scholarly journals Barriers and Facilitators to Genetic Testing for Familial Hypercholesterolemia in the United States: A Review

2019 ◽  
Vol 9 (3) ◽  
pp. 32 ◽  
Author(s):  
Rachele M. Hendricks-Sturrup ◽  
Kathleen M. Mazor ◽  
Amy C. Sturm ◽  
Christine Y. Lu
Keyword(s):  
United States ◽  
Genetic Testing ◽  
Familial Hypercholesterolemia ◽  
Systematic Approach ◽  
The United States ◽  
Barriers And Facilitators ◽  
Clinical Settings ◽  
Vascular Events ◽  
Potential Barriers ◽  
The Us

Familial Hypercholesterolemia (FH) is an underdiagnosed condition in the United States (US) and globally, affecting an estimated 1/250 individuals. It is a genetic risk factor for premature cardiovascular disease and is responsible for an estimated 600,000 to 1.2 million preventable vascular events. Studies show that FH genetic testing can identify a causal gene variant in 60 to 80% of clinically suspected FH cases. However, FH genetic testing is currently underutilized in clinical settings in the US despite clinical recommendations and evidence supporting its use. Reasons for underutilization are not well understood. We conducted a literature review in the PubMed/MEDLINE database and eight peer-reviewed journals. After filtering for and reviewing 2340 articles against our inclusion criteria, we included nine commentaries or expert opinions and eight empirical studies reported between January 2014 and March 2019 in our review. After applying the Consolidated Framework for Implementation Research (CFIR), we identified a total of 26 potential barriers and 15 potential facilitators (estimated barrier to facilitator ratio of 1.73). We further estimated ratios of potential barriers to facilitators for each CFIR domain (Characteristics of Intervention, Outer Setting, Inner Setting, Characteristics of Individuals, and Process). Findings derived from our systematic approach to the literature and calculations of estimated baseline ratios of barriers and facilitators can guide future research to understand FH genetic testing implementation in diverse clinical settings. Our systematic approach to the CFIR could also be used as a model to understand or compare barriers and facilitators to other evidence-based genetic testing processes in health care settings in the US and abroad.

scholarly journals Understanding Implementation Challenges to Genetic Testing for Familial Hypercholesterolemia in the United States

2019 ◽  
Vol 9 (1) ◽  
pp. 9 ◽  
Author(s):  
Rachele Hendricks-Sturrup ◽  
Christine Lu
Keyword(s):  
United States ◽  
Genetic Testing ◽  
Familial Hypercholesterolemia ◽  
Ethnic Diversity ◽  
Heart Association ◽  
The United States ◽  
Cvd Risk ◽  
Implementation Challenges ◽  
The Us ◽  
Control And Prevention

Cardiovascular disease (CVD) is the leading cause of death in the United States (US), with familial hypercholesterolemia (FH) being a major inherited and genetic risk factor for premature CVD and atherosclerosis. Genetic testing has helped patients and providers confirm the presence of known pathogenic and likely pathogenic variations in FH-associated genes. Key organizations, such as the Centers for Disease Control and Prevention (CDC), American Heart Association (AHA), FH Foundation, and National Lipid Association (NLA), have recognized the clinical utility of FH genetic testing. However, FH genetic testing is underutilized in clinical practice in the US for reasons that are underexplored through the lens of implementation science. In this commentary, we discuss seven key implementation challenges that must be overcome to strengthen the clinical adoption of FH genetic testing in the US. These implementation challenges center on evidence of cost-effectiveness, navigating patient and provider preferences and concerns, gender and ethnic diversity and representation in genetic testing, and establishing clinical consensus around FH genetic testing based on the latest and most relevant research findings. Overcoming these implementation challenges is imperative to the mission of reducing CVD risk in the US.

scholarly journals A Global Review on the Utility of Genetic Testing for Familial Hypercholesterolemia

