Objective: This meta-analysis evaluated the efficacy of acupuncture in improving cognitive impairment of post-stroke patients.Design: Randomized controlled trials investigating the effects of acupuncture compared with no treatment or sham acupuncture on post-stroke cognitive impairment before December 2019 were identified from databases. The literature searching and data extracting were independently performed by two investigators. Study quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analyses were performed for the eligible RCTs with Revman 5.3 software.Results: Thirty-seven RCTs (...) were included in this meta-analysis. Merged Random-effects estimates of the gain of MMSE or MoCA were calculated for the comparison of acupuncture with no acupuncture or sham acupuncture. Following 2–8 weeks of intervention with acupuncture, pooled results demonstrated significant effects of acupuncture in improving PSCI assessed by MMSE or MoCA.Conclusion: The results suggest that acupuncture was effective in improving PSCI and supported the needs of more rigorous design with large-scale randomized clinical trials to determine its therapeutic benefits. (shrink)

BACKGROUND -/- The importance of ontologies in the biomedical domain is generally recognized. However, their quality is often too poor for large-scale use in critical applications, at least partially due to insufficient training of ontology developers. -/- OBJECTIVE -/- To show the efficacy of guideline-based ontology development training on the performance of ontology developers. The hypothesis was that students who received training on top-level ontologies and design patterns perform better than those who only received training in the basic principles of (...) formal ontology engineering. -/- METHODS -/- A curriculum was implemented based on a guideline for ontology design. A randomized controlled trial on the efficacy of this curriculum was performed with 24 students from bioinformatics and related fields. After joint training on the fundamentals of ontology development the students were randomly allocated to two groups. During the intervention, each group received training on different topics in ontology development. In the assessment phase, all students were asked to solve modeling problems on topics taught differentially in the intervention phase. Primary outcome was the similarity of the students’ ontology artefacts compared with gold standard ontologies developed by the authors before the experiment; secondary outcome was the intra-group similarity of group members’ ontologies. -/- RESULTS -/- The experiment showed no significant effect of the guideline-based training on the performance of ontology developers (a) the ontologies developed after specific training were only slightly but not significantly closer to the gold standard ontologies than the ontologies developed without prior specific training; (b) although significant differences for certain ontologies were detected, the intra-group similarity was not consistently influenced in one direction by the differential training. -/- CONCLUSION -/- Methodologically limited, this study cannot be interpreted as a general failure of a guideline-based approach to ontology development. Further research is needed to increase insight into whether specific development guidelines and practices in ontology design are effective. (shrink)

This afterword extends and refines the arguments presented in Cohen and Jacobs . The main point made by the authors is that the antidepressant randomized controlled trial world is a make-believe world in which researchers act as if a bona fide medical experiment is being conducted. From the assumed existence of the “disorder” and the assumed homogeneity of the treatment groups, through the validity of rating scales and the meaning of their scores, to the presentations of researchers’ ratings as (...) the genuine outcome of interest — all aspects of such trials are make-believe. The continued acceptance of randomized controlled trials as appropriate mechanisms to ascertain the actual effects of psychoactive drugs on human beings in distress confirms that researchers are inextricably dependent on large-scale organizational and financial interests that require the sustained production of make-believe results about psychoactive drugs. (shrink)

In a randomized clinical trial (RCT), a group of patients, initially assembled through a mixture of deliberation (involving explicit inclusion and exclusion criteria) and serendipity (which patients happen to walk into which doctor’s clinic while the trial is in progress), are divided by some random process into an experimental group (members of which will receive the therapy under test) and a control group (members of which will receive some other treatment – perhaps placebo, perhaps the currently standard treatment for (...) the condition at issue). In a ‘double blind’ trial neither the patient nor the clinician knows to which of the groups a particular patient belongs. The results of double blind randomized controlled trials are almost universally regarded as providing the ‘gold standard’ for evidence in medicine. Fairly extreme claims to this effect can be found in the literature. For example the statistician Tukey wrote (1977, p. 679) “almost the only source of reliable evidence [in medicine] … is that obtained from … carefully conducted randomised trials”. And the clinician Victor Herbert claimed (1977, p. 690) “..the only source of reliable evidence rising to the level of proof about the usefulness of any new therapy is that obtained from wellplanned and carefully conducted randomized, and, where possible, coded (double blind) clinical trials. [Other] studies may point in a direction, but cannot be evidence as lawyers use the term evidence to mean something probative … [that is] tending to prove or actually proving”. Finally, the still very influential movement in favour of ‘Evidence Based Medicine’ (EBM) that began at McMaster University in the 1980s was initially often regarded as endorsing the claim that only RCTs provide real scientifically telling evidence. (shrink)

The volume of clinical research is increasing exponentially—far beyond our ability to process and absorb the results. Given this situation, it may be beneficial to consider reducing the flow at its source. In what follows, I will motivate and critically evaluate the following proposal: researchers should conduct fewer clinical trials. More specifically, I c onsider whether researchers should be permitted to conduct only clinical research of very high quality and, in turn, whether research ethics committees should prohibit all other, (...) lower-quality research, even when it might appear to meet some minimal ethical standard. Following a close analysis of the social-value requirement of ethical clinical research, I argue that this proposal is defensible. The problem identified in this paper has two parts, quantity and quality, and some clarification is needed about the latter because “quality” is a highly contested term in the medical literature. When some scholars advocate for high-quality trials, they mean large-scale, simple, explanatory randomized controlled trials. Others, including myself, have defended a different characterization of high-quality research that tends more toward pragmatic trial design and the use of methods other than RCTs. Pragmatic trials aim to provide evidence that directly supports clinical decision-making in “usual” care settings. Unlike explanatory trials, which aim to abstract away from particular settings and patients, in the hopes of creating ideal conditions for the success of an intervention, pragmatic trials deliberately pursue knowledge of high applicability, through the use of representative subjects, clinically important questions, flexible treatment protocols, patient-oriented outcome measures, and so on. I see applicability as a marker of high-quality research. The context in which research is meant to be applied should be the context in which new interventions are evaluated. (shrink)

In this essay, we defend the design of the Salk polio vaccine trial and try to put some limits on the role schemata should play in designing clinical research studies. Our presentation is structured as a response to de Freitas and Pietrobon who identified the CONSORT statement as a schema that would have, had it existed at the time, ruled out the design of the Salk polio vaccine trial of 1954 in favor of a completely randomized controlled clinical trial. (...) We argue that large-scale public health interventions often require evidence beyond simple efficacy, the limit of what an RCT can provide, and that the design actually adopted for the Salk trial represented a reasonable—albeit imperfect—compromise. This is of more than historical interest in that many contemporary studies are of the scale and scope to require a more pragmatic, rather than explanatory, approach to study design. (shrink)

Robert Truog describes the controversial randomized controlled trials (RCTs) of extracorporeal membrane oxygenation (ECMO) therapy in newborns. Because early results with ECMO indicated that it might be a great advance, saving many lives, Truog argues that ECMO should not have been tested using RCTs, but that a long-term, large-scale observational study of actual clinical practice should have been conducted instead. Central to Truog’s argument, however, is the idea that ECMO is an unusual case. Thus, it is an open (...) question whether Truog’s conclusions can be extended to other areas of medical research. In this paper, I look at epistemological and ethical issues arising in the care of patients with chronic diseases, using ECMO as a starting point. Both the similarities and the dissimilarities of these two cases highlight important issues in biomedical research and support a conclusion similar to Truog’s. Observational studies of clinical practice provide the best evidence to inform the treatment of patients with chronic disease. (shrink)

BackgroundMany journals prohibit the use of declarative titles that state study findings, yet a few journals encourage or even require them. We compared the effects of a declarative versus a descriptive title on readers’ perceptions about the strength of evidence in a research abstract describing a randomized trial.MethodsStudy participants (medical or dental students or doctors attending lectures) read two abstracts describing studies of a fictitious treatment (Anticox) for a fictitious condition (Green’s syndrome). The first abstract (A1) described an uncontrolled, (...) 10-patient, case series, and the second (A2) described a randomized, placebo-controlled trial involving 48 patients. All participants rated identical A1 abstracts (with a descriptive title) to provide baseline ratings and thus reduce the effects of inter-individual variability. Participants were randomized so that half rated a version of A2 with a descriptive title and half with a declarative title. For each abstract, participants indicated their agreement with the statement “Anticox is an effective treatment for pain in Green’s syndrome” using 100 mm visual analogue scales (VAS) ranging from “disagree completely” to “agree completely.” VAS scores were measured by an investigator who was unaware of group allocation.ResultsOne hundred forty-four participants from four centres completed the study. There was no significant difference between the declarative and the descriptive title groups’ confidence in the study conclusions as expressed on VAS scales—in fact, the mean difference between A1 and A2 was smaller for the declarative title group than that for the descriptive title group (32.6 mm, SD 27.4 vs. 39.8 mm, SD 22.6, respectively, p = 0.09).ConclusionsWe found no evidence that the use of a declarative title affected readers’ perceptions about study conclusions. This suggests that editors’ fears that declarative titles might unduly influence readers’ judgements about study conclusions may be unfounded, at least in relation to reports of randomized trials. However, our study design had several limitations, and our findings may not be generalizable to other situations. (shrink)

