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The article presents the recommended design features of future clinical trials of antibacterial agents for community-acquired pneumonia (CAP). The efficaciousness of new antibiotics for the treatment of CAP has been assessed and compared with that of established antibiotics in noninferiority clinical trials. But the U.S. Food and Drug Administration is reassessing the appropriateness of a noninferiority trial design for CAP. Based on the pertinent data, there is a definitive and substantial treatment effect of antibiotic therapy for CAP. The evidence supporting a treatment effect of antibiotics includes higher mortality rates among patients with CAP, immediate decline in the mortality due to CAP, higher rates of treatment failure among patients infected with organisms and many others.

Background Although current efforts are made to diminish the incidence and burden of disease, cancer is still widely identified late at stage. This study aims to conduct a systematic review mapping the existent and emerging clinical research on artificial intelligence (AI) in the treatment of cancer and to underpin its integration challenges and opportunities in the European Union (EU) health sector. Methods A systematic literature review (SLR) evaluating global clinical trials (CTs; published between 2010 and 2020 or forthcoming) was concluded. Additionally, a horizon scanning (HS) exercise focusing on emerging trends (published between 2017 and 2020) was conducted. Results Forty-four CTs were identified and analyzed. Selected CTs were divided into three research areas: (i) potential of AI combined with imaging techniques, (ii) AI's applicability in robotic surgery interventions and (iii) AI's potential in clinical decision making. Twenty-one studies presented an interventional nature, nine papers were observational and 14 articles did not explicitly mention the type of study performed. The papers presented an increased heterogeneity in sample size, type of tumour, type of study and reporting of results. In addition, a shift in research is observed and only a small fraction of studies were completed in the EU. These findings could be further linked to the current socio-economic, political, scientific, technological and environmental state of the EU in regard to AI innovation. Conclusion To overcome the challenges threatening the EU's integration of such technology in the healthcare field, new strategies taking into account the EU's socio-economic and political environment are deemed necessary. [ABSTRACT FROM AUTHOR]

Background: the worldwide number of dementia cases is increasing, and this is a trend that is expected to continue as a growing proportion of the population ages. However, conducting research with persons suffering from dementia can be fraught due to fears surrounding research risks in vulnerable populations. This can make seeking approval for studies difficult. As research directly involving persons with dementia is key for the development of evidence-based best practice, the development of a coherent ethical strategy to perform such research feasibly and effectively is of paramount importance. Objective: this paper aims to review and synthesise ethical challenges in performing research with persons who have dementia. Methods: in undertaking a systematic review of the current research literature, we will identify the central issues and arguments characterising research that concerns the ethical dimensions of research participation in the dementia population. Data were analysed using both inductive and deductive content analysis. Ethical considerations in research involving persons with dementia primarily concern the representation of the interests of the person with dementia and protection of their vulnerabilities and rights. Results: a total of 2,894 results were returned from initial searches, following deduplication. In total, 2,458 were excluded at title review, and following abstract review 158 papers remained; 29 papers were included for analysis after full paper review and data extraction. Papers ranged between 1995 and 2013. Conclusion: this review has highlighted a lack of consensus in current research and guidelines addressing these concerns; a clear stance on ethical governance of studies is important for future research and best evidence-based practice in dementia. [ABSTRACT FROM AUTHOR]

We examined the importance of understanding and incorporating cultural context within Aotearoa/New Zealand when engaging in clinical research and practice. This paper reports on the qualitative findings of a mixed methods study aimed at determining what effect a cardiac risk reduction exercise and lifestyle management programme, embedded within a kaupapa Māori methodological approach, had on Māori participants. This methodology saw participants able to redevelop a western model cardiac risk reduction programme by introducing a Māori worldview. Our study revealed how the kaupapa Māori approach empowered participants to examine and evaluate not only their own health and lifestyle choices, but those of family and the wider community. Combining biomedical and kaupapa Māori components into the programme was found to benefit participants' mental, physical, spiritual and family well-being. [ABSTRACT FROM AUTHOR]

Online citizen panels are an innovative way to collect information about populations. They can help explain social determinants of health while involving citizens in research, allowing researchers to help the community, and advance cardiovascular research. This paper discusses the advantages and disadvantages of collecting information via online citizen panels and assesses these panels' potential in cardiovascular research. To exemplify such panels' use, we discuss a case study that utilized the Swedish Citizen Panel. [ABSTRACT FROM AUTHOR]

Objectives. To describe existing techniques of US-guided synovial biopsy (USG-SB) and critically appraise the literature on this technology through the OMERACT filter. Methods. USG-SB techniques are described and compared. A systematic literature search of PubMed and Embase was performed for original research reports including US and SB. The subjects, procedure protocols and reported results were analysed. A future research agenda is proposed. Results. USG-SB can be performed using a portal-and-forceps or a dedicated semi-automatic guillotine-type biopsy needle approach. Of 50 reports identified, 7 were included in the review. Large, intermediate and small joints were all amenable to USG-SB. We found great heterogeneity with regard to indications for and definition of a successful procedure and of synovitis. Adverse events were assessed in most papers with an overall major complication rate of 0.4%. However, there was a lack of construct validity using a histological comparator. Relatively few papers reported details on the technique used, tissue processing, synovitis scoring and blinding for tissue analysis. Conclusion. USG-SB can be regarded as a valuable tool for large-scale synovial tissue sampling. Standardization of the techniques of USG-SB and tissue processing is needed. Future research should focus on the reliability, responsiveness and feasibility of this procedure in prospective studies. [ABSTRACT FROM AUTHOR]

