Early versus delayed initiation of renal replacement therapy in cardiac-surgery associated acute kidney injury: an economic perspective.

BACKGROUND: Timing for renal replacement therapy (RRT) initiation for cardiac-surgery associated acute kidney surgery (CSA-AKI) is subject to debate. Evidence suggests earlier initiation leads to shorter length of stay (LoS). We investigated differences in healthcare costs associated with timing of RRT initiation in CSA-AKI. METHODS: A cost-consequences model compared costs of Early (<24 h) vs. Delayed (>24 h) RRT initiation. Data were from the ELAIN trial in Germany, and the HiDenIC database, a US multi-hospital database. Resource utilization was determined by RRT duration, ICU, and hospital LoS. All resources were costed from a US healthcare perspective. Extensive sensitivity analyses (SA) were conducted, notably regarding the proportion of patients not initiated on RRT with the Delayed strategy. RESULTS: Early RRT initiation exhibited cost savings compared to Delayed RRT initiation. With ELAIN data, savings reached -$122,188 (ranging from -$157,707 to -$74,763 in the SA). Findings were confirmed with HiDenIC data; Early RRT initiation showed savings of -$77,303 (ranging from -$108,971 to -$47,012 in the SA). CONCLUSIONS: Our costing model indicates that Early RRT initiation for CSA-AKI may result in appreciable cost savings. Delaying RRT, in the setting of CSA-AKI, may lead to longer LoS and increased healthcare costs.

The health economics burden of sarcopenia: a systematic review.

Despite of better knowledge about sarcopenia, an optimal understanding of its consequences from a public health perspective remains a challenge. Specifically, the economic burden of the illness is unclear. As a support for the public health policy makers and other health actors, our objective was to perform a systematic review of the literature comparing healthcare costs between sarcopenic and non-sarcopenic patients (under the registration number CRD42018099291). A search for relevant articles was conducted on the Medline and Scopus databases. Rigorous eligibility criteria were established (e.g., subjects with sarcopenia, both men and women, mean age of the sarcopenic population) and applied by two investigators to identify suitable studies. The first screening phase, performed by 2 independent reviewers, covered 455 references. Fourteen relevant studies were included in the final analysis. Overall, we noted an important heterogeneity between studies in the way of assessing sarcopenia (i.e. operational definitions, tools and cut-offs used). There were also large variations between studies in their cost analysis settings (i.e., discrepancies in time horizon, types and sources of economic data). Most of the studies focused on hospitalization costs following surgery for a specific disease such as cancer. Finally, 11 out of the 14 studies reported higher healthcare costs for sarcopenic patients. However, most of the included studies have important methodological bias (e.g. potential confusion factors rarely taken into account), and low to moderate quality scores. More standardized research, taking into account all the limitations of the published studies, should be conducted to assess the true impact of sarcopenia on healthcare consumption.

Hepatitis C in Lebanon: the burden of the disease and the value of comprehensive screening and treatment.

PURPOSE: To analyze the hepatitis C virus (HCV) burden in Lebanon and the value of comprehensive screening and treatment for different age groups and fibrosis stages. METHODS: We used a multicohort, health-state-transition model to project the number of HCV genotype 1 and 4 patients achieving a sustained virologic response 12 weeks after treatment or progressing to compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver-related death (LrD) from 2016 to 2036. In the low/medium/high screening scenarios, the proportion of patients screened for HCV was projected to increase to 60%/85%/99%, respectively, by 2036. We analyzed four treatment strategies: 1) no treatment, 2) all-oral direct-acting antivirals (DAAs) given to F3-F4 (CC) patients only, 3) all-oral DAAs to F2-F3-F4 (CC) patients, and 4) all-oral DAAs to all fibrosis patients. RESULTS: Low, medium, and high HCV screening scenarios projected that 3,838, 5,665, and 7,669 individuals will be diagnosed with HCV infection, respectively, from 2016 to 2036, or 40% of those aged 18-39 years, and 60% of those aged 40-80 years. With no treatment, the projected number of patients reaching CC, DCC, HCC, or LrD in 2036 was 899, 147, 131, and 147, respectively, for the 18-39 years age group. For the 40-80 years age group, these projections were substantially greater: 2,828 CC, 736 DCC, 668 HCC, and 958 LrD. The overall economic burden without treatment reached 150 million EUR. However, introducing DAAs for F0-F4 patients was projected to increase the proportion of remaining life-years spent in sustained virologic response 12 weeks after treatment by 43% and 62% compared to DAAs given at F2-F4 or F3-F4 only, respectively. CONCLUSION: An enhanced screening policy combined with broader access to DAAs can diminish the future clinical and economic burden of HCV in the Lebanese population and, for the middle-aged and elderly, provide the greatest health benefit with net cost savings.