Coronavirus disease 2019 (COVID-19) is a fast-developing viral pandemic spreading across the globe. Due to lack of availability of proven medicines against COVID-19, physicians have resorted to treatments through large trials of investigational drugs with poor evidence or those used for similar diseases. Large trials randomize 100–500+ patients at multiple hospitals in different countries to either receive these drugs or standard treatment. In order to expedite the process, some regulatory agencies had also given permission to use drugs approved (...) for other diseases, despite a lack of evidence of efficacy in COVID-19. In this review, we highlight the potential ethical issues that should be addressed during the use of investigational drugs with little prior evidence as a treatment options during a pandemic. We discuss the impact of design of randomized clinical trials using LOTUS trial as an example and that of off-label use of drugs like chloroquine/hydroxychloroquine (CQ/HQ) on the safety of patients during COVID-19. We conclude that the adaptive randomized clinical trial designs offer a flexible and efficient approach, enabling patients to quickly switch to successful treatments, while minimizing the number of patients on standard of care. Randomized clinical trial design should consider blinding of investigators and only representative patients who can provide consent should be included. We also conclude the emergency approvals of drugs should be carefully issued and off-label use should be restricted in pandemics. Streamlined regulatory guidelines for emergency drug use in a pandemic can also help in providing benefit and minimizing harm to patients in the future. (shrink)

The temptation to use prospective observational studies (POS) instead of conducting difficult trials (RCTs) has always existed, but with the advent of powerful computers and large databases, it can become almost irresistible. We examine the potential consequences, were this to occur, by comparing two hypothetical studies of a new treatment: one RCT, and one POS. The POS inevitably submits more patients to inferior research methodology. In RCTs, patients are clearly informed of the research context, and 1:1 randomized allocation (...) between experimental and validated treatment balances risks for each patient. In POS, for each patient, the risks of receiving inferior treatment are impossible to estimate. The research context and the uncertainty are down-played, and patients and clinicians are at risk of becoming passive research subjects in studies performed from an outsider’s view, which potentially has extraneous objectives, and is conducted without their explicit, autonomous, and voluntary involvement and consent. (shrink)

Children who live on the margins of society are disadvantaged in achieving their developmental potential because of the lack of a necessary stable environment and nurturing care. Many early prevention programs aim at mitigating such effects, but often the evaluation of their long-term effect is missing. The aim of the study presented here was to evaluate such long-term effects in two prevention programs for children-at-risk growing up in deprived social environments focusing on child attachment representation as the primary outcome as (...) well as on self-reflective capacities of teachers taking care of these children. The latter was a key component for promoting resilient behavior in children. Five hundred and twenty-six children aged 36 to 60 months at risk due to immigration status, low family socio-economic status and child behavior were examined in a cluster-randomized study comparing two preventions, the psychodynamic, attachment-based holistic approach EARLY STEPS (ES) with the classroom based FAUSTLOS (FA) for their efficacy. Primary outcome was the child attachment representation measured by the Manchester Child Attachment Story Task (MCAST). Secondary outcomes were derived from (a) the Caregiver-Teacher Report Form (C-TRF: problem behaviors, including anxiety/depressive symptoms, emotional-reactive and somatic problems, social withdrawal, aggressive behavior, and attention deficit), from (b) the Strength and Difficulties Questionnaire (SDQ, parent version: resilience and wellbeing) and (c) Self-Reflective Scales for teachers (SRS: self-reflective capacities of teachers). Compared to baseline, attachment and behavioral problems improved in both programs. ES led to more secure and more organized attachment representations (medium effect sizes). Aggressive behavior and externalizing problems were reduced in the FA group compared with ES, particularly in boys (medium effect sizes). Self-reflective capacities of the teachers increased only in the ES group. High correlation between children’s attachment type with the number of social risk factors and the increase of problematic social behavior strongly indicate that an increase in teachers’ self-reflective capacities helps to change children’s attachment patterns which thus strengthens the resilience of these children-at-risk [An ethical vote from LPPKJP 2009-02-25 was obtained and the trial registered; Clinical trial registration information: The trial was registered 14.02.2012 (DRKS00003500;https://www.drks.de)]. (shrink)

: Recent controversial decisions to terminate several large clinical trials have called attention to the need for developing a sound ethical framework to determine when trials should be stopped in light of emerging efficacy data. Currently, the fundamental rationale for stopping trials early is based on the principle that equipoise has been disturbed. We present an analysis of the ethical and practical problems with the "equipoise disturbed" position and describe an alternative ethical framework based on the principle (...) of nonexploitation. This framework acknowledges the need for balancing the dual ethical obligations of clinical research, the protection of human subjects and the generation of new medical knowledge. Based on this framework, we put forward a proposal to make early stopping guidelines more stringent under specified conditions. The temporary withholding of apparent benefits in certain circumstances is justified by achieving a fair contract with the research participants, one that protects them from undue harm and exploitation while reducing the many uncertainties surrounding new investigational treatments that arise when trials are stopped prematurely. (shrink)

Objective Diabetes is a global public health concern. Management of diabetes depends on successful implementation of strategies to alleviate decline in executive functions (EFs), a characteristic of diabetes progression. In this review, we describe recent research on the relationship between diabetes and EF, summarize the existing evidence, and put forward future research directions and applications. Methods Herein, we provide an overview of recent studies, to elucidate the relationship between DM and EF. We identified new screening objectives, management tools, and intervention (...) targets for diabetes management. We also discuss the implications for clinical practice. Results In both types 1 and 2 diabetes mellitus (DM), hyperglycemia substantially impairs EF in people of all age groups and ethnicities. Hypoglycemia can similarly impair EF. Interestingly, a decline in EF contributes to DM progression. Glucose dysregulation and EF decline exacerbate each other in a vicious cycle: poor blood glucose control, impaired EF, diabetes management task failure, then back to poor blood glucose control. Many pathophysiological indexes (e.g., obesity, metabolic index, inflammatory and immune factors), neuropsychological indexes (e.g., compliance, eating habits, physical exercise, sleep, and depression), and genetic factors are changed by this pathological interaction between DM and EF. These changes can provide insight into the pathophysiological mechanisms of diabetes-related EF decline. Conclusion Further studies, including large-scale prospective and randomized controlled trials, are needed to elucidate the mechanism of the interaction between diabetes and EF and to develop novel strategies for breaking this cycle. (shrink)

BackgroundParent-mediated intervention has been studied in promoting skill acquisition or behavior change in the children with autism spectrum disorder. Most studies emphasize on the improvement of child’s core symptoms or maladaptive behaviors, making parental perceived competence and self-efficacy secondary. Yet, the evaluations of intervention implementation are under-reported, especially when translating such interventions into a new population or context. This research investigated the intervention implementation of a 12-week parent coaching intervention which was delivered through telehealth and tailored to Chinese population. The (...) intervention was based on the Parent-mediated Early Start Denver Model with culturally adapted lectures, manuals, and demonstration and commentary videos. This study aimed to evaluate the intervention implementation by assessing parents’ satisfaction, acceptability, appropriateness, and feasibility.MethodA randomized controlled trial was conducted with two telehealth conditions: self-directed and web+group therapy. Parents in the self-directed condition received intervention individually through the online learning platform. The web+group therapy condition navigated the same program with weekly 1.5-h group coaching sessions via videoconferencing. This mixed-methods study used a concurrent convergent design to evaluate the intervention implementation at post-intervention. The quantitative data was collected from the Program Evaluation Survey and the qualitative data was collected from five focus groups.ResultsParents in self-directed group reported significantly lower scores in total perceived competence than parents in web+group therapy condition, while there was no group difference on the total self-efficacy. Tailored feedback, demonstration and commentary videos, peer commenting, live coaching, and guided reflection were the top-five acceptable telehealth strategies that were strongly endorsed by parents. Family centered care, home-based intervention, strategies relative to daily activities, the remote learning platform, and the program-based community were elements that parents considered when evaluating the program’s appropriateness. Parent modeling, step-by-step instructions, and tailored feedback were key components in making intervention strategies feasible for parents to implement at home.ConclusionFindings indicate the application of telehealth was acceptable, appropriate, and feasible for Chinese parents. Group-based parent coaching intervention via videoconferencing could be a promising home-based service model to increase parental perceived competence. A large-scale RCT is needed to investigate the effectiveness of group-based PMI via telehealth. (shrink)

Randomized controlled trials sometimes test interventions that aim to improve existing services targeted to a subset of individuals identified after randomization. Accordingly, the treatment could affect the composition of service recipients and the offered services. With such bias, intention-to-treat estimates using data on service recipients and nonrecipients may be difficult to interpret. This article develops causal estimands and inverse probability weighting estimators for complier populations in these settings, using a generalized estimating equation approach that adjusts the standard errors (...) for estimation error in the IPW weights. While our focus is on more general clustered RCTs, the methods also apply to nonclustered RCTs. Simulations show that the estimators achieve nominal confidence interval coverage under the assumed identification conditions. An empirical application demonstrates the methods using data from a large-scale RCT testing the effects of early childhood services on children’s cognitive development scores. An R program for estimation is available for download. (shrink)

Objective: Ethical guidelines are designed to ensure benefits, protection and respect of participants in clinical research. Clinical trials must now be registered on open-access databases and provide details on ethical considerations. This systematic survey aimed to determine the extent to which recently registered clinical trials report the use of standard of care and post-trial obligations in trial registries, and whether trial characteristics vary according to setting. Methods: We selected global randomized trials registered on http://www.clinicaltrials.gov and http://www.controlled- (...) class='Hi'>trials.com. We searched for intervention trials of HIV/AIDS, malaria, and tuberculosis from 9 October 2004, the date of the most recent version of the Helsinki Declaration, to 10 April 2007. Results: We collected data from 312 trials. Fifty-eight percent (58%, 95% CI = 53 to 64) of trial protocols report informed consent. Fifty-eight percent (58%, 95% CI = 53 to 64) of trials report active controls. Almost no trials (1%, 95% CI = 0.5 to 3) mention post-trial provisions. Most trials measure surrogate outcomes. Twenty percent (20%, 95% CI = 16 to 25) of trials measure patient-important outcomes, such as death; and the odds that these outcomes are in a low income country are five times greater than for a developed country (odds ratio (OR) 5.03, 95% CI = 2.70 to 9.35, p = < 0.001). Pharmaceutical companies are involved in 28% (CI = 23 to 33) of trials and measure surrogate outcomes more often than nonpharmaceutical companies (OR 2.45, 95% CI = 1.18 to 5.09, p = 0.31). Conclusion: We found a large discrepancy in the quality of reporting and approaches used in trials in developing settings compared to wealthier settings. (shrink)

