Budget impact of adding ivabradine to standard of care in patients with chronic systolic heart failure in the United States

BACKGROUND: Heart failure (HF) costs $21 billion annually in direct health care costs, 80 OBJECTIVE: To estimate the budget impact of ivabradine from a U.S. commercial payer perspective. METHODS: A budget impact model estimated the per-member-per month (PMPM) impact of introducing ivabradine to existing formularies by comparing a reference scenario (SoC) and a new drug scenario (ivabradine + SoC) in hypothetical 1 million-member commercial and Medicare Advantage plans. In both scenarios, U.S. claims data were used for the reference cumulative annual rates of hospitalizations (HF, non-HF cardiovascular [CV], and non-CV), and hospitalization rates were adjusted using SHIFT data. The model controlled for mortality risk using SHIFT and U.S. life table data, and hospitalization costs were obtained from U.S. claims data: HF-related =$37,507; non-HF CV = $28,951; and non-CV =$17,904. The annualized wholesale acquisition cost of ivabradine was $4,500, with baseline use for this new drug at 2 RESULTS: Based on the approved U.S. indication, approximately 2,000 commercially insured patients from a 1 million-member commercial plan were eligible to receive ivabradine. Ivabradine resulted in a PMPM cost savings of$0.01 and $0.04 in years 1 and 3 of the core model, respectively. After including the acquisition price for ivabradine, the model showed a decrease in total costs in the commercial ($991,256 and $474,499, respectively) and Medicare populations ($13,849,262 and $4,280,291, respectively) in year 1. This decrease was driven by ivabradine’s reduction in hospitalization rates. For the core model, the estimated pharmacy-only PMPM in year 1 was$0.01 for the commercial population and $0.24 for the Medicare Advantage population. CONCLUSIONS: Adding ivabradine to SoC led to lower average annual treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers

Health screenings administered during the domestic medical examination of refugees and other eligible immigrants in nine US states, 2014-2016: A cross-sectional analysis.

BACKGROUND: Refugees and other select visa holders are recommended to receive a domestic medical examination within 90 days after arrival to the United States. Limited data have been published on the coverage of screenings offered during this examination across multiple resettlement states, preventing evaluation of this voluntary program\u27s potential impact on postarrival refugee health. This analysis sought to calculate and compare screening proportions among refugees and other eligible populations to assess the domestic medical examination\u27s impact on screening coverage resulting from this examination. METHODS AND FINDINGS: We conducted a cross-sectional analysis to summarize and compare domestic medical examination data from January 2014 to December 2016 from persons receiving a domestic medical examination in seven states (California, Colorado, Minnesota, New York, Kentucky, Illinois, and Texas); one county (Marion County, Indiana); and one academic medical center in Philadelphia, Pennsylvania. We analyzed screening coverage by sex, age, nationality, and country of last residence of persons and compared the proportions of persons receiving recommended screenings by those characteristics. We received data on disease screenings for 105,541 individuals who received a domestic medical examination; 47% were female and 51.5% were between the ages of 18 and 44. The proportions of people undergoing screening tests for infectious diseases were high, including for tuberculosis (91.6% screened), hepatitis B (95.8% screened), and human immunodeficiency virus (HIV; 80.3% screened). Screening rates for other health conditions were lower, including mental health (36.8% screened). The main limitation of our analysis was reliance on data that were collected primarily for programmatic rather than surveillance purposes. CONCLUSIONS: In this analysis, we observed high rates of screening coverage for tuberculosis, hepatitis B, and HIV during the domestic medical examination and lower screening coverage for mental health. This analysis provided evidence that the domestic medical examination is an opportunity to ensure newly arrived refugees and other eligible populations receive recommended health screenings and are connected to the US healthcare system. We also identified knowledge gaps on how screenings are conducted for some conditions, notably mental health, identifying directions for future research

Health of Special Immigrant Visa holders from Iraq and Afghanistan after arrival into the United States using Domestic Medical Examination data, 2014-2016: A cross-sectional analysis.

BACKGROUND: Since 2008, the United States has issued between 2,000 and 19,000 Special Immigrant Visas (SIV) annually, with the majority issued to applicants from Iraq and Afghanistan. SIV holders (SIVH) are applicants who were employed by, or on behalf of, the US government or the US military. There is limited information about health conditions in SIV populations to help guide US clinicians caring for SIVH. Thus, we sought to describe health characteristics of recently arrived SIVH from Iraq and Afghanistan who were seen for domestic medical examinations. METHODS AND FINDINGS: This cross-sectional analysis included data from Iraqi and Afghan SIVH who received a domestic medical examination from January 2014 to December 2016. Data were gathered from state refugee health programs in seven states (California, Colorado, Illinois, Kentucky, Minnesota, New York, and Texas), one county, and one academic medical center and included 6,124 adults and 4,814 children. Data were collected for communicable diseases commonly screened for during the exam, including tuberculosis (TB), hepatitis B, hepatitis C, malaria, strongyloidiasis, schistosomiasis, other intestinal parasites, syphilis, gonorrhea, chlamydia, and human immunodeficiency virus, as well as elevated blood lead levels (EBLL). We investigated the frequency and proportion of diseases and whether there were any differences in selected disease prevalence in SIVH from Iraq compared to SIVH from Afghanistan. A majority of SIV adults were male (Iraqi 54.0%, Afghan 58.6%) and aged 18-44 (Iraqi 86.0%, Afghan 97.7%). More SIV children were male (Iraqi 56.2%, Afghan 52.2%) and aged 6-17 (Iraqi 50.2%, Afghan 40.7%). The average age of adults was 29.7 years, and the average age for children was 5.6 years. Among SIV adults, 14.4% were diagnosed with latent tuberculosis infection (LTBI), 63.5% were susceptible to hepatitis B virus (HBV) infection, and 31.0% had at least one intestinal parasite. Afghan adults were more likely to have LTBI (prevalence ratio [PR]: 2.0; 95% confidence interval [CI] 1.5-2.7) and to be infected with HBV (PR: 4.6; 95% CI 3.6-6.0) than Iraqi adults. Among SIV children, 26.7% were susceptible to HBV infection, 22.1% had at least one intestinal parasite, and 50.1% had EBLL (≥5 mcg/dL). Afghan children were more likely to have a pathogenic intestinal parasite (PR: 2.7; 95% CI 2.4-3.2) and EBLL (PR: 2.0; 95% CI 1.5-2.5) than Iraqi children. Limitations of the analysis included lack of uniform health screening data collection across all nine sites and possible misclassification by clinicians of Iraqi and Afghan SIVH as Iraqi and Afghan refugees, respectively. CONCLUSION: In this analysis, we observed that 14% of SIV adults had LTBI, 27% of SIVH had at least one intestinal parasite, and about half of SIV children had EBLL. Most adults were susceptible to HBV. In general, prevalence of infection was higher for most conditions among Afghan SIVH compared to Iraqi SIVH. The Centers for Disease Control and Prevention (CDC) Guidelines for the US Domestic Medical Examination for Newly Arriving Refugees can assist state public health departments and clinicians in the care of SIVH during the domestic medical examination. Future analyses can explore other aspects of health among resettled SIV populations, including noncommunicable diseases and vaccination coverage

A Culture of Fire: Identifying Community Risk Perceptions Surrounding Prescribed Burning in the Flint Hills, Kansas

