What is risk in clinical genetics? Designing and piloting tools to evaluate risk in clinical genetics using failure modes and effects analysis.

Chapter 66 - A comparison of fracture risk assessment tools

Validation plan of bone marrow collection, processing and distribution using the failure mode and effect analysis methodology: a technical report

Background: Breast Cancer (BC) incidence and the distribution of BC risk factors vary between racial and ethnic groups within the United States. It has been demonstrated that providing education on individualized breast cancer risk will improve patient uptake to recommended BC screening and prevention strategies. Most clinical risk assessment tools, including the validated IBIS model were derived from data using non-Hispanic white women. Consortia have also now identified over 300 common genetic susceptibility loci for BC, summarized by the polygenic risk score (PRS). When combined with clinical risk assessment tools, such as the IBIS or BCRAT models, the PRS can further refine risk estimation for patients. To date, most studies on the use of PRS have been done in non-Hispanic white women. While these PRS still perform well in racial minorities, there has been a recognized need to improve racial and ethnic diversity in genomic research cohorts. Herein, we aim to combine clinical risk assessment models that are already used in routine clinical practice with information derived from PRS testing in women of racial minorities to determine if this can improve risk estimation, patient understanding, and uptake to recommended breast cancer screening and prevention strategies. Design: This is a minimal risk prospective study with a single arm incorporating the PRS into a standard breast cancer risk reduction consultation, followed by annual surveys over 10 years to determine if and how the information provided by the PRS influenced patient decisions regarding recommended BC screening and prevention. Patients will have IBIS and BCRAT risks calculated at baseline visit. A survey of patient perceptions/understanding of risk, intention to undergo screening, and use of preventive medicine is completed after baseline visit prior to receiving the PRS results. Blood sample is obtained at baseline and DNA samples are analyzed for approximately 300 SNPs on a custom-designed, targeted SNP panel from ThermoFisher Scientific by the Mayo Clinic Genomics Laboratory. This PRS result is then combined with the clinical risk assessments (IBIS and BCRAT scores) using the R package Individualized Coherent Absolute Risk Estimators (iCare) tool to provide a new estimate of breast cancer risk for 5year, 10year, and lifetime risk. Patients are seen for follow-up to review results and then complete a second survey to assess their understanding of the results, BC risk, and how the PRS impacted their decision to undergo screening/prevention strategies. Eligibility Criteria: Women who self-identify as African American/Black or Hispanic/Latinx between 30-75 years old with any of the following: 1.)IBIS score of ≥5% for the 10 year risk OR BCRAT score of ≥ 3 % for the 5 year risk. 2.) History of biopsy proven atypical hyperplasia 3.) History of biopsy proven lobular carcinoma in situ. Specific Aims: Aim 1: The primary aim of this study is to explore if the addition of PRS to the BCRAT and IBIS score will improve intentions to undergo recommended breast cancer screening strategies such as mammography, MRI, or molecular breast imaging in women of underserved racial minorities Aim 2: To explore if the addition of the PRS to the BCRAT and IBIS risk score will aid women of racial minorities in deciding whether to take preventative endocrine therapy. Aim 3: To understand how individualized risk assessment and information on PRS may alter perceived risk of breast cancer. Statistical Methods Analysis will be mostly descriptive. Continuous variables will be summarized as mean (standard deviation) or median (range) and categorical variables will be reported as frequency (percentage). Kaplan-Meier method will be used to estimate the long-term cumulative risk of cancer. Current Accrual: 3. Target Accrual: 50 Citation Format: Lauren Cornell, Sandhya Pruthi, Linda Hasadsri, Sarah McLaughlin. Genetic risk estimation in breast cancer and assessing health disparities [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-02.

Targeting specimen misprocessing safety events with failure modes and effects analysis.