2020 ◽  
Vol 10 (2) ◽  
pp. 23 ◽  
Author(s):  
Rachele M. Hendricks-Sturrup ◽  
Jodi Clark-LoCascio ◽  
Christine Y. Lu
Keyword(s):  
United States ◽  
Genetic Testing ◽  
Familial Hypercholesterolemia ◽  
Clinical Outcomes ◽  
Ldl Cholesterol ◽  
The United States ◽  
Global Perspective ◽  
Ongoing Research ◽  
Increased Risk ◽  
Patient Reported

Familial hypercholesterolemia (FH) is a genetic disorder of cholesterol metabolism that affects an estimated 1/250 persons in the United States and abroad. FH is hallmarked by high low-density lipoprotein (LDL) cholesterol and an increased risk of premature atherosclerotic cardiovascular disease. This review summarizes recent global evidence showing the utility of FH genetic testing across diverse populations. Clinical and other qualitative outcomes following FH genetic testing were improved FH diagnosis, treatment initiation or continued treatment, treatment modification, improved total or LDL cholesterol levels, education on lifestyle management, and genetic counseling. This summary of evidence should be considered by those seeking overall evidence and knowledge gaps on the utility of FH genetic testing from a global perspective and for certain ethnic and age populations. These findings can be used to inform insurance policies and coverage decisions for FH genetic testing, policy recommendations to reduce the clinical and public health burden of FH, clinical practice and guidelines to improve the management of FH populations, and ongoing research involving FH genetic testing. We conclude that further investigations are needed to examine: (1) non-clinical outcomes following FH genetic testing; (2) patient-reported outcomes following FH genetic testing to convey patient experiences, values, and goals; and (3) clinical outcomes following FH genetic testing in non-Caucasian and pediatric populations in the United States and abroad.

Genomic/genetic testing patterns for patients with metastatic castrate-resistant prostate cancer: Results from a real-world study in the United States.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 49-49
Author(s):  
Andrea Leith ◽  
Amanda Ribbands ◽  
Matthew Last ◽  
Alicia Gayle ◽  
Sarah Payne ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Genetic Testing ◽  
Real World ◽  
Patient Characteristics ◽  
The United States ◽  
Molecular Testing ◽  
Cancer Disease ◽  
The Us ◽  
Castrate Resistant

49 Background: In May 2020, Olaparib was approved for HRRm mCRPC post progression on abiraterone and enzalutamide, and rucaparib was approved for BRCAm mCPRC following progression on androgen receptor targeted inhibitors and prior taxane therapy for mCRPC. HRRm are associated with approximately 25% of mCRPC and may be derived from germline or somatic origin. Somatic and germline alterations can be detected by tumour testing, but to differentiate between these, independent germline testing is needed. This study examined real-world genomic/genetic testing (GT) patterns in patients (pts) diagnosed with mCRPC in the United States (US). Methods: Data were drawn from the Adelphi Prostate Cancer Disease Specific Programme; a point-in-time survey administered to oncologists (onc), urologists (uro) and surgeons (sur) between January and August 2020 in the US. Physicians (phys) completed an attitudinal survey and a patient record form for the next four to nine mCRPC pts seen. Study variables included patient demographics, clinical factors and GT patterns. HRRm testers were defined as phys who tested for HRRm. Pts were identified as positive, negative or unknown depending on the outcome of the HRRm test. Results: A total of 72 phys (69% onc/ 29% uro/ 1% sur; 40% academic vs. 60% community) reported on 346 mCRPC pts. 41% of phys were based in the Northeast, 24% Midwest, 23% South and 13% in the West region of the US. 65 phys (90%) reported having access to overall GT; of these 5% identified as having access to germline tests only, while 94% were able to test for germline and somatic mutations. Challenges to conducting GT overall were ‘cost per test’ (50%), ‘having to send out for the tests (within country)’ (25%), ‘inadequate sample available’ (25%) and ‘patient refusal’ (25%). GT was typically conducted at identification of castrate-resistance (52%), metastases (51%) and at initial diagnosis (49%). 72% of total phys were HRRm testers; for these, patient characteristics primarily driving HRRm testing included Ashkenazi Jewish heritage (63%) and ECOG of 2-4 (58%). Other common drivers were family history, young diagnosis age and hormone therapy failure (all 46%). 132 (38% of 326) mCRPC pts were tested for HRRm; 39% of tested pts were identified with a HRRm. Most common HRRm tested were BRCA1 (90%), BRCA2 (89%) and ATM (55%). Conclusions: In this study majority of US phys had access to GT, but testing was only performed in 38% of pts with mCRPC. The higher than expected % of pts identified with an HRRm suggest that molecular testing was prioritised in high risk populations, as identified by the phys. With the recent approval of olaparib and rucaparib, GT may become more routine in clinical practice to identify eligible pts. Broader testing may also depend on addressing other barriers to testing including cost and testing logistics/practicalities.

