Clinical impact of rapid molecular diagnostic tests in patients presenting with viral respiratory symptoms: A systematic literature review.

BACKGROUND: Molecular tests can detect lower concentrations of viral genetic material over a longer period of respiratory infection than antigen tests. Delays associated with central laboratory testing can result in hospital-acquired transmission, avoidable patient admission, and unnecessary use of antimicrobials, all which may lead to increased cost of patient management. The aim of this study was to summarize comparisons of clinical outcomes associated with rapid molecular diagnostic tests (RMDTs) versus other diagnostic tests for viral respiratory infections. METHODS: A systematic literature review (SLR) conducted in April 2023 identified studies evaluating clinical outcomes of molecular and antigen diagnostic tests for patients suspected of having respiratory viral infections. RESULTS: The SLR included 21 studies, of which seven and 14 compared RMDTs (conducted at points of care or at laboratories) to standard (non-rapid) molecular tests or antigen tests to detect SARS-CoV-2 and influenza, respectively. In studies testing for SARS-CoV-2, RMDTs led to reductions in time to test results versus standard molecular tests (range of the reported medians: 0.2-3.8 hours versus 4.3-35.9 hours), with similar length of emergency department stay (3.2-8 hours versus 3.7-28.8 hours). Similarly, in studies testing for influenza, RMDTs led to reductions in time to test results versus standard molecular tests (1-3.5 hours versus 18.2-29.2 hours), with similar length of emergency department stay (3.7-11 hours versus 3.8-11.9 hours). RMDTs were found to decrease exposure time of uninfected patients, rate of hospitalization, length of stay at the hospitals, and frequency of unnecessary antiviral and antibacterial therapy, while improving patient flow, compared to other tests. CONCLUSIONS: Compared to other diagnostic tests, RMDTs improve clinical outcomes, test turnaround time, and stewardship by decreasing unnecessary use of antibiotics and antivirals. They also reduce hospital admission and length of stay, which may, in turn, reduce unnecessary exposure of patients to hospital-acquired infections and their associated costs.

Navigating the Unseen Strain: The Hidden Challenges of Black Nursing Faculty in the Fight Against Anti-Black Racism.

As Black faculty members of a majority-White nursing school, we reflected on our unique experiences as part of a Black community engagement project, aimed at addressing anti-Black racism in nursing education. Our positionality created a complex scenario as we navigated emotionally heavy discussions, grappled with our ability to manage competing interests and care for our own well-being. The invisibility of the undue burden of anti-racism work is discussed. Recommendations for alleviating the burden are proposed based on this lived experience. Nursing schools must recognize the uniqueness of Black faculty members' experiences. Proposed strategies include creating mechanisms and resources for emotional support and incorporating anti-racism initiatives into the nursing school's values and strategic plan.

Sickle Cell Health Awareness, Perspectives, and Experiences (SHAPE) survey: Perspectives of adolescent and adult patients, caregivers, and healthcare professionals on the burden of sickle cell disease.

OBJECTIVES: Sickle cell disease (SCD) is an inherited disorder that causes lifelong complications, substantially impacting the physical and emotional well-being of patients and their caregivers. Studies investigating the effects of SCD on quality of life (QOL) are often limited to individual countries, lack SCD-specific QOL questionnaires, and exclude the caregiver experience. The SHAPE survey aimed to broaden the understanding of the global burden of SCD on patients and their caregivers and to capture the viewpoint of healthcare providers (HCPs). METHODS: A total of 919 patients, 207 caregivers, and 219 HCPs from 10, 9, and 8 countries, respectively, answered a series of closed-ended questions about their experiences with SCD. RESULTS: The symptoms most frequently reported by patients were fatigue/tiredness (84%) and pain/vaso-occlusive crises (71%). Patients' fatigue/tiredness had one of the greatest impacts on both patients' and caregivers' QOL. On average, patients and caregivers reported missing 7.5 days and 5.0 days per month, respectively, of school or work. HCPs reported a need for effective tools to treat fatigue/tiredness and a desire for more support to educate patients on long-term SCD-related health risks. CONCLUSIONS: The multifaceted challenges identified using the SHAPE survey highlight the global need to improve both patient and caregiver QOL.

A cost-consequence analysis of the Xpert Xpress CoV-2/Flu/RSV plus test strategy for the diagnosis of influenza-like illnesses.

