Effectiveness of Nirmatrelvir-Ritonavir for the Prevention of COVID-19-Related Hospitalization and Mortality: A Systematic Literature Review.

BACKGROUND: Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high risk of progression to severe disease (eg, hospitalization and death). Despite being the preferred option for outpatient treatment in the majority of countries worldwide, NMV/r is currently underutilized in real-world clinical practice. AREAS OF UNCERTAINTY: As numerous real-world studies have described patient outcomes following treatment with NMV/r, this systematic literature review provides a comprehensive summary of evidence on NMV/r effectiveness against hospitalization and mortality further organized by clinically meaningful categories, such as acute versus longer-term follow-up, age, underlying health conditions, and vaccination status, to help inform health care decision making. DATA SOURCES: We searched Embase and PubMed (December 22, 2021-March 31, 2023) and congress abstracts (December 1, 2021-December 31, 2022) for reports describing NMV/r effectiveness. THERAPEUTIC ADVANCES: In total, 18 real-world studies met final selection criteria. The evidence showed that NMV/r significantly reduced postinfection risk of all-cause and COVID-19-related hospitalization and mortality in both acute (≤30 days) (21%-92%) and longer-term (>30 days) (1%-61%) follow-up. The reduction in postinfection risk was higher when treatment was received within 5 days of symptom onset. Real-world effectiveness of NMV/r treatment was observed regardless of age, underlying high-risk conditions, and vaccination status. CONCLUSION: The systematic literature review findings demonstrated the effectiveness of NMV/r against hospitalization and mortality during the Omicron period among individuals at high risk of progression to severe COVID-19 disease.

Comparative Costs to Medicare and Medicare Beneficiaries of Alternative AF Stroke Risk Reduction Strategies.

Background: As healthcare costs are increasingly being shifted from payers to patients, it is important to understand the economic consequences of therapeutic strategies to both payers and patients. Objective: To determine the relative costs to Medicare and Medicare beneficiaries (patients) of warfarin, non-vitamin K oral anticoagulants (NOACs), and left atrial appendage closure (LAAC) for stroke risk reduction in nonvalvular atrial fibrillation. Methods: An economic model was developed to assess costs at 5 and 10 years. For warfarin and NOACs, inputs were derived from published meta-analyses; for LAAC with the Watchman device, inputs were derived from pooled 5-year PROTECT AF and PREVAIL trial results. The model captured therapy costs vs clinical event costs, including procedural complications and follow-up clinical outcomes. Costs were based on 2023 Medicare reimbursement and copayment rates. Results: At 10 years, overall LAAC costs ($48,337) were lower than those of NOACs ($81,198) and warfarin ($52,359). Overall LAAC costs were lower than those of NOACs by year 5 and warfarin by year 9. At 5 years, patient LAAC costs were lowest at $4,764, compared to $7,146 and $6,453 for NOACs and warfarin, respectively. LAAC patient costs were lower than those of NOACs by year 3 and warfarin by year 4. Clinical events comprised 96% of overall warfarin costs vs 48% for LAAC and 40% for NOACs. Conclusion: LAAC yielded the lowest overall and patient costs. Warfarin costs were largely driven by clinical events, which may represent an unplanned financial burden for patients. These considerations should be incorporated into shared decision-making discussions about stroke prophylaxis strategies.

The impact of vaccination and outpatient treatment on the economic burden of Covid-19 in the United States omicron era: a systematic literature review.

AIMS: To identify and synthesize evidence regarding how coronavirus disease 2019 (COVID-19) interventions, including vaccines and outpatient treatments, have impacted healthcare resource use (HCRU) and costs in the United States (US) during the Omicron era. MATERIALS AND METHODS: A systematic literature review (SLR) was performed to identify articles published between 1 January 2021 and 10 March 2023 that assessed the impact of vaccination and outpatient treatment on costs and HCRU outcomes associated with COVID-19. Screening was performed by two independent researchers using predefined inclusion/exclusion criteria. RESULTS: Fifty-eight unique studies were included in the SLR, of which all reported HCRU outcomes, and one reported costs. Overall, there was a significant reduction in the risk of COVID-19-related hospitalization for patients who received an original monovalent primary series vaccine plus booster dose vs. no vaccination. Moreover, receipt of a booster vaccine was associated with a lower risk of hospitalization vs. primary series vaccination. Evidence also indicated a significantly reduced risk of hospitalizations among recipients of nirmatrelvir/ritonavir (NMV/r), remdesivir, sotrovimab, and molnupiravir compared to non-recipients. Treated and/or vaccinated patients also experienced reductions in intensive care unit (ICU) admissions, length of stay, and emergency department (ED)/urgent care clinic encounters. LIMITATIONS: The identified studies may not represent unique patient populations as many utilized the same regional/national data sources. Synthesis of the evidence was also limited by differences in populations, outcome definitions, and varying duration of follow-up across studies. Additionally, significant gaps, including HCRU associated with long COVID and various high-risk populations and cost data, were observed. CONCLUSIONS: Despite evidence gaps, findings from the SLR highlight the significant positive impact that vaccination and outpatient treatment have had on HCRU in the US, including periods of Omicron predominance. Continued research is needed to inform clinical and policy decision-making in the US as COVID-19 continues to evolve as an endemic disease.

