Improved Diagnosis and Care for Rare Diseases through Implementation of Precision Public Health Framework.

Public health relies on technologies to produce and analyse data, as well as effectively develop and implement policies and practices. An example is the public health practice of epidemiology, which relies on computational technology to monitor the health status of populations, identify disadvantaged or at risk population groups and thereby inform health policy and priority setting. Critical to achieving health improvements for the underserved population of people living with rare diseases is early diagnosis and best care. In the rare diseases field, the vast majority of diseases are caused by destructive but previously difficult to identify protein-coding gene mutations. The reduction in cost of genetic testing and advances in the clinical use of genome sequencing, data science and imaging are converging to provide more precise understandings of the 'person-time-place' triad. That is: who is affected (people); when the disease is occurring (time); and where the disease is occurring (place). Consequently we are witnessing a paradigm shift in public health policy and practice towards 'precision public health'.Patient and stakeholder engagement has informed the need for a national public health policy framework for rare diseases. The engagement approach in different countries has produced highly comparable outcomes and objectives. Knowledge and experience sharing across the international rare diseases networks and partnerships has informed the development of the Western Australian Rare Diseases Strategic Framework 2015-2018 (RD Framework) and Australian government health briefings on the need for a National plan.The RD Framework is guiding the translation of genomic and other technologies into the Western Australian health system, leading to greater precision in diagnostic pathways and care, and is an example of how a precision public health framework can improve health outcomes for the rare diseases population.Five vignettes are used to illustrate how policy decisions provide the scaffolding for translation of new genomics knowledge, and catalyze transformative change in delivery of clinical services. The vignettes presented here are from an Australian perspective and are not intended to be comprehensive, but rather to provide insights into how a new and emerging 'precision public health' paradigm can improve the experiences of patients living with rare diseases, their caregivers and families.The conclusion is that genomic public health is informed by the individual and family needs, and the population health imperatives of an early and accurate diagnosis; which is the portal to best practice care. Knowledge sharing is critical for public health policy development and improving the lives of people living with rare diseases.

Initiating an undiagnosed diseases program in the Western Australian public health system.

BACKGROUND: New approaches are required to address the needs of complex undiagnosed diseases patients. These approaches include clinical genomic diagnostic pipelines, utilizing intra- and multi-disciplinary platforms, as well as specialty-specific genomic clinics. Both are advancing diagnostic rates. However, complementary cross-disciplinary approaches are also critical to address those patients with multisystem disorders who traverse the bounds of multiple specialties and remain undiagnosed despite existing intra-specialty and genomic-focused approaches. The diagnostic possibilities of undiagnosed diseases include genetic and non-genetic conditions. The focus on genetic diseases addresses some of these disorders, however a cross-disciplinary approach is needed that also simultaneously addresses other disorder types. Herein, we describe the initiation and summary outcomes of a public health system approach for complex undiagnosed patients - the Undiagnosed Diseases Program-Western Australia (UDP-WA). RESULTS: Briefly the UDP-WA is: i) one of a complementary suite of approaches that is being delivered within health service, and with community engagement, to address the needs of those with severe undiagnosed diseases; ii) delivered within a public health system to support equitable access to health care, including for those from remote and regional areas; iii) providing diagnoses and improved patient care; iv) delivering a platform for in-service and real time genomic and phenomic education for clinicians that traverses a diverse range of specialties; v) retaining and recapturing clinical expertise; vi) supporting the education of junior and more senior medical staff; vii) designed to integrate with clinical translational research; and viii) is supporting greater connectedness for patients, families and medical staff. CONCLUSION: The UDP-WA has been initiated in the public health system to complement existing clinical genomic approaches; it has been targeted to those with a specific diagnostic need, and initiated by redirecting existing clinical and financial resources. The UDP-WA supports the provision of equitable and sustainable diagnostics and simultaneously supports capacity building in clinical care and translational research, for those with undiagnosed, typically rare, conditions.

3-Dimensional Facial Analysis-Facing Precision Public Health.

Precision public health is a new field driven by technological advances that enable more precise descriptions and analyses of individuals and population groups, with a view to improving the overall health of populations. This promises to lead to more precise clinical and public health practices, across the continuum of prevention, screening, diagnosis, and treatment. A phenotype is the set of observable characteristics of an individual resulting from the interaction of a genotype with the environment. Precision (deep) phenotyping applies innovative technologies to exhaustively and more precisely examine the discrete components of a phenotype and goes beyond the information usually included in medical charts. This form of phenotyping is a critical component of more precise diagnostic capability and 3-dimensional facial analysis (3DFA) is a key technological enabler in this domain. In this paper, we examine the potential of 3DFA as a public health tool, by viewing it against the 10 essential public health services of the "public health wheel," developed by the US Centers for Disease Control. This provides an illustrative framework to gage current and emergent applications of genomic technologies for implementing precision public health.