AIMS: Influenza-like illnesses (ILI) affect millions each year in the United States (US). Determining definitively the cause of symptoms is important for patient management. Xpert Xpress CoV-2/Flu/RSV plus (Xpert Xpress) is a rapid, point-of-care (POC), multiplex real-time polymerase chain reaction (RT-PCR) test intended for the simultaneous qualitative detection and differentiation of SARS-CoV-2, influenza A/B, and respiratory syncytial virus (RSV). The objective of our analysis was to develop a cost-consequence model (CCM) demonstrating the clinico-economic impacts of implementing PCR testing with Xpert Xpress compared to current testing strategies. METHODS: A decision tree model, with a 1-year time horizon, was used to compare testing with Xpert Xpress alone to antigen POC testing and send-out PCR strategies in the US outpatient setting from a payer perspective. A hypothetical cohort of 1,000,000 members was modeled, a portion of whom develop symptomatic ILIs and present to an outpatient care facility. Our main outcome measure is cost per correct treatment course. RESULTS: The total cost per correct treatment course was $1,131 for the Xpert Xpress strategy compared with a range of $3,560 to $5,449 in comparators. POC antigen testing strategies cost more, on average, than PCR strategies. LIMITATIONS: Simplifying model assumptions were used to allow for modeling ease. In clinical practice, treatment options, costs, and diagnostic test sensitivity and specificity may differ from what is included in the model. Additionally, the most recent incidence and prevalence data was used within the model, which is not reflective of historical averages due to the SARS-CoV-2 pandemic. CONCLUSION: The Xpert Xpress CoV-2/Flu/RSV plus test allows for rapid and accurate diagnostic results, leading to reductions in testing costs and downstream healthcare resource utilization compared to other testing strategies. Compared to POC antigen testing strategies, PCR strategies were more efficient due to improved diagnostic accuracy and reduced use of confirmatory testing.

Relationship between hemoglobin, hemolysis, and transcranial Doppler velocities in children with sickle cell disease: Results from a long-term natural history study in Italy in the era of multimodal therapy.

BACKGROUND: Stroke and cerebral vasculopathy are leading causes of morbidity and mortality in patients with sickle cell disease (SCD). Transcranial Doppler (TCD) is a reliable and validated predictor of stroke risk. Children with conditional or abnormal TCD are at an increased risk for stroke, which can be mitigated by red blood cell transfusion or hydroxyurea. Elucidating the relationship between cerebral hemodynamics and hemolytic anemia can help identify novel therapeutic approaches to reduce stroke risk and transfusion dependence. METHODS: This long-term, real-world study was designed to evaluate the prevalence of TCD imaging (TCDi)-assessed flow velocities in children and to interrogate their relationship with markers of anemia and hemolysis. RESULTS: In total, 155 children (median follow-up 79.8 months, 1358.44 patient-years) had 583 evaluable TCDi results. Only patients with HbSS or HbSß0 had abnormal (1.6%) or conditional (10.9%) TCDi. Children with abnormal or conditional TCDi had lower hemoglobin (Hb) and higher hemolysis markers. A linear correlation was detected between TCD velocity and Hb: an Hb increase of 1 g/dL corresponded to decreases in velocity in the internal carotid and middle cerebral arteries (6.137 cm/s and 7.243 cm/s). Moreover, patients with Hb >9 g/dL presented a lower risk of TCDi-associated events. CONCLUSION: These results support the need to optimize disease-modifying treatments that increase Hb and reduce hemolysis for stroke prevention in young children with SCD.

Patient-Reported Experiences in Voxelotor-Treated Children and Adults with Sickle Cell Disease: A Semistructured Interview Study.

Objective: Voxelotor is a first-in-class sickle hemoglobin-polymerization inhibitor that was approved in 2019 by the US Food and Drug Administration for treatment of patients with sickle cell disease (SCD) aged ≥12 years; in 2021, the approval was extended to children with SCD aged 4 to 11 years. Additionally, both the Ministry of Health and Prevention for the United Arab Emirates and the European Commission granted marketing authorization for voxelotor in September 2021 and February 2022, respectively, for treatment of SCD in adults and pediatric patients aged ≥12 years. Thus, additional information on the patient experience with voxelotor would be useful for patients, caregivers, and healthcare professionals alike. The purpose of this study was to conduct semistructured interviews in an effort to understand the experiences and perspectives of voxelotor-treated patients with SCD. Methods: One-time semistructured interviews with adults, adolescents, and children with SCD and their primary caregivers were conducted in the United States. Twenty-three adults and adolescents were recruited across 4 clinical sites, and 10 children-caregiver dyads were recruited from a single site. The interview was designed to elicit patient perspectives on symptomatic changes with voxelotor and the impact of treatment on patients' perceived health-related quality of life. Individual interview transcripts were analyzed using a thematic analytic approach, and concept saturation was assessed in both cohorts. Results: Most patients reported improvements in their SCD symptoms with voxelotor treatment, specifically regarding pain crises, jaundice, and fatigue. Almost all patients experienced improvements in self-reported health-related quality of life with voxelotor treatment. Conclusions: This study provides patient and caregiver perspectives on the symptomatic benefits of voxelotor treatment. These findings not only highlight the benefits of voxelotor treatment in improving symptoms and increasing health-related quality of life across the entire SCD population but also can inform further research on SCD-specific patient-reported outcomes.