The existing literature indicates that motivation is an important predictor of treatment outcome for people with substance use disorders (SUD). Although researchers have found that music therapy can positively impact motivation for people with SUD, the music therapy and SUD literature base lack a theoretical understanding of motivation. Vroom's expectancy theory of motivation (ETM) is an established theoretical framework positing that motivation depends on three relationships: expectancy, instrumentality, and valence. These relationships consist of four variables: effort, performance, reward, and preference. Based on these four variables, motivation depends on the expectation that an increase in effort will lead to improved performance, thus leading to a reward aligned with an individual's preferences. The purpose of this paper is to apply Vroom's ETM to music therapy and SUD clinical practice and research. We reviewed the existing literature addressing Vroom's ETM within SUD treatment and created a model to depict how to apply Vroom's ETM to music therapy clinical practice for people with SUD. Application of Vroom's ETM may help music therapists understand and augment motivation for people with SUD, potentially leading to relapse prevention and recovery. Implications for clinical practice, limitations, and suggestions for future research are provided. [ABSTRACT FROM AUTHOR]

Many healthcare professions have noted challenges in the integration of Evidence-Based Practice (EBP). Of the three areas that make up EBP (research, clinical expertise and patient preference), research implementation appears to be the biggest hurdle for clinicians to overcome. From the perspective of two clinicians who participate in the design and implementation of research protocols, this paper addresses the issues of reading, understanding, participating in and integrating research evidence, particularly as it pertains to neurological rehabilitation and the use of the neurologic music therapy technique Rhythmic Auditory Stimulation. [ABSTRACT FROM AUTHOR]

Summary. The paper addresses some of the key issues to be considered in analysing intensive longitudinal data after summarization at scheduled landmarks (i.e. prespecified times). In this context, the derivation of outcomes requires rigorous rules and the selection of covariates should be based on a thorough data exploration. To guide the choice of statistical approaches for inferences, we study the missingness mechanism by using a specific dropout model. Then, we compare and contrast statistical approaches based on direct modelling and on multiple imputation applied either to the raw data or to the derived outcomes. The results are interpreted in the light of the model constraints and the missingness mechanism assumption. We show that some statistical approaches based on multiple imputation applied to the raw data are particularly well adapted to our context as they avoid any loss of available information for missing data imputation. We also show that the influence of subjects with incomplete profiles can be described by using individual estimations given by appropriate statistical models. The motivating data set was collected in a double-blind placebo-controlled clinical trial to assess the effect on pain of a new compound in subjects suffering from fibromyalgia. [ABSTRACT FROM AUTHOR]

This paper introduces taxonomy of clinical uncertaintes and argues that the choice of scientific method should match the underlying level of uncertainty. Clinical trial is one of these methods aiming to resolve clinical uncertainties. Whenever possible these uncertainties should be quantified. The paper further shows that the still ongoing debate about the usage of "equipoise" vs. "uncertainty principle" vs. "indifference" as an entry criterion to clinical trials actually refers to the question "whose uncertainty counts". This question is intimately linked to the control of research agenda, which is not quantifiable and hence is not solvable to equal acceptability to all interested parties. The author finally shows that there is a predictable relation between [acknowledgement of] uncertainty (the moral principle) on which trials are based and the ultimate outcomes of clinical trials. That is, [acknowledgement of] uncertainty determines a pattern of success in medicine and drives clinical discoveries. [ABSTRACT FROM AUTHOR]

In many therapeutic areas, the identification and validation of surrogate end points is of prime interest to reduce the duration and/or size of clinical trials. Buyse and co-workers and Burzykowski and co-workers have proposed a validation strategy for end points that are either normally distributed or (possibly censored) failure times. In this paper, we address the problem of validating an ordinal categorical or binary end point as a surrogate for a failure time true end point. In particular, we investigate the validity of tumour response as a surrogate for survival time in evaluating fluoropyrimidine-based experimental therapies for advanced colorectal cancer. Our analysis is performed on data from 28 randomized trials in advanced colorectal cancer, which are available through the Meta-Analysis Group in Cancer. [ABSTRACT FROM AUTHOR]

Background The Harmonising Outcome Measures for Eczema ( HOME) initiative has defined four core outcome domains for a core outcome set ( COS) to be measured in all atopic eczema ( AE) trials to ensure cross-trial comparison: clinical signs, symptoms, quality of life and long-term control. Objectives The aim of this paper is to report on the consensus process that was used to select the core instrument to consistently assess symptoms in all future AE trials. Methods Following the HOME roadmap, two systematic reviews were performed which identified three instruments that had sufficient evidence of validity, reliability and feasibility to be considered for the final COS. Results At the fourth international HOME meeting, there was broad consensus among all stakeholders that the Patient-Oriented Eczema Measure ( POEM) should be used as the core instrument (87·5% agreed, 9·4% unsure, 3·1% disagreed). Conclusions All relevant stakeholders are encouraged to use POEM as the chosen instrument to measure the core domain of symptoms in all future AE clinical trials. Other instruments of interest can be used in addition to POEM. [ABSTRACT FROM AUTHOR]

Distributed networks of health-care data sources are increasingly being utilized to conduct pharmacoepidemio-logic database studies. Such networks may contain data that are not physically pooled but instead are distributed horizontally (separate patients within each data source) or vertically (separate measures within each data source) in order to preserve patient privacy. While multivariable methods for the analysis of horizontally distributed data are frequently employed, few practical approaches have been put forth to deal with vertically distributed healthcare databases. In this paper, we propose 2 propensity score-based approaches to vertically distributed data analysis and test their performance using 5 example studies. We found that these approaches produced point estimates close to what could be achieved without partitioning. We further found a performance benefit (i.e., lower mean squared error) for sequentially passing a propensity score through each data domain (called the "sequential approach") as compared with fitting separate domain-specific propensity scores (called the "parallel approach"). These results were validated in a small simulation study. This proof-of-concept study suggests a new multivariable analysis approach to vertically distributed health-care databases that is practical, preserves patient privacy, and warrants further investigation for use in clinical research applications that rely on health-care databases. [ABSTRACT FROM AUTHOR]