To assess the impact of different forms of use of failure mode and effect analysis methodology for risk prioritization in the ambulatory care process in a mutual benefit association covering work-related accidents and diseases. The study is based on a previously drafted and individually prioritized risk map by a multidisciplinary team made up of patient safety committee members from health care centers and clinics in a mutual benefit association covering work-related accidents and diseases. The professionals mainly carry out their work in the field of management (individual manager group (IMG)). A group formed by clinicians subsequently completed 2 prioritizations: one based on the individual opinions of each of the members (individual clinical group (ICG)) and another in a consensual way (consensual clinical group (CCG)) as recommended by failure mode and effect analysis methodology. The risk prioritization was compared in the 3 groups (IMG, ICG, and CCG). The risk prioritization by the IMG defines 7 extreme risks (risk prioritization ≥ 275). When the clinical group prioritizes them in an individual way (ICG), there is no extreme risk, whereas when it does so in a consensual way (CCG), there are 21 extreme risks. With respect to the coincidences of existing causes between the 3 groups, it is noted that the "risk of falls" is rated by both the clinical and the manager group but prioritized differently. On the other hand, the ICG and CCG coincide in that pressure on health care services can contribute to carrying out incomplete anamnesis. They also both consider that internal and external waiting lists and holiday periods can cause a delay in the starting of rehabilitation. The IMG and the CCG show similarity in the risk assessment of overprescribing medication and that multiple computer sessions are initiated. Finally, the IMG and the ICG coincide in the "lack of delivery of the medication leaflet". The point of view of the clinicians is important in the risk prioritization of the ambulatory health care process. The difference in the risk prioritization between the clinical group at individual level and after consensus is remarkable.

Agalsidase alfa and agalsidase beta in the treatment of Fabry disease: does the dose really matter?

A Method for Evaluating Quality Assurance Needs in Radiation Therapy

The arrival of genomic medicine to the clinic is only the beginning of the journey

In this paper, a fuzzy Failure Mode and Effect Analysis (FMEA) methodology incorporating an analogical reasoning technique is presented. FMEA methodology was introduced as a formal and systematic procedure for evaluation of risk associated with potential failure modes in the 1960s. Bowles and Peláez [1] proposed a Fuzzy Inference System (FIS)-based Risk Priority Number (RPN) model as an alternative to the conventional RPN model. For an FIS-based RPN (a three-input FIS model), a large set of fuzzy rules are required, and it is tedious to collect the full set of rules. With the grid partition strategy, the number of fuzzy rules required increases in an exponential manner, and this phenomenon is known as the “curse of dimensionality” or the combinatorial rule explosion problem. Hence, a rule selection and similarity reasoning technique, i.e., Approximate Analogical Reasoning Schema (AARS) technique are implemented in a fuzzy FMEA in order to solve the problem. The experiment was conducted using a set of data collected from a semiconductor manufacturing line, i.e., underfill dispensing process, and promising results were obtained.

An investment plan for preventing child injuries using risk priority number of failure mode and effects analysis methodology and a multi-objective, multi-dimensional mixed 0-1 knapsack model

Osteoporosis in men is a largely neglected condition in Asia (and elsewhere), despite the fact that one-third of hip fractures occur in men. Moreover, access to bone mineral density (BMD) measurements is limited in many areas of Asia, and inexpensive methods of targeting high risk patients for BMD measurements would be valuable. We have developed a simple clinical assessment tool to identify high risk Asian men for BMD measurements. Information on risk factors was collected from 420 community-dwelling adult Chinese men aged 50 years and above using a structured questionnaire, and the ability of these risk factors to identify subjects with femoral neck BMD T score < or = -2.5 was assessed. Multiple regression analysis and item reduction yielded a final clinical risk assessment tool based on only age and weight, similar to the Osteoporosis Self-assessment Tool for Asians (OSTA), described previously for Asian women. The OSTA values of < or = -1 had a sensitivity of 81% and specificity of 66%, and the area under the receiver operating characteristics curve was 0.83. The index was validated in another sample of 356 men with a sensitivity of 82% and specificity of 67 %, and an AUC of 0.85. The usefulness of OSTA was further compared to calcaneal quantitative bone ultrasound (QUS) in the validation sample of 356 men. The optimal cutoff T score of -1.2 for QUS yielded sensitivity and specificity values of 75 and 67%, respectively. The AUC for QUS was 0.79. Combining OSTA and QUI gave a sensitivity of 88% and specificity of 66% to identify men with low BMD at the femoral neck, and an AUC of 0.86 which was statistically not different from either OSTA or QUI alone. We conclude that OSTA is a simple and effective clinical risk assessment tool for identifying not only female but also male subjects at increased risk of osteoporosis, and its use could facilitate the appropriate and more cost-effective use of bone densitometry in developing countries.

Pharmacogenetic (PGx) testing aims to improve therapeutic outcomes through tailoring treatment based on a patient's genetic risk for non-response and/or an adverse event. Given their expertise, geneticists could facilitate the use of PGx testing; however, the preparedness and perceived role of the clinical genetics community is unclear. To assess the attitudes, preparedness, and perceived roles of geneticists in the delivery of PGx testing, we conducted a survey of 1500 randomly selected board-certified genetic counselors and clinical geneticists in the United States [response rate: 37.8% (n = 516)]. Twelve percent of genetic counselors and 41% of clinical geneticists indicated that they had ordered or coordinated patient care for PGx testing, a seemingly high proportion at this early stage of adoption. Almost all respondents had some education on pharmacogenetics, although only 28% of counselors and 58% of clinical geneticists indicated they felt well-informed about PGx testing. About half of counselors (52%) and clinical geneticists (46%) felt they would play 'some' role in the delivery of PGx testing; 17 and 19%, respectively, felt that they would play 'no' or 'a little' role. At this early stage of PGx testing, the role of geneticists and genetic counselors is unclear. However, their experience may aid in readying PGx testing and informing delivery strategies into clinical practice.

Introduction: Temporary tracheostomy is increasingly used earlier in the management of the general critical care population. With rising numbers of temporary tracheostomies, more patient are being transferred from the Intensive Care Unit (ICU) to general wards, so the care pathway for inpatients has to be considered in both ICU and ward environments (Paul, 2010). International guidelines emphasise that the timely involvement of the multidisciplinary team (MDT) is essential for the good aftercare of patients with a tracheostomy (Global Tracheostomy Collaborative). A number of studies have documented the benefits of a dedicated or outreach tracheostomy MDT to support patient care and weaning from tracheostomy. Reduction in length of stay, time to decannulation, and incidence of adverse events have been reported. Impacts on quality of patient care have not been well documented (Garruba, Turner & Grieveson, 2009). In the Irish context, dedicated tracheostomy teams are less common in regional hospital settings. Little is known about their potential to improve patient outcomes. Objectives: The aim of this project was to: 1. Explore the feasibility of creating a dedicated tracheostomy team in an Irish regional hospital setting 2. Examine the potential for this team to improve outcomes and experience for patients with temporary tracheostomy in a regional hospital setting Method: With the support of a local quality improvement forum, a process mapping exercise was completed examining the journey for the patient with a temporary tracheostomy in a regional hospital setting. An audit of patient charts was completed, and outcomes at various stages of the patient journey were documented. Potential points for co-ordination of MDT care along the patient journey were identified, based on a comparison with international guidelines. A dedicated tracheostomy team was convened, based on need identified from audit findings, and staff resources available. The team consisted of Consultant Intensivist, Physiotherapy, Speech & Language Therapy, Intensive Care Nursing, and Respiratory Nursing. A once weekly MDT tracheostomy ward round was established. Repeat audit of patient charts was completed to evaluate the impact of above. Results: It is feasible to create and maintain a dedicated tracheostomy team in this regional hospital setting. Challenges were encountered, particularly in relation to availability of staff, but these can be addressed through planning and flexibility. The implementation of the team and ward rounds led to improvements in: - clarity of plan for weaning and decannulation - cuff management - time to assessment for basic communication support - time to assessment for speaking valve - time to swallow assessment Conclusion: A dedicated tracheostomy team can contribute to improvements in quality of care for the patient with temporary tracheostomy in a regional hospital setting. Due to the heterogenity of this clinical population, a larger sample size is required to explore its effectiveness, with regards to reducing length of hospital and ICU stay. Process mapping is a useful form of clinical audit. In this instance, multiple potential points for co-ordination of MDT care along the patient journey were identified, which could be addressed with further quality measures going forward.

A developed failure mode and effect analysis for floating offshore wind turbine support structures

In this paper, an original design failure mode and effects analysis methodology that can be applied to all modern and advanced electrical machines has been proposed. The developed methodology application is possible in the real electrical machines manufacture, which is confirmed by “Tekhnodinamika” holding representatives. On the example of the high-torque permanent magnets synchronous motor, the stages of the electrical machine hierarchical decomposition, the definition of the electrical machine and its components functions, the theory of failures and failure modes have been considered. The prospects and the opportunities that failure mode and effects analysis open in the design and in the production of modern and advanced electrical machines have been described. Proposed failure mode and effects analysis methodology application in electrical machines engineering will allow avoiding serious failures in commercially available electrical machines, as well as collecting into one system the rules that should be followed by electrical machines designers and manufacturers. The regulated failure mode and effects analysis methodology usage in the electrical machines design and manufacture should significantly improve the quality of manufactured products, increase its competitiveness and consumer qualities, and also reduce production costs.