The Flash Technique of Eye Movement Desensitization and Reprocessing is widely recognized for its effectiveness in reducing the effects of emotional responses associated with traumatic memories. Using a randomized-controlled trial methodology, this study attempts to establish the efficacy of the EMDR Flash Technique. This study’s sample includes volunteers who were involved in traffic accidents and were given the randomized EMDR Flash Technique and Improving Mental Health Training for Primary Care Residents Stress management module. The participants were given a (...) socio-demographic data form, the Depression-Anxiety-Stress 21 scale, the Impact of Event Scale-Revised, and the WHOQOL Quality of Life scale. Participants were evaluated using measurements taken before and after the application, as well as a one-month follow-up. The mean age of the participants was 36.20 years and 82.1% were female. The DASS-21 Anxiety, IES-R Intrusion, Avoidance, Total, and WHOQOL-BREF Psychological score improvements of the EMDR Flash Technique group were shown to be statistically significant when compared to the mhGAP group. However, no statistically significant difference in the DASS-21 Depression, Stress, Impact of Event Scale-Revised Hyperarousal WHOQOL-BREF General Health, Physical, Social Relationships, and Environment component scores was reported between the two groups. The present study’s findings clearly demonstrate that the EMDR Flash technique, when applied to persons involved in traffic accidents, is successful in improving anxiety, intrusion, avoidance, total traumatic stress, and mental quality of life symptoms for at least 1 month. We believe that these findings will improve the reliability and applicability of the EMDR Flash Technique, which was tested for the first time in a clinical randomized-controlled trial. (shrink)

This paper attempts to take seriously the claim that we can look for causes in order to understand the reality we live (in), and focuses therefore primarily on 'the natural world'. It will be argued that even if we were to fully endorse the programme of looking for antecedents, a dominant driver for many educational researchers, this would still not solve the problems they commonly set out to address. It will illustrate the problem of contextualisation in using an example of (...) educational research that uses the methodology of the randomised field trial. In these kind of studies the paradigm of causality and its experimental laboratory approach is modified to incorporate the exigencies of real life situations. The claim that these studies too do not put one in a position to derive straightforward conclusions for policy makers or more generally for educational practitioners will be substantiated. Finally, some concluding remarks will be offered that indicate what may be expected from large-scale population studies and what their epistemological basis is. (shrink)

OBJECTIVE: Following two randomized controlled trials that demonstrated reduced mortality and better neurological outcome in cardiac arrest patients, mild therapeutic hypothermia was implemented in many intensive care units. Up to now, no large observational studies have confirmed the beneficial effects of mild therapeutic hypothermia. DESIGN: Internet-based survey combined with a retrospective, observational study. PATIENTS: All patients admitted to an intensive care unit in The Netherlands after cardiac arrest from January 1, 1999 until January 1, 2009. DATA SOURCE: Dutch (...) National Intensive Care Evaluation database. METHODS: The moment of implementation of mild therapeutic hypothermia for each hospital participating in the Dutch National Intensive Care Evaluation database was determined with an Internet survey. To compare mortality before and after implementation of mild therapeutic hypothermia, the odds ratio adjusted for Simplified Acute Physiology Score II score, age, gender, propensity score, and in- or out-of-hospital cardiac arrest was calculated. Patients were excluded if 1) they were admitted to an intensive care unit that did not respond to the survey, 2) they were admitted within 3 months after implementation of mild therapeutic hypothermia, 3) they had a Glasgow Coma Scale score of >8, or 4) they did not satisfy the Simplified Acute Physiology Score II inclusion criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 13,962 patients were admitted to an intensive care unit following cardiac arrest. In total 8,645 patients were excluded, 5,544 because of a Glasgow Coma Scale score of >8. Of the resultant 5,317 patients, 1,547 patients were treated before and 3,770 patients after implementation of mild therapeutic hypothermia. Patients admitted after implementation of mild therapeutic hypothermia had lower minimal and maximal temperatures (p < .0001) during the first 24 hrs on the intensive care unit compared to patients admitted before implementation of mild therapeutic hypothermia. The adjusted odds ratio of the hospital mortality of patients treated after implementation of mild therapeutic hypothermia was 0.80 (95% confidence interval of 0.65-0.98, p = .029). CONCLUSION: The results of this retrospective, observational survey suggest that implementation of mild therapeutic hypothermia in Dutch intensive care units is associated with a 20% relative reduction of hospital mortality in cardiac arrest patients. (shrink)

ObjectivesMany older adults with visual impairment also have significant hearing loss. The aim was to investigate the effectiveness of a newly developed Dual Sensory Loss protocol on communication and wellbeing of older persons with DSL and their communication partners in the Netherlands and Belgium.MethodsParticipants and their communication partners were randomized in the “DSL-protocol” intervention group or a waiting-list control group. The intervention took 3 to 5 weeks. Occupational therapists focused on optimal use of hearing aids, home-environment modifications and effective (...) communication strategies. The primary outcome was the Communication Strategies domain of the Communication Profile for the Hearing Impaired. Secondary outcomes measured in participants were the Low Vision Quality Of Life Adjustment subscale, the Center for Epidemiological Studies - Depression Scale, De Jong Gierveld Loneliness Scale and the Fatigue Assessment Scale. The Hearing Handicap and Disability Inventory - Reaction of Others subscale and the Care-related Quality of Life - 7 Dimensions was measured in communication partners. Measurements were taken at baseline and 3-month follow-up. Linear mixed models were used to analyze effects between groups over time for every outcome measure.ResultsIntention-to-treat analyses showed a significant effect of the DSL-protocol on the use of verbal strategies in favor of the control group, however, this effect was non-significant after adjustment for confounding. Effect sizes of other outcomes varied between −0.23 [−0.57, 0.12] and 0.30 [−0.05, 0.64]. The LMM showed a significant effect on the HHDI-Reaction of others scale in favor of communication partners in the treatment group, however, the effect did not remain significant at a 0.01 significance level and the effect size was very small and non-significant 0.12, 95% CI [−0.27 to 0.51]. Adjusted analyses did not reveal treatment effects.ConclusionThe DSL-protocol did not clearly contribute to the enhancement of communication and wellbeing in DSL-patients. Possible reasons for the lack of effects are OTs not being comfortable giving advice on communication and psychosocial issues or the short-term treatment and follow-up period. Further study is warranted to find out how the protocol may be adapted or whether it is necessary to involve mental healthcare professionals.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NTR2843. (shrink)

Social anxiety disorders (SAD) are among the most prevalent mental disorders (lifetime prevalence: 7–12%), with high impact on the life of an affected social system and its individual social system members. We developed a manualized disorder-specific integrative systemic and family therapy (ISFT) for SAD, and evaluated its feasibility in a pilot randomized controlled trial (RCT). The ISFT is inspired by Helm Stierlin’s concept of related individuation developed during the early 1980s, which has since continued to be refined. It integrates (...) solution-focused language, social network diagnostics, and genogram work, as well as resource- and problem orientation for both case conceptualization and therapy planning. Post-Milan symptom prescription to fluidize the presented symptoms is one of the core interventions in the ISFT. Theoretically, the IFST is grounded in radical constructivism and “Cybern-Ethics,” multi-directional partiality, and a both/and attitude toward a disorder-specific vs. non-disorder-specific therapy approach. SAD is understood from the viewpoint of social systems theory, especially in adaptation to a socio-psycho-biological explanatory model of social anxiety. In a prospective multicenter, assessor-blind pilot RCT, we included 38 clients with SAD (ICD F40.1; Liebowitz Social Anxiety Scale, LSAS-SR > 30): 18 patients participated in the ISFT, and 20 patients in Cognitive Behavioral Therapy (CBT; age:M = 36 years,SD = 14). Within-group, simple-effect intention-to-treat analyses showed significant reduction in social anxiety (LSAS-SR; ISFT:d = 1.67; CBT:d = 1.04), while intention-to-treat mixed-design ANOVA demonstrated the advantage of ISFT (d = 0.81). Per-protocol analyses supported these results. The remission rate based on blind diagnosticians’ ratings was good to satisfactory (Structured Clinical Interview, SCID; 78% in ST, 45% in CBT,p = 0.083); this has yet to be verified in a subsequent confirmatory RCT. The article will present the ISFT rationale and manual, including a special focus on multi-person settings, and the central findings from our pilot RCT. (shrink)

Objective: To systematically analyze the effectiveness of technology-based interventions for reducing loneliness in older adults.Methods: We searched relevant electronic databases from inception to April 2021, which included Cochrane Library, PubMed, Web of Science, SpringerLink, EMBASE, CNKI, and Wanfang. The following criteria were used: study design—randomized controlled trial designs, people—older adults, intervention—technology-based interventions in which a core component involved the use of technology to reduce loneliness in older adults; and outcome—reduction of loneliness level in terms of rating scale scores. Two (...) reviewers independently identified eligible studies, extracted data, and assessed the risk of bias in the included studies. A third reviewer resolved any conflicts. The Cochrane Collaboration's bias assessment tool was used to evaluate the risk of bias for the included studies, and Review Manager 5.4 software was used for the meta-analysis. A random effects model was adopted to measure estimates of loneliness reduction, and standard mean differences with a 95% confidence interval were calculated for each intervention-control contrast, and the I2 statistic was applied to examine heterogeneity.Results: A total of 391 participants from six RCTs were included in the review. Of these, three studies were rated as low-quality, and the remaining three were rated as moderate-quality studies. The meta-analysis showed that the evidence regarding the effects on loneliness of technology-based interventions compared with control groups was uncertain, and suggested that technology-based interventions resulted in little to no difference in loneliness reduction compared to control groups. Two types of technology-based interventions were identified: smartphone-based video calls and computer-based training with Internet usage. The subgroup analysis found low-quality evidence to support the effectiveness of both intervention types.Conclusions: We found no current evidence to support that technology-based interventions were effective compared to different control conditions in reducing loneliness in older adults. This suggests that more research is needed to investigate the effects of technology-based interventions on loneliness in older adults. (shrink)