Real-world effectiveness of voxelotor for treating sickle cell disease in the US: a large claims data analysis.

BACKGROUND: Sickle cell disease (SCD) is a genetic disease that impacts patients' quality of life, healthcare costs, and life expectancy. Elevated sickle hemoglobin (HbS), which readily polymerizes, causes red blood cell sickling, leading to chronic hemolytic anemia and complications often requiring hospitalization and transfusions. In 2019, voxelotor, which inhibits HbS polymerization, was approved for SCD treatment. OBJECTIVES: This study uses real-world evidence to assess voxelotor's effectiveness in SCD patients in typical clinical practice from 2019 to 2021 using a national medical claims database (N = 3128). RESULTS: After initiating voxelotor, 60.8% of patients with available hemoglobin (Hb) laboratory data (n = 74) showed a Hb increase >1 g/dL. Mean transfusion rate per patient-year dropped 52% in patients with ≥1 transfusion before treatment (n = 190). In patients with ≥1 of the corresponding events (n = 1065), decreases were observed in mean vaso-occlusive crisis (VOC) frequency (-23%); mean VOC-related hospitalizations and length of stay (LOS) time (-34% and -30%, respectively); mean all-cause hospitalization and LOS time (-37% and -23%, respectively); outpatient visits (-10%); iron chelation use (-46%); and prescribed opioids (-13%). CONCLUSION: These data align with randomized controlled trial results showing voxelotor improvements and support that voxelotor may lower transfusion and VOC rates in clinical practice.

Cost-effectiveness of andexanet alfa versus four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-related intracranial hemorrhage in the US.

AIM: To conduct a cost-effectiveness analysis (CEA) on the use of andexanet alfa for the treatment of factor Xa inhibitor-related intracranial hemorrhage (ICH) from the US third-party payer and societal perspectives. METHODS: CEA compared andexanet alfa to prothrombin complex concentrate for the treatment of patients receiving factor Xa inhibitors admitted to hospital inpatient care with an ICH. The model comprised two linked phases. Phase 1 utilized a decision tree to model the acute treatment phase (admission of a patient with ICH into intensive care for the first 30 days). Phase 2 modeled long-term costs and outcomes using three linked Markov models comprising the six health states defined by the modified Rankin score. RESULTS: The analysis showed that the strategy of using andexanet alfa for the treatment of factor Xa inhibitor-related ICH is cost-effective, with incremental cost-effectiveness per quality-adjusted life-year gained of $35,872 from a third-party payer perspective and $40,997 from a societal perspective over 20 years. LIMITATIONS: (1) Absence of head-to-head trials comparing therapies included in the economic model, (2) lack of comparative long-term data on treatment efficacy, and (3) bias resulting from the study designs of published literature. CONCLUSION: Given these results, the use of andexanet alfa for the reversal of anticoagulation in patients with factor Xa inhibitor-related ICH may improve quality of life and is likely to be cost-effective in a US context.

Burden-of-Illness Associated with Bleeding-Related Hospitalizations in Atrial Fibrillation Patients: Findings from the Nationwide Readmission Database.

