Experiences of antibiotic use among Brazilian healthcare users: An exploratory study.

INTRODUCTION: This article analyzes experiences of antibiotic use and bacterial infections among Primary Health Care users of the Brazilian Unified Health System (SUS) and the possible implications for antimicrobial resistance (AMR). The aim is to map aspects that shape users' lay knowledge regarding antibiotics use and AMR. METHODS: This is an exploratory study, which consists primarily of individual in-depth interviews with 19 respondents. Recurrent interview topics were coded and analysed according to thematic content analysis. RESULTS: Our findings show users' lived experiences constitute three dimensions related to users' previous antibiotic use: (1) lay knowledge about medicines; (2) previous bacterial infections and (3) communication during the consultation. Lay knowledge encompasses the users' understanding of how antibiotics work in comparison to other drugs and experimentations they make with medication. Users' narratives about bacterial infections are divided into situations of urinary tract infections and antibiotic treatments for other conditions. Communication during the consultation is mainly characterized by a lack of shared knowledge and trust in the doctor-patient relationship. DISCUSSION: Users bring together knowledge learned from their own experiences to create the rationale, which shapes how they understand antibiotic use, bacterial infections and medical advice. These experiences are interwoven with information received from healthcare professionals (HPs) on these topics, creating a scenario that goes beyond professional information about antibiotic use. Users have knowledge about medication, antibiotics use and bacterial infection but do not have room to share it with HP, allowing lived experiences to take precedence over professional information. CONCLUSION: Users ascribe symbolic meanings to antibiotics creating a lay knowledge frame, even if this knowledge is not scientifically correct. The personal experiences of bacterial infections and their treatment are also an important source of knowledge about antibiotic use and AMR among users. Users demand from their HPs both trust and willingness to listen to their health narratives and experiences. By considering lay knowledge as part of the assessment of a user's health condition, rather than dismissing it as erroneous and therefore unworthy of attention, HPs may enhance the compliance of users. PATIENT OR PUBLIC CONTRIBUTION: Patients or community members did not participate in the design stage of the study. Primary Care patients were invited to participate as respondents of in-depth interviews, which were carried out by the first author at a Primary Care Unit (PCU) in the suburb of Campo Limpo, Southern region of São Paulo, Brazil. Patients were interviewed after reading and signing a Free and Informed Consent Form, holding with them a copy of the Form. Among the final activities of the project, a feedback session at the same PCU is planned to report on the results of the study. All respondents will have the opportunity to contribute further information regarding their antibiotic use and exchange knowledge and experiences on antimicrobial resistance.

The Enigmatic Metallothioneins: A Case of Upward-Looking Research.

In the mid-1950s, Bert Lester Vallee and his colleague Marvin Margoshes discovered a molecule referred to today as metallothionein (MT). Meanwhile, MTs have been shown to be common in many biological organisms. Despite their prevalence, however, it remains unclear to date what exactly MTs do and how they contribute to the biological function of an organism or organ. We investigate why biochemical research has not yet been able to pinpoint the function(s) of MTs. We shall systematically examine both the discovery of and recent research on Dr. Vallee's beloved family of MT proteins utilizing tools from philosophy of science. Our analysis highlights that Vallee's initial work exhibited features prototypical of a developing research tradition: it was upward-looking, exploratory, and utilized mere interactions. Since the 1960s, MT research has increasingly become intervention- and hypothesis-based while it remained largely upward-looking in character. Whilst there is no reason to think that upward-looking research cannot successfully yield structure-function mappings, it has not yet been successful in the case of MTs. Thus, we suggest it might be time to change track and consider other research strategies looking into the evolution of MTs. Recent studies in mollusks render research in this direction worthy of pursuit.

Measuring health promotion research impact - What researchers think?

