Diagnostic Misconceptions Research Articles

Genomics Research with Undiagnosed Children: Ethical Challenges at the Boundaries of Research and Clinical Care

To explore the perspectives of parents of undiagnosed children enrolled in genomic diagnosis research regarding their motivations for enrolling their children, their understanding of the potential burdens and benefits, and the extent to which their experiences ultimately aligned with or diverged from their original expectations. In-depth interviews were conducted with parents, audio-recorded and transcribed. A structured codebook was applied to each transcript, after which iterative memoing was used to identify themes. Fifty-four parents participated, including 17 (31.5%) whose child received a diagnosis through research. Themes describing parents' expectations and experiences of genomic diagnosis research included (1) the extent to which parents' motivations for participation focused on their hope that it would directly benefit their child, (2) the ways in which parents' frustrations regarding the research process confused the dual clinical and research goals of their participation, and (3) the limited clinical benefits parents ultimately experienced for their children. Our results suggest that parents of undiagnosed children seeking enrollment in genomic diagnosis research are at risk of a form of therapeutic misconception-in this case, diagnostic misconception. These findings indicate the need to examine the processes and procedures associated with this research to communicate appropriately and balance the potential burdens and benefits of study participation.

Feedback of individual genetic and genomics research results: A qualitative study involving grassroots communities in Uganda.

Genetics and genomics research (GGR) is associated with several challenges including, but not limited to, methods and implications of sharing research findings with participants and their family members, issues of confidentiality, and ownership of data obtained from samples. Additionally, GGR holds significant potential risk for social and psychological harms. Considerable research has been conducted globally, and has advanced the debate on return of genetic and genomics testing results. However, such investigations are limited in the African setting, including Uganda where research ethics guidance on return of results is deficient or suboptimal at best. The objective of this study was to assess perceptions of grassroots communities on if and how feedback of individual genetics and genomics testing results should occur in Uganda with a view to improving ethics guidance. This was a cross-sectional study that employed a qualitative exploratory approach. Five deliberative focus group discussions (FGDs) were conducted with 42 participants from grassroots communities representing three major ethnic groupings. These were rural settings and the majority of participants were subsistence farmers with limited or no exposure to GGR. Data were analysed through thematic analysis, with both deductive and inductive approaches applied to interrogate predetermined themes and to identify any emerging themes. NVivo software (QSR international 2020) was used to support data analysis and illustrative quotes were extracted. All the respondents were willing to participate in GGR and receive feedback of results conditional upon a health benefit. The main motivation was diagnostic and therapeutic benefits as well as facilitating future health planning. Thematic analysis identified four themes and several sub-themes including 1) the need-to-know health status 2) paternity information as a benefit and risk; 3) ethical considerations for feedback of findings and 4) extending feedback of genetics findings to family and community. Participation in hypothetical GGR as well as feedback of results is acceptable to individuals in grassroots communities. However, the strong therapeutic and/or diagnostic misconception linked to GGR is concerning given that hopes for therapeutic and/or diagnostic benefit are unfounded. Viewing GGR as an opportunity to confirm or dispute paternity was another interesting perception. These findings carry profound implications for consent processes, genetic counselling and research ethics guidance. Privacy and confidentiality, benefits, risks as well as implications for sharing need to be considered for such feedback of results to be conducted appropriately.

Informed consent in a tuberculosis genetic study in Cameroon: information overload, situational vulnerability and diagnostic misconception

Concerns around comprehension and recall of consent information by research participants have typically been associated with low health and research literacy levels. In genomics research, this concern is heightened as the scientific and ethical complexities of genetics research, such as biobanking, genetic susceptibility, data sharing, and incidental findings may be more difficult for potential research participants to understand. However, challenges to research participants’ comprehension of consent information may be compounded by factors beyond health and research literacy levels. To identify factors that may impact research participants’ understanding and recall of consent information, we designed a qualitative study to explore whether participants enrolled in a tuberculosis genetics study (TBGEN-Africa) in Cameroon understood the objectives of the study, the risks and benefits and certain key aspects of the study such as biobanking and data sharing. The results showed that research participants had limited understanding and/or recall of the TBGEN-Africa study goals and methods. Some participants were of the opinion that TBGEN-Africa was not a genetics study because tuberculosis is not an inheritable condition. Factors that may have hindered understanding and/or recall of study information are diagnostic misconception (research participants consider research as part of medical diagnosis), and information overload and situational vulnerability (consent at a time of physical and emotional distress). There is a need for improved practices to support research participants’ understanding of consent information in genetics studies including designing the consent process in ways that minimize psychological distress and diagnostic/therapeutic misconception.

