Rituximab or cyclosporine a for the treatment of membranous nephropathy: Economic evaluation of the MENTOR trial.

BACKGROUND AND HYPOTHESIS: The MENTOR trial (MEmbranous Nephropathy Trial Of Rituximab) showed that rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria and was superior in maintaining proteinuria remission. However, the cost of rituximab may prohibit first-line use for some patients and health care payers. METHODS: A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of rituximab compared with cyclosporine for the treatment membranous nephropathy from the perspective of a health care payer with a life-time time horizon. The model was informed by data from the MENTOR trial where possible; additional parameters including cost and utility inputs were obtained from the literature. Sensitivity analyses were performed to evaluate the impact of reduced cost biosimilar rituximab. RESULTS: Rituximab for the treatment of membranous nephropathy was cost-effective (assuming a willingness-to-pay threshold of ${\$}$50 000 per quality adjusted life year (QALY) gained; ${\$}$US 2021) compared with cyclosporine, with an ICER of ${\$}$8 373/QALY over a lifetime time horizon. The incremental cost of rituximab therapy was ${\$}$28 007 with an additional 3.34 QALYs compared with cyclosporine. Lower cost of rituximab biosimilars resulted in a more favourable ICER, and in some cases resulted in rituximab being dominant (lower cost and great benefit) compared to cyclosporine. CONCLUSIONS: Despite the greater cost of rituximab, it may be a cost-effective option for the treatment of membranous nephropathy when compared with cyclosporine. The cost-effectiveness of rituximab is further improved with the use of less expensive biosimilars.

Health resource utilization and cost before versus after initiation of second-generation long-acting injectable antipsychotics among adults with schizophrenia in Alberta, Canada: a retrospective, observational single-arm study.

BACKGROUND: Long-acting injectable (LAI) antipsychotics, along with community treatment orders (CTOs), are used to improve treatment effectiveness through adherence among individuals with schizophrenia. Understanding real-world medication adherence, and healthcare resource utilization (HRU) and costs in individuals with schizophrenia overall and by CTO status before and after second generation antipsychotic (SGA)-LAI initiation may guide strategies to optimize treatment among those with schizophrenia. METHODS: This retrospective observational single-arm study utilized administrative health data from Alberta, Canada. Adults (≥ 18 years) with schizophrenia who initiated a SGA-LAI (no use in the previous 2-years) between April 1, 2014 and March 31, 2016, and had ≥ 1 additional dispensation of a SGA-LAI were included; index date was the date of SGA-LAI initiation. Medication possession ratio (MPR) was determined, and paired t-tests were used to examine mean differences in all-cause and mental health-related HRU and costs (Canadian dollars), comprised of hospitalizations, physician visits, emergency department visits, and total visits, over the 2-year post-index and 2-year pre-index periods. Analyses were stratified by presence or absence of an active CTO during the pre-index and/or post-index periods. RESULTS: Among 1,211 adults with schizophrenia who initiated SGA-LAIs, 64% were males with a mean age of 38 (standard deviation [SD] 14) years. The mean overall antipsychotic MPR was 0.39 (95% confidence interval [CI] 0.36, 0.41) greater during the 2-year post-index period (0.84 [SD 0.26]) compared with the 2-year pre-index period (0.45 [SD 0.40]). All-cause and mental health-related HRU and costs were lower post-index versus pre-index (p < 0.001) for hospitalizations, physician visits, emergency department visits, and total visits; mean total all-cause HRU costs were $33,788 (95% CI -$38,993, -$28,583) lower post- versus pre-index ($40,343 [SD $68,887] versus $74,131 [SD $75,941]), and total mental health-related HRU costs were $34,198 (95%CI -$39,098, -$29,297) lower post- versus pre-index ($34,205 [SD $63,428] versus $68,403 [SD $72,088]) per-patient. Forty-three percent had ≥ 1 active CTO during the study period; HRU and costs varied according to CTO status. CONCLUSIONS: SGA-LAIs are associated with greater medication adherence, and lower HRU and costs however the latter vary according to CTO status.

Age, multimorbidity and dementia with health care costs in older people in Alberta: a population-based retrospective cohort study.

BACKGROUND: The growing burden associated with population aging, dementia and multimorbidity poses potential challenges for the sustainability of health systems worldwide. We sought to examine how the intersection among age, dementia and greater multimorbidity is associated with health care costs. METHODS: We did a retrospective population-based cohort study in Alberta, Canada, with adults aged 65 years and older between April 2003 and March 2017. We identified 31 morbidities using algorithms (30 algorithms were validated), which were applied to administrative health data, and assessed costs associated with hospital admission, provider billing, ambulatory care, medications and long-term care (LTC). Actual costs were used for provider billing and medications; estimated costs for inpatient and ambulatory patients were based on the Canadian Institute for Health Information's resource intensive weights and Alberta's cost of a standard hospital stay. Costs for LTC were based on an estimated average daily cost. RESULTS: There were 827 947 people in the cohort. Dementia was associated with higher mean annual total costs and individual mean component costs for almost all age categories and number of comorbidities categories (differences in total costs ranged from $27 598 to $54 171). Similarly, increasing number of morbidities was associated with higher mean total costs and component costs (differences in total costs ranged from $4597 to $10 655 per morbidity). Increasing age was associated with higher total costs for people with and without dementia, driven by increasing LTC costs (differences in LTC costs ranged from $115 to $9304 per age category). However, there were no consistent trends between age and non-LTC costs among people with dementia. When costs attributable to LTC were excluded, older age tended to be associated with lower costs among people with dementia (differences in non-LTC costs ranged from -$857 to -$7365 per age category). INTERPRETATION: Multimorbidity, older age and dementia were all associated with increased use of LTC and thus health care costs, but some costs among people with dementia decreased at older ages. These findings illustrate the complexity of projecting the economic consequences of the aging population, which must account for the interplay between multimorbidity and dementia.