ISSUES ADDRESSED: The significant investment in health research has resulted in an increased focus to determine suitable approaches to measure health promotion research impact. This research was undertaken at the request of a nationally competitive research organisation that funds health promotion research, to explore how Chief Investigators (CIs) on their funded projects understood research impact, its measurement and associated challenges. METHODS: Participants were required to be or have been a CI on an Australian competitive research (exploratory or intervention) grant focussed on health promotion. The qualitative study used thematic analysis from one-on-one interviews. Themes were created and descriptive quotes were selected to illustrate the main findings. RESULTS: The majority of participants were female (n = 13) working at a university (n = 13). Three themes emerged: a) defining health research impact; b) complexity and simplicity of measuring health research impact; c) challenges of measuring health research impact: i) differing language; ii) differing assessment; iii) attribution and timing; and iv) resourcing and skills. CONCLUSION: Researchers recognised that there are significant challenges in measuring the impact of health promotion research. The most significant factors identified by participants were the disciplinary background of the researchers undertaking the measurement, their skills and experience and the resources (including time) available to assess impact. SO WHAT?: Research impact assessment is complex, time consuming and requires specific skills to facilitate measurement of impact provision of funding for this activity in research grants and research impact training is required.

[Natural Latex Rubber Condom Inspection and Exploratory Research Analysis].

According to the situation of 34 batches of natural rubber latex condoms tested by our center in 2018, the unqualified items in the product inspection items and the exploratory research results of D4 and D5 content in silicone oil lubricants are analyzed. We make recommendations on product technical requirements or standards to strengthen the quality supervision of products.

Genomic sequencing identifies secondary findings in a cohort of parent study participants.

PURPOSE: Clinically relevant secondary variants were identified in parents enrolled with a child with developmental delay and intellectual disability. METHODS: Exome/genome sequencing and analysis of 789 "unaffected" parents was performed. RESULTS: Pathogenic/likely pathogenic variants were identified in 21 genes within 25 individuals (3.2%), with 11 (1.4%) participants harboring variation in a gene defined as clinically actionable by the American College of Medical Genetics and Genomics. These 25 individuals self-reported either relevant clinical diagnoses (5); relevant family history or symptoms (13); or no relevant family history, symptoms, or clinical diagnoses (7). A limited carrier screen was performed yielding 15 variants in 48 (6.1%) parents. Parents were also analyzed as mate pairs (n = 365) to identify cases in which both parents were carriers for the same recessive disease, yielding three such cases (0.8%), two of which had children with the relevant recessive disease. Four participants had two findings (one carrier and one noncarrier variant). In total, 71 of the 789 enrolled parents (9.0%) received secondary findings. CONCLUSION: We provide an overview of the rates and types of clinically relevant secondary findings, which may be useful in the design and implementation of research and clinical sequencing efforts to identify such findings.

The Wakan-yaku Universe: A Useful Authorized Traditional Concept for Developing Novel Therapeutic Categories and Medicinal Drugs.

This review article mentions about the following points, and proposes its importance and positive thinking. 1) Wakan-yaku (Japanese oriental medicines) is covered by the national health insurance system in Japan as therapeutic drugs to be actively used in medical practice to treat illness. 2) Applications of Wakan-yaku is accomplished based on the reliable own theories which are established with long histories. 3) Promotion of studies based on these theories will be highly expected to find novel view points which breaks conventional concepts and to novel standards for developing new medicinal drugs. Although studies based on the reliable Wakan-yaku theories are not advancing satisfactorily till now, the possibilities to obtain the advanced resources for drugs and novel viewpoints for experiments by studies about Wakan-yaku theories are discussed in this review.

Why Patients Decline Genomic Sequencing Studies: Experiences from the CSER Consortium.

Clinical and research settings are increasingly incorporating genomic sequencing (GS) technologies. Previous research has explored reasons for declining genetic testing and participation in genetic studies; however, there is a dearth of literature regarding why potential participants decline participation in GS research, and if any of these reasons are unique to GS. This knowledge is essential to promote informed decision-making and identify potential barriers to research participation and clinical implementation. We aggregated data from seven sites across the National Institutes of Health's Clinical Sequencing Exploratory Research (CSER) consortium on each project's procedures for recruitment, and rates of and reasons for decline. Data were analyzed using descriptive statistics. The decline rate for enrollment at the seven CSER sites ranged from 12 to 64% (median 28%) and varied based on age and disease status. Projects differed in their protocols for approaching potential participants and obtaining informed consent. Reasons for declining GS research were reported for 1088 potential participants. Commonly cited reasons were similar to those reported for clinical single gene testing and non-GS genetic research. The most frequently cited reason for decline was study logistics (35%); thus, addressing logistical barriers to enrollment may positively impact GS study recruitment. Privacy and discrimination concerns were cited by 13% of decliners, highlighting the need for researchers and providers to focus educational efforts in this area. The potential psychological burden of pursuing and receiving results from GS and not wanting to receive secondary findings, a concern specific to GS, have been cited as concerns in the literature. A minority of potential participants cited psychological impact (8%) or not wanting to receive secondary findings (2%) as reasons for decline, suggesting that these concerns were not major barriers to participation in these GS studies. Further research is necessary to explore the impact, if any, of different participant groups or study protocols on rates of decline for GS studies. Future studies exploring GS implementation should consider using standardized collection methods to examine reasons for decline in larger populations and more diverse healthcare settings.

