to determine its prognostic significance. Methods: A retrospective observational study was conducted on 241 consecutive TAVR patients between January 2011 and December 2014 in our institution. We excluded 15 patients with documented chronic hepatic or biliary disorders, or prior liver transplant. Hyperbilirubinemia was defined as any value above the upper limit of normal total bilirubin within 1 week of TAVR. Results: Eighty-two patients out of 226 (36.3%) had post-TAVR hyperbilirubinemia. After adjustment for confounders, there was no significant difference in in-hospital mortality (3.7% (3 of 82) vs. 1.4% (2 of 144); p-value = 0.26) and 1-year mortality (7.3% (6 of 82) vs 5.6% (8 of 144); p-value = 0.60) between patients with and without elevated bilirubin following TAVR. However, there was a trend for hyperbilirubinemic patients to have a longer intensive care unit stay (145.3 +/-202.2 hours vs. 113.2 +/-93.4 hours; p-value = 0.14) and hospital stay (14.1 +/-11.2 days vs. 12.1 +/-8.6 days; p-value = 0.16). Multivariable analysis revealed that preoperative hyperbilirubinemia (hazard ratio 62.88, 95% confidence interval 15.80 to 250.32; p-value <0.0001) and preoperative atrial fibrillation (hazard ratio 2.40, 95% confidence interval 1.21 to 4.78; p-value = 0.01) were strongly associated with post-TAVR hyperbilirubinemia. Conclusions: The cause of post-TAVR hyperbilirubinemia may be multifactorial. It is not a rare event and may impact the short-term outcomes. Thus, monitoring bilirubin should be considered an integrated part of TAVR patient care. Optimal management of post-TAVR hyperbilirubinemia remains challenging.

Intranasal Oxytocin and Vasopressin Modulate Divergent Brainwide Functional Substrates.

The neuropeptides oxytocin (OXT) and vasopressin (AVP) have been identified as modulators of emotional social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction. Experimental and therapeutic use of OXT and AVP via the intranasal route is the subject of extensive clinical research. However, the large-scale functional substrates directly engaged by these peptides and their functional dynamics remain elusive. By using cerebral blood volume (CBV) weighted fMRI in the mouse, we show that intranasal administration of OXT rapidly elicits the transient activation of cortical regions and a sustained activation of hippocampal and forebrain areas characterized by high oxytocin receptor density. By contrast, intranasal administration of AVP produced a robust and sustained deactivation in cortico-parietal, thalamic and mesolimbic regions. Importantly, intravenous administration of OXT and AVP did not recapitulate the patterns of modulation produced by intranasal dosing, supporting a central origin of the observed functional changes. In keeping with this notion, hippocampal local field potential recordings revealed multi-band power increases upon intranasal OXT administration. We also show that the selective OXT-derivative TGOT reproduced the pattern of activation elicited by OXT and that the deletion of OXT receptors does not affect AVP-mediated deactivation. Collectively, our data document divergent modulation of brainwide neural systems by intranasal administration of OXT and AVP, an effect that involves key substrates of social and emotional behavior. The observed divergence calls for a deeper investigation of the systems-level mechanisms by which exogenous OXT and AVP modulate brain function and exert their putative therapeutic effects.