Scotland is a small nation, yet it leads the field in key areas of aging research. With the creation of a devolved government with authority over health and social services, the country has witnessed practice and policy developments that offer distinctive opportunities for innovative research. With multidisciplinary groups of internationally recognized researchers, Scotland is able to take advantage of a unique set of opportunities for aging research: a well-profiled population brings opportunities in population data and linkage to understand people's interactions with health, social care, and other public services; while research on technology and telecare is a distinctive area where Scotland is recognized internationally for using technology to develop effective, high-quality and well-accepted services at relatively low financial cost. The paper also considers free personal care for older people and the national dementia strategy in Scotland. The potential to evaluate the impact of free personal care will provide valuable information for other global health and social care systems. Exploring the impact of the national dementia strategy is another unique area of research that can advance understanding in relation to quality of life and the development of services. The paper concludes that, while Scotland benefits from unique opportunities for progressive public policy and innovative aging research that will provide valuable lessons at the forefront of a globally aging population, the challenges associated with an aging population and increasing cultural diversity must be acknowledged and addressed to ensure that the vision of equality and social justice for all is realized. [ABSTRACT FROM AUTHOR]

For the analysis of longitudinal or repeated measures data, generalized linear mixed-effects models provide a flexible and powerful tool to deal with heterogeneity among subject response profiles. However, the typical statistical design adopted in usual randomized controlled trials is an analysis of covariance type analysis using a pre-defined pair of "pre-post" data, in which pre-(baseline) data are used as a covariate for adjustment together with other covariates. Then, the major design issue is to calculate the sample size or the number of subjects allocated to each treatment group. In this paper, we propose a new repeated measures design and sample size calculations combined with generalized linear mixed-effects models that depend not only on the number of subjects but on the number of repeated measures before and after randomization per subject used for the analysis. The main advantages of the proposed design combined with the generalized linear mixed-effects models are (1) it can easily handle missing data by applying the likelihood-based ignorable analyses under the missing at random assumption and (2) it may lead to a reduction in sample size, compared with the simple pre-post design. The proposed designs and the sample size calculations are illustrated with real data arising from randomized controlled trials. [ABSTRACT FROM AUTHOR]

The article reports disparity and social unrest amid COVID-19 pandemic. It mentions Black, Latinx, and other non-White individuals account for 60 per cent of COVID-19 deaths; and also mentions genetic or physiologic reason that COVID-19 is a more serious infection among Black or Latinx people than White people, then race or ethnicity should be an independent predictor of mortality.

Background. In this paper, we provide background and context regarding the potential for a new data-sharing platform, the Project Data Sphere (PDS) initiative, funded by financial and in-kind contributions from the CEO Roundtable on Cancer, to transform cancer research and improve patient outcomes. Given the relatively modest decline in cancer death rates over the past several years, a new research paradigm is needed to accelerate therapeutic approaches for oncologic diseases. Phase III clinical trials generate large volumes of potentially usable information, often on hundreds of patients, including patients treated with standard of care therapies (i.e., controls). Both nationally and internationally, a variety of stakeholders have pursued data-sharing efforts to make individual patient-level clinical trial data available to the scientific research community. Potential Benefits and Risks of Data Sharing. For researchers, shared data have the potential to foster amore collaborative environment, to answer research questions in a shorter time frame than traditional randomized control trials, to reduce duplication of effort, and to improve efficiency. For industry participants, use of trial data to answer additional clinical questions could increase research and development efficiency and guide future projects through validation of surrogate end points, development of prognostic or predictive models, selection of patients for phase II trials, stratification in phase III studies, and identification of patient subgroups for development of novel therapies. Data transparency also helps promote a public image of collaboration and altruism among industry participants. For patient participants, data sharing maximizes their contribution to public health and increases access to information that may be used to develop better treatments. Concerns about data-sharing efforts include protection of patient privacy and confidentiality. To alleviate these concerns, data sets are deidentified to maintain anonymity. To address industry concerns about protection of intellectual property and competitiveness, we illustrate several models for data sharing with varying levels of access to the data and varying relationships between trial sponsors and data access sponsors. The Project Data Sphere Initiative. PDS is an independent initiative of the CEO Roundtable on Cancer Life Sciences Consortium, built to voluntarily share, integrate, and analyze comparator arms of historical cancer clinical trial data sets to advance future cancer research. The aim is to provide a neutral, broad-access platform for industry and academia to share raw, deidentified data from late-phase oncology clinical trials using comparator-arm data sets. These data are likely to be hypothesis generating or hypothesis confirming but, notably, do not take the place of performing a well-designed trial to address a specific hypothesis. Prospective providers of data to PDS complete and sign a data sharing agreement that includes a description of the data they propose to upload, and then they follow easy instructions on the website for uploading their deidentified data. The SAS Institute has also collaborated with the initiative to provide intrinsic analytic tools accessible within the website itself. As of October 2014, the PDS website has available data from 14 cancer clinical trials covering 9,000 subjects, with hopes to further expand the database to include more than 25,000 subject accruals within the next year. PDS differentiates itself from other data-sharing initiatives by its degree of openness, requiring submission of only a brief application with background information of the individual requesting access and agreement to terms of use. Data from several different sponsors may be pooled to develop a comprehensive cohort for analysis. In order to protect patient privacy, data providers in the U.S. are responsible for deidentifying data according to standards set forth by the Privacy Rule of the U.S. Health Insurance Portability and Accountability Act of 1996. Using Data Sharing to Improve Outcomes in Cancer: The "Prostate Cancer Challenge." Control-arm data of several studies among patients with metastatic castration-resistant prostate cancer (mCRPC) are currently available through PDS. These data sets have multiple potential uses. The "Prostate Cancer Challenge" will ask the cancer research community to use clinical trial data deposited in the PDS website to address key research questions regarding mCRPC. General themes that could be explored by the cancer community are described in this article: prognostic models evaluating the influence of pretreatment factors on survival and patient-reported outcomes; comparative effectiveness research evaluating the efficacy of standard of care therapies, as illustrated in our companion article comparing mitoxantrone plus prednisone with prednisone alone; effects of practice variation in dose, frequency, and duration of therapy; level of patient adherence to elements of trial protocols to inform the design of future clinical trials; and age of subjects, regional differences in health care, and other confounding factors that might affect outcomes. Potential Limitations and Methodological Challenges. The number of data sets available and the lack of experiment alarm data limit the potential scope of research using the current PDS. The number of trials is expected to grow exponentially over the next year and may include multiple cancer settings, such as breast, colorectal, lung, hematologic malignancy, and bone marrow transplantation. Other potential limitations include the retrospective nature of the data analyses performed using PDS and its generalizability, given that clinical trials are often conducted among younger, healthier, and less racially diverse patient populations. Methodological challenges exist when combining individual patient data from multiple clinical trials; however, advancements in statistical methods for secondary database analysis offer many tools for reanalyzing data arising from disparate trials, such as propensity score matching. Despite these concerns, few if any comparable data sets include this level of detail across multiple clinical trials and populations. Conclusion. Access to large, late-phase, cancer-trial data sets has the potential to transform cancer research by optimizing research efficiency and accelerating progress toward meaningful improvements in cancer care. This type of platform provides opportunities for unique research projects that can examine relatively neglected areas and that can construct models necessitating large amounts of detailed data.The full potential of PDS will be realized only when multiple tumor types and larger numbers of data sets are available through the website. [ABSTRACT FROM AUTHOR]