Background Ethical decision‑making and behavior of nurses are major factors that can affect the quality of nursing care. Moral development of nurses to making better ethical decision-making is an essential element for managing the care process. The main aim of this study was to examine and comparison the effect of training in ethical decision-making through lectures and group discussions on nurses’ moral reasoning, moral distress and moral sensitivity. Methods In this randomized clinical trial study with a pre- and post-test (...) design, 66 nurses with moral reasoning scores lower than the average of the community were randomly assigned into three equal groups (n = 22) including two experimental groups and one control group. Ethical decision-making training to experimental groups was provided through the lectures and group discussions. While, the control group did not receive any training. Data were collected using sociodemographic questionnaire, the nursing dilemma test (NDT), the moral distress scale (MDS) and the moral sensitivity questionnaire (MSQ). Unadjusted and adjusted binary logistic regression analysis was reported using the odds ratio (OR) and 95% confidence intervals. Results Adjusted regression analysis showed that the probability of increasing the nursing principle thinking (NPT) score through discussion training was significantly higher than lecture (OR: 13.078, 95% CI: 3.238–15.954, P = 0.008), as well as lecture (OR: 14.329, 95% CI: 16.171–2.005, P < 0.001) and discussion groups compared to the control group (OR: 18.01, 95% CI: 22.15–5.834, P < 0.001). The possibility of increasing moral sensitivity score through discussion training was significantly higher than lecture (OR: 10.874, 95%CI: 6.043–12.886, P = 0.005) and control group (OR: 13.077, 95%CI: 8.454–16.774, P = 0.002). Moreover, the moral distress score was significantly reduced only in the trained group compared to the control, and no significant difference was observed between the experimental groups; lecture group vs. control group (OR: 0.105, 95% CI: 0.015–0.717, P = 0.021) and discussion group vs. control group (OR: 0.089, 95% CI: 0.015–0.547, P = 0.009). Conclusions The results of this study indicate that ethical decision-making training is effective on empowerment of ethical reasoning. Whereas the group discussion was also effective on increasing the ethical sensitivity, it is recommended the training plan provided in this study to be held as workshop for all nurses in health and treatment centers and placed in curricular plan of nursing students. Registration This randomized clinical trial was registered in Iranian Registry of Clinical Trials under code (IRCT2015122116163N5) in 02/07/2016. (shrink)

In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased quantification of the real-world treatment effect. To address the problem of lack of generalizability for the treatment effect estimated by the RCT sample, we leverage observational studies with large samples that are representative of the target population. This article concerns evaluating treatment effects on survival outcomes for a target population and (...) considers a broad class of estimands that are functionals of treatment-specific survival functions, including differences in survival probability and restricted mean survival times. Motivated by two intuitive but distinct approaches, i.e., imputation based on survival outcome regression and weighting based on inverse probability of sampling, censoring, and treatment assignment, we propose a semiparametric estimator through the guidance of the efficient influence function. The proposed estimator is doubly robust in the sense that it is consistent for the target population estimands if either the survival model or the weighting model is correctly specified and is locally efficient when both are correct. In addition, as an alternative to parametric estimation, we employ the nonparametric method of sieves for flexible and robust estimation of the nuisance functions and show that the resulting estimator retains the root- n n consistency and efficiency, the so-called rate-double robustness. Simulation studies confirm the theoretical properties of the proposed estimator and show that it outperforms competitors. We apply the proposed method to estimate the effect of adjuvant chemotherapy on survival in patients with early-stage resected non-small cell lung cancer. (shrink)