Cost-effectiveness of left atrial appendage closure with Watchman for non-valvular atrial fibrillation patients in Japan.

AIMS: Left atrial appendage closure (LAAC) has been demonstrated to be cost-saving relative to oral anticoagulants for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF) in the United States and Europe. This study assessed the cost-effectiveness of LAAC with the Watchman device relative to warfarin and direct oral anticoagulants (DOACs) for stroke risk reduction in NVAF from a Japanese public healthcare payer perspective. METHODS: A Markov model was developed with 70-year-old patients using a lifetime time horizon. LAAC clinical inputs were from pooled, 5-year PROTECT AF and PREVAIL trials; warfarin and DOAC inputs were from published meta-analyses. Baseline stroke and bleeding risks were from the SALUTE trial on LAAC. Cost inputs were from the Japanese Medical Data Vision database. Probabilistic and one-way sensitivity analyses were performed. RESULTS: Over the lifetime time horizon, LAAC was less costly than warfarin (savings of JPY 1,878,335, equivalent to US $17,600) and DOACs (savings of JPY 1,198,096, equivalent to US $11,226). LAAC also provided 1.500 more incremental quality-adjusted life years (QALYs) than warfarin and 0.996 more than DOACs. In probabilistic sensitivity analysis, LAAC was cost-effective relative to warfarin and DOACs in 99.98% and 99.73% of simulations, respectively. LAAC dominated (had higher cumulative QALYs and was less costly than) warfarin and DOACs in 89.94% and 83.35% of simulations, respectively. CONCLUSIONS: Over a lifetime time horizon, LAAC is cost-saving relative to warfarin and DOACs for stroke risk reduction in NVAF patients in Japan and is associated with improved quality-of-life.

This study examined the cost-effectiveness of left atrial appendage closure (LAAC) compared to oral anticoagulants for stroke risk reduction among individuals with a specific type of irregular heart rhythm called non-valvular atrial fibrillation (NVAF). This study evaluated the cost-effectiveness of LAAC using the Watchman device in comparison to warfarin and direct oral anticoagulants (DOACs) from the perspective of Japan's public healthcare system. To investigate this, a computer-based model was developed involving 70-year-old patients over their lifetime. Data from notable studies such as the PROTECT AF and PREVAIL trials (covering 5 years) for LAAC and published meta-analyses for warfarin and DOACs were incorporated into the model. Baseline stroke and bleeding risks were derived from the SALUTE trial on LAAC. Cost inputs were based on data from the Japanese Medical Data Vision database. Additionally, we performed thorough cost-effectiveness analyses, including probabilistic and one-way sensitivity assessments. Our findings revealed that, over a lifetime, LAAC was more cost-effective than both warfarin and DOACs. Further, LAAC contributed an additional 1.500 quality-adjusted life years (QALYs) compared to warfarin and 0.996 QALYs compared to DOACs. In the long-term, adopting LAAC as an alternative to warfarin and DOACs is a cost-effective strategy for reducing stroke risk in NVAF patients in Japan. Moreover, it is associated with enhanced quality-of-life. These findings hold significant implications for informing decision-making in healthcare policies and clinical practices for NVAF patients.

Clinical and economic impact of blue light cystoscopy in the management of NMIBC at US ambulatory surgical centers: what is the site-of-service disparity?

INTRODUCTION AND OBJECTIVE: Management of non-muscle-invasive bladder cancer (NMIBC) significantly impacts healthcare resource utilization due to requirements for ongoing surveillance. White light cystoscopy (WLC) represents the traditional approach to NMIBC disease surveillance, though physicians utilizing WLC alone may fail to detect all cancerous lesions. The approval of blue light cystoscopy (BLC) as an adjunct to WLC enhances the urologist's ability to more readily detect cancerous tissue. A more complete resection will reduce recurrences and could result in reduced costs for the US healthcare system. This analysis quantifies the clinical and economic impact of the incorporation of BLC in the management of NMIBC in ambulatory surgical centers (ASCs) considering current Center for Medicare Services (CMS) patient-physician coverage and reimbursement. METHODS AND MATERIALS: A budget impact model was developed to assess projected ASC costs for a cohort of 50 newly diagnosed bladder cancer patients over a 2-year follow-up comparing WLC alone vs. WLC + BLC. Treatment and surveillance intervals were based on AUA/SUO clinical guidelines. Clinical and cost metrics for staging and biopsy rates were assessed, with cost inputs based on Medicare reimbursement rates. RESULTS: Use of WLC + BLC for NMIBC surveillance resulted in the identification of 5 additional NMIBC recurrences compared to WLC alone. There was an associated increased cost of performing BLC in an ASC setting, with a net increase in the total cost of care for NMIBC of $110 per cystoscopy over a 2-year period. If recurrences missed using WLC alone were to progress prior to detection, the model projects an increase in treatment costs borne by Medicare of $9,097 to $34,538 due to more intensive treatments required for the increased risk of recurrence. CONCLUSIONS: Modeled results suggests that the Medicare program will incur increased costs, due to the gap between added costs per cystoscopy due to BLC. The current discrepancy in reimbursement disincentivizes community-based ASCs from adopting BLC, resulting in suboptimal patient care while increasing downstream treatment costs to Medicare, necessitated when missed disease progresses to higher stage/grade disease. The findings have important clinical implications for the optimal management of NMIBC and should inform healthcare policies that promote cost-effectiveness and enhanced patient outcomes.

Macro and microeconomics of blue light cystoscopy with CYSVIEW® in non-muscle invasive bladder cancer.

OBJECTIVE: To determine the estimated budget impact to practices that incorporate blue light cystoscopy (BLC) with hexaminolevulinate HCl (HAL) for the surveillance of non-muscle-invasive bladder cancer (NMIBC) in the clinic setting. With the introduction of advanced technologies in the clinic setting such as HAL, further cost comparative research is needed to justify HAL as a high value option. MATERIAL AND METHODS: A budget impact model was developed from the facility perspective assessing projected costs at 2 years for a simulated facility with 50 newly diagnosed bladder cancer patients. Treatment and surveillance cystoscopy intervals were based on clinical guidelines. Clinical inputs, including tumor stage and grade at diagnosis, rates of recurrence and relative risk reduction when using BLC with HAL, were derived from published studies. Cost inputs were based on Medicare reimbursement rates and facility costs. RESULTS: Use of BLC identified 9 additional recurrences over two years compared to white light cystoscopy alone. Use of flexible BLC for surveillance marginally increased costs to the practice, with a net difference of $0.76 per cystoscopy over 2 years. CONCLUSIONS: From the office/clinic perspective, the model suggests that the use of flexible BLC for the surveillance of NMIBC may not impact cost per cystoscopy and identifies 9 recurrences over 2 years that would be missed using white light cystoscopy alone. These findings could have important implications in the management of NIMBC and help guide clinical practice guidelines that promote cost-effective care and improved patient outcomes.

Real-World Burden of Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is associated with an increase in healthcare resource use and poor health-related quality of life (HRQoL). We assessed the humanistic and economic burden of NASH, disease management, and patient journey. METHODS: We performed a cross-sectional analysis of data, collected from July through November 2017, from the Growth from Knowledge Disease Atlas Real-World Evidence program, reported by physicians in United States, France, and Germany. We extracted demographic and medical data from medical records. Some patients voluntarily completed a survey that provided information on disease history, treatment satisfaction, and patient-reported outcomes. RESULTS: We analyzed data from 1216 patients (mean age, 54.9±12.3 years; 57.5% male; mean body mass index, 31.7±6.9); 64.6% had biopsy-confirmed NASH and comorbidities were recorded for 41.3%. Treatments included lifestyle modification (64.6%) or use of statins (25.0%), vitamin E (23.5%), or metformin (20.2%). Patients with biopsy-confirmed NASH reported more physician (4.5 vs 3.7) and outpatient visits (1.8 vs1.4) than patients with suspected NASH not confirmed by biopsy. Among the 299 patients who completed the survey, 47.8% reported various symptoms associated to their NASH. Symptomatic patients reported significantly lower HRQoL than patients without symptoms. CONCLUSIONS: In an analysis of data from 3 countries, we found NASH to be associated with regular use of medical resources; patients with symptoms of NASH had reduced HRQoL. The burden of NASH appears to be underestimated. Studies are needed to determine the burden of NASH by fibrosis stage and disease severity.