The effect of placebo observed in schizophrenia clinical trials represents a growing problem that interferes with signal detection for treatments, increases costs of development, discourages investment in schizophrenia research and delays the introduction of new treatments. This paper seeks to clarify key issues related to this problem and identify potential solutions to them. Differences between placebo effect and response are characterized. Recent insights into the central nervous system mechanisms of placebo effect are described. This is followed by a description of protocol/study design and study conduct issues that are contributing to a growing placebo effect in clinical trials. Potential solutions to these problems are provided. [ABSTRACT FROM AUTHOR]

Clinical trials often include binary end points. In some cases, no successes are observed and the usual large sample estimates of relative risk are undefined. The paper proposes an estimator for relative risk based on the median unbiased estimator. The relative risk estimator proposed is well defined and performs satisfactorily for a wide range of data configurations. To facilitate the use of the estimator, a deterministic bootstrap confidence interval is also proposed, and an SAS macro is available to perform the necessary calculations. An on-going randomized clinical trial motivated the development of the estimator and is used to illustrate the approach. [ABSTRACT FROM AUTHOR]

Dr Shepard has made remarkable contributions to the profession of physical therapy through her accomplishments across all areas of practice, education, research, publication, and service. She was one of the pioneers who introduced qualitative research methods to the profession and, with her colleagues, went on to apply the principles of these methods to study differences between "master" and "novice" clinicians. Her work in this area has been vital as the profession continues to grapple with effective ways to prepare professional students, clinical specialists, interns, and residents in physical therapy. Her scholarly work includes more than 60 papers and book chapters and coauthorship of 3 textbooks. She has been invited to speak at state, national, and international professional meetings and has held visiting professorships in Sweden and South Africa. She was the "first" for several invited lectures, including the Polly Cerasoli Lecture at APTA's Combined Sections Meeting and the Eleanor Branch Lecture at Duke University. Dr Shepard's list of awards and honors includes APTA's Dorothy E Baethke-Eleanor J Carlin Award for Excellence in Academic Teaching, Golden Pen Award (now the Jules M Rothstein Golden Pen Award for Scientific Writing), Dorothy Briggs Memorial Scientific Inquiry Award (3 times), and Lucy Blair Service Award. In 1989, Dr Shepard was elected as a Catherine Worthingham Fellow of AFFA. She has received awards for outstanding contributions to physical therapy education from Stanford University and Temple University and the APTA Education Section's Leadership Award, and she holds an honorary doctor of science degree from the University of Indianapolis. [ABSTRACT FROM AUTHOR]

This qualitative study compares the barriers to eating more fruit and vegetables reported before and after participation in a 6-month randomized controlled trial in primary care. At the initial intervention appointment of a primary care intervention to promote eating five or more portions of fruit and vegetables a day, participants were asked to identify the barriers that they thought they might encounter. Barriers were discussed again at the final appointment 6 months later. At the end of the study, a purposive sample of 40 of the trial participants was interviewed to explore their experiences in greater detail. Transcripts of tape recordings of the intervention appointments and the semi-structured interview were analysed using qualitative methods. This paper presents the results of a qualitative analysis of these appointment and interview transcripts (results of the trial are published elsewhere). Women reported that children and male partners were obstructive to their attempts to eat more fruit and vegetables, whilst men reported that their partners were supportive of the change. The perception that fruit and vegetables were expensive was a relatively intractable barrier for those with inflexible food budgets. Some barriers, including the problem of getting fruit and vegetables when travelling or when the daily routine is disrupted such as at weekends, were not anticipated and only encountered when participants tried to make changes. However, while all but three of the interview respondents described experiencing at least one barrier to eating more fruit and vegetables, three quarters (29 of 40) reported an increase in intake of between one and five daily portions. This study adds to the existing literature in that it investigates those barriers that were reported at the end of, as well as before, a 6-month trial of a dietary intervention. The findings show that trial participants were not always able to anticipate what might be a barrier to change at the initial intervention appointment. The flexible action plan meant that if participants found their initial plan hard to maintain, they were able to adapt it rather than give up. This suggests that health behaviour interventions that are negotiated and non-prescriptive may be more successful than those that are relatively inflexible. [ABSTRACT FROM AUTHOR]