ABSTRACT I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments. INTRODUCTION In contrast to the classic model of randomized-control trials, often with a (...) large number of subjects enrolled, precision medicine attempts to optimize therapeutic outcomes by focusing on the individual.[i] A recent publication highlights the strengths and weakness of both traditional evidence-based medicine and precision medicine.[ii] Plus, it outlines a tension in the shift from evidence-based medicine’s inductive reasoning style (the collection of data to postulate general theories) to precision medicine’s abductive reasoning style (the generation of an idea from the limited data available).[iii] The paper’s main example is the application of precision medicine for the treatment of cancer.[iv] I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. As the name suggests, brain-computer interfaces are a significant advancement in neurotechnology that directly connects someone’s brain to external or implanted devices.[v] Among the various kinds of brain-computer interfaces, adaptive deep brain stimulation devices require numerous personalized adjustments to their settings during the implantation and computation stages in order to provide adequate relief to patients with treatment-resistant disorders. What makes these devices unique is how adaptive deep brain stimulation integrates a sensory component to initiate the stimulation. While not commonly at the level of sophistication as self-supervising or generative large language models,[vi] they currently allow for a semi-autonomous form of neuromodulation. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments.[vii] ANALYSIS I. The State of Precision Medicine in Oncology and the Epistemological Shift While a thorough overview of precision medicine for the treatment of cancer is beyond the scope of this article, its practice can be roughly summarized as identifying clinically significant characteristics a patient possesses (e.g., genetic traits) to land on a specialized treatment option that, theoretically, should benefit the patient the most.[viii] However, in such a practice of stratification patients fall into smaller and smaller populations and the quality of evidence that can be applied to anyone outside these decreases in turn.[ix] As inductive logic helps to articulate, the greater the number of patients that respond to a particular therapy the higher the probability of its efficacy. By straying from this logical framework, precision medicine opens the treatment of cancer to more uncertainty about the validity of these approaches to the resulting disease subcategories.[x] Thus, while contemporary medical practices explicitly describe some treatments as “personalized”, they ought not be viewed as inherently better founded than other therapies.[xi] A relevant contemporary case of precision medicine out of Norway focuses on the care of a patient with cancer between the ventricles of the heart and esophagus, which had failed to respond to the standard regimen of therapies over four years.[xii] In a last-ditch effort, the patient elected to pay out-of-pocket for an experimental immunotherapy (nivolumab) at a private hospital. He experienced marked improvements and a reduction in the size of the tumor. Understandably, the patient tried to pursue further rounds of nivolumab at a public hospital. However, the hospital initially declined to pay for it given the “lack of evidence from randomised clinical trials for this drug relating to this [patient’s] condition.”[xiii] In rebuttal to this claim, the patient countered that he was actually similar to a subpopulation of patients who responded in “open‐label, single arm, phase 2 studies on another immune therapy drug” (pembrolizumab).[xiv] Given this interpretation of the prior studies and the patient’s response, further rounds of nivolumab were approved. Had the patient not had improvements in the tumor’s size following a round of nivolumab, then pembrolizumab’s prior empirical evidence in isolation would have been insufficient, inductively speaking, to justify his continued use of nivolumab.[xv] The case demonstrates a shift in reasoning from the traditional induction to abduction. The phenomenon of ‘cancer improvement’ is considered causally linked to nivolumab and its underlying physiological mechanisms.[xvi] However, “the weakness of abductions is that there may always be some other better, unknown explanation for an effect. The patient may for example belong to a special subgroup that spontaneously improves, or the change may be a placebo effect. This does not mean, however, that abductive inferences cannot be strong or reasonable, in the sense that they can make a conclusion probable.”[xvii] To demonstrate the limitations of relying on the abductive standard in isolation, commentators have pointed out that side effects in precision medicine are hard to rule out as being related to the initial intervention itself unless trends from a group of patients are taken into consideration.[xviii] As artificial intelligence (AI) assists the development of precision medicine for oncology, this uncertainty ought to be taken into consideration. The implementation of AI has been crucial to the development of precision medicine by providing a way to combine large patient datasets or a single patient with a large number of unique variables with machine learning to recommend matches based on statistics and probability of success upon which practitioners can base medical recommendations.[xix] The AI is usually not establishing a causal relationship[xx] – it is predicting. So, as AI bleeds into medical devices, like brain-computer interfaces, the same cautions about using abductive reasoning alone should be carried over. II. Responsive Neurostimulation, AI, and Personalized Medicine Like precision medicine in cancer treatment, computer-brain interface technology similarly focuses on the individual patient through personalized settings. In order to properly expose the intersection of AI, precision medicine, abductive reasoning, and implantable neurotechnologies, the descriptions of adaptive deep brain stimulation systems need to deepen.[xxi] As a broad summary of adaptive deep brain stimulation, to provide a patient with the therapeutic stimulation, a neural signal, typically referred to as a local field potential,[xxii] must first be detected and then interpreted by the device. The main adaptive deep brain stimulation device with premarket approval, the NeuroPace Responsive Neurostimulation system, is used to treat epilepsy by detecting and storing “programmer-defined phenomena.”[xxiii] Providers can optimize the detection settings of the device to align with the patient’s unique electrographic seizures as well as personalize the reacting stimulation’s parameters.[xxiv] The provider adjusts the technology based on trial and error. One day machine learning algorithms will be able to regularly aid this process in myriad ways, such as by identifying the specific stimulation settings a patient may respond to ahead of time based on their electrophysiological signatures.[xxv] Either way, with AI or programmers, adaptive neurostimulation technologies are individualized and therefore operate in line with precision medicine rather than standard treatments based on large clinical trials. Contemporary neurostimulation devices are not usually sophisticated enough to be prominent in AI discussions where the topics of neural networks, deep learning, generative models, and self-attention dominate the conversation. However, implantable high-density electrocorticography arrays (a much more sensitive version than adaptive deep brain stimulation systems use) have been used in combination with neural networks to help patients with neurologic deficits from a prior stroke “speak” through a virtual avatar.[xxvi] In some experimental situations, algorithms are optimizing stimulation parameters with increasing levels of independence.[xxvii] An example of neurostimulation that is analogous to the use of nivolumab in Norway surrounds a patient in the United States who was experiencing both treatment-resistant OCD and temporal lobe epilepsy.[xxviii]Given the refractory nature of her epilepsy, implantation of an adaptive deep brain stimulation system was indicated. As a form of experimental therapy, her treatment-resistant OCD was also indicated for the off-label use of an adaptive deep brain stimulation set-up. Another deep brain stimulation lead, other than the one implanted for epilepsy, was placed in the patient’s right nucleus accumbens and ventral pallidum region given the correlation these nuclei had with OCD symptoms in prior research. Following this, the patient underwent “1) ambulatory, patient-initiated magnet-swipe storage of data during moments of obsessive thoughts; (2) lab-based, naturalistic provocation of OCD-related distress (naturalistic provocation task); and (3) lab-based, VR [virtual reality] provocation of OCD-related distress (VR provocation task).”[xxix] Such signals were used to identify when to deliver the therapeutic stimulation in order to counter the OCD symptoms. Thankfully, following the procedure and calibration the patient exhibited marked improvements in their OCD symptoms and recently shared her results publicly.[xxx] In both cases, there is a similar level of abductive justification for the efficacy of the delivered therapy. In the case study in which the patient was treated with adaptive deep brain stimulation, they at least had their neural activity tested in various settings to determine the optimum parameters for treatment to avoid them being based on guesswork. Additionally, the adaptive deep brain stimulation lead was already placed before the calibration trials were conducted, meaning that the patient had already taken on the bulk of the procedural risk before the efficacy could be determined. Such an efficacy test could have been replicated in the first patient’s cancer treatment, had it been biopsied and tested against the remaining immunotherapies in vitro. Yet, in the case of cancer with few options, one previous dose of a drug that appeared to work on the patient may justify further doses. However, as the Norwegian case presents, corroboration with known responses to a similar drug (from a clinical trial) could be helpful to validate the treatment strategy. (It should be noted that both patients were resigned to these last resort options regardless of the efficacy of treatment.) There are some elements of inductive logic seen with adaptive deep brain stimulation research in general. For example, abductively the focus could be that patient X’s stimulation parameters are different from patient Y’s and patient Z’s. In contrast, when grouped as subjects who obtained personalized stimulation, patients X, Y, and Z demonstrate an inductive aspect to this approach’s safety and/or efficacy. The OCD case holds plenty of abductive characteristics in line with precision medicine’s approach to treating cancer and as more individuals try the method, there will be additional data. With the gradual integration of AI into brain-computer interfaces in the name of efficacy, this reliance on abduction will continue, if not grow, over time. Moving forward, if a responsive deep brain stimulation treatment is novel and individualized (like the dose of nivolumab) and there is some other suggestion of efficacy (like clinical similarities to other patients in the literature), then it may justify insurance coverage for the investigative intervention, absent other unrelated reasons to deny it. III. Ethical Implications and Next Steps While AI’s use in oncology and neurology is not yet as prominent as its use in other fields (e.g., radiology), it appears to be on the horizon for both.[xxxi] AI can be found in both the functioning of the neurotechnologies as well as the implementation of precision medicine. The increasing use of AI may serve to further individualize both oncologic and neurological therapies. Given these implications and the handful of publications cited in this article, it is important to have a nuanced evaluation of how these treatments, which heavily rely on abductive justification, ought to be managed. The just use an abductive approach may be difficult as AI infused precision medicine is further pursued. At baseline, such technology relies on a level of advanced technology literacy among the general public and could exclude populations who lack access to basic technological infrastructure or know-how from participation.[xxxii] Even among nations with adequate infrastructure, as more patients seek out implantable neurotechnologies, which require robust healthcare resources, the market will favor patient populations that can afford this complex care.[xxxiii] If patients already have the means to pay for an initial dose/use of a precision medicine product out of pocket, should insurance providers be required to cover subsequent treatments?[xxxiv] That is, if a first dose of a cancer drug or a deep brain stimulator over its initial battery life is successful, patients may feel justified in having the costs of further treatments covered. The Norwegian patient’s experience implies there is a precedent for the idea that some public insurance companies ought to cover successful cancer therapies, however, insurance companies may not all see themselves as obligated to cover neurotechnologies that rely on personalized settings or that are based on precision/abductive research more than on clinical trials. CONCLUSION The fact that the cases outlined above rely on abductive style of reasoning implies that there may not be as strong a justification for coverage by insurance, as they are both experimental and individualized, when compared to the more traditional large clinical trials in which groups have the same or a standardized protocol (settings/doses). If a study is examining the efficacy of a treatment with a large cohort of patients or with different experimental groups/phases, insurance companies may conclude that the resulting symptom improvements are more likely to be coming from the devices themselves. A preference for inductive justification may take priority when ruling in favor of funding someone’s continued use of an implantable neurostimulator. There are further nuances to this discussion surrounding the classifications of these interventions as research versus clinical care that warrant future exploration, since such a distinction is more of a scale[xxxv] than binary and could have significant impacts on the “right-to-try” approach to experimental therapies in the United States.[xxxvi] Namely, given the inherent limitations of conducting large cohort trials for deep brain stimulation interventions on patients with neuropsychiatric disorders, surgically innovative frameworks that blend abductive and inductive methodologies, like with sham stimulation phases, have traditionally been used.[xxxvii] Similarly, for adaptive brain-computer interface systems, if there are no large clinical trials and instead only publications that demonstrate that something similar worked for someone else, then, in addition to the evidence that the first treatment/dose worked for the patient in question, the balance of reasoning would be valid and arguably justify insurance coverage. As precision approaches to neurotechnology become more common, frameworks for evaluating efficacy will be crucial both for insurance coverage and for clinical decision making. ACKNOWLEDGEMENT This article was originally written as an assignment for Dr. Francis Shen’s “Bioethics & AI” course at Harvard’s Center for Bioethics. I would like to thank Dr. Shen for his comments as well as my colleagues in the Lázaro-Muñoz Lab for their feedback. - [i] Jonathan Kimmelman and Ian Tannock, “The Paradox of Precision Medicine,” Nature Reviews. Clinical Oncology 15, no. 6 (June 2018): 341–42, https://doi.org/10.1038/s41571-018-0016-0. [ii] Henrik Vogt and Bjørn Hofmann, “How Precision Medicine Changes Medical Epistemology: A Formative Case from Norway,” Journal of Evaluation in Clinical Practice 28, no. 6 (December 2022): 1205–12, https://doi.org/10.1111/jep.13649. [iii] David Barrett and Ahtisham Younas, “Induction, Deduction and Abduction,” Evidence-Based Nursing 27, no. 1 (January 1, 2024): 6–7, https://doi.org/10.1136/ebnurs-2023-103873. [iv] Vogt and Hofmann, “How Precision Medicine Changes Medical Epistemology,” 1208. [v] Wireko Andrew Awuah et al., “Bridging Minds and Machines: The Recent Advances of Brain-Computer Interfaces in Neurological and Neurosurgical Applications,” World Neurosurgery, May 22, 2024, S1878-8750(24)00867-2, https://doi.org/10.1016/j.wneu.2024.05.104. [vi] Mark Riedl, “A Very Gentle Introduction to Large Language Models without the Hype,” Medium (blog), May 25, 2023, https://mark-riedl.medium.com/a-very-gentle-introduction-to-large-language-models-without-the-hype-5 f67941fa59e. [vii] David E. Burdette and Barbara E. Swartz, “Chapter 4 - Responsive Neurostimulation,” in Neurostimulation for Epilepsy, ed. Vikram R. Rao (Academic Press, 2023), 97–132, https://doi.org/10.1016/B978-0-323-91702-5.00002-5. [viii] Kimmelman and Tannock, 2018. [ix] Kimmelman and Tannock, 2018. [x] Simon Lohse, “Mapping Uncertainty in Precision Medicine: A Systematic Scoping Review,” Journal of Evaluation in Clinical Practice 29, no. 3 (April 2023): 554–64, https://doi.org/10.1111/jep.13789. [xi] Kimmelman and Tannock, “The Paradox of Precision Medicine.” [xii] Vogt and Hofmann, 1206. [xiii] Vogt and Hofmann, 1206. [xiv] Vogt and Hofmann, 1206. [xv] Vogt and Hofmann, 1207. [xvi] Vogt and Hofmann, 1207. [xvii] Vogt and Hofmann, 1207. [xviii] Vogt and Hofmann, 1210. [xix] Mehar Sahu et al., “Chapter Three - Artificial Intelligence and Machine Learning in Precision Medicine: A Paradigm Shift in Big Data Analysis,” in Progress in Molecular Biology and Translational Science, ed. David B. Teplow, vol. 190, 1 vols., Precision Medicine (Academic Press, 2022), 57–100, https://doi.org/10.1016/bs.pmbts.2022.03.002. [xx] Stefan Feuerriegel et al., “Causal Machine Learning for Predicting Treatment Outcomes,” Nature Medicine 30, no. 4 (April 2024): 958–68, https://doi.org/10.1038/s41591-024-02902-1. [xxi] Sunderland Baker et al., “Ethical Considerations in Closed Loop Deep Brain Stimulation,” Deep Brain Stimulation 3 (October 1, 2023): 8–15, https://doi.org/10.1016/j.jdbs.2023.11.001. [xxii] David Haslacher et al., “AI for Brain-Computer Interfaces,” 2024, 7, https://doi.org/10.1016/bs.dnb.2024.02.003. [xxiii] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 103–4; “Premarket Approval (PMA),” https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100026. [xxiv] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 104. [xxv] Burdette and Swartz, 126. [xxvi] Sean L. Metzger et al., “A High-Performance Neuroprosthesis for Speech Decoding and Avatar Control,” Nature 620, no. 7976 (August 2023): 1037–46, https://doi.org/10.1038/s41586-023-06443-4. [xxvii] Hao Fang and Yuxiao Yang, “Predictive Neuromodulation of Cingulo-Frontal Neural Dynamics in Major Depressive Disorder Using a Brain-Computer Interface System: A Simulation Study,” Frontiers in Computational Neuroscience 17 (March 6, 2023), https://doi.org/10.3389/fncom.2023.1119685; Mahsa Malekmohammadi et al., “Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson’s Disease,” Movement Disorders 31, no. 3 (2016): 426–28, https://doi.org/10.1002/mds.26482. [xxviii] Young-Hoon Nho et al., “Responsive Deep Brain Stimulation Guided by Ventral Striatal Electrophysiology of Obsession Durably Ameliorates Compulsion,” Neuron 0, no. 0 (October 20, 2023), https://doi.org/10.1016/j.neuron.2023.09.034. [xxix] Nho et al. [xxx] Nho et al.; Erik Robinson, “Brain Implant at OHSU Successfully Controls Both Seizures and OCD,” OHSU News, accessed March 3, 2024, https://news.ohsu.edu/2023/10/25/brain-implant-at-ohsu-successfully-controls-both-seizures-and-ocd. [xxxi] Awuah et al., “Bridging Minds and Machines”; Haslacher et al., “AI for Brain-Computer Interfaces.” [xxxii] Awuah et al., “Bridging Minds and Machines.” [xxxiii] Sara Green, Barbara Prainsack, and Maya Sabatello, “The Roots of (in)Equity in Precision Medicine: Gaps in the Discourse,” Personalized Medicine 21, no. 1 (January 2024): 5–9, https://doi.org/10.2217/pme-2023-0097. [xxxiv] Green, Prainsack, and Sabatello, 7. [xxxv] Robyn Bluhm and Kirstin Borgerson, “An Epistemic Argument for Research-Practice Integration in Medicine,” The Journal of Medicine and Philosophy: A Forum for Bioethics and Philosophy of Medicine 43, no. 4 (July 9, 2018): 469–84, https://doi.org/10.1093/jmp/jhy009. [xxxvi] Vijay Mahant, “‘Right-to-Try’ Experimental Drugs: An Overview,” Journal of Translational Medicine 18 (June 23, 2020): 253, https://doi.org/10.1186/s12967-020-02427-4. [xxxvii] Michael S. Okun et al., “Deep Brain Stimulation in the Internal Capsule and Nucleus Accumbens Region: Responses Observed during Active and Sham Programming,” Journal of Neurology, Neurosurgery & Psychiatry 78, no. 3 (March 1, 2007): 310–14, https://doi.org/10.1136/jnnp.2006.095315. (shrink)