Hepatitis C in Lebanon: burden of the disease and value of comprehensive screening and treatment.

INTRODUCTION: As few reliable data on the burden of hepatitis C virus (HCV) are available from the Middle East, we analyzed HCV burden in the Lebanese population and the value of comprehensive screening and treatment at different age groups and fibrosis stages. METHODOLOGY: A multi-cohort, health-state-transition model was developed to project the number of HCV patients achieving a sustained virologic response 12 weeks after treatment (SVR12) or progressing to compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), and liver-related death (LrD) from 2016 to 2036. Epidemiology and mortality data were extracted from the Ministry of Health bulletin while costs were collected from insurance claims. The proportion of patients screened for HCV was projected to increase to 60%/85%/99% (low/medium/high screening scenarios) in 2036, with a new cohort being diagnosed each year. SVR12 rates were extracted from clinical trials. Separate models were used for 18-39 and 40- 80 age groups to account for different prevalence and screening rates. RESULTS: Low, medium and high HCV screening scenarios showed that 3,838, 5,665 and 7,669 individuals would be diagnosed with HCV infection from 2016 to 2036, 40% aged 18-39 and 60% aged 40-80. In the absence of treatment, the projected number of patients reaching CC, DCC, HCC and LrD in 2036 was 899, 147, 131 and 147 respectively for the 18-39 age groups. In the 40-80 age groups, these projections were substantially greater: 2,828 CC, 736 DCC, 668 HCC and 958 LrD. The overall economic burden of these complications would reach 150 million €. However, introducing direct-acting antivirals (DAAs) for F0-F4 patients would increase by 43% and 62% the proportion of remaining life-years (LYs) spent in SVR12 compared to DAAs given to F2-F4 or to F3-F4 only, respectively. Although DAAs for F0-F4 increase the cost of HCV treatment, they also provide the greatest health benefit and lowest cost per LY gained in SVR12. Compared to no treatment and screening, adopting the high screening variant and DAAs access to F0-F4 would cost an additional 1,957 € for every LY gained in SVR12 for patients aged 18-39 and -168 € for the 40-80 age group. CONCLUSION: An enhanced screening policy coupled with broader access to DAAs will diminish the future burden of HCV in the Lebanese population and provide the greatest health benefits among middle-aged and elder adults with net cost savings.

Public health impact of comprehensive hepatitis C screening and treatment in the French baby-boomer population.

OBJECTIVE: To estimate the public health impact of comprehensive hepatitis C virus (HCV) screening and access to all-oral, interferon (IFN)-free direct-acting antivirals (DAAs) in the French baby-boomer population (1945-1965 birth cohorts). METHODS: A sequential, multi-cohort, health-state transition model was developed to assess the impact of different hepatitis C screening and treatment strategies on clinical and economic outcomes in the 1945-1965 birth cohorts. Patients newly-diagnosed with chronic HCV were projected each year from 2016 to 2036 under three screening scenarios (70% [low], 75% [intermediate], and 80% [high] HCV awareness in 2036). Healthcare costs and clinical outcomes (number of liver-related deaths, quality-adjusted life-years [QALYs], life-years [LYs] spent in sustained virologic response [SVR] or with decompensated cirrhosis, hepatocellular carcinoma, or liver transplant) were compared among five treatment strategies (no antiviral therapy; IFN + ribavirin + protease inhibitor for fibrosis stages F2-F4, IFN-based DAAs for stages F2-F4, IFN-free DAAs for stages F2-F4, and IFN-free DAAs for stages F0-F4). RESULTS: Diagnosis of HCV genotype 1 was projected for 4,953, 6,600, and 8,368 individuals in the low, intermediate, and high screening scenarios, respectively. In the intermediate scenario, IFN-free DAAs for stages F0-F4 had a favorable cost-effectiveness profile vs IFN-based or IFN-free treatment strategies for F2-F4 and offered the greatest return on investment (0.899 LYs gained in SVR and 0.933 QALYs per €10,000 invested). CONCLUSION: Comprehensive HCV screening and access to all-oral, IFN-free DAAs is a cost-effective strategy that could help diminish the upcoming burden of HCV in the French baby-boomer population.