scholarly journals MON-066 17B-hydroxysteroid dehydrogenase Type 3 Deficiency: An Under-Recognized Cause of 46,XY DSD in the United States?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
J Whitehead ◽  
Elizabeth Yerkes ◽  
Emilie Johnson ◽  
Diane Chen ◽  
Allison Goetsch ◽  
...  
Keyword(s):  
United States ◽  
Genetic Testing ◽  
Gender Identity ◽  
Diagnostic Testing ◽  
Autosomal Recessive Disorder ◽  
Hydroxysteroid Dehydrogenase ◽  
The United States ◽  
Primary Amenorrhea ◽  
The Us ◽  
Type 3

Abstract Title: 17β-hydroxysteroid dehydrogenase type 3 deficiency: An under-recognized cause of 46,XY DSD in the United States? Introduction: The 17β-hydroxysteroid dehydrogenase type 3 (17BHSD3) enzyme, expressed in the testes, converts androstenedione (A) to testosterone (T). 17BHSD3 deficiency causes a 46,XY difference of sex development (DSD), or intersex condition, characterized by lack of prenatal virilization followed by marked virilization at puberty due to peripheral conversation of A to T by other 17BHSD isoenzymes. Diagnosis is suspected with an abnormal T:A ratio of <0.8 and confirmed by HSD17B3 sequencing and deletion/duplication analysis. 17BHSD3 deficiency may present similarly to complete or partial androgen insensitivity syndrome (CAIS, PAIS) due to undervirilization in infancy, and to 5α-reductase deficiency due to virilization during puberty. Previously, only 12 cases of this autosomal recessive disorder have been reported in the US. We report 3 cases of 17BHSD3 deficiency diagnosed at a single pediatric center in the US. Clinical Cases: Patient A had atypical genitalia at birth and a presumed diagnosis of PAIS though sequencing of AR was normal. He underwent multiple genital surgeries throughout childhood, had significant psychiatric and behavioral concerns, and was referred to our multidisciplinary clinic at age 16 years. Additional diagnostic testing revealed a T:A ratio of 0.29 consistent with 17BHSD3 deficiency; confirmatory genetic testing was deferred per family preference. Patient B was noted to have testicular tissue present at age 3 years during an inguinal hernia repair and was diagnosed with CAIS. She presented to our institution at age 14 years with clitoromegaly. T:A ratio was 0.29 and genetic testing revealed a pathogenic splice site variant in HSD17B3. She requested gonadectomy due to unwanted virilization inconsistent with her female gender identity. Following gonadectomy at age 16 years, she began estrogen treatment and vaginal dilations. Patient C presented to our institution at age 18 years with pubertal delay and primary amenorrhea. She was noted to have palpable gonads and clitoromegaly. Evaluation revealed a 46,XY karyotype and a T:A ratio of 0.32. She was raised as a girl and identified as female. She requested gonadectomy to avoid further virilization, after which she began estrogen for pubertal induction. She deferred confirmatory genetic testing. Conclusions: Previous studies noted 17BHSD3 deficiency to be rare in the US, but the presence of 2 suspected and 1 confirmed diagnoses at a single US institution suggests it is likely more common and may be misdiagnosed as other types of DSD. Differentiating 17BHSD3 deficiency from other causes of 46,XY DSD is essential to inform accurate counseling about sex designation, gender identity, gonadal function, malignancy risk, potential fertility and heritability.