Objectives: This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to improve subjective well-being (SWB), including evaluative, hedonic, and eudemonic well-being, and the mental component of quality of life (QOL) of working population. Methods: A literature search was conducted, using PubMed, Embase, PsycINFO, and PsycARTICLES. Eligible studies included those that were RCTs of any intervention, conducted among healthy workers, measured SWB as a primary outcome, and original articles in English. Study characteristics, intervention, (...) outcomes, and results on SWB outcomes were extracted by the investigators independently. After a brief narrative summarizing and classifying the contents of the interventions, the included outcomes were categorized into each aspect of SWB (evaluative, hedonic, and eudemonic well-being, and the mental component of QOL). Finally, the characteristics of the effective interventions for increasing each aspect were summarized, and the pooled effect of interventions on SWB was investigated by a meta-analysis. Publication bias was investigated by drawing a funnel plot and conducting Egger's test. Results: From the 5,450 articles found, 39 met the inclusion criteria for the systematic review. The interventions included in this review were classified into six categories (physical activity, ergonomics, psychological, environmental, multicomponent intervention, and others). The meta-analysis from 31 studies showed that the pooled effect of included interventions on SWB was significantly positive (standardized mean difference (SMD) = 0.51; standard error (SE) = 0.10). A funnel plot showed there were extremely large or small SMDs, and Egger's test was significant. Thus, we conducted sensitivity analysis, excluding these extreme SMDs, and confirmed that the estimated pooled effect was also significantly positive. Subgroup analyses for separate types of interventions showed the effects of psychological interventions (e.g., mindfulness, cognitive behavioral based approach, and other psychological interventions) were also significantly positive. Conclusion: The current study revealed the effectiveness of interventions for increasing SWB. Specifically, psychological interventions (e.g., mindfulness, cognitive behavioral based approach, and other psychological interventions) may be useful for improving SWB. (shrink)

Background: In this study, we aimed to investigate the effects of a mindfulness program including Mindfulness-Based Stress Reduction on the mental health of student teachers when offered at their educational institution in a real-life context.Methods: A parallel randomized controlled trial was conducted among self-selected student teachers at a Danish undergraduate program for teacher education in the autumns of 2019 and 2020. Participation was not recommended in case of clinical depression or a diagnosis of psychosis or schizophrenia, abuse of alcohol, (...) drugs, and/or medicine. Randomization was performed by a Statistician who was blinded to the identity of the students. Data was collected using self-reported questionnaires. The primary outcome was a change in perceived stress 3 months from baseline. Secondary outcome measures were symptoms of anxiety and depression, well-being, resilience, mindfulness, and thoughts and feelings during rest. The effects were analyzed according to the intention-to-treat principle using mixed-effect linear regression models. Mediating effects of mindfulness skills on the mental health outcomes were explored using structural equation modeling.Results: The study group included 67 student teachers with 34 allocated to the intervention group ; and 33 students allocated to a waiting list control group. At baseline, mean Perceived Stress Scale scores were 18.88 in the intervention group and 17.91 in the waiting list control group. A total of 56 students completed the questionnaire at a 3-month follow-up. Statistically significant effects of the intervention were found on perceived stress, symptoms of anxiety and depression, well-being, and on three of seven resting-state dimensions. No effects were found on resilience or mindfulness. Statistically significant mediated effects via resting-state dimensions were found.Conclusion The findings suggested that offering a mindfulness program at an undergraduate program for teacher education could significantly improve the mental health among self-selected students within 3 months. Results of mediation analysis supported the hypothesis that some of the effects might be explained by reduced distracting thoughts.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04558099]. (shrink)

ObjectiveThis study aimed to examine the effectiveness and safety of the Brain-computer interface in treatment of upper limb dysfunction after stroke.MethodsEnglish and Chinese electronic databases were searched up to July 2021. Randomized controlled trials were eligible. The methodological quality was assessed using Cochrane’s risk-of-bias tool. Meta-analysis was performed using RevMan 5.4.ResultsA total of 488 patients from 16 RCTs were included. The results showed that the meta-analysis of BCI-combined treatment on the improvement of the upper limb function showed statistical (...) significance [standardized mean difference : 0.53, 95% CI: 0.26–0.80, P < 0.05]; BCI treatment can improve the abilities of daily living of patients after stroke, and the analysis results are statistically significant ; and the BCI-combined therapy was not statistically significant for the analysis of the Modified Ashworth Scale.ConclusionThe meta-analysis indicates that the BCI therapy or BCI combined with other therapies such as conventional rehabilitation training and motor imagery training can improve upper limb dysfunction after stroke and enhance the quality of daily life. (shrink)

Many women are initially unable to contract the pelvic floor muscles (PFMs) properly, activating other muscle groups before, or instead of, PFM. Numerous authors have proved that biofeedback can be an ideal tool supporting learning of the PFM contraction. However, there is currently a lack of scientific data on how many biofeedback sessions are necessary in this educational process. In this study we aimed at assessing the effects of one-time electromyography (EMG) biofeedback session on the order in which PFM are (...) activated (so called firing order) during conscious contractions in relation to selected synergistic muscles in pregnant, continent women. A randomized controlled trial was conducted in 90 healthy nulliparous women with uncomplicated pregnancies and without diagnosed urinary incontinence. We divided the participants into a biofeedback group (50) and a control group (40). They were, respectively: 30 ± 4 and 30 ± 4 years old, at their 23 ± 5 or 25 ± 7 week of gestation and presented 23 ± 5 or 24 ± 5 kg/m2 BMI value (M + SD). Surface EMG with vaginal probes has been used to assess the PFM firing order in selected tasks: in five 3-s maximal contractions (quick flicks), five 10-s contractions, and in a 60-s contraction (static hold). We used the 1–5 scale, where “1” meant the best score, awarded when PFM was activated first in order. The most important finding of our study is that a single EMG biofeedback substantially improved the PFM contractions in pregnant women. First, when applying one-time biofeedback session, more women maintained correct technique or improved it in the second assessment, compared to the control group (73 vs. 65%). Secondly, using the quantitative and qualitative analysis with the Chi-square McNamara B/C test, in the biofeedback group we observed a statistically significant improvement of PFM firing order in four tasks: in the first quick flicks (p = 0.016), third quick flicks (p = 0.027), fifth quick flicks (p = 0.008), and in the first 10-s contractions (p = 0.046). In the control group we observed better outcome only in one motor task: in the fourth 10-s contraction (p = 0.009). Given the positive effects of a single session of EMG biofeedback on the firing order in the PFM contractions, it should be recommended for pregnant women without urinary incontinence to teach them how to perform PFM exercises correctly. (shrink)