Cost-Effectiveness of Left Atrial Appendage Closure for Stroke Reduction in Atrial Fibrillation: Analysis of Pooled, 5-Year, Long-Term Data.

Background Recent publications reached conflicting conclusions about the cost-effectiveness of left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, Marlborough, MA) for stroke risk reduction in nonvalvular atrial fibrillation (AF). This analysis sought to assess the cost-effectiveness of LAAC relative to both warfarin and nonwarfarin oral anticoagulants (NOACs) using pooled, long-term data from the randomized PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin) trials. Methods and Results A Markov model was constructed from a US payer perspective with a lifetime (20-year) horizon. LAAC clinical event rates and stroke outcomes were from pooled PROTECT AF and PREVAIL trial 5-year data. Warfarin and NOAC inputs were derived from published meta-analyses. The model was populated with a cohort of 10 000 patients, aged 70 years, at moderate stroke and bleeding risk. Sensitivity analyses were performed. LAAC was cost-effective relative to warfarin by year 7 ($48 674/quality-adjusted life-year) and dominant (more effective and less costly) by year 10. LAAC became cost-effective and dominant compared with NOACs by year 5. Over a lifetime, LAAC provided 0.60 more quality-adjusted life-years than warfarin and 0.29 more than NOACs. In sensitivity analyses, LAAC was cost-effective relative to warfarin and NOACs in 98% and 95% of simulations, respectively. Conclusions Using pooled, 5-year PROTECT AF and PREVAIL trial data, LAAC proved to be not only cost-effective, but cost saving relative to warfarin and NOACs. LAAC with the Watchman device is an economically viable stroke risk reduction strategy for patients with AF seeking an alternative to lifelong anticoagulation.

Cost-Effectiveness of Left Atrial Appendage Closure With the WATCHMAN Device Compared With Warfarin or Non-Vitamin K Antagonist Oral Anticoagulants for Secondary Prevention in Nonvalvular Atrial Fibrillation.

BACKGROUND AND PURPOSE: Once a patient with atrial fibrillation experiences an embolic event, the risk of a recurrent event increases 2.6-fold. New treatments have emerged as viable treatment alternatives to warfarin for stroke risk reduction in secondary prevention populations. This analysis sought to assess the cost-effectiveness of left atrial appendage closure (LAAC) compared with warfarin and the non-vitamin K antagonist oral anticoagulants dabigatran 150 mg, apixaban and rivaroxaban in the prevention of stroke in nonvalvular atrial fibrillation patients with a prior stroke or transient ischemic attack. METHODS: A Markov model was constructed using data from the secondary prevention subgroup analyses of the non-vitamin K antagonist oral anticoagulant and LAAC pivotal trials. Costs were from 2016 US Medicare reimbursement rates and the literature. The cost-effectiveness analysis was conducted from a US Medicare perspective over a lifetime (20 years) horizon. The model was populated with a cohort of 10 000 patients aged 70 years with a CHA2DS2-VASc score of 7 (annual stroke risk=9.60%) and HAS-BLED score of 3 (annual bleeding risk=3.74%). RESULTS: LAAC achieved cost-effectiveness relative to dabigatran at year 5 and warfarin and apixaban at year 6. At 10 years, LAAC had more quality-adjusted life years (4.986 versus 4.769, 4.869, 4.888, and 4.810) and lower costs ($42 616 versus $53 770, $58 774, $55 656, and $58 655) than warfarin, dabigatran, apixaban, and rivaroxaban, respectively, making LAAC the dominant (more effective and less costly) stroke risk reduction strategy. LAAC remained the dominant strategy over the lifetime analysis. CONCLUSIONS: Upfront procedure costs initially make LAAC higher cost than warfarin and the non-vitamin K antagonist oral anticoagulants, but within 10 years, LAAC delivers more quality-adjusted life years and has lower total costs, making LAAC the most cost-effective treatment strategy for secondary prevention of stroke in atrial fibrillation.

Clinical and economic consequences of hospital-acquired resistant and multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis.