Background: Trials in surgery pose some special problems. This paper examines these with reference to 10 years of methodological research sponsored by the UK National Health Service Research and Development programme. Methods: Solutions to common problems encountered in surgical studies were considered, such as issues of blinding, dependence of results on technical skill and continued evolution of technology. Results: Numerous methodological developments are described, including the tracker trial concept in which trial design can be adapted to take account of technical developments and interim results. The governance of trials, solutions to ethical conundra and the rising importance of databases are also discussed. Conclusion: Like surgery itself, the methodological toolkit for evaluation of surgical procedures continues to evolve. The rules of statistical and scientific probity provide plenty of scope for imaginative design solutions for surgical trials. [ABSTRACT FROM AUTHOR]

Developing and implementing the scientific agenda of the Antibacterial Resistance Leadership Group (ARLG) by soliciting input and proposals, transforming concepts into clinical trials, conducting those trials, and translating trial data analyses into actionable information for infectious disease clinical practice is the collective role of the Scientific Leadership Center, Clinical Operations Center, Statistical and Data Management Center, and Laboratory Center of the ARLG. These activities include shepherding concept proposal applications through peer review; identifying, qualifying, training, and overseeing clinical trials sites; recommending, developing, performing, and evaluating laboratory assays in support of clinical trials; and designing and performing data collection and statistical analyses. This article describes key components involved in realizing the ARLG scientific agenda through the activities of the ARLG centers. [ABSTRACT FROM AUTHOR]

In May 2019, the US Food and Drug Administration (FDA) released the Framework for FDA's Real-World Evidence (RWE) Program, a draft guidance to evaluate the potential use of real-world data in facilitating regulatory decisions. As a result, pharmaceutical companies and medical communities see patient registries, which are large, prospective, noninterventional cohort studies, as becoming increasingly important in providing evidence of treatment effectiveness and safety in clinical practice. Patient registries are designed to collect longitudinal clinical data on a broad population to address critical medical questions over time. With their large sample sizes and broad inclusion criteria, patient registries are often used to generate RWE in the general and underrepresented patient populations that are less likely to be studied in controlled clinical trials. Here, we describe the value of industry-sponsored patient registries in oncology/hematology settings to healthcare stakeholders, in drug development, and in fostering scientific collaboration. [ABSTRACT FROM AUTHOR]

Background African countries are underrepresented in cancer research, partly because of a lack of structured curricula on clinical research during medical education. To address this need, the MD Anderson and Zambia Virtual Clinical Research Training Program (MOZART) was developed jointly by MD Anderson Cancer Center (MDA) and the Cancer Diseases Hospital in Zambia (CDH) for Zambian clinical oncology trainees. We explored participant perspectives to provide insight for implementation of similar efforts. Materials and Methods The MD Anderson and Zambia Virtual Clinical Research Training Program consisted of weekly virtual lectures and support of Zambian-led research protocols through longitudinal mentorship groups that included CDH faculty and MDA peer and faculty mentors. Participants were contacted via email to take part in semi-structured interviews, which were conducted via teleconference and audio-recorded, transcribed, and coded. Emergent themes were extracted and are presented with representative verbatim quotations. Results Thirteen of the 14 (93%) trainees were interviewed. Emergent themes included (1) participants having diverse educational backgrounds but limited exposure to clinical research, (2) importance of cancer research specific to a resource-constrained setting, (3) complementary roles of peer mentors and local and international faculty mentors, (4) positive impact on clinical research skills but importance of a longitudinal program and early exposure to clinical research, and (5) challenges with executing research protocols. Conclusion To our knowledge, this is the first qualitative study of African clinical oncology trainees participating in a virtual clinical research training program. The lessons learned from semi-structured interviews with participants in MOZART provided valuable insights that can inform the development of similar clinical research training efforts and scale-up. [ABSTRACT FROM AUTHOR]

Introduction Communication breakdown is a factor in the majority of all instances of medical error. Despite the importance, a relative paucity of time is invested in communication skills in postgraduate curricula. Our objective is to systematically review the literature to identify the current tools used to assess communication skills in postgraduate trainees in the latter 2 years of training and in established practice. Methods Two reviewers independently reviewed the literature identifying communication skill assessment tools, for postgraduate trainees in the latter 2 years of training and in established practice following Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, and inclusion/exclusion criteria from January 1990 to 15 August 2014. Databases: PubMed/ CINAHL/ERIC/EMBASE/PsycInfo/Psyc Articles/Cochrane. Results 222 articles were identified; after review, 34 articles fulfilled criteria for complete evaluation; the majority (26) had a high level of evidence scoring 3 or greater on the Best Evidence Medical Education guide. 22 articles used objective structured clinical examination/ standardised patient (SP)-based formats in an assessment or training capacity. Evaluation tools included author-developed questionnaires and validated tools. Nineteen articles demonstrated an educational initiative. Conclusions The reviewed literature is heterogeneous for objectives and measurement techniques for communication. Observed interactions, with patients or SPs, is the current favoured method of evaluation using author-developed questionnaires. The role of self-evaluation of skill level is questioned. The need for a validated assessment tool for communication skills is highlighted. [ABSTRACT FROM AUTHOR]

To deliver optimal patient care, evidence-based care is advocated and research is needed to support health care staff of all disciplines in deciding which options to use in their daily practice. Due to the increasing complexity of cardiac care across the life span of patients combined with the increasing opportunities and challenges in multidisciplinary research, the Science Committee of the Council on Cardiovascular Nursing and Allied Professionals (CCNAP) recognised the need for a position statement to guide researchers, policymakers and funding bodies to contribute to the advancement of the body of knowledge that is needed to further improve cardiovascular care. In this paper, knowledge gaps in current research related to cardiovascular patient care are identified, upcoming challenges are explored and recommendations for future research are given. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses articles in the issue on topics including treatments/exposure groups are weighted to help minimize bias in comparisons, and the random intercepts cross-lagged panel model is discussed as a method of causal inference.