Pediatric oncology social workers' experience of compassion fatigue.

Pediatric oncology social workers play an important role in supporting cancer patients and their families as they learn to talk about and cope with the physical and psychological impacts of cancer. As a result, social workers are particularly vulnerable to compassion fatigue and the associated psychological and physical impacts. The purpose of this qualitative study was to understand the experience of compassion fatigue among 27 pediatric oncology social workers. Four main themes emerged throughout the five focus groups: Conditions that contribute to compassion fatigue; the influence of compassion fatigue; coping strategies to alleviate compassion fatigue; and desire for systematic support to prevent compassion fatigue. Our study findings emphasize the importance of developing programs, policies and research geared toward the prevention of compassion fatigue, in addition to coping with symptoms. Further, this study brings attention to the importance of including pediatric oncology social workers in efforts to develop and implement systemic supports.

Ethical Considerations in Ending Exploratory Brain-Computer Interface Research Studies in Locked-in Syndrome.

Brain-computer interface (BCI) is a promising technology for restoring communication in individuals with locked-in syndrome (LIS). BCI technology offers a potential tool for individuals with impaired or absent means of effective communication to use brain activity to control an output device such as a computer keyboard. Exploratory studies of BCI devices for communication in people with LIS are underway. Research with individuals with LIS presents not only technological challenges, but ethical challenges as well. Whereas recent attention has been focused on ethical issues that arise at the initiation of studies, such as how to obtain valid consent, relatively little attention has been given to issues at the conclusion of studies. BCI research in LIS highlights one such challenge: How to decide when an exploratory BCI research study should end. In this article, we present the case of an individual with presumed LIS enrolled in an exploratory BCI study. We consider whether two common ethical frameworks for stopping randomized clinical trials-equipoise and nonexploitation-can be usefully applied to elucidating researcher obligations to end exploratory BCI research. We argue that neither framework is a good fit for exploratory BCI research. Instead, we apply recent work on clinician-researcher fiduciary obligations and in turn offer some preliminary recommendations for BCI researchers on how to end exploratory BCI studies.

[The pilot studies for the development of the combined methods of rehabilitation of the patients as exemplified by the application of phyto- and physiotherapeutic modalities]. / Poiskovye issledovaniia pri razrabotke kompleksnykh metodov reabilitatsii bol'nykh na primere fito- i fizioterapii.

Under the modern market conditions, the process of development of the methods for the combined rehabilitation of the patients is becoming increasingly more complicated. For the reduction of potential risks and leveling the factors responsible for the uncertain market situation influencing the creation of new methods, it is necessary to carry out the full-scale pilot studies with the use of the marketing analysis methods. The objective of the present work was to create and elaborate the rationale for the graphological structure (the scheme) of the process of exploratory research with a view to the development of the combined rehabilitation methods as exemplified by phyto- and physiotherapeutic modalities. The work is based on the application of the existing approaches to the structural, comparative, systemic, and situational analyses. The proposed graphological structure (scheme) of the exploratory research process consists of 6 stages. Its distinctive features are as follows: a fractional stage by stage evaluation of a variety of issues including the study of physical factors, characteristic of the means of herbal medicine with special reference to the mechanisms of their production and application under the current market conditions, monitoring the marketing environment with the constant focus on the trends and behavior of the target market, the parallel pursuing of serial studies with the application of the iterative procedures; the use of the previously created data bank to expand medical services at the stages of development and maturation of the life cycle, the evaluation of the possibility of establishment of the industry of parapharmaceutical products.

An Exploratory Study on the Conceptualization of Burnout among the Professional Esports Athletes: Focused on League of Legends Champions Korea League.