Cost-Utility of Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure: An Economic Evaluation.

Background Recent trials comparing catheter ablation to medical therapy in patients with heart failure (HF) with symptomatic atrial fibrillation despite first-line management have demonstrated a reduction in adverse outcomes. We performed an economic evaluation to estimate the cost-utility of catheter ablation as second line therapy in patients with HF with reduced ejection fraction. Methods and Results A Markov model with health states of alive, dead, and alive with amiodarone toxicity was constructed, using the perspective of the Canadian healthcare payer. Patients in the alive states were at risk of HF and non-HF hospitalizations. Parameters were obtained from randomized trials and Alberta health system data for costs and outcomes. A lifetime time horizon was adopted, with discounting at 3.0% annually. Probabilistic and 1-way sensitivity analyses were performed. Costs are reported in 2018 Canadian dollars. A patient treated with catheter ablation experienced lifetime costs of $64 960 and 5.63 quality-adjusted life-years (QALY), compared with $49 865 and 5.18 QALYs for medical treatment. The incremental cost-effectiveness ratio was $35 360/QALY (95% CI, $21 518-77 419), with a 90% chance of being cost-effective at a willingness-to-pay threshold of $50 000/QALY. A minimum mortality reduction of 28%, or a minimum duration of benefit of >1 to 2 years was required for catheter ablation to be attractive at this threshold. Conclusions Catheter ablation is likely to be cost-effective as a second line intervention for patients with HF with symptomatic atrial fibrillation, with incremental cost-effectiveness ratio $35 360/QALY, as long as over half of the relative mortality benefit observed in extant trials is borne out in future studies.

The real-world cost-effectiveness of bariatric surgery for the treatment of severe obesity: a cost-utility analysis.

BACKGROUND: Severe obesity is associated with adverse health outcomes and increased risk of death. This study evaluates the real-world cost-utility of therapy for severe obesity, from the publicly funded health care system and societal perspectives. METHODS: We conducted a cost-utility analysis using primary data from a prospective observational cohort of adults living with severe obesity (BMI ≥ 35 kg/m2 and a major medical comorbidity or BMI ≥ 40 kg/m2) who were enrolled in a regional obesity program over 2 years. We extrapolated 10-year and lifetime Markov models, validated and supplemented with literature sources, to compare medical, surgical and standard care therapies. We performed deterministic and probabilistic sensitivity analyses. RESULTS: The cohort included 500 adults living with severe obesity, 150 of whom received laparoscopic surgical therapy. From a publicly funded health system perspective, at 2 years, surgical therapy had an incremental cost-effectiveness ratio (ICER) of $54 456 per quality-adjusted life-year (QALY) compared with standard care therapy. Over a lifetime, it had an ICER of $14 056 per QALY. From the societal perspective, at 2 years, surgical therapy had an ICER of $340 per QALY; over a lifetime, it was the dominant option. The results were robust to sensitivity analysis. INTERPRETATION: From a public health care perspective, surgery for severe obesity is cost effective, and when approached from a societal perspective, it becomes cost saving. Real-world data support using surgical therapy for severe obesity, and our results contribute to the health economic and clinical literature with regard to a robust analysis from a societal perspective.

Burden of noninfluenza respiratory viral infections in adults admitted to hospital: analysis of a multiyear Canadian surveillance cohort from 2 centres.