The United States and the Iranian Nuclear Programme

2018 ◽  
Author(s):  
Steven Hurst
Keyword(s):  
United States ◽  
Decision Making ◽  
Domestic Politics ◽  
The United States ◽  
Nixon Administration ◽  
Comprehensive Plan ◽  
The Us ◽  
Nuclear Issue ◽  
The Relationship

The United States, Iran and the Bomb provides the first comprehensive analysis of the US-Iranian nuclear relationship from its origins through to the signing of the Joint Comprehensive Plan of Action (JCPOA) in 2015. Starting with the Nixon administration in the 1970s, it analyses the policies of successive US administrations toward the Iranian nuclear programme. Emphasizing the centrality of domestic politics to decision-making on both sides, it offers both an explanation of the evolution of the relationship and a critique of successive US administrations' efforts to halt the Iranian nuclear programme, with neither coercive measures nor inducements effectively applied. The book further argues that factional politics inside Iran played a crucial role in Iranian nuclear decision-making and that American policy tended to reinforce the position of Iranian hardliners and undermine that of those who were prepared to compromise on the nuclear issue. In the final chapter it demonstrates how President Obama's alterations to American strategy, accompanied by shifts in Iranian domestic politics, finally brought about the signing of the JCPOA in 2015.

‘To see oursels as ithers see us’: Reflections on Scottish Independence from the United States

2014 ◽  
Vol 23 (3) ◽  
pp. 381-388 ◽  
Author(s):  
Euan Hague ◽  
Alan Mackie
Keyword(s):  
United States ◽  
The United States ◽  
The Us ◽  
Scottish Independence ◽  
The Uk ◽  
Scottish Diaspora

The United States media have given rather little attention to the question of the Scottish referendum despite important economic, political and military links between the US and the UK/Scotland. For some in the US a ‘no’ vote would be greeted with relief given these ties: for others, a ‘yes’ vote would be acclaimed as an underdog escaping England's imperium, a narrative clearly echoing America's own founding story. This article explores commentary in the US press and media as well as reporting evidence from on-going interviews with the Scottish diaspora in the US. It concludes that there is as complex a picture of the 2014 referendum in the United States as there is in Scotland.

Palestine Unbound

2018 ◽  
Vol 47 (3) ◽  
pp. 130-134
Keyword(s):  
United States ◽  
Human Rights ◽  
Task Force ◽  
The United States ◽  
Donald Trump ◽  
Tel Aviv ◽  
The Us ◽  
Intention To Move ◽  
Arab Israeli Conflict ◽  
The U.S

This section, updated regularly on the blog Palestine Square, covers popular conversations related to the Palestinians and the Arab-Israeli conflict during the quarter 16 November 2017 to 15 February 2018: #JerusalemIstheCapitalofPalestine went viral after U.S. president Donald Trump recognized Jerusalem as the capital of Israel and announced his intention to move the U.S. embassy there from Tel Aviv. The arrest of Palestinian teenager Ahed Tamimi for slapping an Israeli soldier also prompted a viral campaign under the hashtag #FreeAhed. A smaller campaign protested the exclusion of Palestinian human rights from the agenda of the annual Creating Change conference organized by the US-based National LGBTQ Task Force in Washington. And, UNRWA publicized its emergency funding appeal, following the decision of the United States to slash funding to the organization, with the hashtag #DignityIsPriceless.

Against Slave Power? Slavery and Runaway Slaves in Mexico-United States Relations, 1821–1857

2019 ◽  
Vol 35 (2) ◽  
pp. 143-170
Author(s):  
Gerardo Gurza-Lavalle
Keyword(s):  
United States ◽  
Foreign Policy ◽  
The United States ◽  
The South ◽  
Runaway Slaves ◽  
The Us ◽  
El Alto ◽  
Upper South ◽  
Lower South