Introduction A paucity of contemporary data examining bleeding-related hospitalization outcomes in atrial fibrillation (AF) patients exists. Methods Adults in the Nationwide Readmissions Database (January 2016-November 2016) with AF and hospitalized for intracranial hemorrhage (ICH), gastrointestinal, genitourinary, or other bleeding were identified. Association between bleed types and outcomes were assessed using multivariable regression (gastrointestinal defined as referent) and reported as crude incidences and adjusted odds ratios (ORs) or mean differences with 95% confidence intervals (CIs). Results In total, 196,878 index bleeding-related hospitalizations were identified in this AF cohort (CHA2DS2VASc score ≥2 in 95.1%), with 70.8% classified as gastrointestinal. The overall incidences of in-hospital mortality, need for post-discharge out-of-home care, and 30-day readmission were 4.9, 50.8, and 18.2%, respectively. Multivariable regression suggested traumatic and nontraumatic ICHs were associated with higher odds of in-hospital mortality (OR = 3.99, 95% CI = 3.79, 4.19; OR = 13.09, 95% CI = 12.24, 13.99) and need for post-discharge out-of-home care (OR = 2.92, 95% CI = 2.83, 3.01; OR = 2.74, 95% CI = 2.59, 2.90), and increases in mean index hospitalization length-of-stay (8.31 days, 95% CI = 8.03, 8.60, 6.27 days, 95% CI = 5.97, 6.57) versus gastrointestinal bleeding. Genitourinary and other bleeds were associated with lower mortality (OR = 0.37, 95% CI = 0.25, 0.55; OR = 0.59, 95% CI = 0.53, 0.64) and reduced length-of-stays (-2.84 days, 95% CI = - 2.91, -2.76; -2.06 days, 95% CI = - 2.11, -2.01) versus gastrointestinal bleeding. Genitourinary bleeds were also associated with a reduced need for post-discharge out-of-home care (OR = 0.86, 95% CI = 0.77, 0.97). Conclusion The burden of bleeding-related hospitalizations was notably driven by relatively rare but severe and life-threatening ICH, and less morbid but more frequent gastrointestinal bleeding. There is need for continued research on bleeding risk factors and mitigation techniques to avoid bleeding-related patient hospitalizations.

Association of tenofovir disoproxil fumarate exposure with chronic kidney disease and osteoporotic fracture in US veterans with HIV.

BACKGROUND: Tenofovir disoproxil fumarate (TDF)-based regimens have been associated with impaired kidney function and loss of bone mineral density among patients living with HIV (PLWH). We assess the association between TDF exposure and the odds of chronic kidney disease (CKD) and osteoporotic fracture in HIV patients. METHODS: Demographics, administrative claims, and pharmacy dispensation were extracted from the Veterans Affairs Informatics and Computing Infrastructure (VINCI). Patients were categorized based on TDF utilization. Incidence rates for patients exposed and unexposed to TDF were calculated per 1000 patient-years (PYs). Logistic regression was used to calculate the odds of outcome after adjusting for baseline and clinical characteristics. RESULTS: The sample included 4,630 PLWH who were currently exposed to TDF and 1,181 who were never exposed to TDF for the CKD analyses. For fracture analyses, the sample included 6,883 PLWH who were currently exposed to TDF and 1,951 who were never exposed to TDF. In adjusted models, current TDF exposure was associated with increased odds of CKD compared to never having been exposed (OR: 1.48, 95% CI: 1.18-1.85). Odds of fracture were 2.32 times higher for patients who were currently on a TDF regimen (OR: 2.32, 95% CI: 1.58-3.42) compared to those who had never been exposed to TDF in adjusted models. CONCLUSIONS: In a large cohort of US veterans with HIV, current exposure to TDF was associated with a 48% higher odds of CKD and a greater than two-fold increase in the odds of osteoporotic fracture.

Real-world adherence and persistence for newly-prescribed HIV treatment: single versus multiple tablet regimen comparison among US medicaid beneficiaries.