BackgroundPost-stroke depression is one of the most common neuropsychiatric diseases in patients with stroke, and it can increase the disability rate, mortality, and recurrence rate of stroke. Currently, many clinical studies have indicated that traditional Chinese medicine, such as acupuncture and herbs, Western medicine, rehabilitation, repeated transcranial magnetic stimulation, and other treatment methods, are effective in treating PSD. However, no study has formulated a comprehensive treatment plan that integrates TCM, Western medicine, and rehabilitation for PSD. Thus, this trial aims to (...) assess the efficacy and safety of integrative medicine for treating PSD.MethodsThis multicenter, prospective, randomized, controlled study aims to form a set of effective clinical treatment schemes that integrate TCM, Western medicine, and rehabilitation for PSD. A total of 202 participants recruited from four centers will be randomized into either the integrative medicine or standard care group. Standard care—basic treatment, general nursing care, and exercise therapy—will be provided to all participants. The integrative medicine group will also receive acupuncture, Chinese herbs, and repeated transcranial magnetic stimulation. Participants will receive acupuncture and rTMS treatments five times per week for 4 weeks and will be administered Chinese herbs, basic treatment, general nursing care, and exercise therapy for 4 weeks. The primary outcomes include the Hamilton Depression Scale, Self-Rating Depression Scale, and Activity of Daily Living Scale. And the secondary outcomes include the Montreal Cognitive Assessment Scale, the Fugl-Meyer Assessment Scale, and the Pittsburgh Sleep Quality Index. All outcome measures will be evaluated at baseline, week 4, and week 8. Safety assessments will be performed throughout the study.DiscussionThis study is expected to verify the efficacy and safety of integrative medicine for treating PSD, providing an evidence-based clinical reference for the future development of a standardized scheme.Clinical trial registrationClinicalTrials.gov, identifier: NCT05187975. (shrink)

There are more large-scale pregnancy trials that implement lifestyle interventions than ever before; yet, there is a dearth of information on pregnant peoples’ experiences in such trials. Contemporary lifestyle pregnancy trials draw on epigenetics and DOHaD research to design and justify prenatal interventions on the material environment to reduce health risks in future generations. This article draws on ethnographic data from a prenatal trial in the United Kingdom and focuses specifically on the experiences of pregnant participants during (...) the intervention phase. In this article, I develop the politics of postgenomic reproduction as a feminist and critical race framework to examine the complex and mercurial stakes of contemporary pregnancy trials. I argue that narratives of control and responsibility in epigenetic models are echoed and preceded by participants’ own embodied experience. The pregnant narratives show at once how their bodies are exposed to unpredictable and uncontrollable environmental exposures and that they are required to respond as if they have absolute control and responsibility. Attending to trial participants’ narratives from a feminist and critical race framework reveals how individualized lifestyle interventions are deeply political and racial, and carry implications for how pregnancy trials influence postgenomic reproduction. (shrink)

BackgroundIn many Western countries like Germany, the social integration of children with an immigrant background has become an urgent social tasks. The probability of them living in high-risk environments and being disadvantaged regarding health and education-related variables is still relatively higher. Yet, promoting language acquisition is not the only relevant factor for their social integration, but also the support of earlier developmental processes associated with adequate early parenting in their first months of life. The Emotional Availability Scales measure the quality (...) of caregiver-child-interactions as an indicator of the quality of their relationship and thus of such early parenting, focusing on mutual and emotional aspects of their interaction.MethodThis pilot study examined in a randomized controlled trial the effects of the prevention project First Steps regarding the hypothesis that the Emotional Availability improved to a greater extent in “difficult-to-reach” immigrant mother-child dyads in a psychoanalytically oriented early intervention compared to a usual care intervention offered by paraprofessionals with an immigrant background. A sample of N = 118 immigrant women in Germany from 37 different countries and their children was compared with regard to the parental EA-dimensions sensitivity, structuring, non-intrusiveness and non-hostility and the child dimensions responsiveness to and involvement of the caregiver in the pre-post RCT design.Results and ConclusionDifferent from what was expected, repeated ANOVAs revealed no significant pre-post group differences for the parental dimensions. For the child dimensions the effect of time of measurement was highly significant, which can be interpreted as mostly natural developmental effects. Still, on the level of simple main effects for each intervention, only in the FIRST STEPS groups child responsiveness significantly improved. When controlled for confounding variables, a significant interaction effect for maternal sensitivity in favor of the FIRST STEPS intervention was found. The systematic group differences indicate that the more extensive and professional intervention, focusing on the individual needs of the participants, is more suitable to support the quality of the mother-child-relationship amongst immigrant mother-child dyads than usual care. The results are discussed taking into account the context of the maternal migration process and potential maternal traumatization.Clinical Trial Registration[https://clinicaltrials.gov], identifier [DRKS00004632]. (shrink)

ObjectivePreviously Mindfulness-Based Swinging Technique 's immediate efficacy for overcoming psychological concerns has recently received empirical support, yet its longer-term efficacy needed to be evaluated among women with breast cancer. The objective of this study was to assess and report the efficacy of MBST intervention among breast cancer patients for hopelessness, anxiety, depression, self-efficacy, oxygen intensity, and heart rate-beats per minute at an 8-week period.MethodThe State-Trait Anxiety Inventory, The Emotion Thermometer, Hospital Anxiety and Depression Scale, Self-Efficacy for Managing Chronic Disease, and (...) Beck's Hopelessness Scale were used for assessing the intervention's outcome; 149 BC patients were randomly assigned into two groups. The participants in the control group received Cognitive Behavioural Therapy -Cognitive-Disputation for 20 min, and intervention group received MBST intervention. No additional psychological interventions were given between week-1 and week-8.ResultOutcomes of the 8-week post-treatment follow-up exhibited significantly higher improvements in all evaluated-measurements for CG, and some for IG with large effect size in the following: anxiety and depression levels. It increased self-efficacy for managing disease and hopefulness, and saturation levels measured by pulse-meter/oximeter.ConclusionsBoth CBT-CD and MBST have been found to be efficacious interventions to shorten the psychotherapy duration for reducing clinical anxiety and hopelessness as well as increase self-efficacy for BC women. This may have a distinct clinical importance for supporting BC patient's adherence-to-treatment since CBT-CD could be an alternative technique to MBST as a brief intervention. In future studies, the effectiveness of MBST through adapting to virtual reality and other online delivery methods should be examined. (shrink)

BackgroundRandomized Controlled Trials are the gold standard for assessing whether an intervention is effective; however, they require large sample sizes in order to detect small effects. For rare or complex populations, we advocate a case series approach as a more realistic and useful first step for intervention evaluation. We consider the importance of randomization to such designs, and advocate for the use of Randomization Tests and Between Case Effect Sizes to provide a robust and statistically powerful evaluation of outcomes. (...) In this tutorial, we describe the method, procedures, and analysis code necessary to conduct robust single case series, using an empirical example with minimally verbal autistic children.MethodWe applied a pre-registered randomized baseline design with between-case effect size to a case series, to test the efficacy of a novel, parent-mediated, app-based speech production intervention for minimally verbal autistic children. Parent-rated probe scores were used to densely sample performance accuracy over time.ResultsParents were able to reliably code their children’s speech productions using BabbleBooster. A non-significant Randomization Test and small Between-Case Effect Size, suggested there was no evidence that BabbleBooster improved speech production in minimally verbal autistic children, relative to baseline scores, during this brief period of intervention.ConclusionThe current analyses exemplify a more robust approach to examining treatment effects in rare or complex populations, where RCT may be difficult or premature to implement. To facilitate adoption of this method by researchers and practitioners, we provide analysis code that can be adapted using open source R packages. Future studies could use this case series design to evaluate interventions aiming to improve speech and language outcomes for minimally verbal autistic children, and other heterogeneous and hard to reach populations. (shrink)

Background: There is evidence that household point-of-use water treatment products can reduce the enormous burden of water-borne illness. Nevertheless, adoption among the global poor is very low, and little evidence exists on why. Methods: We gave 600 households in poor communities in Dhaka, Bangladesh randomly-ordered two-month free trials of four water treatment products: dilute liquid chlorine, sodium dichloroisocyanurate tablets, a combined flocculant-disinfectant powdered mixture, and a silver-coated ceramic siphon filter. Consumers also received education on the dangers of untreated drinking (...) water. We measured which products consumers used with self-reports, observation, and chlorine tests. We also measured drinking water's contamination with E. coli. Findings: Households reported highest usage of the filter, although no product had even 30% usage. E. coli concentrations in stored drinking water were generally lowest when households had Water Guard. Households that self-reported product usage had large reductions in E. coli concentrations with any product as compared to controls. Conclusion: Traditional arguments for the low adoption of POU products focus on affordability, consumers' lack of information about germs and the dangers of unsafe water, and specific products not meshing with a household's preferences. In this study we provided free trials, repeated informational messages explaining the dangers of untreated water, and a variety of product designs. The low usage of all products despite such efforts makes clear that important barriers exist beyond cost, information, and variation among these four product designs. Without a better understanding of the choices and aspirations of the target end-users, household-based water treatment is unlikely to reduce morbidity and mortality substantially in urban Bangladesh and similar populations. © 2011 Luoto et al. (shrink)

The unprecedented rise and fall in silver's price during 1979 and 1980 resulted in charges against the Hunt brothers of Dallas of monopolization and market manipulation, charges which led to a lengthy trial. This book focuses on the economic analysis used at this trial. Drawing upon interviews with the judge, jury, attorneys and expert witnesses, it investigates the elusive definition of manipulation in sophisticated markets, the difficulties of interpreting statistical evidence, the imprecision in calculating damages, the hidden assumptions behind inferences (...) concerning intent, and the hazards introduced when economic analysis enters complex litigation. The author concludes that these problems induce courtroom procedures to oversimplify the economic analysis and cause the law on market manipulation to be created retroactively. Yet the failure lies not with the legal institutions but with the futures exchanges who had not developed in advance the rules to minimize large-scale trading during the unusual price moves. (shrink)