In the Flint Hills region of eastern Kansas, there is a long tradition of spring prescribed burns. However, air quality concerns in downwind communities have sparked conversation regarding the environmental and social impacts of these burns. This study aimed to identify the risk perceptions associated with prescribed burns using two theoretical frameworks: the social amplification of risk framework and the protective action decision model. In April 2022, we conducted 18 in-depth, semi-structured interviews with Flint Hills community members from different social stations. Participants identified several benefits of prescribed burns: cattle production gains, invasive species management, prairie ecological health maintenance, and wildfire prevention. Some participants viewed prescribed burning as a protective response. However, risk perceptions differed between rural and urban participants: rural community members were primarily concerned with prescribed fires that went out of control, while those in downwind cities were primarily concerned with smoke exposure. Participants sometimes used protective actions to mitigate their risks, but also explained the complexities of changing burn practices that are integral to the local culture, economies, and greater society. Additionally, formal communication of health and safety risks from prescribed burns is not uniform across Kansas counties. We therefore recommend systematic county and statewide communication of burn practices and protective behaviors. Understanding community perceptions of the risks and effects of prescribed burns, and any protective actions taken, can inform how professional communicators approach burning in similar agricultural and ranching communities

Budget impact of adding ivabradine to standard of care in patients with chronic systolic heart failure in the United States

BACKGROUND: Heart failure (HF) costs $21 billion annually in direct health care costs, 80 OBJECTIVE: To estimate the budget impact of ivabradine from a U.S. commercial payer perspective. METHODS: A budget impact model estimated the per-member-per month (PMPM) impact of introducing ivabradine to existing formularies by comparing a reference scenario (SoC) and a new drug scenario (ivabradine + SoC) in hypothetical 1 million-member commercial and Medicare Advantage plans. In both scenarios, U.S. claims data were used for the reference cumulative annual rates of hospitalizations (HF, non-HF cardiovascular [CV], and non-CV), and hospitalization rates were adjusted using SHIFT data. The model controlled for mortality risk using SHIFT and U.S. life table data, and hospitalization costs were obtained from U.S. claims data: HF-related =$37,507; non-HF CV = $28,951; and non-CV =$17,904. The annualized wholesale acquisition cost of ivabradine was $4,500, with baseline use for this new drug at 2 RESULTS: Based on the approved U.S. indication, approximately 2,000 commercially insured patients from a 1 million-member commercial plan were eligible to receive ivabradine. Ivabradine resulted in a PMPM cost savings of$0.01 and $0.04 in years 1 and 3 of the core model, respectively. After including the acquisition price for ivabradine, the model showed a decrease in total costs in the commercial ($991,256 and $474,499, respectively) and Medicare populations ($13,849,262 and $4,280,291, respectively) in year 1. This decrease was driven by ivabradine’s reduction in hospitalization rates. For the core model, the estimated pharmacy-only PMPM in year 1 was$0.01 for the commercial population and $0.24 for the Medicare Advantage population. CONCLUSIONS: Adding ivabradine to SoC led to lower average annual treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers

Two alternative methods for the retrieval of somatic cell populations from the mouse ovary

Many modern techniques employed to uncover the molecular fundamentals underlying biological processes require dissociated cells as their starting point/substrate. Investigations into ovarian endocrinology or folliculogenesis therefore necessitate robust protocols for dissociating the ovary into its constituent cell populations. While in the mouse, methods to obtain individual, mature follicles are well-established, the separation and isolation of single cells of all types from early mouse follicles, including somatic cells, has been more challenging. Herein we present two methods for the isolation of somatic cells in the ovary. These methods are suitable for a range of applications relating to the study of folliculogenesis and mouse ovarian development. First, an enzymatic dissociation utilising collagenase and a temporary, primary cell culture step using neonatal mouse ovaries which yields large quantities of granulosa cells from primordial, activating, and primary follicles. Second, a rapid papain dissociation resulting in a high viability single cell suspension of ovarian somatic cells in less than an hour, which can be applied from embryonic to adult ovarian samples. Collectively these protocols can be applied to a broad array of investigations with unique advantages and benefits pertaining to both

Spontaneous Isomerization of Long-Lived Proteins Provides a Molecular Mechanism for the Lysosomal Failure Observed in Alzheimer's Disease.