BACKGROUND: Once-daily, single-tablet regimens (STRs) have been associated with improved patient outcomes compared to multi-tablet regimens (MTRs). This study evaluated real world adherence and persistence of HIV antiretroviral therapy (ART), comparing STRs and MTRs. METHODS: Adult Medicaid beneficiaries (aged ≥ 18 years) initiating ART with ≥ 2 ART claims during the identification period (January 1, 2015-December 31, 2016) and continuous health plan enrollment for a 12-month baseline period were included. For STRs, the first ART claim date was defined as the index date; for MTRs, the prescription fill claim date for the last drug in the regimen was defined as the index date, and prescription fills were required to occur within a 5-day window. Adherence was assessed in 30-day intervals over a 6-month period, with adherence defined as having less than a 5-day gap between fills. Persistence was evaluated as median number of days on therapy and percent persistence at 12 months. Cox Proportional Hazard models were used to evaluate risk of discontinuation, controlling for baseline and clinical characteristics. RESULTS: A total of 1,744 (STR = 1290; MTR = 454) and 2409 (STR = 1782; MTR = 627) patients newly prescribed ART had available data concerning adherence and persistence, respectively. Average age ranged 40-42 years. The patient population was predominantly male. Adherence assessments showed 22.7% of STR initiators were adherent to their index regimens over a 6-month period compared to 11.7% of MTR initiators. Unadjusted persistence analysis showed 36.3% of STR initiators discontinued first-line therapy compared to 48.8% for MTR initiators over the 2-year study period. Controlling for baseline demographic and clinical characteristics, MTR initiators had a higher risk of treatment discontinuation (hazard ratio [HR] = 1.6, p < 0.0001). Among STRs, compared to the referent elvitegravir(EVG)/cobicistat(COBI)/emtricitabine(FTC)/tenofovir alafenamide(TAF), risk of discontinuation was higher for efavirenz(EFV)/FTC/tenofovir disoproxil fumarate(TDF) (HR = 3.6, p < 0.0001), EVG/COBI/FTC/TDF (HR = 2.8, p < 0.0001), and abacavir (ABC)/lamivudine (3TC)/dolutegravir (DTG) (HR = 1.8, p = 0.004). Among backbones, FTC/TAF was associated with lower risk of discontinuation than FTC/TDF (HR = 4.4, p < 0.0001) and ABC/3TC (HR = 2.2, p < 0.0001). CONCLUSIONS: Among patients newly prescribed ART, STR initiators were significantly less likely to discontinue therapy and had greater adherence and persistence compared to MTR initiators. Regimens containing FTC/TAF as a backbone had higher persistence than those consisting of other backbones.

Estimation of the Incremental Cumulative Cost of HIV Compared with a Non-HIV Population.

OBJECTIVE: There are limited real-world data comparing cumulative incremental healthcare costs in people living with HIV (PLWH) and those without HIV. This study evaluated all-cause cumulative and incremental costs in PLWH in the US using a matched-cohort design. MATERIALS AND METHODS: This retrospective, multi-year, cross-sectional analysis evaluated annual costs from 2013 to 2017, and projected cumulative costs of HIV from age 25 to 69 years. IQVIA's commercial adjudicated claims database was used to identify patients with HIV and match them with patients without HIV (controls). Cumulative all-cause costs were derived from the health plan-allowed costs incurred from ages 25-69 years. Undiscounted, discounted, and incremental costs between PLWH and non-HIV populations were reported in 2017 US dollars (US$), and annual all-cause costs were estimated for each year by 10-year age bands. RESULTS: A total of 25,261, 24,134, 31,654, 35,374, and 29,039 PLWH and 75,783, 72,402, 94,962, 106,122, and 87,117 matched controls were identified in the years 2013 through 2017, respectively. The mean undiscounted cumulative costs were $1,840,554 for PLWH and $285,065 for controls, an incremental cost difference of $1,555,489, while the mean discounted cumulative cost for PLWH was $983,897 compared with $133,340 for controls, an incremental cost difference of $850,557. Mean all-cause annual and cumulative costs were up to seven times higher for PLWH compared with controls. There was a trend for costs to increase each year with increasing age. LIMITATIONS AND CONCLUSIONS: While cumulative all-cause cost estimates only approximate total cost burden for any given patient, and the results of this study may not be generalizable to all population subgroups, this is one of the first US studies to examine annual and cumulative costs in a real-world cohort of commercially insured PLWH compared with a population without HIV. In this large, representative sample of commercially insured US adults with HIV, PLWH had substantially higher all-cause cumulative costs than individuals without HIV.

Treatment Adherence And Persistence Among HIV-1 Patients Newly Starting Treatment.

OBJECTIVE: To assess adherence and persistence with first-line single-tablet regimen (STR) and multi-tablet regimen (MTR) antiretroviral therapy (ART) in newly treated HIV-1 patients. METHODS: Retrospective analysis of longitudinal pharmacy claims among US patients initiating ART between 1/1/2016 and 5/31/2016 (index date was defined by first ART claim for STRs, and fill date for the last therapy in the regimen for MTRs). Adherence was assessed over a 12-month period and reported as the proportion of adherent or non-adherent (defined as ≤5-day and > a 5-day gap between successive fills, respectively) patients. Sensitivity analysis using ≤7-day and ≤14-day gap thresholds to define adherence was performed. Persistence was assessed as the number of days on therapy from index until treatment discontinuation (>90 day gap in therapy). Kaplan-Meier curves and Cox Proportional Hazard models were generated to evaluate discontinuation rates. Assessments were performed on STRs vs MTRs overall and by regimen. RESULTS: Patients initiating ART (STR: n=10,623; MTR: n=2504) had a mean age of 42.8 years; 76.0% were male. STR patients were >2 times more likely to be adherent over 12 months than MTR patients (24.9% vs 11.7%, respectively). Patients using EVG/COBI/FTC/TAF had greater adherence than those using other STRs. Among MTRs, patients were more adherent with FTC/TDF+DTG (15.1%) than other MTRs. Persistence was also greater with STRs, with MTR patients being 61% more likely to discontinue therapy. Persistence was best for FTC/TAF-based regimens. Predictors of treatment discontinuation included younger age, female gender, and Medicare or Medicaid insurance type. CONCLUSION: Patients receiving STRs were significantly less likely to discontinue therapy and were more adherent with their regimens, providing further evidence of greater adherence and persistence with STRs versus MTRs. However, there was a large proportion of patients who interrupted or discontinued treatment. Further research examining treatment patterns beyond first line is warranted.