Research on the stress and burnout experienced by athletes in the esports field remains limited, necessitating an approach that considers the unique environment and circumstances of esports athletes. This study aims to explore the conceptualization of burnout experiences among professional esports athletes. The participants included 88 athletes from the League of Legends Championship Korea (LCK). Among these, in-depth interviews were conducted with 7 athletes who had experience in international tournaments (the World Championship), while an open-ended survey was completed by 81 athletes. Data collected through in-depth interviews and an open-ended survey were digitized and utilized for analysis. Through critical review by another author and inductive categorization, the conceptual components of esports athletes' burnout were derived. Through the analysis of 251 raw datum, it was conceptualized into five conceptual factors: performance, overtraining, interpersonal relationships, physical and psychological exhaustion, and career and motivation. The results of this study confirm that esports athletes, like athletes in other conventional sports, experience burnout during their careers, highlighting issues in their unique environment, particularly in aspects of interpersonal relationships and training and rest conditions. This research can serve as a foundational resource for effective athletes' psychological health management in the esports field and underscores the need for further research on burnout among esports athletes.

Theory Use in Project Management Research: An Exploratory Content Analysis Approach.

The frequency and richness of the theories developed, tested, and used by researchers in an academic discipline exemplify several pertinent factors, namely, the growth, the maturity, the independence, the legitimacy, and the influence of the discipline. Although organizations have been working on projects for centuries, Project Management (PM) is a considerably new academic discipline with emerging research themes, models, methodologies, frameworks, and paradigms. These PM concepts are anchored on or reinforced by new or existing theories. This exploratory study aims to add to the existing PM body of knowledge by investigating the prevalence of theory use in PM research. A systematic content analysis of 9200 PM research articles published from 2000 to 2019 (20 years) in the leading PM journals identified 248 unique theories. These results reveal that the PM discipline is increasingly embracing the use of theories with game theory, fuzzy theory, agency theory, contingency theory, and stakeholder theory emerging as the most dominant theories in the reviewed research articles. Also, although PM is developing its theories, the results revealed that PM researchers continue to heavily use theories borrowed from other academic disciplines such as psychology, sociology, mathematics, and economics.

The Exposure Peaks of Traffic-Related Ultrafine Particles Associated with Inflammatory Biomarkers and Blood Lipid Profiles.

In this article, we explored the effects of ultrafine particle (UFP) peak exposure on inflammatory biomarkers and blood lipids using two novel metrics-the intensity of peaks and the frequency of peaks. We used data previously collected by the Community Assessment of Freeway Exposure and Health project from participants in the Greater Boston Area. The UFP exposure data were time-activity-adjusted hourly average concentration, estimated using land use regression models based on mobile-monitored ambient concentrations. The outcome data included C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-alpha receptor 2 (TNF-RII), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides and total cholesterol. For each health indicator, multivariate regression models were used to assess their associations with UFP peaks (N = 364-411). After adjusting for age, sex, body mass index, smoking status and education level, an increase in UFP peak exposure was significantly (p < 0.05) associated with an increase in TNF-RII and a decrease in HDL and triglycerides. Increases in UFP peaks were also significantly associated with increased IL-6 and decreased total cholesterol, while the same associations were not significant when annual average exposure was used. Our work suggests that analysis using peak exposure metrics could reveal more details about the effect of environmental exposures than the annual average metric.

Dynamics of self-control during choice and post-choice consumption quantity.

Observed choices between options representing a relative vice and a relative virtue have commonly been used as a measure of eating self-control in the literature. However, even though self-control operations may manifest across the post-choice consumption stage, either similarly or in different ways from the choice stage, most prior research has ignored consumption quantity of the chosen option. While the behavior of choosing a virtue instead of a vice does manifest self-control, we examine how this plays out in post-choice consumption. Specifically, we find that when processing resources are limited, after having chosen a virtue food, unrestrained eaters ironically consumed greater quantities and therefore more calories than restrained eaters (Study 1). This reflects more persistent self-control in the post-choice consumption stage among restrained eaters than unrestrained eaters, and occurs because choosing a virtue lowers accessibility of the self-control goal among unrestrained eaters relative to restrained eaters (Study 2), thereby increasing intake of the virtuous food. In contrast, subsequent to having chosen a vice, unrestrained eaters and restrained eaters did not show any such difference in intake (Study 1) or goal accessibility (Study 2). Together, these results reveal that persistence of self-control in the post-choice consumption stage depends on individuals' dietary restraint and their initial exercise of self-control in the choice decision. The mere act of choosing a virtue satisfies unrestrained eaters' self-control goal and leads to increased food intake, whereas the same act keeps the same goal activated among restrained eaters who reduce intake of the chosen virtue. Put differently, persistent self-control across choice and quantity decisions is observed only when those with a dietary goal show successful self-control enactment in the choice stage. We therefore highlight that the operation of self-control can be dynamic within a consumption episode, and thus, choice and post-choice quantity are both informative of self-control.