Proteinaceous aggregation is a well-known observable in Alzheimer's disease (AD), but failure and storage of lysosomal bodies within neurons is equally ubiquitous and actually precedes bulk accumulation of extracellular amyloid plaque. In fact, AD shares many similarities with certain lysosomal storage disorders though establishing a biochemical connection has proven difficult. Herein, we demonstrate that isomerization and epimerization, which are spontaneous chemical modifications that occur in long-lived proteins, prevent digestion by the proteases in the lysosome (namely, the cathepsins). For example, isomerization of aspartic acid into l-isoAsp prevents digestion of the N-terminal portion of Aβ by cathepsin L, one of the most aggressive lysosomal proteases. Similar results were obtained after examination of various target peptides with a full series of cathepsins, including endo-, amino-, and carboxy-peptidases. In all cases peptide fragments too long for transporter recognition or release from the lysosome persisted after treatment, providing a mechanism for eventual lysosomal storage and bridging the gap between AD and lysosomal storage disorders. Additional experiments with microglial cells confirmed that isomerization disrupts proteolysis in active lysosomes. These results are easily rationalized in terms of protease active sites, which are engineered to precisely orient the peptide backbone and cannot accommodate the backbone shift caused by isoaspartic acid or side chain dislocation resulting from epimerization. Although Aβ is known to be isomerized and epimerized in plaques present in AD brains, we further establish that the rates of modification for aspartic acid in positions 1 and 7 are fast and could accrue prior to plaque formation. Spontaneous chemistry can therefore provide modified substrates capable of inducing gradual lysosomal failure, which may play an important role in the cascade of events leading to the disrupted proteostasis, amyloid formation, and tauopathies associated with AD

Health of Asylees Compared to Refugees in the United States Using Domestic Medical Examination Data, 2014-2016: A Cross-Sectional Analysis.

Background: Between 2008 and 2018, persons granted asylum (asylees) increased by 168% in the United States. Asylees are eligible for many of the same domestic benefits as refugees under the US Refugee Admissions Program (USRAP), including health-related benefits such as the domestic medical examination. However, little is known about the health of asylees to guide clinical practice. Methods: We conducted a retrospective cross-sectional analysis of domestic medical examination data from 9 US sites from 2014 to 2016. We describe and compare demographics and prevalence of several infectious diseases such as latent tuberculosis infection (LTBI), hepatitis B and C virus (HBV, HCV), and select sexually transmitted infections and parasites by refugee or asylee visa status. Results: The leading nationalities for all asylees were China (24%) and Iraq (10%), while the leading nationalities for refugees were Burma (24%) and Iraq (19 %). Approximately 15% of asylees were diagnosed with LTBI, and 52% of asylee adults were susceptible to HBV infection. Prevalence of LTBI (prevalence ratio [PR] = 0.8), hepatitis B (0.7), hepatitis C (0.5), and Strongyloides (0.5) infections were significantly lower among asylees than refugees. Prevalence of other reported conditions did not differ by visa status. Conclusions: Compared to refugees, asylees included in our dataset were less likely to be infected with some infectious diseases but had similar prevalence of other reported conditions. The Centers for Disease Control and Prevention\u27s Guidance for the US Domestic Medical Examination for Newly Arrived Refugees can also assist clinicians in the care of asylees during the routine domestic medical examination

Blood Lead Levels Among Afghan Children in the United States, 2014-2016

Lead poisoning disproportionately affects children and can result in permanent neurologic damage.1 Although blood lead levels (BLLs) declined among children in the United States over the past several decades, children resettling to the United States from other countries emerged as a population at risk for BLLs that are higher than the United States blood lead reference value of $5 mg/dL at the time of this analysis.2 Among children screened for lead shortly after resettlement, children from Afghanistan have a higher prevalence of BLLs$5 mg/dL compared with children from other countries,3,4 but timely sources of data available for analysis are limited. In 2021, the United States troop withdrawal from Afghanistan prompted the rapid evacuation and resettlement of more than 76 000 Afghans to the United States.5 We analyzed existing data from domestic medical examinations (DMEs) conducted from 2014 to 2016 for refugees and eligible populations #90 days after arrival in multiple states. We described and compared the prevalence of BLL $5 mg/dL among Afghan and non-Afghan refugee children screened and evaluated select characteristics associated with BLL$5 mg/dL among Afghan children