What do we know about the safety of corticosteroids in rheumatoid arthritis?

BACKGROUND: Clear information is still lacking on the safety of corticosteroids (GCs) therapy in RA despite six decades of clinical experience. SCOPE: We performed a literature search in Ovid MEDLINE from January 2000 to December 2012. Our Population Intervention Comparator Outcomes (PICO) strategy search was: rheumatoid arthritis [Population], corticosteroids or glucocorticoids [Intervention], any comparison [Comparator], adverse effects [Outcome]. Studies were selected if they reported any measure of association between GCs intake and potential adverse effects in RA patients. FINDINGS: We identified 1030 papers and selected for analysis 26 observational studies and six systematic reviews. The major side effects of GCs in RA are bone loss, risk of cardiovascular events and risk of infections as evidenced by large observational studies and not necessarily RCTs. Others associations were reported with herpes zoster, tuberculosis, hyperglycemia, cutaneous abnormalities, gastrointestinal perforation, respiratory infection and self-reported health problems such as cushingoid phenotype, ecchymosis, parchment-like skin, epistaxis, weight gain and sleep disturbance. Other potential adverse effects of GCs were studied but no association was found. These included psychological disorders, dermatophytosis, brain diseases, interstitial lung disease, memory deficit, metabolic syndrome, lymphoma, non-Hodgkin's lymphoma, renal function and cerebrovascular accidents. Most of the evidence emanates from observational researches and the inherent limitations of such data should be kept in mind. CONCLUSION: Recent observational data and systematic reviews suggest that GCs can lead to relatively alarming and burdensome side effects in RA. This is particularly true for patients who have longer term and higher dose therapies. GCs are largely used in RA and knowing their safety profile is essential to improve patients care. The design of new therapeutic strategies intended to minimize the daily dosing of GCs while conserving their beneficial effect should be encouraged.

Potential clinical and economic impact of nonadherence with osteoporosis medications.

This study aims to estimate the potential clinical and economic implications of therapeutic adherence to bisphosphonate therapy. A validated Markov microsimulation model was used to estimate the impact of varying adherence to bisphosphonate therapy on outcomes (the number of fractures and the quality-adjusted life-years [QALYs]), health-care costs, and the cost-effectiveness of therapy compared with no treatment. Adherence was divided into persistence and compliance, and multiple scenarios were considered for both concepts. Analyses were performed for women aged 65 years with a bone mineral density T-score of -2.5. Health outcomes and the cost-effectiveness of therapy improved significantly with increasing compliance and/or persistence. In the case of real-world persistence and with a medical possession ratio (MPR; i.e., the number of doses taken divided by the number of doses prescribed) of 100%, the QALY gain and the number of fractures prevented represented only 48 and 42% of the values estimated assuming full persistence, respectively. These proportions fell to 27 and 23% with an MPR value of 80%. The costs per QALY gained, for branded bisphosphonates (and generic alendronate), were estimated at 19,069 euros (4,871 euros), 32,278 euros (11,985 euros), and 64,052 euros (30,181 euros) for MPR values of 100, 80, and 60%, respectively, assuming real-world persistence. These values were 16,997 euros (2,215 euros), 24,401 euros (6,179 eruos), and 51,750 euros (20,569 euros), respectively, assuming full persistence. In conclusion, poor compliance and failure to persist with osteoporosis medications results not only in deteriorating health outcomes, but also in a decreased cost-effectiveness of drug therapy. Adherence therefore remains an important challenge for health-care professionals treating osteoporosis.