Estimated Impact of Targeted Pre-Exposure Prophylaxis: Strategies for Men Who Have Sex with Men in the United States.

Pre-exposure prophylaxis (PrEP) effectively reduces human immunodeficiency virus (HIV) transmission. We aimed to estimate the impact of different PrEP prioritization strategies among Black and Latino men who have sex with men (MSM) in the United States, populations most disproportionately affected by HIV. We developed an agent-based simulation to model the HIV epidemic among MSM. Individuals were assigned an HIV incidence risk index (HIRI-MSM) based on their sexual behavior. Prioritization strategies included PrEP use for individuals with HIRI-MSM ≥10 among all MSM, all Black MSM, young (≤25 years) Black MSM, Latino MSM, and young Latino MSM. We estimated the number needed to treat (NNT) to prevent one HIV infection, reductions in prevalence and incidence, and subsequent infections in non-PrEP users avoided under these strategies over 5 years (2016-2020). Young Black MSM eligible for PrEP had the lowest NNT (NNT = 10) followed by all Black MSM (NNT = 33) and young Latino MSM (NNT = 35). All Latino MSM and all MSM had NNT values of 63 and 70, respectively. Secondary infection reduction with PrEP was the highest among young Latino MSM (53.2%) followed by young Black MSM (37.8%). Targeting all MSM had the greatest reduction in prevalence (14.7% versus 2.9%-3.9% in other strategies) and incidence (49.4% versus 9.4%-13.9% in other groups). Using data representative of the United States MSM population, we found that a strategy of universal PrEP use by MSM was most effective in reducing HIV prevalence and incidence of MSM. Targeted use of PrEP by Black and Latino MSM, however, especially those ≤25 years, had the greatest impact on HIV prevention.

Adherence to HIV treatment regimens: systematic literature review and meta-analysis.

BACKGROUND: Antiretroviral therapy (ART), when taken consistently, reduces morbidity and mortality associated with human immunodeficiency virus and viral transmission. Suboptimal treatment adherence is associated with regimen complexity and high tablet burden. Single-tablet regimens (STRs) provide a complete treatment regimen in a single tablet. This study examined the relationship between STRs (vs multiple-tablet regimens [MTRs]), treatment adherence, and viral suppression. METHODS: A systematic review was conducted to identify studies investigating at least one of the following: (1) STR/MTR use and adherence; (2) levels of adherence and viral suppression; and (3) STR/MTR use and viral suppression. Meta-analysis was performed to assess the relationship between STR vs MTR use and adherence in observational settings at ≥95% and ≥90% adherence thresholds. RESULTS: In total, 29 studies were identified across the three objectives; two studies were relevant for all objectives. STRs were associated with higher treatment adherence than MTRs in 10/11 observational studies: a 63% greater likelihood of achieving ≥95% adherence (95% CI=1.52-1.74; P<0.001) and a 43% increase in the likelihood of achieving ≥90% adherence (95% CI=1.21-1.69; P<0.001). Higher adherence rates were associated with higher levels of viral suppression in 13/18 studies. Results were mixed in five studies investigating the association between STR or MTR use and viral suppression. CONCLUSION: Although the direct effect of STRs vs MTRs on viral suppression remains unclear, this study provided a quantitative estimate of the relationship between STRs and ART adherence, demonstrating that STRs are associated with significantly higher ART adherence levels at 95% and 90% thresholds. Findings from the systematic review showed that improved adherence results in an increased likelihood of achieving viral suppression in observational settings. Future research should utilize similar measures for adherence and evaluate viral suppression to improve assessment of the relationship between pill burden, adherence, and viral suppression.