BACKGROUND: Increasing rates of resistant and multidrug-resistant (MDR) P. aeruginosa in hospitalized patients constitute a major public health threat. We present a systematic review of the clinical and economic impact of this resistant pathogen. METHODS: Studies indexed in MEDLINE and Cochrane databases between January 2000-February 2013, and reported all-cause mortality, length of stay, hospital costs, readmission, or recurrence in at least 20 hospitalized patients with laboratory confirmed resistant P. aeruginosa infection were included. We accepted individual study definitions of MDR, and assessed study methodological quality. RESULTS: The most common definition of MDR was resistance to more than one agent in three or more categories of antibiotics. Twenty-three studies (7,881 patients with susceptible P. aeruginosa, 1,653 with resistant P. aeruginosa, 559 with MDR P. aeruginosa, 387 non-infected patients without P. aeruginosa) were analyzed. A random effects model meta-analysis was feasible for the endpoint of all-cause in-hospital mortality. All-cause mortality was 34% (95% confidence interval (CI) 27% - 41%) in patients with any resistant P. aeruginosa compared to 22% (95% CI 14% - 29%) with susceptible P. aeruginosa. The meta-analysis demonstrated a > 2-fold increased risk of mortality with MDR P. aeruginosa (relative risk (RR) 2.34, 95% CI 1.53 - 3.57) and a 24% increased risk with resistant P. aeruginosa (RR 1.24, 95% CI 1.11 - 1.38), compared to susceptible P. aeruginosa. An adjusted meta-analysis of data from seven studies demonstrated a statistically non-significant increased risk of mortality in patients with any resistant P. aeruginosa (adjusted RR 1.24, 95% CI 0.98 - 1.57). All three studies that reported infection-related mortality found a statistically significantly increased risk in patients with MDR P. aeruginosa compared to those with susceptible P. aeruginosa. Across studies, hospital length of stay (LOS) was higher in patients with resistant and MDR P. aeruginosa infections, compared to susceptible P. aeruginosa and control patients. Limitations included heterogeneity in MDR definition, restriction to nosocomial infections, and potential confounding in analyses. CONCLUSIONS: Hospitalized patients with resistant and MDR P. aeruginosa infections appear to have increased all-cause mortality and LOS. The negative clinical and economic impact of these pathogens warrants in-depth evaluation of optimal infection prevention and stewardship strategies.

The cost-effectiveness of blue light cystoscopy in bladder cancer detection: United States projections based on clinical data showing 4.5 years of follow up after a single hexaminolevulinate hydrochloride instillation.

INTRODUCTION: Several studies, including the recently published phase III study by Stenzl and colleagues have demonstrated that hexaminolevulinate hydrochloride, when used with blue light fluorescence cystoscopy, improves detection of non-muscle invasive bladder tumors compared to white light cystoscopy and transurethral resection of bladder tumors (TURB) alone. MATERIALS AND METHODS: The objective of this study was to conduct a detailed assessment of the cost-effectiveness of using hexaminolevulinate hydrochloride with blue light cystoscopy as an adjunct to white light versus white light cystoscopy alone at time of initial TURB in the United States. A probabilistic decision tree model, using TreeAge Pro 2011 software, was developed using base case scenario cost and utility estimates. RESULTS: Incorporation of hexaminolevulinate hydrochloride into diagnostic cystoscopy results in lower costs over 5 years ($25,921) as compared to those patients who initially receive white light cystoscopy ($30,581). Those patients who initially receive hexaminolevulinate hydrochloride blue light TURB also experience a lower overall cancer burden. CONCLUSIONS: Hexaminolevulinate hydrochloride may be cost effective when used at first TURB for patients with suspected new or recurrent non-muscle invasive bladder cancer.

An economic assessment model for in-center, conventional home, and more frequent home hemodialysis.

More intensive and/or frequent hemodialysis may provide clinical benefits to patients with end-stage renal disease; however, these dialysis treatments are more convenient to the patients if provided in their homes. Here we created a standardized model, based on a systematic review of available costing literature, to determine the economic viability of providing hemodialysis in the home that arrays costs and common approaches for assessing direct medical and nonmedical costs. Our model was based on data from Australia, Canada, and the United Kingdom. The first year start-up costs for all hemodialysis modalities were higher than in subsequent years with modeled costs for conventional home hemodialysis lower than in-center hemodialysis in subsequent years. Modeled costs for frequent home hemodialysis was higher than both in-center and conventional home hemodialysis in the United Kingdom, but lower than in-center hemodialysis and higher than conventional home hemodialysis in Australia and Canada in subsequent years. The higher costs of frequent compared to conventional home hemodialysis were because of higher consumable usage due to dialysis frequency. Thus, our findings reinforce the conclusions of previous studies showing that home-based conventional and more frequent hemodialysis may provide clinical benefit at reasonable costs.