Cost-effectiveness of osteoporosis screening followed by treatment: the impact of medication adherence.

OBJECTIVE: To estimate the impact of medication adherence on the cost-effectiveness of mass-screening by bone densitometry followed by alendronate therapy for women diagnosed with osteoporosis. METHODS: A validated Markov microsimulation model with a Belgian health-care payer perspective and a lifetime horizon was used to assess the cost per quality-adjusted life year (QALY) gained of the screening/treatment strategy compared with no intervention. Real-world adherence to alendronate therapy and full adherence over 5 years were both investigated. The real-world adherence scenario employed adherence data from published observational studies, and medication adherence was divided into persistence, compliance, and primary adherence. Uncertainty was investigated using one-way and probabilistic sensitivity analyses. RESULTS: At 65 years of age, the costs per QALY gained because of the screening/treatment strategy versus no intervention are euro32,008 and euro16,918 in the real-world adherence and full adherence scenarios, respectively. The equivalent values are euro80,836 and euro40,462 at the age of 55 years, and they decrease to euro10,600 and euro1229 at the age of 75 years. Sensitivity analyses show that the presence of the upfront cost of case finding has a substantial role in the impact of medication adherence on cost-effectiveness. CONCLUSION: This study indicates that nonadherence with osteoporosis medications substantially increases the incremental cost-effectiveness ratio of osteoporosis screening strategies. All aspects of medication adherence (i.e., compliance, persistence, and primary adherence) should therefore be reported and included in pharmacoeconomic analyses, and especially in the presence of the upfront cost of case finding (such as screening cost).

Primary prevention of osteoporosis: mass screening scenario or prescreening with questionnaires? An economic perspective.

UNLABELLED: This study focuses on the controversy surrounding selective approaches to screen for osteoporosis. Seven screening approaches were compared in terms of cost-effectiveness and incremental cost-effectiveness ratios in a sample of 4035 postmenopausal women. Our results show that certain prescreening strategies are more efficient than DXA-based approaches. These results are of considerable value for health policy decision-makers and the scientific community. INTRODUCTION: There is no general consensus on the most efficient strategy to use bone densitometry for osteoporosis screening. Two distinct approaches have progressively emerged: mass screening using DXA and prescreening strategies using user-friendly risk indices. This study was designed to compare the efficiency of these approaches. MATERIALS AND METHODS: A database of 4035 medical records from postmenopausal women above 45 years was analyzed. In the first scenario, women were systematically referred to DXA if above 45, 50, or 65 years of age. The second scenario involved the validated prescreening tools SCORE, ORAI, OST, and OSIRIS and assessed two separate ways of handling their results (theoretical and pragmatic). The cost of a DXA test was set as the median Belgian value: 40.14 Euros. All strategies were compared in terms of cost exposed per osteoporotic patient detected and in terms of incremental cost-effectiveness ratios. RESULTS: In the systematic DXA strategies, the cost per patient detected ranged from 123 Euros when measuring all women >45 years of age to 91 Euros when focusing on women >65 years of age. The corresponding percentage of cases detected ranged from 100% (age > 45 years) to 50% (age > 65 years). When considering prescreening under the theoretical and pragmatic scenarios, the OSIRIS index provided the best efficiency, with costs of 74 Euros (theoretical) to 85 Euros (pragmatic) per case detected, followed by ORAI (75 Euros and 96 Euros), OST (84 Euros and 94 Euros), and SCORE (96 Euros and 103 Euros). The corresponding percentage of cases detected ranged from 89% (SCORE) to 75% (OSIRIS). The cost-effectiveness analysis showed that mass screening strategies over 50 and 65 years of age and using ORAI were best. CONCLUSIONS: Our study sets the grounds for considering, in a health economics perspective, prescreening tools as valuable, cost-effective, approaches to significantly reduce the economic burden of osteoporosis screening.

Health-related quality of life in total hip and total knee arthroplasty. A qualitative and systematic review of the literature.