Healthcare Professional Perspectives on the Impact of the Physical Health Nurse Consultant.

Early mortality experienced by people living with mental health issues (hereon termed consumers) is largely preventable. Healthcare professionals perceive healthcare system inadequacies such as diagnostic overshadowing, stigma and fragmentation of physical and mental healthcare services can be resolved through effective integration approaches. Service- and individual-level integration approaches involve multidisciplinary teams collaborating and coordinating care to holistically meet consumers' physical and mental health needs. Evidence suggests appropriately trained healthcare professionals can deliver effective integrated treatment without financial or organisational restructuring. Specialist nursing positions such as Physical Health Nurse Consultants can support and integrate physical and mental health care. Consumers report the Physical Health Nurse Consultant as providing dedicated, integrated, coordinated and holistic mental and physical health care. This study aimed to explore the Physical Health Nurse Consultant role from the perspectives of healthcare professionals. A qualitative exploratory study design was used. Fourteen healthcare professionals participated in individual interviews or focus groups. Interview recordings were transcribed, and thematically analysed. Three themes were identified: (i) role functions, including integration of physical and mental health care, (ii) impact on consumer physical health outcomes and (iii) impact on service delivery. Healthcare professionals perceive the Physical Health Nurse Consultant effectively integrates physical and mental health care and subsequently support the continuation and embedding of the role in routine practice. Future research is required to explore healthcare professionals' experiences and perceptions of how these roles be translated to routine clinical practice. Examining the professional development requirements, service provider constraints and economic implication to achieve these outcomes also warrants attention.

Lessons learned from exploratory research about viral hepatitis.

The Centers for Disease Control and Prevention conducted exploratory research as part of planning a national education campaign to raise awareness about viral hepatitis in the United States. The purpose of this qualitative research was to assess the baseline knowledge, attitudes, and screening behaviors of four population groups. Sixteen focus groups were conducted during a 6-week period in the fall of 2009, with a total of 119 adults aged 35 to 60 years in Boston, Massachusetts; Chicago, Illinois; and Houston, Texas. The groups were stratified by Asian Americans, African Americans, gay or bisexual men, and general population. Group size ranged from three to nine participants, and each session was approximately 90 minutes in length. Both awareness and knowledge of viral hepatitis were low among all participants, including those at increased risk for the disease. Little was known about the different types of hepatitis, risk factors, or how the viruses are transmitted. Regarding the last, many indicated that the disease was airborne. In addition, participants incorrectly assumed that if they had viral hepatitis, they would have symptoms and know they were infected. Many participants also believed that they had been tested for the disease since their health care providers routinely "test their blood." The findings indicate that significant and concerted educational efforts are needed to improve basic knowledge of viral hepatitis, as well as knowledge about transmission, risk factors, screening, and treatment. As a result, a general awareness and education campaign must precede and support efforts to encourage screening.

Preparing for NICU discharge: mothers' concerns.

PURPOSE: To quantify mothers' concerns in anticipation of their infant's discharge from the NICU. DESIGN: An exploratory, cross-sectional survey design was used. SAMPLE: A convenience sample of 150 mothers. MAIN OUTCOME VARIABLE: The focus was the mothers' concerns about their infant's impending discharge. RESULTS: The mothers expressed confidence in their ability as a caregiver but expressed concern about being tired, the need for readmission to the hospital, and missing a change in the infant's conditions.

Telehealth nursing interventions for phenotypes of older adults with COPD: an exploratory study.