This work analyses the diplomatic conflicts that slavery and the problem of runaway slaves provoked in relations between Mexico and the United States from 1821 to 1857. Slavery became a source of conflict after the colonization of Texas. Later, after the US-Mexico War, slaves ran away into Mexican territory, and therefore slaveholders and politicians in Texas wanted a treaty of extradition that included a stipulation for the return of fugitives. This article contests recent historiography that considers the South (as a region) and southern politicians as strongly influential in the design of foreign policy, putting into question the actual power not only of the South but also of the United States as a whole. The problem of slavery divided the United States and rendered the pursuit of a proslavery foreign policy increasingly difficult. In addition, the South never acted as a unified bloc; there were considerable differences between the upper South and the lower South. These differences are noticeable in the fact that southerners in Congress never sought with enough energy a treaty of extradition with Mexico. The article also argues that Mexico found the necessary leeway to defend its own interests, even with the stark differential of wealth and resources existing between the two countries. El presente trabajo analiza los conflictos diplomáticos entre México y Estados Unidos que fueron provocados por la esclavitud y el problema de los esclavos fugitivos entre 1821 y 1857. La esclavitud se convirtió en fuente de conflicto tras la colonización de Texas. Más tarde, después de la guerra Mexico-Estados Unidos, algunos esclavos se fugaron al territorio mexicano y por lo tanto dueños y políticos solicitaron un tratado de extradición que incluyera una estipulación para el retorno de los fugitivos. Este artículo disputa la idea de la historiografía reciente que considera al Sur (en cuanto región), así como a los políticos sureños, como grandes influencias en el diseño de la política exterior, y pone en tela de juicio el verdadero poder no sólo del Sur sino de Estados Unidos en su conjunto. El problema de la esclavitud dividió a Estados Unidos y dificultó cada vez más el impulso de una política exterior que favoreciera la esclavitud. Además, el Sur jamás operó como unidad: había diferencias marcadas entre el Alto Sur y el Bajo Sur. Estas diferencias se observan en el hecho de que los sureños en el Congreso jamás se esforzaron en buscar con suficiente energía un tratado de extradición con México. El artículo también sostiene que México halló el margen de maniobra necesario para defender sus propios intereses, pese a los fuertes contrastes de riqueza y recursos entre los dos países.

Pathways to Legalization: Undocumented Mexican Immigrants in the US/Mexico Borderlands, 1942–1956

2015 ◽  
Vol 2 (2) ◽  
Author(s):  
Ana Elizabeth Rosas
Keyword(s):  
United States ◽  
Family Relationships ◽  
Mexican Immigrants ◽  
Extended Family ◽  
The United States ◽  
Mexican Immigrant ◽  
Agricultural Laborers ◽  
The Us ◽  
Us Government ◽  
Contract Laborers

In the 1940s, curbing undocumented Mexican immigrant entry into the United States became a US government priority because of an alleged immigration surge, which was blamed for the unemployment of an estimated 252,000 US domestic agricultural laborers. Publicly committed to asserting its control of undocumented Mexican immigrant entry, the US government used Operation Wetback, a binational INS border-enforcement operation, to strike a delicate balance between satisfying US growers’ unending demands for surplus Mexican immigrant labor and responding to the jobs lost by US domestic agricultural laborers. Yet Operation Wetback would also unintentionally and unexpectedly fuel a distinctly transnational pathway to legalization, marriage, and extended family formation for some Mexican immigrants.On July 12, 1951, US president Harry S. Truman’s signing of Public Law 78 initiated such a pathway for an estimated 125,000 undocumented Mexican immigrant laborers throughout the United States. This law was an extension the Bracero Program, a labor agreement between the Mexican and US governments that authorized the temporary contracting of braceros (male Mexican contract laborers) for labor in agricultural production and railroad maintenance. It was formative to undocumented Mexican immigrant laborers’ transnational pursuit of decisively personal goals in both Mexico and the United States.Section 501 of this law, which allowed employers to sponsor certain undocumented laborers, became a transnational pathway toward formalizing extended family relationships between braceros and Mexican American women. This article seeks to begin a discussion on how Operation Wetback unwittingly inspired a distinctly transnational approach to personal extended family relationships in Mexico and the United States among individuals of Mexican descent and varying legal statuses, a social matrix that remains relatively unexplored.

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