BACKGROUND: Total hip and total knee arthroplasties are well accepted as reliable and suitable surgical procedures to return patients to function. Health-related quality-of-life instruments have been used to document outcomes in order to optimize the allocation of resources. The objective of this study was to review the literature regarding the outcomes of total hip and knee arthroplasties as evaluated by health-related quality-of-life instruments. METHODS: The Medline and EMBASE medical literature databases were searched, from January 1980 to June 2003, to identify relevant studies. Studies were eligible for review if they met the following criteria: (1). the language was English or French, (2). at least one well-validated and self-reported health-related quality of life instrument was used, and (3). a prospective cohort study design was used. RESULTS: Of the seventy-four studies selected for the review, thirty-two investigated both total hip and total knee arthroplasties, twenty-six focused on total hip arthroplasty, and sixteen focused on total knee arthroplasty exclusively. The most common diagnosis was osteoarthritis. The duration of follow-up ranged from seven days to seven years, with the majority of studies describing results at six to twelve months. The Short Form-36 and the Western Ontario and McMaster University Osteoarthritis Index, the most frequently used instruments, were employed in forty and twenty-eight studies, respectively. Seventeen studies used a utility index. Overall, total hip and total knee arthroplasties were found to be quite effective in terms of improvement in health-related quality-of-life dimensions, with the occasional exception of the social dimension. Age was not found to be an obstacle to effective surgery, and men seemed to benefit more from the intervention than did women. When improvement was found to be modest, the role of comorbidities was highlighted. Total hip arthroplasty appears to return patients to function to a greater extent than do knee procedures, and primary surgery offers greater improvement than does revision. Patients who had poorer preoperative health-related quality of life were more likely to experience greater improvement. CONCLUSIONS: Health-related quality-of-life data are valuable, can provide relevant health-status information to health professionals, and should be used as a rationale for the implementation of the most adequate standard of care. Additional knowledge and scientific dissemination of surgery outcomes should help to ensure better management of patients undergoing total hip or total knee arthroplasty and to optimize the use of these procedures.

Evaluation of proposals of Belgian Social Security Institute for reimbursement of bone densitometry tests. Toward a cost-effective strategy for osteoporosis screening?

BACKGROUND AND AIMS: The Belgian Social Security Institute (hereafter INAMI) proposes a list of conditions to be considered as a prerequisite for reimbursement of Bone Mineral Density (BMD) measurements. The aim of this paper was to evaluate the diagnostic accuracy of the proposed criteria for identifying osteoporosis, and to gauge how useful they are for more rational application of densitometry tests. METHODS: 3748 Caucasian women aged at least 50 years old were recruited consecutively from an outpatient university center, from the database of which all relevant data corresponding to the INAMI list of clinical factors, as well as patients' age, weight and height, were collected. BMD measurements using dual X-ray absorptiometry were reported at the spine and hip regions. Diagnostic accuracy was evaluated through measures of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Additionally, from ROC analysis, benchmark values for age and body mass index were identified and then, used alone and in combination with the INAMI test, were applied to define various screening strategies. For each of them, associated costs per osteoporotic patient detected were estimated. Cost estimates refer only to the costs associated with the densitometric procedure from the perspective of the reimbursement health authorities. RESULTS: Applying INAMI criteria for detecting osteoporosis at any of the considered sites yielded sensitivity of 68.9%, specificity of 50.7%, PPV of 42.9% and NPV of 57.3%. Comparison of incremental costs per patient of the different strategies revealed that, with 67.1 Euros, the option of opening BMD coverage to women on the basis of the INAMI conditions would be more cost-effective than mass screening (90.1 Euros) or applying the age criterion alone (70.2 Euros). However, the BMI condition seems to act as a better indicator of risk than the INAMI criteria in those meeting the age condition (35.4 Euros). CONCLUSIONS: The accuracy of the INAMI proposal turns out to be quite unsatisfactory, and did not adequately cover the population at risk of osteoporosis. From a resource allocation perspective, the best strategy by far would be to recommend using concomitantly INAMI, age and BMI-selective criteria. Some adaptations could enhance the usefulness of the INAMI proposals as a selective approach for BMD referral and reimbursement.