The COVID-19 pandemic resulted in catastrophic levels of morbidity and mortality for care home residents. Despite this, research platforms for COVID-19 in care homes arrived late in the pandemic compared with other care settings. The Prophylactic Therapy in Care Homes Trial (PROTECT-CH) was established to provide a platform to deliver multi-centre cluster-randomized clinical trials of investigational medicinal products for COVID-19 prophylaxis in UK care homes. Commencing set-up in January 2021, this involved the design and development of novel infrastructure for contracting and recruitment, remote consent, staff training, research insurance, eligibility screening, prescribing, dispensing and adverse event reporting; such infrastructure being previously absent. By the time this infrastructure was in place, the widespread uptake of vaccination in care homes had changed the epidemiology of COVID-19 rendering the trial unfeasible. While some of the resources developed through PROTECT-CH will enable the future establishment of care home platform research, the near absence of care home trial infrastructure and nationally linked databases involving the care home sector will continue to significantly hamper progress. These issues are replicated in most other countries. Beyond COVID-19, there are many other research questions that require addressing to provide better care to people living in care homes. PROTECT-CH has exposed a clear need for research funders to invest in, and legislate for, an effective care home research infrastructure as part of national pandemic preparedness planning. Doing so would also invigorate care home research in the interim, leading to improved healthcare delivery specific to those living in this sector. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Patient-reported outcome measures (PROMs) make it possible to assess health-status problems from the perspective of persons suffering from a disease. The objective of the paper is to examine and compare the contents of PROMs related to IBD based on the World Health Organization''s International Classification of Functioning, Disability and Health (ICF) as the frame of reference. Methods: A systematic literature review (1999–2009) in the databases Medline, EMBASE, PsycINFO, CINAHL and CENTRAL was performed to select IBD-specific PROMs. Abstracts and full-text articles were checked applying predefined eligibility criteria; IBD-specific PROMs were identified. The contents of the identified PROMs were examined by linking the items to ICF categories. The linked ICF categories of the PROMs were then compared. Results: The review resulted in the selection of eight IBD-specific PROMs (e.g., Cleveland Global Quality of Life, Inflammatory Bowel Disease Quality of Life Questionnaire, Inflammatory Bowel Disease Questionnaire-32, Rating Form of IBD Patient Concerns, Short Inflammatory Bowel Disease Questionnaire). In total, 129 items were identified, the majority of which (n=90; 69.8%) could be linked to specific ICF categories. None of the linked categories were contained in all PROMs. The most frequently identified categories were ‘b1300 Energy level’, ‘b5254 Flatulence’, ‘d910 Community life’ and ‘d920 Recreation and leisure’. Conclusion: The present study provides an overview of IBD-specific PROMs and their items. The results of the content comparison provide valuable information to facilitate and account for the selection of appropriate PROMs for different purposes of data collection in clinical and research settings. [Copyright &y& Elsevier]

There is widespread evidence both of the exclusion of older people from clinical research, and of under-recruitment to clinical trials. This review and opinion piece provides practical advice to assist researchers both to adopt realistic, achievable recruitment rates and to increase the number of older people taking part in research. It analyses 14 consecutive recently published trials, providing the number needed to be screened to recruit one older participant (around 3:1), numbers excluded (up to 49%), drop out rates (5–37%) and whether the planned power was achieved. The value of planning and logistics are outlined, and approaches to optimising recruitment in hospital, primary care and care home settings are discussed, together with the challenges of involving older adults with mental incapacity and those from minority groups in research. The increasingly important task of engaging older members of the public and older patients in research is also discussed. Increasing the participation of older people in research will improve the generalisability of research findings and inform best practice in the clinical management of the growing older population. [ABSTRACT FROM PUBLISHER]

Background. Tuberculosis (TB) coinfection with human immunodeficiency virus (HIV) is a substantial problem in South Africa. There has been a presumption that drug-resistant strains of TB are common in South Africa, but few studies have documented this impression. Methods. In Phidisa, a joint observational and randomized HIV treatment study for South African National Defence Force members and dependents, an initiative was launched to test subjects (by use of microbiologic TB test) who appeared to be at high risk. We report results for HIV-infected subjects. Results. TB was identified by culture in 116 (19.9%) of 584 patients selected for sputum examination on the basis of suggestive symptoms. Smear was an insensitive technique for confirming the diagnosis: only 33% of culture-positive patients were identified by smear, with a 0.2% false-positive rate. Of the 107 culture-positive individuals with susceptibility testing, 22 (20.6%) were identified to be multidrug resistant (MDR), and 4 (3.7%) were identified to be extensively drug resistant. Culture-positive cases with a history of TB treatment had more than twice the rate of MDR than those without (27.1% vs 11.9%; P=.05). Conclusions. TB is common in this cohort of HIV-infected patients. Smear was not a sensitive technique for identifying culture-positive cases in this health system. Drug susceptibility testing is essential to proper patient management because MDR was present in 20.6% of culture-positive patients. Better management strategies are needed to reduce the development of MDR TB, because so many of these patients had received prior antituberculous therapy that was presumably not curative. [ABSTRACT FROM AUTHOR]

A correction to the article "Health Research and Knowledge Translation for Achieving the Sustainable Development Goals: Tackling the Hurdles" that was published in the March 23, 2020 issue is presented.

This perspective provides an overview of the randomized controlled trials, systematic reviews, and evidence-based clinical practice guidelines in physical therapy. Data from the Physiotherapy Evidence Database (PEDro) are used to describe key events in the history of physical therapy research and the growth of evidence of effects of interventions used in the various subdisciplines of physical therapy. The 11,494 records that were identified reveal a rich history of physical therapy research dating back to the first trial in 1929. Most of the randomized controlled trials, systematic reviews, and evidence-based clinical practice guidelines in physical therapy have been published since the year 2000. This rapid growth presents a challenge for physical therapists who want to keep up to date in clinical practice. [ABSTRACT FROM AUTHOR]

The article illustrates how evidence is gathered and used to guide clinical decision making. It presents several studies that illustrate this research practice. A paper by D. Trudel et al. was categorized as a systematic review, implying that the authors used specific methods to retrieve and critically analyze pertinent studies in the literature. Meanwhile, a study by F. Baskurt et al. is self-described as a randomized controlled trial, but there is no control group. The researchers treated one group with phonophoresis using a nonsteroidal anti-inflammatory drug. A study by M. D. Klaiman et al. was another study that could not be classified as a true RCT because there was no control group.