The rare and undiagnosed diseases diagnostic service - application of massively parallel sequencing in a state-wide clinical service.

BACKGROUND: The Rare and Undiagnosed Diseases Diagnostic Service (RUDDS) refers to a genomic diagnostic platform operating within the Western Australian Government clinical services delivered through Genetic Services of Western Australia (GSWA). GSWA has provided a state-wide service for clinical genetic care for 28 years and it serves a population of 2.5 million people across a geographical area of 2.5milion Km(2). Within this context, GSWA has established a clinically integrated genomic diagnostic platform in partnership with other public health system managers and service providers, including but not limited to the Office of Population Health Genomics, Diagnostic Genomics (PathWest Laboratories) and with executive level support from the Department of Health. Herein we describe report presents the components of this service that are most relevant to the heterogeneity of paediatric clinical genetic care. RESULTS: Briefly the platform : i) offers multiple options including non-genetic testing; monogenic and genomic (targeted in silico filtered and whole exome) analysis; and matchmaking; ii) is delivered in a patient-centric manner that is resonant with the patient journey, it has multiple points for entry, exit and re-entry to allow people access to information they can use, when they want to receive it; iii) is synchronous with precision phenotyping methods; iv) captures new knowledge, including multiple expert review; v) is integrated with current translational genomic research activities and best practice; and vi) is designed for flexibility for interactive generation of, and integration with, clinical research for diagnostics, community engagement, policy and models of care. CONCLUSION: The RUDDS has been established as part of routine clinical genetic services and is thus sustainable, equitably managed and seeks to translate new knowledge into efficient diagnostics and improved health for the whole community.

Knowledge, understanding, and uptake of noninvasive prenatal testing among Latina women.

OBJECTIVE: The aim of this study is to assess Latina patient understanding of noninvasive prenatal testing (NIPT) and identify what factors influence uptake/refusal to NIPT to adapt counseling to the needs and interests of this population. METHODS: Mixed-methods survey in English and Spanish administered to pregnant Latina patients throughout pregnancy. RESULTS: Sixty-three women participated in our study (67% response rate); 34.9% chose to do NIPT, and 65.1% declined. Approximately half of participants (44%) had an NIPT knowledge score of ≤3 out of six total questions. Two of the most significant factors influencing uptake of NIPT were a higher reported educational level (p = 0.015) and a higher NIPT knowledge score (p = 0.014); 42.9% of participants knew that NIPT only screens for certain chromosomal conditions; 39% of women who declined NIPT would never consider NIPT in the future. CONCLUSIONS: One-third of Latina women elected NIPT; a higher reported educational level and language were most predictive of this choice. Overall knowledge was significantly lower for women who declined NIPT. Lower knowledge may suggest that not all women are making informed decisions because of varying degrees of informed consent. Providing culturally tailored information can help women navigate the complexities of prenatal testing in order to make decisions most aligned with their values.

The decision to continue a pregnancy affected by Down syndrome: timing of decision and satisfaction with receiving a prenatal diagnosis.

In order to provide the best genetic counseling possible for women who learn of a diagnosis of Down syndrome prenatally, we sought to assess the timing of the decision to continue a pregnancy and the satisfaction these women had with learning this information. Fifty-six mothers of children with Down syndrome diagnosed prenatally between 2007 and 2010 completed a survey regarding their experience with decision-making after prenatal diagnosis. Approximately one third (17/56) of participants reported they knew before getting pregnant that they would not terminate for any reason, and almost half of the participants (24/56) reported they did not decide to continue their pregnancy until after the diagnosis. Many participants (82 %; 42/56) stated that learning the diagnosis during pregnancy increased their anxiety. The majority (88 %; 45/56) also reported that if they could do it over again, they would undergo prenatal testing for preparation purposes, despite increased anxiety. Religious and spiritual beliefs as well as feeling attached to the baby were the personal factors that had the greatest impact on most women's decision-making. Despite increased anxiety caused by learning the diagnosis prenatally, most women favored prenatal diagnosis as it allowed them time to process the information and prepare for the birth of their child.