Treatment Patterns, Statin Intolerance, and Subsequent Cardiovascular Events Among Japanese Patients With High Cardiovascular Risk Initiating Statin Therapy.

BACKGROUND: This study examined treatment patterns, possible statin intolerance, and incidence of cardiovascular events (CVEs) in 2 cohorts of patients with high cardiovascular risk (i.e., patients with atherosclerotic cardiovascular disease [ASCVD] and patients with diabetes mellitus).Methods and Results:A retrospective cohort study examined adults initiating either a statin or ezetimibe from 1 January 2006 to 31 May 2014 in the Japan Medical Data Center database. The first observed statin or ezetimibe prescription defined the index date. Patients had ≥12 months of pre- and post-index date plan enrollment. Two high-risk cohorts, the ASCVD cohort and diabetes cohort, were created based on diagnoses observed during the 12 months' pre-index date. Treatment patterns, possible statin intolerance, and incidence of CVEs were reported. In the ASCVD cohort (n=5,302), 32.9% discontinued therapy, 7.7% switched to a non-index statin or non-statin lipid-lowering therapy, and 11.2% augmented index therapy in the 12 months' post-index date; only 0.3% were using high-intensity statins and 10% had possible statin intolerance. Also, 8.1% had any new CVE during the follow-up period. Treatment patterns and incidence of CVEs among the diabetes cohort were similar to those of the ASCVD cohort. CONCLUSIONS: High cardiovascular risk Japanese patients had frequent treatment modifications, although use of high-intensity statin doses was rare. These patterns may indicate that alternative therapies for lipid lowering are needed.

Estimated burden of cardiovascular disease and value-based price range for evolocumab in a high-risk, secondary-prevention population in the US payer context.

AIM: To estimate real-world cardiovascular disease (CVD) burden and value-based price range of evolocumab for a US-context, high-risk, secondary-prevention population. MATERIALS AND METHODS: Burden of CVD was assessed using the UK-based Clinical Practice Research Datalink (CPRD) in order to capture complete CV burden including CV mortality. Patients on standard of care (SOC; high-intensity statins) in CPRD were selected based on eligibility criteria of FOURIER, a phase 3 CV outcomes trial of evolocumab, and categorized into four cohorts: high-risk prevalent atherosclerotic CVD (ASCVD) cohort (n = 1448), acute coronary syndrome (ACS) (n = 602), ischemic stroke (IS) (n = 151), and heart failure (HF) (n = 291) incident cohorts. The value-based price range for evolocumab was assessed using a previously published economic model. The model incorporated CPRD CV event rates and considered CV event reduction rate ratios per 1 mmol/L reduction in low-density lipoprotein-cholesterol (LDL-C) from a meta-analysis of statin trials by the Cholesterol Treatment Trialists Collaboration (CTTC), i.e. CTTC relationship. RESULTS: Multiple-event rates of composite CV events (ACS, IS, or coronary revascularization) per 100 patient-years were 12.3 for the high-risk prevalent ASCVD cohort, and 25.7, 13.3, and 23.3, respectively, for incident ACS, IS, and HF cohorts. Approximately one-half (42%) of the high-risk ASCVD patients with a new CV event during follow-up had a subsequent CV event. Combining these real-world event rates and the CTTC relationship in the economic model, the value-based price range (credible interval) under a willingness-to-pay threshold of $150,000/quality-adjusted life-year gained for evolocumab was $11,990 ($9,341-$14,833) to $16,856 ($12,903-$20,678) in ASCVD patients with baseline LDL-C levels ≥70 mg/dL and ≥100 mg/dL, respectively. CONCLUSION: Real-world CVD burden is substantial. Using the observed CVD burden in CPRD and the CTTC relationship, the cost-effectiveness analysis showed that, accounting for uncertainties, the expected value-based price for evolocumab is higher than its current annual cost, as long as the payer discount off list price is greater than 20%.

Effects of Epoetin Alfa Titration Practices, Implemented After Changes to Product Labeling, on Hemoglobin Levels, Transfusion Use, and Hospitalization Rates.