POS-774 Role of Noro virus infection in post renal transplant persistent diarrhea

Diarrhea is common gastrointestinal problem in kidney transplant recipients. Numerous cases of post-transplant diarrhea in the past have been ascribed solely to the toxicity of immunosuppressive drugs, leading to diagnostic misconceptions. Noro Virus, one of the common cause of acute diarrhea in adult is emerging as important cause of persistent diarrhea in solid organ transplant recipients.Here, we are presenting our experience with chronic Noro virus infection in renal transplant recipients.

The impact of reporting magnetic resonance imaging incidental findings in the Canadian alliance for healthy hearts and minds cohort

BackgroundIn the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.MethodsBetween 2013 and 2019, 8252 participants (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported.ResultsSevere structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy.ConclusionThe management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT02220582.

Neonatal Hereditary Fructose Intolerance: Diagnostic Misconceptions and the Role of Genomic Sequencing

Hereditary fructose intolerance (HFI) is a rare inborn error of metabolism due to deficiency of the enzyme aldolase B, preventing metabolism of fructose. Patients remain asymptomatic until exposed to fructose, sucrose, or sorbitol. HFI presenting as acute liver failure in the neonatal period is rare due to lack of exposure as breast milk and infant formulas are considered to be fructose free. Diagnosis can be delayed due to vague symptoms and lack of specific biomarkers. Recent advances in genetic testing have led to rapid diagnosis and favorable outcomes. We present the case of a formula-fed neonate who presented with acute liver failure where definitive diagnosis of HFI was made using expedited whole exome sequencing. Through this communication, we aim to bring attention to neonatal presentations of HFI from exposure to fructose in infant formulas and also highlight advances in rapid turnaround genomic testing in diagnosis.

Comparative Study of Secondary School Students' and Pre-Service Teachers' Misconception about Simple Electric Circuit

The purpose of this study is to compare the misconceptions of secondary school students (junior and senior high school) and pre-service physics teachers about simple electrical circuits. The study involved 92 people consisting of 30 junior high school students, 32 senior high school students, and 30 pre-service physics teachers. The diagnostic misconception instrument was adapted from the Simple Electric Circuits Diagnostic Test (SECDT). Data were analyzed by descriptive and inferential analysis. The results of the study indicated that there are 11 misconceptions types that the student had. The clashing current is a type of misconception that is most often found both in high school students and in pre-service teacher. The inferential test showed that there were significant differences of misconception scores among junior high school students, senior high school students, and pre-service physics teachers (KW=12,689, df=2, p< 0.05). Teachers could use the misconception profile as a consideration in planning classroom instruction.

Development of an online mathematical misconception instrument

The misconception is one phenomenon that often occurs in the fields of science, including mathematics. To find a solution, diagnostic needs to be done about misconceptions on the basic concepts of mathematics. The purpose of this study was to develop an online diagnostic misconception test instrument. The research method used is development research using the ADDIE model. There are five stages of research, namely: analyze, design, develop, implement, and evaluate. Proof of validity is done using the Aiken index involving five judgment experts. The validation results show that the instrument has high content validity. Likewise, with the results of the instrument trials, it shows that the instruments developed are valid and reliable. These results indicate that the developed instrument can be used for misconception diagnostic tests of basic mathematical concepts. The instrument can be used to diagnose misconceptions among students, students, teachers and other communities.

Proposal of the Polygonal Model for Representing Biomolecules as a Tool for Teaching Metabolism