Introduction: Inconclusive results exist around the effectiveness of telemonitoring for patients with COPD, and studies recommended conducting subgroup analyses to identify patient phenotypes that could benefit from these services. This exploratory study investigated what type of COPD patients were receiving which type of telenursing interventions more frequently using the telemonitoring platform. Methods: A sample of 36 older adults with COPD were receiving telenursing services for 12 months and were asked to answer five COPD-symptom related questions and submit their vital signs daily. Results: Findings revealed two phenotypes of older adults for whom the frequency of telenursing calls and related interventions differed. Although no statistically significant differences were observed in participants' GOLD grades and hospitalizations, cluster one participants used their COPD action plan significantly more frequently, and were in frequent contact with the telenurse. Discussion: It is paramount that further research is needed on the development of patient phenotypes who may benefit from telemonitoring.

Sonographic, Demographic, and Clinical Characteristics of Pre- and Postmenopausal Women with Endometrial Cancer; Results from a Post Hoc Analysis of the IETA4 (International Endometrial Tumor Analysis) Multicenter Cohort.

In this study, we conducted a comparative analysis of demographic, histopathological, and sonographic characteristics between pre- and postmenopausal women diagnosed with endometrial cancer, while also examining sonographic and anthropometric features in 'low' and 'intermediate/high-risk' cases, stratified by menopausal status. Our analysis, based on data from the International Endometrial Tumor Analysis (IETA) 4 cohort comprising 1538 women (161 premenopausal, 1377 postmenopausal) with biopsy-confirmed endometrial cancer, revealed that premenopausal women, compared to their postmenopausal counterparts, exhibited lower parity (median 1, IQR 0-2 vs. 1, IQR 1-2, p = 0.001), a higher family history of colon cancer (16% vs. 7%, p = 0.001), and smaller waist circumferences (median 92 cm, IQR 82-108 cm vs. 98 cm, IQR 87-112 cm, p = 0.002). Premenopausal women more often had a regular endometrial-myometrial border (39% vs. 23%, p < 0.001), a visible endometrial midline (23% vs. 11%, p < 0.001), and undefined tumor (73% vs. 84%, p = 0.001). Notably, despite experiencing a longer duration of abnormal uterine bleeding (median 5 months, IQR 3-12 vs. 3 months, 2-6, p < 0.001), premenopausal women more often had 'low' risk disease (78% vs. 46%, p < 0.001). Among sonographic and anthropometric features, only an irregular endometrial-myometrial border was associated with 'intermediate/high' risk in premenopausal women. Conversely, in postmenopausal women, multiple features correlated with 'intermediate/high' risk disease. Our findings emphasize the importance of considering menopausal status when evaluating sonographic features in women with endometrial cancer.

Open-label use of an aliphatic polyamine immunomodulator in patients hospitalized with COVID-19.

Background: Evidence-based therapies used to treat coronavirus disease (COVID-19) remain limited. Azoximer bromide (AZB; Polyoxidonium®) is an immunomodulating molecule frequently used in the Russian Federation. It offers demonstrable therapeutic benefit in upper respiratory tract infections. This study evaluated the safety and efficacy of AZB when used in combination with standard of care treatment in patients hospitalized with COVID-19. Methods: Hospitalized patients with COVID-19 (n=81; nine sites) received AZB 12 mg intravenously once daily for 3 days then intramuscularly every other day until day 17. The primary endpoint included clinical status at day 15 versus baseline. Historical control data of 100 patients from a randomized, controlled, open-label trial conducted in China were included to serve as a direct control group. Results: Notable clinical improvement, assessed by seven-point ordinal scale (OS) score and National Early Warning Score, was observed. Mean duration of hospitalization was 19.3 days. Indicators of pneumonia and lung function showed gradual recovery to normalization. No patients died but, by day 28, one patient still required respiratory support; this patient died on day 34. A higher proportion of patients receiving AZB required invasive or non-invasive ventilation (OS 5 or 6) at baseline compared with the historical control group. Improvement in mean OS score by day 14/15 was not notable in the control group (OS 3.99-3.87) but was clear in the AZB group (OS 4.36-2.90). Mean duration of hospitalization was similar in the control group (16.0 days); however, day 28 mortality was higher, at 25.0% (n=25). Conclusion: AZB combined with standard of care was safe and well tolerated. An apparent clinical improvement could not be fully evaluated due to the lack of a direct control group; further assessment of AZB for the treatment of COVID-19 in a randomized, placebo-controlled study is warranted.