BACKGROUND: Little is known about epoetin alfa (EPO) dosing at dialysis centers after implementation of the US Medicare prospective payment system and revision of the EPO label in 2011. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Approximately 412,000 adult hemodialysis patients with Medicare Parts A and B as primary payer in 2009 to 2012 to describe EPO dosing and hemoglobin patterns; of these, about 70,000 patients clustered in about 1,300 dialysis facilities to evaluate facility-level EPO titration practices and patient-level outcomes in 2012. PREDICTOR: Facility EPO titration practices when hemoglobin levels were <10 and >11g/dL (grouped treatment variable) determined from monthly EPO dosing and hemoglobin level patterns. OUTCOMES: Patient mean hemoglobin levels, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates using a facility-based analysis. MEASUREMENTS: Monthly EPO dose and hemoglobin level, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates. RESULTS: Monthly EPO doses declined across all hemoglobin levels, with the greatest decline in patients with hemoglobin levels < 10g/dL (July-October 2011). In 2012, nine distinct facility titration practices were identified. Across groups, mean hemoglobin levels differed slightly (10.5-10.8g/dL) but within-patient hemoglobin standard deviations were similar (∼0.68g/dL). Patients at facilities implementing greater dose reductions and smaller dose escalations had lower hemoglobin levels and higher transfusion rates. In contrast, patients at facilities that implemented greater dose escalations (and large or small dose reductions) had higher hemoglobin levels and lower transfusion rates. There were no clinically meaningful differences in all-cause or cause-specific hospitalization events across groups. LIMITATIONS: Possibly incomplete claims data; excluded small facilities and those without consistent titration patterns; hemoglobin levels reported monthly; inferred facility practice from observed dosing. CONCLUSIONS: Following prospective payment system implementation and labeling revisions, EPO doses declined significantly. Under the new label, facility EPO titration practices were associated with mean hemoglobin levels (but not standard deviations) and transfusion use, but not hospitalization rates.

Epoetin Alfa and Outcomes in Dialysis amid Regulatory and Payment Reform.

Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in patients with CKD, including those receiving dialysis, although clinical trials have identified risks associated with ESA use. We evaluated the effects of changes in dialysis payment policies and product labeling instituted in 2011 on mortality and major cardiovascular events across the United States dialysis population in an open cohort study of patients on dialysis from January 1, 2005, through December 31, 2012, with Medicare as primary payer. We compared observed rates of death and major cardiovascular events in 2011 and 2012 with expected rates calculated on the basis of rates in 2005-2010, accounting for differences in patient characteristics and influenza virulence. An abrupt decline in erythropoietin dosing and hemoglobin concentration began in late 2010. Observed rates of all-cause mortality, cardiovascular mortality, and myocardial infarction in 2011 and 2012 were consistent with expected rates. During 2012, observed rates of stroke, venous thromboembolic disease (VTE), and heart failure were lower than expected (absolute deviation from trend per 100 patient-years [95% confidence interval]: -0.24 [-0.08 to -0.37] for stroke, -2.43 [-1.35 to -3.70] for VTE, and -0.77 [-0.28 to -1.27] for heart failure), although non-ESA-related changes in practice and Medicare payment penalties for rehospitalization may have confounded the results. This initial evidence suggests that action taken to mitigate risks associated with ESA use and changes in payment policy did not result in a relative increase in death or major cardiovascular events and may reflect improvements in stroke, VTE, and heart failure.

Anemia management practice patterns in small dialysis organizations following implementation of the prospective payment system.

BACKGROUND: The impact of the United States Prospective Payment System (PPS) "bundle payment system" on anemia management within small dialysis organizations (SDOs) was studied to evaluate the financia burden on SDOs. METHODS: Facilities enrolled in the original study on SDOs were grouped into three hemoglobin (Hb) categories by subject-months: > 25% of subjectmonths with Hb < 10 g/dL (sub-10); > 25% of subject-months with Hb > 12 g/dL (super-12); remaining facilities (10 - 12 group). Subjectlevel data aggregated to facility level for Hb concentration, intravenous (IV) epoetin ± (EA) dose per administration, dose titration, and EA administration frequency during the baseline and follow-up periods were described. RESULTS: Baseline demographic characteristics were imbalanced between the sub-10 (n = 7) and super-12 facilities (n = 5). Mean (SD) Hb concentrations were similar for sub-10 (11.1 (3.0) g/dL) and super-12 (11.6 (2.2) g/dL) facilities during the baseline period, but differed during the follow-up period (10.4 (2.7) vs. 11.4 (2.3) g/dL). The median (Q1, Q3) EA IV dose per administration during follow-up was 3,726 (3,467, 3,961) and 5,712 (4,816, 7,324) units in the sub-10 and super-12 facilities, respectively. A small trend toward upward titration was seen. CONCLUSIONS: Results suggest a difference in anemia management between sub-10 and super-12 facilities during the first year of PPS implementation. Future analyses evaluating patterns of reimbursement and shifts in clinical practice guidelines are warranted globally.