INTRODUCTION: Fischer projections are widely used for representing organic molecules, including the intermediates of metabolism. With the high number of molecules involving in metabolic processes and sometimes the relatively short time of learning of metabolism available for the students, it would be very useful an easier way to learn the structure of biomolecules and the involved reactions in metabolic pathways. OBJECTIVES: In this work it is presented the polygonal model, which consists in a new form of notation of biomolecules using geometric forms for representing the chemical groups in a biomolecule. MATERIALS AND METHODS: In this model, the carbonic chain is presented vertically using points of intersection or small black circles for carbon atoms, triangles, squares and circles represent, respectively, the hydroxyl, carbonyl and carboxyl groups, and the phosphate and amine groups are showed as, respectively, as yellow and blue circles. The stereoisomers and cis-trans isomers are clearly distinguishing as well. A form of familiarizing the student with the proposed notation can be to make an activity in class, furnishing a material which includes a short explanation of the model using examples, and some proposed activities of “transforming” molecules to polygonal model form from Fischer projections, and vice and versa. DISCUSSION AND RESULTS: It was observed that the average time necessary to complete this activity was less than 40 min. Polygonal model found to have several advantages, as no loss of information of the molecule, the simplicity to show the reactions in a metabolic pathway, good receptivity by the students, capacity to diagnostic misconceptions of the students in organic chemistry. CONCLUSION: This method is much faster to represent the molecules. This is important in the dynamics of the class.

\u201cI passed the test!\u201d Evidence of diagnostic misconception in the recruitment of population controls for an H3Africa genomic study in Cape Town, South Africa

BackgroundAdvances in genetic and genomic research have introduced challenges in obtaining informed consent for research in low and middle-income settings. However, there are only few studies that have explored challenges in obtaining informed consent in genetic and genomic research in Africa and none in South Africa. To start filling this gap, we conducted an empirical study to investigate the efficacy of informed consent procedures for an H3Africa genomic study on Rheumatic Heart Disease (RHDGen) at the University of Cape Town in South Africa. The main aim of the study was to understand ethical challenges in obtaining informed consent in the RHDGen study.MethodsWe used a qualitative study methodology involving in-depth interviews and participant observations. Our study participants were RHDGen cases (patients), healthy controls and research staff involved in the recruitment of RHDGen cases and controls. In total, we conducted 32 in-depth interviews with RHDGen cases and controls, 2 in-depth interviews with research staff and 57 direct observations of the consent procedures of RHDGen cases and controls. The interviews were conducted in English, audio-recorded and transcribed verbatim. Data were analyzed using thematic content analysis. The study was conducted in 3 sites within Cape Town, South Africa.ResultsMost healthy controls joined the RHDGen study in order to be screened for rheumatic heart disease (diagnostic misconception). A majority of RHDGen cases decided to join the RHDGen study because of therapeutic misconception.ConclusionThe ethical challenges that impacted on obtaining informed consent in the RHDGen study were complex. In this study, the main challenges were diagnostic misconception among RHDGen controls and therapeutic misconception among RHDGen cases.

Giving samples or "getting checked": measuring conflation of observational biospecimen research and clinical care in Latino communities.

BackgroundExpectations of receiving personal health information as a fringe benefit of biospecimen donation—termed diagnostic misconception—are increasingly documented. We developed an instrument measuring conflation of observational biospecimen-based research and clinical care for use with Latino communities, who may be particularly affected by diagnostic misconception due to limited health care access.MethodsThe instrument was developed using prior qualitative research, revised through cognitive interviewing and expert review, and field tested in a convenience sample of 150 Latino adults in Eastern Washington State. It was further refined through exploratory factor analysis and validated against existing measures of genetic knowledge and researcher trust.ResultsThe final instrument demonstrated high internal consistency, evidence of content and construct validity, and no floor and ceiling effects. Individuals who were unemployed, spoke only Spanish, had no health insurance, received health care outside of traditional venues, and had good self-rated health received higher scores, indicating greater conflation of biospecimen-based research and clinical care.ConclusionsThe ability to systematically measure beliefs related to diagnostic misconception will help facilitate ethically-informed efforts to recruit Latinos into biospecimen-based research studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12910-015-0041-9) contains supplementary material, which is available to authorized users.

Why do participants enroll in population biobank studies? A systematic literature review

Therapeutic misconception has been extensively studied and addressed within clinical trials. An equivalent in the genetic research context has been identified as diagnostic misconception. There is not much data on this phenomenon in population-based biobank studies. Since misconceptions may generate undue motives to enroll, the authors aimed at reviewing studies addressing the reasons to participate in biobank studies. The main databases were searched using relevant keywords. Studies were included if peer-reviewed, in English and describing the reasons to enroll was provided by actual and apparently healthy donors. Although the 13 studies retrieved were heterogeneous, a scheme summarizing the main aspects involved in the decision-making process was developed. Expectation of personal benefit through health-related information was found in eight studies. Three of them discussed whether this expectation could be considered a form of therapeutic misconception. The magnitude of this phenomenon is an important ethical concern and ought to be further studied.