ABSTRACTRelatively little has been written about the ethics of conducting early phase clinical trials involving subjects from the developing world. Below, I analyze ethical issues surrounding one of gene transfer’s most widely praised studies conducted to date: in this study, Italian investigators recruited two subjects from the developing world who were ineligible for standard of care because of economic considerations. Though the study seems to have rendered a cure in these two subjects, it does not appear to have complied (...) with various international guidelines that require that clinical trials conducted in the developing world be responsive to their populations’ health needs. Nevertheless, policies devised to address large scale, late stage trials, such as the AZT short‐course placebo trials, map somewhat awkwardly to early phase studies. I argue that interest in conducting translational research in the developing world, particularly in the context of hemophilia trials, should motivate more rigorous ethical thinking around clinical trials involving economically disadvantaged populations. (shrink)

Background: Ideas always have and always will change the world; with ideas-engagement enabling individuals to become more knowledgeable, better able to make good decisions and better positioned to re-align their values in response to new progressive norms and beliefs. Given these potential benefits, of primary interest is how citizens can be most effectively encouraged to engage with new ideas. Methods: With this study we test the efficacy of two approaches designed to enhance citizen’s perceptions regarding the value of ideas-engagement. Specifically, (...) we recontextualise a previously undertaken small-scale randomised control trial designed to stimulate states of either curiosity or pragmatic prospection amongst two randomly allocated groups of respondents. Our target variables involve the importance respondents attribute to staying up to date, as well as to four related attitudinal variables. Our target audience is the voting age population of England. Results: 515 participants took part in the experiment, with 269 receiving the curiosity stimulating intervention and 246, the prospection intervention. Our findings suggest that, by the end of four weeks, only the intervention designed to promote pragmatic prospection had significantly impacted on the importance respondents attribute to staying up to date. It also positively impacted the value- scores for one of the secondary attitudinal variables (relating to the importance of supporting physical and mental-health). Conclusions: While this study provides useful insight regarding ideas-engagement, further work is needed. In particular, future studies will require a larger sample, so as to ascertain the impact of these approaches on ‘ideas refusers’. Also required is the inclusion of a control group to provide a definitive counter factual. Furthermore, since positive changes in attitudes towards ideas- engagement also ideally leads to changes in behaviours, questions are also needed to examine the sources of ideas respondents subsequently engage with (or not) as a result of these interventions. (shrink)

Background: The new human coronavirus that leads to COVID-19 has spread rapidly around the world and has a high degree of lethality. In more severe cases, patients remain hospitalized for several days under treatment of the health team. Thus, it is important to develop and use technologies with the aim to strengthen conventional therapy by encouraging movement, physical activity, and improving cardiorespiratory fitness for patients. In this sense, therapies for exposure to virtual reality are promising and have been shown to (...) be an adequate and equivalent alternative to conventional exercise programs.Aim: This is a study protocol with the aim of comparing the conventional physical therapy intervention with the use of a non-immersive VR software during COVID-19 hospitalization.Methods: Fifty patients hospitalized with confirmed diagnosis of COVID-19 will be divided in two groups under physiotherapy treatment using conventional or VR intervention: Group A: participants with COVID-19 will start the first day of the protocol with VR tasks in the morning and then in the second period, in the afternoon, will perform the conventional exercises and Group B: participants with COVID-19 will start the first day with conventional exercises in the morning and in the second period, in the afternoon, will perform activity with VR. All participants will be evaluated with different motor and physiologic scales before and after the treatment to measure improvements.Conclusion: Considering the importance of benefits from physical activity during hospitalization, VR software shows promise as a potential mechanism for improving physical activity. The results of this study may provide new insights into hospital rehabilitation.Trial Registration:ClinicalTrials.gov, identifier: NCT04537858. Registered on 01 September 2020. (shrink)

Disease control has increasingly shifted towards large scale, disease specific, public health interventions. The emerging problems of HIV, hepatitis, malaria, typhoid, tuberculosis, childhood pneumonia, and meningitis have made community based trials of interventions a cost effective long term investment for the health of a population. The authors conducted this study to explore the complexities involved in obtaining informed consent to participation in rural north India, and how people there make decisions related to participation in clinical research.

Ethics guidance increasingly recognises that researchers and sponsors have obligations to consider provisions for post-trial access to interventions that are found to be beneficial in research. Yet, there is little information regarding whether and how such plans can actually be implemented. Understanding practical experiences of developing and implementing these plans is critical to both optimising their implementation and informing conceptual work related to PTA. This viewpoint is informed by experiences with developing and implementing PTA plans for six large-scale multicentre HIV (...) prevention trials supported by the HIV Prevention Trials Network. These experiences suggest that planning and implementing PTA often involve challenges of planning under uncertainty and confronting practical barriers to accessing healthcare systems. Even in relatively favourable circumstances where a tested intervention medication is approved and available in the local healthcare system, system-level barriers can threaten the viability of PTA plans. The aggregate experience across these HIV prevention trials suggests that simply referring participants to local healthcare systems for PTA will not necessarily result in continued access to beneficial interventions for trial participants. Serious commitments to PTA will require additional efforts to learn from future approaches, measuring the success of PTA plans with dedicated follow-up and further developing normative guidance to help research stakeholders navigate the complex practical challenges of realising PTA. (shrink)

The ideology of evidence-base medicine (EBM) has dramatically altered the way we think, conceptualize, philosophize and practice medicine. One of its major pillars is the appraisal and classification of evidence. Although important and beneficial, this process currently lacks detail and is in need of reform. In particular, it largely focuses on three key dimensions (design, [type I] alpha error and beta [type II] error) to grade the quality of evidence and often omits other crucial aspects of evidence such as biological (...) plausibility, reproducibility, generalizability, temporality, consistency and coherence. It also over-values the randomized trial and meta-analytical techniques, discounts the biasing effect of single centre execution and gives insufficient weight to large and detailed observational studies. Unless these aspects are progressively included into systems for grading, evaluating and classifying evidence and duly empirically assessed (according to the EBM paradigm), the EBM process and movement will remain open to criticism of being more evidence-biased than evidence-based. (shrink)

Cluster randomized controlled trials (cluster RCTs) randomize whole clusters of individuals in testing two or more competing interventions. Here we will present the ethical problems raised by cluster RCTs concerning their effect on inequality. We argue that some inequalities generated by cluster RCTs are larger in scope than those generated from individual RCTs. We also argue that any cluster RCT-generated inequalities, which divide groups rather than individuals, are more problematic in type than the inequalities created in individual RCTs. (...) These concerns should be taken into consideration when designing research at the cluster level, and those conducting the research should consider modified research design strategies in cases where they believe the risk of generating inequalities is large. (shrink)

In an adaptive clinical trial , key trial characteristics may be altered during the course of the trial according to predefined rules in response to information that accumulates within the trial itself. In addition to having distinguishing scientific features, adaptive trials also may involve ethical considerations that differ from more traditional randomized trials. Better understanding of clinical trial experts’ views about the ethical aspects of adaptive designs could assist those planning ACTs. Our aim was to elucidate the (...) opinions of clinical trial experts regarding their beliefs about ethical aspects of ACTs. (shrink)

Many children in the USA are prescribed psychotropic drugs that have not been fully investigated in paediatric clinical trials. The common practice of prescribing psychotropic drugs off-label poses unknown and potentially serious short- and long-term consequences for these children. This paper briefly reviews the factors associated with the lack of paediatric clinical trials. We advocate a shift toward increasing paediatric trials with psychotropic drugs through a combination of adequate safety controls, additional reimbursement/compensation, a more organised and large-scale (...) effort to collate results and outcomes across researchers and studies and additional public education about the importance of this research. In addition, we encourage the re-examination of the ethical standards for children's participation in phase 1 clinical trials as well as argue for longitudinal developmental studies on children who are prescribed off-label psychotropic drugs. (shrink)

BackgroundOver the last decades there has been a change in the way schooling is perceived recognizing that children’s learning is closely linked to children’s health. Children spend most of their time at school, which is often the place where problems are identified and interventions are offered, not only for treatment but also prevention. Embedding arts therapies into the educational system may help address children’s emerging needs and have a positive impact on their wellbeing.MethodsA pilot cross-over randomized controlled design was (...) employed to investigate the effectiveness of an arts therapies intervention on a series of child- and teacher-reported outcome measures, specifically, health related quality of life, wellbeing and life functioning, emotional and behavioral difficulties, as well as duration of sleep. Sample size calculations for future large-scale studies were also performed, and the sustained impact of the intervention was evaluated at 3, 6, and 12 months follow-up. The pluralistic theoretical and therapeutic framework of this intervention was informed by a systematic review on school-based arts therapies interventions and is presented in detail in the study protocol. Participants were 62 children with mild emotional and behavioral difficulties.ResultsImprovements in HRQOL and CORS were greater in those engaged in the arts therapies intervention than the control groups and were maintained at the follow-up stages. Significant improvements were only found for duration of sleep and SDQ. Minimal clinically important differences as defined in the published protocol were found for CORS, SDQ and duration of sleep, but not HRQOL.DiscussionFindings indicate that the arts therapies interventions were having a clinically significant effect on life functioning, duration of sleep, emotional and behavioral difficulties. Findings also indicate a small effect size for health related quality of life, suggesting the intervention was having a small positive effect on this outcome measure. The study indicates that all outcome measures assessed here would be suitable for inclusion in a larger randomized controlled study utilizing these arts therapies interventions, and that a sample size of 225 participants would be required if these outcome measures were used. (shrink)