Variables influencing pregnancy termination following prenatal diagnosis of fetal chromosome abnormalities.

The objective of this study was to identify variables that may influence the decision to terminate or continue a pregnancy affected by a chromosome abnormality. We performed a retrospective cohort analysis of 286 pregnancies diagnosed with a chromosome abnormality following genetic counseling and prenatal diagnosis. Data obtained included procedure type, chromosome results, ethnicity, maternal age, use of fertility treatments, and uptake of genetic counseling after results, among other factors. Wilcoxon rank sum test, Fisher's exact test, and univariate and multivariate logistic regression models were used for data analysis. The overall termination rate in this study was 82.9 %. A lower likelihood to terminate was found in pregnancies with a diagnosis of a sex chromosome abnormality (OR 0.05, p < .0001), Filipina race (OR 0.10, p = .03), and uptake of second genetic counseling session (OR 0.05, p < .0001). Prior history of termination was associated with increased likelihood to terminate (OR 8.6, p = .02). Factors revealing no statistically significant association with termination included maternal age, gestational age, clinic site, fetal gender, ultrasound anomalies, reason for referral and who informed the patient. Our data affirm the complexity of the decision making process and reinforce that providers should refrain from making assumptions regarding a patient's likelihood to terminate based on factors such as maternal age, gestational age, type of procedure, or ultrasound.

Nurse manager orientation.

On the basis of the principles of management and leadership, our organization has worked over the years to formalize the orientation program for new nurse managers. This program meets the needs of new nurse managers and responds to today's complex health care system needs. This article describes the components of a nurse manager orientation program for the novice nurse manager and methods for evaluating nurse manager effectiveness.

Mosaic tetrasomy 12p with triplication of 12p detected by array-based comparative genomic hybridization of peripheral blood DNA.

A patient whose dysmorphism at birth was not diagnostic for Pallister-Killian syndrome (PKS) was found to have mosaic tetrasomy 12p by an array-based comparative genomic hybridization of peripheral blood DNA. He was determined to be mosaic for 46,XY,trp(12)(p11.2 --> p13) in cultured skin fibroblasts. His appearance was typical for PKS at 4 months of age.

Troubled units: creating change.

Your unit may be in trouble. Are conversations among team members authentic or do real conversations happen in the hallways after the meeting? Are staff afraid of voicing their disagreements for fear of being labeled, while other team members complacently agree to a consensus, then go off and work from their own agenda? Some units have fallen into the habit of disrespectful communication and uncaring behaviors toward team members. The impact this has on staff, units, and organizations can be deleterious. More importantly, these behaviors impact the quality of patient care a unit is able to provide. Fostering teamwork must be a top priority for leaders. In a healthy team, differences and conflict exist, but they are acknowledged and dealt with openly. Creating change in a troubled unit is not a fast fix, but rather needs a well-devised plan. This article describes how leaders can seek out appropriate resources, develop strategies, and intervene to create a healthy, professional work environment.

Medical humanities and cultural studies: lessons learned from an NEH Institute.

In this essay, the directors of an NEH Institute on "Medicine, Literature, and Culture" consider the lessons they learned by bringing humanities scholars to a teaching hospital for a month-long institute that mingled seminar discussions, outside speakers and clinical observations. In an exchange of letters, they discuss the productive tensions inherent in approaching medicine from multiple perspectives, and they argue the case for a broader conception of medical humanities that incorporates the methodologies of cultural studies.

Humanities education at Pennsylvania State University College of Medicine, Hershey, Pennsylvania.

The Department of Humanities at Pennsylvania State University's (Penn State) College of Medicine, created at the founding of the College in 1967, was the first of its kind at any medical school. This article begins by describing how the department has developed over the years, and then discusses its present configuration, including kinds of faculty appointments, information about how it is funded, specific courses that comprise the department's four-year curriculum, and activities it sponsors. That a College of Medicine would make the teaching and practice of humanistic medicine a major and explicit commitment attracted the notice of Drs. Lawrence and Jane Kienle, who made possible the Doctors Kienle Center for Humanistic Medicine. The Humanities Department is closely allied with the Doctors Kienle Center, which integrates the College and the Medical Center by supporting a variety of projects, research, and awards that further the teaching and practice of humanistic medicine. Faculty in the department are encouraged to demonstrate excellence in scholarship and in teaching, but are also expected to become engaged in the life of the Medical Center, especially in furthering humanistic patient care. As such, the Humanities Department plays a major role in furthering the mission of the Pennsylvania State University's College of Medicine.