Undesirable Implications of Disclosing Individual Genetic Results to Research Participants

Ravitsky and Wilfond (2006) correctly highlight the need for uniform guidelines to assist investigators and institutional review boards (IRBs) in determining whether to disclose individual genetic results to research participants. However, their results-evaluation framework, like other proposals that call for the disclosure of individual results to research participants (Partridge and Winer 2002; Rothstein 2006; Shalowitz and Miller 2005), is troublesome for two related reasons. First, their justification for disclosure rests on the mistaken view that principles of beneficence, respect, reciprocity, and/or justice ethically require researchers to offer participants individual genetic results. Whereas these principles and others obligate physicians to share individually relevant results with patients in the clinical care setting, they do not similarly obligate investigators to share such information with participants in the research setting. Second, because Ravitsky and Wilfond’s proposal conflates the aims of clinical research with those of clinical care, participants may suffer from a therapeutic or diagnostic misconception (Clayton and Ross 2006), researchers may be inclined to overstate the benefits of enrollment, and institutional review boards (IRBs) may face unforeseen difficulties in assessing trial risks and benefits. Beneficence, respect for persons, reciprocity, and justice are important components of ethical research, but none of these principles are violated or diminished when investigators do not share individual genetic results from research. Beneficence requires investigators to maximize possible benefits to participants and society at large while minimizing possible harms. Whether a clinical trial meets the requirement of beneficence is determined ab initio by an IRB before any participants are enrolled. At this stage of review, an IRB cannot weigh the possibility that some participants may gain individually useful results from participation. There is no guarantee that any given trial will produce such results. In contrast, if a study does generate individual information, it may apply only to participants with certain genomic characteristics. And even in this case it is not possible to determine whether a given participant will perceive the information as a benefit or harm once confronted with it. Because a clinical trial must meet the requirements of beneficence regardless of whether it returns individual research results, it cannot be the case that beneficence requires investigators to offer results.

Eating disorders and gynecology, knowledge and attitudes among clinicians

Eating disorders are common, responsive to treatment and affect women at a peak age of reproductive function, often presenting via gynecological and obstetric sequelae. The author wished to examine gynecologists' knowledge and attitudes towards them. Following a pilot study, a questionnaire concerning eating disorders was designed covering aspects of diagnosis, characteristic gynecological manifestations, treatment, and attitudes. All gynecologists and obstetricians with more than 1 year of experience from four teaching hospitals in Australia and the United Kingdom were sent the anonymous, confidential postal questionnaire. One hundred and fifteen doctors replied, with a response rate of 86%. Only 20% of respondents were confident of diagnosing eating disorders. Various diagnostic misconceptions were revealed; for example, 42% overestimated weight loss in anorexia nervosa by 20% or more, and 28% wrongly believed that a sense of strict dietary control' was a feature of bulimia nervosa. Clinicians had least knowledge of bulimia nervosa, underestimating its treatment response. Surprisingly, the greatest deficits in knowledge were of endocrinology and gynecological sequelae. For example, 79% underestimated amenorrhea in anorexia nervosa by 25%, and 85% wrongly believed that regular menses was characteristic of bulimia nervosa at normal weight. Consultants demonstrated significantly more knowledge than junior grades. Thirty-one percent of respondents held pejorative attitudes to eating disorders, which over-represented men (p=0.045) who were also more likely than women to see bulimia nervosa as untreatable (p=0.01). The author suggests that these deficits might be addressed by development of simpler screening questionnaires for non-specialists, and elucidation of the interface between eating disorders and reproductive physiology.

Diagnostic Discrepancy in Personal Accounts of Patients With 'Schizophrenia'

Five published accounts of patients with "schizophrenia" were reviewed in the light of the DSM-III diagnostic criteria. None of the accounts unequivocally met the DSM-III criteria for schizophrenia, but all did meet the criteria for some other psychiatric condition, especially affective disorders. The survey results suggest that popular accounts of "schizophrenia" present a confusing picture of schizophrenia. Inasmuch as these accounts often are invoked to support "cures," the reading pubic is doubly misled, as when a naturally remitting condition such as depression is mistakenly called schizophrenia. The psychiatric profession has a responsibility to clarify diagnostic misconceptions put forth in popular literature, and DSM-III might provide more objective guidelines for this much-needed clarification.