BACKGROUND: Data on the outcomes of noninfluenza respiratory virus (NIRV) infections among hospitalized adults are lacking. We aimed to study the burden, severity and outcomes of NIRV infections in this population. METHODS: We analyzed pooled patient data from 2 hospital-based respiratory virus surveillance cohorts in 2 regions of Canada during 3 consecutive seasons (2015/16, 2016/17, 2017/18; n = 2119). We included patients aged ≥ 18 years who developed influenza-like illness or pneumonia and were hospitalized for management. We included patients confirmed positive for ≥ 1 virus by multiplex polymerase chain reaction assays (respiratory syncytial virus [RSV], human rhinovirus/enterovirus (hRV), human coronavirus (hCoV), metapneumovirus, parainfluenza virus, adenovirus, influenza viruses). We compared patient characteristics, clinical severity conventional outcomes (e.g., hospital length-of stay, 30-day mortality) and ordinal outcomes (5 levels: discharged, receiving convalescent care, acute ward or intensive care unit [ICU] care and death) for patients with NIRV infections and those with influenza. RESULTS: Among 2119 adults who were admitted to hospital, 1156 patients (54.6%) had NIRV infections (hRV 14.9%, RSV 12.9%, hCoV 8.2%) and 963 patients (45.4%) had influenza (n = 963). Patients with NIRVs were younger (mean 66.4 [standard deviation 20.4] yr), and more commonly had immunocompromising conditions (30.3%) and delay in diagnosis (median 4.0 [interquartile range (IQR) 2.0-7.0] days). Overall, 14.6% (12.4%-19.5%) of NIRV infections were acquired in hospital. Admission to ICU (18.2%, median 6.0 [IQR 3.0-13.0] d), hospital length-of-stay (median 5.0 [IQR 2.0-10.0] d) and 30-day mortality (8.4%; RSV 9.5%, hRV 6.6%, hCoV 9.2%) and the ordinal outcomes were similar for patients with NIRV infection and those with influenza. Age > 60 years, immunocompromised state and hospital-acquired viral infection were associated with worse outcomes. The estimated median cost per acute care admission was $6000 (IQR $2000-$16 000). INTERPRETATION: The burden of NIRV infection is substantial in adults admitted to hospital and associated outcomes may be as severe as for influenza, suggesting a need to prioritize therapeutics and vaccines for at-risk people.

The Cost of Care for People With Chronic Kidney Disease.

BACKGROUND: As the adverse clinical outcomes common in patients with chronic kidney disease (CKD) can be prevented or delayed, information on the cost of care across the spectrum of CKD can inform investments in CKD care. OBJECTIVES: To determine the cost of caring for patients with CKD who are not on dialysis or transplant at baseline. DESIGN: Population-based cohort study using administrative health data. SETTING: Alberta, Canada. PATIENTS: Cohort of 219 641 adults with CKD categorized by estimated glomerular filtration rate (eGFR) between April 1, 2012, and March 31, 2014, into Kidney Disease: Improving Global Outcomes (KDIGO) CKD categories, excluding patients on dialysis or transplant at baseline. MEASUREMENTS: The primary outcome was 1-year cumulative unadjusted health care costs, including the cost of drugs, physician visits, emergency department visits, outpatient procedures (including dialysis and other day medicine and surgery procedures), and hospitalizations for the year following each patient's index date. METHODS: Mean 1-year direct medical costs were estimated for the cohort as a whole and for patients in the different KDIGO CKD categories as defined at baseline. Costs were further categorized according to baseline demographic and clinical characteristics, and by type of care (ie, kidney care and cardiovascular care). RESULTS: In 219 641 adults with CKD, the mean unadjusted cumulative 1-year cost of care was Can$14 634 per patient (median = Can$3672; Q1 = Can$1496, Q3 = Can$10 221). Costs were higher for those with more comorbidity, those with lower eGFR, and those with more severe albuminuria. The cost of kidney and cardiovascular care was Can$230 (1.6% of total costs) and Can$720 (4.9% of total costs), respectively, for the cohort overall. These costs increased substantially for patients with lower eGFR, averaging Can$14 169 (32.3% of total costs) and Can$2395 (5.5% of total costs) for kidney and cardiovascular care, respectively, for people with eGFR<15 mL/min/1.73 m2 at baseline. LIMITATIONS: We only have estimates of the cost of health care for people with CKD, and not the costs borne by patients or their families. As we have not included costs for people without CKD in this analysis, we are unable to assess the incremental costs associated with CKD. CONCLUSIONS: We identified that patients with CKD, even when not on dialysis at baseline, had high health care costs (more than twice the cost per person in Canada in 2015), with a graded association between severity of CKD and costs. Our findings can inform current and future cost estimates across the spectrum of CKD, including an estimate of potential savings that might result from interventions that slow or prevent kidney disease.

CONTEXTE: Les événements cliniques indésirables qui surviennent fréquemment chez les patients atteints d'insuffisance rénale chronique (IRC) peuvent être prévenus ou retardés. Connaître le coût des soins liés à l'ensemble du spectre de la maladie pourrait éclairer les investissements en santé rénale. OBJECTIFS: Établir le coût des soins prodigués aux patients atteints d'IRC non dialysés ou transplantés au moment de l'inclusion. TYPE D'ÉTUDE: Une étude de cohorte représentative de la population réalisée à partir des données administratives en santé. CADRE: Alberta, Canada. SUJETS: Une cohorte de 219 641 adultes atteints d'IRC qui ont été classés entre le 1er avril 2012 et le 31 mars 2014 dans les catégories du KDIGO selon leur DFGe. Les patients dialysés ou transplantés ont été exclus. MESURES: Le résultat principal était le coût cumulatif non ajusté des soins de santé sur un an. Pour l'année suivant la date indice de chaque patient, le total incluait les coûts des médicaments, des consultations médicales, des visites aux urgences, des procédures ambulatoires (dialyse et différentes procédures de chirurgie et de médecine d'un jour) et des hospitalisations. MