Location, Location, Location: Reassessing Erythropoiesis Stimulating Agents (ESAs) in the United States (US), Canada, and Europe (2007−2011)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4753-4753
Author(s):  
Leann Norris ◽  
Donald Mattison ◽  
Zaina Parvez Qureshi ◽  
Charles Bennett
Keyword(s):  
United States ◽  
Clinical Guidelines ◽  
Conflicts Of Interest ◽  
Safety Data ◽  
The United States ◽  
Phase Iii ◽  
Dialysis Patients ◽  
Erythropoiesis Stimulating Agents ◽  
Mortality Risks ◽  
The Us

Abstract Abstract 4753 Background: Erythropoiesis stimulating agents (ESAs) are approved for preventing transfusions (United States (US)) or treating symptomatic anemia (Canada/Europe) among chemotherapy or chronic kidney disease (CKD) patients. Extensive reassessments of safety, efficacy, dosing, and target hemoglobin levels have occurred. Methods: Regulatory agencies', ESA manufacturer notifications, clinical guidelines, phase III trials and meta-analyses cited in clinical guidelines were reviewed (2007 to 2011). Results: CKD and Cancer: Quality of life benefits are reported in Europe and Canada. In the US, product labels report exercise capacity improvements for CKD patients. CKD: Clinical trials reported cardiovascular, cerebrovascular, and mortality risks with ESAs targeting high versus low hemoglobin levels or cardiovascular and mortality risks with ESAs versus placebo. 2011 US' advisories recommend ESA doses sufficient to prevent transfusions among dialysis patients and caution with ESA administration to non-dialysis patients. Canadian and European recommendations target hemoglobin levels between 10 and 12 g/dl and 11 to 12 g/dl, respectively. Following these recommendations among non-dialysis US patients, ESA use decreased 16%. Most US dialysis CKD patients receive ESAs, with lower achieved hemoglobin levels, and 30% decreased ESA usage since 2008. In Europe and Canada, which initially had substantially lower ESA use, there has been a gradual increase. Cancer: Trials identified mortality, tumor progression, and venous thromboembolism risks with ESAs targeting higher versus lower hemoglobin levels. US labels warn against administering ESAs with potentially curative chemotherapy. European guidelines recommend ESAs for symptomatic patients at hemoglobin levels of 9 to 11 g/dL and consider for asymptomatic patients at levels of 11 to 11.9 g/dL. Canadian advisories report cost-utility ratios exceeding accepted standards. ESA use decreased by 70% in the US. Current ESA utilization rates for cancer are higher in Europe and lower in Canada. Conclusions: International differences in interpreting efficacy and safety data and ESA utilization exist. The changes have been most apparent in the US. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Implementation of Anatomic Pathology Services in Mirebalais, Haiti

2018 ◽  
Vol 4 (Supplement 1) ◽  
pp. 31s-31s
Author(s):  
Fabienne Anglade ◽  
Myrlene Mompremier ◽  
Kayleigh Bhangdia ◽  
Lauren Greenberg ◽  
Juan Daniel Orozco ◽  
...  
Keyword(s):  
United States ◽  
Rural Areas ◽  
Conflicts Of Interest ◽  
The United States ◽  
Turnaround Time ◽  
University Hospital ◽  
Phase Iii ◽  
Middle Income ◽  
Resource Limited ◽  
And Training

Abstract 97 Purpose Despite great barriers, implementing pathology services in resource-limited rural settings is achievable. Challenges include the lack of infrastructure, trained personnel, supply chain, and decentralized services, and have hindered the appropriate provision of cancer care to those who live in resource-limited settings. In Haiti, we began treating cancer at University Hospital Mirebalais (HUM) before pathology services existed, sending samples to the United States for diagnoses. This model allowed patients to receive treatment, but turnaround time was often delayed. Our goal is to implement pathology services at HUM that can provide high-quality diagnostics to patients who are enrolled in the cancer program. We demonstrate that, by rolling out a phased implementation of local pathology services with appropriate commitment from local and international partners, accurate pathologic diagnoses can exist in low- and middle-income countries. Methods Phase I—infrastructure and personnel—occurred fall 2016 with the construction of the laboratory and the hiring of a pathologist and laboratory technicians, which allowed samples to be grossed into paraffin blocks before being sent to Boston. Phase II—technology transfer and training—occurred fall 2017 with the procurement of additional equipment and hands-on histology training, which allowed samples to be cut, stained, and diagnosed on-site. In this phase, only complex samples that needed additional immunohistochemistry or a second opinion were sent to Boston. Phase III—testing capacity expansion—will occur summer 2018 and involves procuring immunohistochemistry and training, which will further limit the need to send cases to the United States. Phase IV—routine testing and quality assurance—will occur in tandem with phase III and involves implementing a telepathology system on-site in the HUM laboratory. Results Outcomes of this phased implementation will result in decentralized pathology services in the public sector and ultimately decreased turnaround times, producing better clinical outcomes. Our model demonstrates that it is possible to build local pathology capacity in rural areas. Since the opening of our laboratory, more than 1,000 cases have been processed into paraffin blocks before being sent to Boston. In September 2017, the first cases were diagnosed in country, and more than 100 cases have been processed and reported in Haiti. Conclusion Building on the foundational phases, the next phases of implementation involve long-term diagnostic support that will correlate directly with a substantial decrease in turnaround time. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.

How Rare Is Rare? Carrier Frequencies for Fanconi Anemia In the United States and Israel

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2229-2229
Author(s):  
Philip S Rosenberg ◽  
Hannah Tamary ◽  
Blanche P. Alter
Keyword(s):  
United States ◽  
Fanconi Anemia ◽  
Carrier Frequency ◽  
Large Scale ◽  
Conflicts Of Interest ◽  
Demographic Data ◽  
New York State ◽  
The United States ◽  
Ashkenazi Jews ◽  
The Us

Abstract Abstract 2229 Background: Although carrier frequencies for Fanconi anemia (FA) have been estimated for several founder populations, carrier frequencies in different countries remain unclear. One exception is Israel. In Jewish populations, founder mutations have been identified, e.g. the FANCC IVS+4 A>T mutation in Ashkenazi Jews, and the FANCA 2172–2173insG mutation in Moroccan Jews. The ability to test for specific mutations has enabled screening studies: the carrier frequency in Israeli Ashkenazi Jews is around 1:85; limited available data suggest that carrier frequencies in other Israeli Jewish subgroups may be similar (Tamary et al. BJH 2000). FA also occurs in Israeli Arab populations but carrier frequencies have not been determined. In contrast, there are much less data for the United States (US). Swift (Nature 1971) estimated the US FA carrier frequency as 1:300, but this estimate was based on surprisingly limited data - in total, the 12 persons with FA born in New York State from 1956 until 1967 who were known to the author among the corresponding total of 4.2 million live births. Nonetheless, this figure remains widely cited and has not been updated even after 40 years. We sought to update this estimate given the biological importance of the FA pathway. Methods: We applied Swift's approach (knowledge of the number of FA cases born during a given period with a known overall birth rate) to contemporary data for the United States and Israel. Specifically, we used the Hardy-Weinberg Law and demographic data from the Fanconi Anemia Research Fund (FARF, 488 FA) and the Israeli Fanconi Anemia Registry (ISFAR, 66 FA). Results: On average during the 1990s, 15 persons with FA were born each year in the US who eventually became known to the FARF, amongst the 4.0 million persons born each year in the US during that period. The corresponding Hardy-Weinberg carrier frequency is 1:257 (95% Confidence Interval: 1:240 – 1:277). This range describes a lower bound because ascertainment in FARF must be less than 100%. Even so, the lower confidence limit is significantly greater that 1:300. The true ascertainment in FARF is unknown. We propose that values between 40% – 60% are plausible. Using this range to adjust the observed birth incidence upwards, we obtained a plausible range for the carrier frequency of 1:156 – 1:209 [midpoint 1:182]. We applied the same approach to the ISFAR where 2.6 births per year were observed. We assumed 50% – 100% ascertainment by ISFAR since cases were identified through a country-wide hospital network. For the entire country of Israel (Jews and non-Jews combined), we obtained a plausible range for the carrier frequency of 1:66 – 1:128 [midpoint 1:93]. Hence, the range for Israel derived using Swift's indirect approach (estimated from birth rates) is broadly consistent with direct surveys. Conclusions: The FA carrier frequency in the US may be higher than previously thought, around 1:200 or perhaps even higher. From the perspective of population genetics, our results suggest there is less difference between the average carrier frequency in the US and higher carrier frequencies of around 1:100 reported for a number of ethnic groups including Ashkenazi Jews. This is consistent with the facts that the general US population is heterogeneous mixture of descendents of many ancestral groups, and FA is found world-wide. Our results also suggest that some European populations may have higher carrier frequencies than currently recognized. Our findings are sensitive to a number of assumptions. Going forwards, large scale re-sequencing studies could more precisely determine how many persons in the general population carry causative alleles for FA and other rare recessive syndromes. Disclosures: No relevant conflicts of interest to declare.

Erythropoiesis-stimulating agents for cancer patients: Increasingly restrictive guidelines and policies in the United States and Europe

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20725-e20725
Author(s):  
A. T. Samaras ◽  
S. Y. Lai ◽  
B. Kim ◽  
D. P. West ◽  
J. M. McKoy ◽  
...  
Keyword(s):  
Advisory Committee ◽  
Cancer Patients ◽  
Clinical Guidelines ◽  
The United States ◽  
Erythropoiesis Stimulating Agents ◽  
Mortality Risks ◽  
Human Use ◽  
Meta Analyses ◽  
Cancer Network ◽  
The U.S

e20725 Background: Erythropoiesis stimulating agents (ESAs) have transformed the treatment of cancer-associated anemia worldwide. However, recent reports of venous thromboembolism (VTE), tumor progression, and mortality risks associated with ESA administration to cancer patients have resulted in reassessments of the safety and appropriate usage of these agents. The present study investigated the disparate factors that contributed to the transformation of ESA policies. Methods: We reviewed meta-analyses, advisory committee recommendations, manufacturer label revisions, clinical guidelines, reimbursement policies from the Centers for Medicare and Medicaid Services (CMS), updated clinical guidelines, and ESA usage trends. Results: See Table . Conclusions: The risks and benefits of ESAs for cancer patients have been reassessed, resulting in increasingly restrictive guidelines and labels in the U.S. and Europe. In response to the 2008 ESA labeling change mandated by the U.S. Food and Drug Administration (FDA), the European advisory committee, Committee for Medicinal Products for Human Use (CHMP), convened to reassess the risk-benefit profile of ESAs and determined that for patients with reasonably long life expectancies, the benefits of ESAs do not outweigh the risks. Additionally, the U.S. National Comprehensive Cancer Network (NCCN) revised clinical guidelines in accordance with the FDA labeling change. Therefore, FDA actions combined with the CMS reimbursement policy have provided the impetus for increasingly restrictive use of ESAs. [Table: see text] [Table: see text]

scholarly journals Projected COVID-19 epidemic in the United States in the context of the effectiveness of a potential vaccine and implications for social distancing and face mask use

2020 ◽  
Author(s):  
Mingwang Shen ◽  
Jian Zu ◽  
Christopher K. Fairley ◽  
José A. Pagán ◽  
Li An ◽  
...  
Keyword(s):  
United States ◽  
Negative Impact ◽  
Social Contact ◽  
Face Mask ◽  
The United States ◽  
Vaccine Effectiveness ◽  
Phase Iii ◽  
Effective Vaccine ◽  
Social Distancing ◽  
The Us

ABSTRACTBackgroundMultiple candidates of COVID-19 vaccines have entered Phase III clinical trials in the United States (US). There is growing optimism that social distancing restrictions and face mask requirements could be eased with widespread vaccine adoption soon.MethodsWe developed a dynamic compartmental model of COVID-19 transmission for the four most severely affected states (New York, Texas, Florida, and California). We evaluated the vaccine effectiveness and coverage required to suppress the COVID-19 epidemic in scenarios when social contact was to return to pre-pandemic levels and face mask use was reduced. Daily and cumulative COVID-19 infection and death cases were obtained from the Johns Hopkins University Coronavirus resource center and used for model calibration.ResultsWithout a vaccine, the spread of COVID-19 could be suppressed in these states by maintaining strict social distancing measures and face mask use levels. But relaxing social distancing restrictions to the pre-pandemic level without changing the current face mask use would lead to a new COVID-19 outbreak, resulting in 0.8-4 million infections and 15,000-240,000 deaths across these four states over the next 12 months. In this scenario, introducing a vaccine would partially offset this negative impact even if the vaccine effectiveness and coverage are relatively low. However, if face mask use is reduced by 50%, a vaccine that is only 50% effective (weak vaccine) would require coverage of 55-94% to suppress the epidemic in these states. A vaccine that is 80% effective (moderate vaccine) would only require 32-57% coverage to suppress the epidemic. In contrast, if face mask usage stops completely, a weak vaccine would not suppress the epidemic, and further major outbreaks would occur. A moderate vaccine with coverage of 48-78% or a strong vaccine (100% effective) with coverage of 33-58% would be required to suppress the epidemic. Delaying vaccination rollout for 1-2 months would not substantially alter the epidemic trend if the current interventions are maintained.ConclusionsThe degree to which the US population can relax social distancing restrictions and face mask use will depend greatly on the effectiveness and coverage of a potential COVID-19 vaccine if future epidemics are to be prevented. Only a highly effective vaccine will enable the US population to return to life as it was before the pandemic.

scholarly journals CONFLICTS OF INTEREST IN PAKISTAN AND UNITED STATES RELATIONS (2008-2019)

2020 ◽  
Vol 3 (2) ◽  
pp. 211-219
Keyword(s):  
United States ◽  
Conflicts Of Interest ◽  
Primary Source ◽  
The United States ◽  
The Us ◽  
Source Data ◽  
Foreign Office ◽  
The Times ◽  
Analytical Approaches ◽  
Buck Passing

The ambit of Pakistan’s relationship with the United States is based on convergence as well as divergence of interests, whereby the United States kept intense engagement followed by periods of utter indifference. Most of the times mutual mistrust and suspicions makeshift the policy parameters to the strategic impasse. Considering the trends of the relations, the US policy revolves around the struggle for global hegemony with policy parameters of off-shore balancing and buck-passing, and Pakistan is mainly focused on security imperatives. This piece of research investigates that what are grounds of conflicts between Pakistan and the United States relations? The study is conducted by explanatory and analytical approaches. Data sources are both primary and secondary where for primary source data was collected through Interviews with ministry of defence and foreign office. The United States and Pakistan relations remained uneasy due to mistrust and accusations and the US preference to India in the region in general and in Afghanistan in particular and the China’s growing influence in the region. The need is to understand Pakistan’s security concerns, an acknowledgment of the contribution to the war against terror and above all to revive cooperation for regional peace and prosperity.

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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