In this article, music therapy researchers and clinicians share lessons learned through engaging in collaborative research with healthcare providers in community settings. Practical aspects of conducting research in community health settings are discussed, including consulting on-site music therapists, healthcare providers, and administrators in the earliest stages of research planning; integration of research team members with community healthcare providers; and strategies for successful study implementation. We present our experiences of challenges surrounding the aspects of study implementation, such as recruitment, obtaining consent, and collecting outcome data, as well as opportunities that have resulted from our work, such as increased visibility for music therapy services, collaboration on protocol refinement, and continuing music therapy services beyond the study. Throughout the article, we refer to two research studies that illustrate the collaborative process as well as offer practical examples of challenges and problem-solving. [ABSTRACT FROM AUTHOR]

Aim The purpose of this brief narrative review is to address the complexities and benefits of extending animal alcohol addiction research to the human domain, emphasizing Allostasis and Incentive Sensitization, two models that inform many pre-clinical and clinical studies. Methods The work reviewed includes a range of approaches, including: a) animal and human studies that target the biology of craving and compulsive consumption; b) human investigations that utilize alcohol self-administration and alcohol challenge paradigms, in some cases across 10 years; c) questionnaires that document changes in the positive and negative reinforcing effects of alcohol with increasing severity of addiction; and d) genomic structural equation modeling based on data from animal and human studies. Results Several general themes emerge from specific study findings. First, positive reinforcement is characteristic of early stage addiction and sometimes diminishes with increasing severity, consistent with both Allostasis and Incentive Sensitization. Second, evidence is less consistent for the predominance of negative reinforcement in later stages of addiction, a key tenant of Allostasis. Finally, there are important individual differences in motivation to drink at a given point in time as well as person-specific change patterns across time. Conclusions Key constructs of addiction, like stage and reinforcement, are by necessity operationalized differently in animal and human studies. Similarly, testing the validity of addiction models requires different strategies by the two research domains. Although such differences are challenging, they are not insurmountable, and there is much to be gained in understanding and treating addiction by combining pre-clinical and clinical approaches. [ABSTRACT FROM AUTHOR]

Information about the papers discussed at the workshop held by the Infectious Diseases Society of America (IDSA) on the conduct of clinical trials of antibacterial drugs is presented. It mentions the design and conduct of clinical trials of antibacterial drugs in the treatment of community-acquired pneumonia (CAP). It stresses the reevaluation of the appropriateness of noninferiority design which has been influenced by insights from extensive methodological research.

The article reports on the movement of patient group in seeking legislative action that would overhaul the clinical trial system of the U.S. Food and Drug Administration (FDA). Intricately, forces are allied to challenge FDA's authority in regulating the safety and efficacy of new drugs as well as its drug approval standards. The case of the Abigail Alliance for Better Access to Developmental Drugs and the Washington Legal Foundation against the FDA is tackled.

Shortcomings in the current pipeline of infectious disease physician scientists are well documented. With a focus on the transition of early stage investigators to research independence, we outline challenges in existing training pathways for physician scientists. We urge leaders of infectious disease societies, divisions, and governmental and nongovernmental funding organizations to reinvigorate a vision for nurturing trainees with interests in research, to seek transparency in physician scientist funding mechanisms, and to encourage efforts to improve the reproducibility of outcomes for talented junior investigators. We feel that the alternative to making these changes will lead to further drop-off in the physician scientist pipeline in a field that has a perpetual need for research. [ABSTRACT FROM AUTHOR]

The Department of Epidemiology at Johns Hopkins School of Hygiene and Public Health was founded in 1919, with Wade Hampton Frost as inaugural chair. In our Centennial Year, we review how our research and educational programs have changed. Early years focused on doctoral education in epidemiology and some limited undergraduate training for practice. Foundational work on concepts and methods linked to the infectious diseases of the day made major contributions to study designs and analytical methodologies, largely still in use. With the epidemiologic transition from infectious to chronic disease, new methods were developed. The Department of Chronic Diseases merged with the Department of Epidemiology in 1970, under the leadership of Abraham Lilienfeld. Leon Gordis became chair in 1975, and multiple educational tracks were developed. Genetic epidemiology began in 1979, followed by advances in infectious disease epidemiology spurred by the human immunodeficiency virus/acquired immune deficiency syndrome epidemic. Collaborations with the Department of Medicine led to development of the Welch Center for Prevention, Epidemiology, and Clinical Research in 1989. Between 1994 and 2008, the department experienced rapid growth in faculty and students. A new methods curriculum was instituted for upper-level epidemiologic training in 2006. Today's research projects are increasingly collaborative, taking advantage of new technologies and methods of data collection, responding to "big data" analysis challenges. In our second century, the department continues to address issues of disease etiology and epidemiologic practice. [ABSTRACT FROM AUTHOR]

Authors aiming to estimate causal effects from observational data frequently discuss 3 fundamental identifiability assumptions for causal inference: exchangeability, consistency, and positivity. However, too often, studies fail to acknowledge the importance of measurement bias in causal inference. In the presence of measurement bias, the aforementioned identifiability conditions are not sufficient to estimate a causal effect. The most fundamental requirement for estimating a causal effect is knowing who is truly exposed and unexposed. In this issue of the Journal , Caniglia et al. (Am J Epidemiol. 2019;000(00):000–000) present a thorough discussion of methodological challenges when estimating causal effects in the context of research on distance to obstetrical care. Their article highlights empirical strategies for examining nonexchangeability due to unmeasured confounding and selection bias and potential violations of the consistency assumption. In addition to the important considerations outlined by Caniglia et al. authors interested in estimating causal effects from observational data should also consider implementing quantitative strategies to examine the impact of misclassification. The objective of this commentary is to emphasize that you can't drive a car with only three wheels, and you also cannot estimate a causal effect in the presence of exposure misclassification bias. [ABSTRACT FROM AUTHOR]

