Incidental Results Research Articles

The Role of Early Diagnosis and Intervention in Improving Outcomes for Lung Cancer

Introduction : For lung cancer patients, early diagnosis and treatments are essential to battering outcomes. The objective of this world is to compare early diagnosis vs late diagnosis in terms of overall survival ,progression _free survival, quality of life and adverse events associated to treatment. Methodology: A Prospective cohort trial of seventy_ eight lung cancer patients was Conducted at Hayatabad Medical Complex in Peshawar from December 2021 to March 2024. 39 patients had early diagnosis (n=39) while 39 received late diagnosis(n=39) . Low_ dose Computed Tomography (DCT) screening and prompt symptom presentation lead to early diagnosis; incidental or symptomatic results were the basis for late diagnosis. Overall Survival(OS) , progression_ free survival (PFS), quality of life(QoL) , and frequency of serious adverse events associated to therapy were the outcomes. Results: At a median 'OS of 38 months compared to 14 months in the late diagnosis group (p<0.001) and median PFS of 34 months compared to 10 months(p<0.001), the early diagnosis group showed noticeably superior results. At 12 months, 'the early diagnosis group had a better QoL scores' a mean global health status of 75 compared to 55(p<0.01). Early diagnosis group (18%) had a lower frequency of serious adverse effects than did the late diagnosis group(45%). Conclusion: In patients with lung cancer, early detection and intervention greatly increases survival rates, prolong intervals without progression, improves quality of life, and lower serious side effects associated to therapy. The results emphasized the need of early diagnosis techniques and efficient screening programs in the treatment of lung cancer. Keywords: lung Cancer, early diagnosis, low dose computed tomography, overall survival, progression free survival, quality of life, treatment related adverse events

Re-examining regular expressions with backreferences

Most modern regular expression matching libraries (one of the rare exceptions being Google's RE2) allow backreferences, operations which bind a substring to a variable, allowing it to be matched again verbatim. However, both real-world implementations and definitions in the literature use different syntactic restrictions and have differences in the semantics of the matching of backreferences. Our aim is to compare these various flavors by considering the classes of formal languages that each can describe, establishing, as a result, a hierarchy of language classes. Beyond the hierarchy itself, some complexity results are given, and as part of the effort on comparing language classes new pumping lemmas are established, old classes are extended to new ones, and several incidental results on the nature of these language classes are given.

Preadmission testing for COVID-19 as a screening strategy: a retrospective chart review from a tertiary hospital in Kenya

BackgroundSince COVID-19 was declared a pandemic in March 2020, hospitals and patient care facilities have faced challenges in protecting healthcare workers and patients from being exposed to the infection. The main challenge has been how exposure to COVID-19 can be controlled when asymptomatic patientscan transmit the infection. This study aims to evaluate pre-admission testing of COVID-19 in patients at the Aga Khan University Hospital, Nairobi as a screening strategy for understanding, preventing and controlling exposure to COVID-19. MethodsThis was a descriptive retrospective chart review study that analysed the incidence of COVID-19, incidental detection of laboratory-confirmed COVID-19 and effects on plan of care in patients prior to admission at the Aga Khan University Hospital from April to December 31, 2020. Demographic data, clinical characteristics, COVID-19 test report and plan of care were retrieved from patients medical records review. ResultsA total of 8837 pre-admission tests were done between April 2020 and December 2020, with a COVID-19 prevalence rate of 10.9% (961/8837). Among the positive pre-admission tests, 14.3% were incidental positive results (138/961). Among the 138 incidental positive tests 21% (30) had their plan of care affected, 14.5% [20] had their care interventions delayed, 4.3% [6] had their hospital stay shortened, 1.4% [2] their hospital stay prolonged and 0.7% [1] had their care diagnostics delayed. ConclusionWhile community spread of COVID-19 fluctuated during this period; depending on the level of compliance to infection control measures, pre-admission prevalence rates were increasing as the year progressed. Mandatory testing of COVID-19 in hospital facilities remains an important admission requirement in controlling asymptomatic transmission of the virus. COVID-19 health burden justifies resource allocation for universal screening of all patients before hospital admission.

Addressing the Drivers of Medical Test Overuse and Cascades: User-Centered Design to Improve Patient-Doctor Communication.

Low-value medical testing is a major component of health care overuse, both directly and through the potential for borderline and/or incidental results to trigger cascades (downstream services of uncertain value). The costs and harms from marginal test results and their cascades can add up. It is thus important to both prevent low-value tests at the outset and mitigate cascades when they arise. Informed by a framework for understanding and reducing overuse of care, this study employed user-centered design methods (focus groups and 1:1 design meetings) with patients and primary care physicians (PCPs) to understand the problem and iteratively develop an intervention. Design meetings with 15 PCPs, 12 patients, and 3 patient focus groups revealed myriad drivers for medical test overuse and cascades. Patients commonly believed that all medical tests yield definitive results and lack downsides. PCPs cited expert recommendations, limited time during visits, fear of lawsuits, and desire to be responsive to patients as reasons for ordering potentially low-value medical tests. To address these issues, an intervention was designed using patient pre-visit educational materials, clinician reference materials on test interpretation and incidental findings, and clinician peer comparison on test overuse. Overuse of medical testing is driven by a range of factors related to PCPs, patients, and their interactions. Multipronged interventions may have the potential to address these drivers after they are rigorously tested.

Considerations of Autonomy in Guiding Decisions around the Feedback of Individual Genetic Research Results from Genomics Research: Expectations of and Preferences from Researchers in Botswana.

Background The Human Health and Heredity (H3Africa) Consortium continues to generate large amounts of genomic data leading to new insights into health and disease among African populations. This has however generated debate among stakeholders involved in developing, implementing, and applying ethical standards and policies for the return of individual genetic research results. The key questions are about when results must, should, may, or must not be returned and by whom. This study aimed to explore the views on the feedback of individual pertinent and incidental genetic research results of researchers, ethics committee members, and policymakers in Botswana. Methods In-depth interviews were conducted with 16 key stakeholders from academic, research institutions, and regulatory bodies in Botswana. An analysis of the coded data was done through an iterative process of analytic induction to document and interpret themes and patterns. Results Overall, the study indicated that researchers have at least a partial obligation to return individual genetic research results to research participants. Respondents placed emphasis on the ethical principle of autonomy. They felt that it was inappropriate for researchers to make decisions about the return of results on participants' behalf except in situations of avoiding participant self-harm or harm to society. Conclusion Findings helped to highlight the importance of considering participants' autonomy in the development of sustainable and credible guidelines for feedback of findings from genomics research in Botswana, which can be explained during community engagement and consent processes. Such guidelines would ultimately be used to develop policies, guide African genomics research, and promote participant autonomy, transparency, and possibly participant trust in research.

Is Pathological Exam for Disorders of the Appendix Testis Necessary?

Testicular appendages are remnants of embryologic structures commonly encountered during pediatric operations. The literature is vague on the management of incidentally discovered testicular appendages found intraoperatively. We performed a retrospective review of 93 pediatric patients who were found to have an incidental testicular appendage during inguinal hernia repair, cryptorchidism, or testicular torsion cases from December 2017 to June 2020. 100% of the incidental testicular appendage pathology results were benign. All of the specimens were 1.0 cm or less in their largest dimension. Removal of these specimens is considered the standard of care at our institution to help prevent torsion of the testicular appendage, which is one of the leading causes of acute scrotum in children. The authors of this study argue that pathological analysis is unnecessary and may result in excessive use of resources without proven benefit.

Incorporating genetic counseling into the evaluation of pediatric bone marrow failure.

The timely identification of germline genetic causes of pediatric bone marrow failure (BMF) impacts medical screening practices, family counseling, therapeutic decision-making, and risk of progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). At diagnosis, treatment decisions need to be made quickly to mitigate risks associated with profound cytopenias. As genetic testing options are rapidly evolving, an efficient multi-disciplinary approach and algorithm, including early involvement of a genetics team, is needed to expedite diagnosis and therapeutic decision-making. This process aids in the identification of appropriate candidates for molecular genetic testing. We present our single center experience reviewing the implementation of genetic counseling and a diagnostic and therapeutic algorithm used to guide genetic evaluation of pediatric BMF. Disease-specific next-generation sequencing (NGS) panels were most often pursued in patients who presented with a clinical phenotype consistent with a known inherited BMF syndrome and when trying to reduce incidental or uninformative results. Broader BMF NGS panels were most often utilized when unable to narrow the suspected etiology to a single disorder. Whole exome sequencing helped with optimizing treatment decision-making in higher risk children with BMF who required expedited hematopoietic stem cell transplantation. The experience has led to improvements to our process for evaluating patients with BMF.

Whole-exome sequencing increases the diagnostic rate for prenatal fetal structural anomalies

BackgroundPrenatal whole-exome sequencing (WES) is becoming increasingly used when karyotype and microarray tests are not diagnostic of fetal malformations. Although the value of WES clearly emerges in terms of higher diagnostic rates, the limitations of prenatal phenotyping together with the counseling challenges for variants of uncertain significance and incidental results suggest that the routine application of prenatal WES is not yet easy. MethodsStructurally abnormal fetuses with a mean gestational age of 24 weeks (range 13–38 weeks) were recruited from the Chong Qing Health Center for Women and Children. We performed a retrospective WES investigation in 85 fetuses, using DNA from amniotic fluid (66 samples, 77.6%), umbilical cord blood (10 samples, 11.8%), and fetal tissues (9 samples, 10.6%). Parental DNA was extracted from peripheral blood. ResultsMolecular diagnosis was obtained in 16 of the 85 fetuses (18.8%). According to the variant segregation mode and family history, 7 fetuses (43.75%) were affected by an autosomal dominant condition (6 variants were de novo and 1 variant was inherited from an unknowingly affected father), 7 fetuses (43.75%) had an autosomal recessive syndrome always associated with compound heterozygosity, and 2 fetuses (12.5%) had an X-linked condition (one mother was a carrier). In addition, the highest diagnostic rate was observed in fetuses with multisystem abnormalities (38.9%, 7/18). A variant of uncertain significance was detected in 16 samples (18.8%, 16/85). ConclusionOur study confirms that prenatal WES is an efficient tool for studying fetal abnormalities, although further improvements are needed to establish stronger fetal genotype-phenotype correlations.

DNA-based screening and personal health: a points to consider statement for individuals and health-care providers from the American College of Medical Genetics and Genomics (ACMG)

DNA-based screening and personal health: a points to consider statement for individuals and health-care providers from the American College of Medical Genetics and Genomics (ACMG)

A review of the circularity gap in the construction industry through scientometric analysis

The circular economy (CE) concept has gained popularity among scholars and practitioners as the best way to circumvent the effects of the linear economy and create an effective platform to attain sustainable development within industries including the construction industry. However, understanding parameters of the knowledge body and key issues which needs to be harnessed to enhance the application of concept to the construction industry has been a challenge. In this study, a scientometric analysis was employed to analyze 486 bibliometrics-searched filtered articles of CE in the construction industry to provide a critical understanding of current research trends and applications. Content analysis of selected articles were provided to elucidate key findings, challenges, and proposed strategies, and a SWOT analysis was conducted to appraise the incidental results of applying various circularity strategies to the construction industry. The study has found that key influential areas such as circular product design, end-of-life consideration including the quality, economics, and modular integrated construction were narrowly covered in existing studies. Moreover, there is still a lack of practical CE approach which can integrate the holistic performance assessment tool with the circular business model for the construction industry. Based on the circularity gaps identified through the content analysis, a research framework which consists of eight different research themes including the circular design; manufacture and supply; strategies for CE adoption; consideration of end-of-life principle; CE outcomes/consequences; information exchanges; construction process; and waste management strategies is developed. In addition, a compressive methodological framework is proposed for the effective CE implementation and evaluation. The circularity gaps, key influential areas, research themes, and CE approach highlighted in this study can be used as a guide for future scholarly work and practical adoption of CE in the construction industry.

The need for sleep and circadian education in Australian high schools: incidental results from a survey of university students.

To describe the need for high school sleep education from the perspective of undergraduate university students. Undergraduate students who completed an online course on sleep and circadian health were surveyed 6months after course completion. Students were asked whether a similar course would have benefited them as high school students, and about the need for sleep education in high schools. Thematic analysis of this qualitative data was carried out. Eighty-nine students who had attended 71 unique high schools provided responses. Eight-one per cent thought they would have benefitted from a similar course during high school and identified domains of sleep knowledge particularly relevant to high school students. They cited environmental barriers to healthy sleep present during high school and believed that sleep education could improve students' lifestyle, sleep and performance. Nineteen per cent of students said they would not have benefited, because they perceived sleeping patterns during high school to be nonmodifiable or believed that previous sleep education was sufficient. Of the respondents who did not think students would benefit, 53% would still tell their high school principal that there was a need for sleep education. The findings support the need for engaging sleep education for high school students. Future studies should examine the perspectives of students in high school directly, rather than undergraduate students who have already shown an interest in sleep health. SO WHAT?: Sleep health is missing from the Australian school curriculum. Online courses may be an engaging method of promoting sleep and circadian health to high school students.

Moving altarpieces: tracing the provenance of Netherlandish carved altarpieces in Sweden

Modern-day Sweden houses 38 Netherlandish carved altarpieces, about ten retable fragments, and two poupées de Malines. Some Netherlandish carved altarpieces in Sweden are still preserved in their original location. The majority of these altarpieces, however, are no longer stored in their authentic environment, as many of them have moved from one location to another over the past centuries. Therefore, the aim of this article is to trace back as far as possible the provenance of Netherlandish carved altarpieces in Sweden. A first source that regularly reveals a retable’s provenance consists of archival documents. Secondly, antiquarians’ travel notes often either confirm an altarpiece has remained at its current location for several centuries, or unveil the artwork’s previous whereabouts. More frequently, however, no archival documents or antiquarians’ notes exist. In that case, the presence of these stunning works of art often awakened people’s fascination for their provenance and made them wonder how such high-quality Netherlandish altarpieces ended up in small Swedish churches. This fascination has given rise to multiple unfounded legends, asserting the altarpieces were incidental results of shipwrecks, carriage breakdowns or spoils of war, primarily from the Thirty Years’ War. In the course of the last five centuries, retables were taken out of their original context not only by moving from one church to another, but also because, from the nineteenth century onwards, they were included in museum collections. The present research thus reflects on the fact that most Netherlandish carved altarpieces in Sweden are decontextualised in their present-day environment.

Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trial

IntroductionGenomic sequencing has rapidly transitioned into clinical practice, improving diagnosis and treatment options for patients with hereditary disorders. However, large-scale implementation of genomic sequencing faces challenges, especially with regard to...

Development of patient "profiles" to tailor counseling for incidental genomic sequencing results.

Guidelines recommend thatproviders engage patients in shared decision-making about receiving incidental results (IR) prior to genomic sequencing (GS), but this can be time-consuming, given the myriad of IR and variation in patients' preferences. We aimed to develop patient profiles to inform pre-test counseling for IR. We conducted semi-structured interviews with participants as a part of a randomized trial of the GenomicsADvISER.com, a decision aid for selecting IR. Interviews explored factors participants considered when deliberating over learning IR. Interviews were analyzed by thematic analysis and constant comparison. Participants were mostly female (28/31) and about half of them were over the age of 50 (16/31). We identified five patient profiles that reflect common contextual factors, attitudes, concerns, and perceived utility of IR. Information Enthusiasts self-identified as "planners" and valued learning most orall IR to enable planning and disease prevention because "knowledge is power". Concerned Individuals defined themselves as "anxious,"and were reluctant to learn IR, anticipating negative psychological impacts from IR. Contemplators were discerning about the value and limitations of IR, weighing health benefits with the impacts of not being able to "un-know" information. Individuals of Advanced Life Stage did not consider IR relevant for themselves andprimarily considered their implications for family members. Reassurance Seekers were reassured by previous negative genetic test results which shaped their expectations for receiving no IR: "hopefully [GS will] be negative, too. And then I can rest easy". These profiles could inform targeted counseling for IR by providing a framework to address common values, concerns. and misconceptions.

Design margins: a hidden issue in industry

In complex products the values of parameters are rarely exactly the required values, rather they often have a margin that might be designed in deliberately or be the incidental results of other design decisions. These margins play a critical role in design processes in managing engineering change and iteration. While engineers often talk about margins informally, designers and researchers also use other terms for specific margin concepts. This paper reviews the existing literature on related concepts and defines margins formally. It discusses the role margins play in handling uncertainty by distinguishing between buffer and excess. Buffer deals with uncertainty and excess with the remaining overcapacity of the design. Buffer can transition into excess of the design solution if the uncertainty can be reduced. The concepts are applied to the temperature margins of several candidate materials for a non-rotary jet engine component. This shows that a clear understanding of margins can help a company to select design alternatives.

The Genomics ADvISER: development and usability testing of a decision aid for the selection of incidental sequencing results.

Guidelines recommend patients be informed of their incidental results (IR) when undergoing genomic sequencing (GS), yet there are limited tools to support patients' decisions about learning IR. The aim of this study is to develop and test the usability of a decision aid (DA) to guide patients' selection of IR, and to describe patients' preferences for learning IR following use of the DA. We developed and evaluated a DA using an iterative, mixed-methods process consisting of (1) prototype development, (2) feasibility testing, (3) cognitive interviews, (4) design and programming, and (5) usability testing. We created an interactive online DA called the Genomics ADvISER, a genomics decision AiD about Incidental SEquencing Results. The Genomics ADvISER begins with an educational whiteboard video, and then engages users in a values clarification exercise, knowledge quiz and final choice step, based on a 'binning' framework. Participants found the DA acceptable and intuitive to use. They were enthusiastic towards GS and IR; all selected multiple categories of IR. The Genomics ADvISER is a new patient-centered tool to support the clinical delivery of incidental GS results. The Genomics ADvISER fills critical care gaps, given the health care system's limited genomics expertise and capacity to convey the large volume of IR and their myriad of implications.

Evaluation of a decision aid for incidental genomic results, the Genomics ADvISER: protocol for a mixed methods randomised controlled trial

IntroductionGenome sequencing, a novel genetic diagnostic technology that analyses the billions of base pairs of DNA, promises to optimise healthcare through personalised diagnosis and treatment. However, implementation of genome sequencing...

New possibilities of application of DSC as a new clinical diagnostic method

Differential scanning calorimetry (DSC) is the most often used method in thermal analysis. Recently, there is growing clinical use for it. With this method, we can measure the effects of drugs and we can quantify and characterize changes in different organs or parts of body. This way it is possible to conclude short- and long-term effects in a predictive way. Our team were examined the effects of cyclophosphamide on guinea pigs equivalent to human protocol in experimental conditions. Besides of its beneficial effects, cyclophosphamides may have got severe life-threatening side effects and complications because of the actual plasma level and high cumulative dosage. In the first step of our experiment, we examined the effects of cyclophosphamide on guinea pigs’ nerve–muscle complex with oncological indication by using a dosage protocol based on body mass. As a second step with the same method and cyclophosphamide dosage, we examined its effect on the heart left ventricle. The third step was in the further clinical application experiment with unchanged parameters on blood plasma as well as blood cells too, exhibiting dosage-dependent changes on plasma and blood cells. Alterations in different materials caused by using different cyclophosphamide dosage and not uniform treatment length produced well correlated and clearly detected changes with DSC. Based on our results, we found detectable and partway quantified alterations with DSC on blood plasma components; therefore, it can be used in clinical routine because it is relatively simple and cheap. In long-term treatments, incidental severe results and side effects caused by cumulative dose may become also predictive with this method. All these show a new promising area in DSC usage which passed out of mind in the last 10 years.

Identification of Genomic Somatic Variants in Cancer: From Discovery to Actionability.

The perfect method to discover and validate actionable somatic variants in cancer has not yet been developed, yet significant progress has been made toward this goal. There have been huge increases in the throughput and cost of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sequencing technologies that have led to the burgeoning possibility of using sequencing data in clinical settings. Discovery of somatic mutations is relatively simple and has been improved recently due to laboratory methods optimization, bioinformatics algorithms development, and the expansion of various databases of population genomic information. Tiered systems of evidence evaluation are currently being used to classify genomic variants for clinicians to more rapidly and accurately determine actionability of these aberrations. These efforts are complicated by the intricacies of communicating sequencing results to physicians and supporting its biological relevance, emphasizing the need for increasing education of clinicians and administrators, and the ongoing development of ethical standards for dealing with incidental results. This chapter will focus on general aspects of DNA and RNA tumor sequencing technologies, data analysis and interpretation, assessment of biological and clinical relevance of genomic aberrations, ethical aspects of germline sequencing, and how these factors impact cancer personalized care.

Research Participants' Preferences for Hypothetical Secondary Results from Genomic Research.

Secondary or incidental results can be identified in genomic research that increasingly uses whole exome/genome sequencing. Understanding research participants' preferences for secondary results and what influences these decisions is important for patient education, counseling, and consent, and for the development of policies regarding return of secondary results. Two hundred nineteen research participants enrolled in genomic studies were surveyed regarding hypothetical preferences for specific types of secondary results, and these preferences were correlated with demographic information and psychosocial data. The majority of research participants (73%) indicated a preference to learn about all results offered, with no clear pattern regarding which results were not desired by the remaining participants. Participants who reported greater interest in genetic privacy were less likely to indicate a preference to learn all results, as were individuals who self-identified as Jewish. Although most research participants preferred to receive all secondary results offered, a significant subset preferred to exclude some results, suggesting that an all-or-none policy would not be ideal for all participants. The correlations between preferences to receive secondary results, religious identification, and privacy concerns demonstrate the need for culturally sensitive counseling and educational materials accessible to all education levels to allow participants to make the best choices for themselves.