Background routine frailty identification and management is national policy in England, but there remains a lack of evidence on the impact of frailty on healthcare resource use. We evaluated the impact of frailty on the use and costs of general practice and hospital care. Methods retrospective longitudinal analysis using linked routine primary care records for 95,863 patients aged 65–95 years registered with 125 UK general practices between 2003 and 2014. Baseline frailty was measured using the electronic Frailty Index (eFI) and classified in four categories (non, mild, moderate, severe). Negative binomial regressions and ordinary least squares regressions with multilevel mixed effects were applied on the use and costs of general practice and hospital care. Results compared with non-frail status, annual general practitioner consultation incidence rate ratios (IRRs) were 1.24 (95% CI: 1.21–1.27) for mild, 1.41 (95% CI: 1.35–1.47) for moderate, and 1.52 (95% CI: 1.42–1.62) for severe frailty. For emergency hospital admissions, the respective IRRs were 1.64 (95% CI 1.60–1.68), 2.45 (95% CI 2.37–2.53) and 3.16 (95% CI: 3.00–3.33). Compared with non-frail people the IRR for inpatient days was 7.26 (95% CI 6.61–7.97) for severe frailty. Using 2013/14 reference costs, extra annual cost to the healthcare system per person was £561.05 for mild, £1,208.60 for moderate and £2,108.20 for severe frailty. This equates to a total additional cost of £5.8 billion per year across the UK. Conclusions increasing frailty is associated with substantial increases in healthcare costs, driven by increased hospital admissions, longer inpatient stay, and increased general practice consultations. [ABSTRACT FROM AUTHOR]

Background: Infectious disease interventions are increasingly tested using cluster-randomized trials (CRTs). These trial settings tend to involve a set of sampling units, such as villages, whose geographic arrangement may present a contamination risk in treatment exposure. The most widely used approach for reducing contamination in these settings is the so-called fried-egg design, which excludes the outer portion of all available clusters from the primary trial analysis. However, the fried-egg design ignores potential intra-cluster spatial heterogeneity and makes the outcome measure inherently less precise. Whereas the fried-egg design may be appropriate in specific settings, alternative methods to optimize the design of CRTs in other settings are lacking.Methods: We present a novel approach for CRT design that either fully includes or fully excludes available clusters in a defined study region, recognizing the potential for intra-cluster spatial heterogeneity. The approach includes an algorithm that allows investigators to identify the maximum number of clusters that could be included for a defined study region and maintain randomness in both the selection of included clusters and the allocation of clusters to either the treatment group or control group. The approach was applied to the design of a CRT testing the effectiveness of malaria vector-control interventions in southern Malawi.Conclusions: Those planning CRTs to evaluate interventions should consider the approach presented here during trial design. The approach provides a novel framework for reducing the risk of contamination among the CRT randomization units in settings where investigators determine the reduction of contamination risk as a high priority and where intra-cluster spatial heterogeneity is likely. By maintaining randomness in the allocation of clusters to either the treatment group or control group, the approach also permits a randomization-valid test of the primary trial hypothesis. [ABSTRACT FROM AUTHOR]

The risk difference scale is often of primary interest when evaluating public health impacts of interventions on binary outcomes. However, few investigators report findings in terms of additive interaction, probably because the models typically used for binary outcomes implicitly measure interaction on the multiplicative scale. One measure with which to assess additive interaction from multiplicative models is the relative excess risk due to interaction (RERI). The RERI measure has been applied in many contexts, but one limitation of previous approaches is that clustering in data has rarely been considered. We evaluated the RERI metric for the setting of clustered data using both population-averaged and cluster-conditional models. In simulation studies, we found that estimation and inference for the RERI using population-averaged models was straightforward. However, frequentist implementations of cluster-conditional models including random intercepts often failed to converge or produced degenerate variance estimates. We developed a Bayesian implementation of log binomial random-intercept models, which represents an attractive alternative for estimating the RERI in cluster-conditional models. We applied the methods to an observational study of adverse birth outcomes in mothers with human immunodeficiency virus, in which mothers were clustered within clinical research sites. [ABSTRACT FROM AUTHOR]

Background: This was an 8-year follow-up of an RCT comparing ultrasound-guided foam sclerotherapy (UGFS) with high ligation and surgical stripping (HL/S) of the great saphenous vein (GSV). Methods: Patients were randomized to UGFS or HL/S of the GSV. The primary outcome was the recurrence of symptomatic GSV reflux. Secondary outcomes were patterns of reflux according to recurrent varices after surgery, Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification, Venous Clinical Severity Score (VCSS) and EuroQol Five Dimensions (EQ-5D™) quality-of-life scores. Results: Of 430 patients originally randomized (230 UGFS, 200 HL/S), 227 (52.8 per cent; 123 UGFS, 103 HL/S) were available for analysis after 8 years. The proportion of patients free from symptomatic GSV reflux at 8 years was lower after UGFS than HL/S (55.1 versus 72.1 per cent; P = 0.024). The rate of absence of GSV reflux, irrespective of venous symptoms, at 8 years was 33.1 and 49.7 per cent respectively (P = 0.009). More saphenofemoral junction (SFJ) failure (65.8 versus 41.7 per cent; P = 0.001) and recurrent reflux in the above-knee GSV (72.5 versus 20.4 per cent; P = 0.001) was evident in the UGFS group. The VCSS was worse than preoperative scores in both groups after 8 years; CEAP classification and EQ-5D® scores were similar in the two groups. Conclusion: Surgical stripping had a technically better outcome in terms of recurrence of GSV and SFJ reflux than UGFS in the long term. Long-term follow-up suggests significant clinical progression of venous disease measured by VCSS in both groups, but less after surgery. [ABSTRACT FROM AUTHOR]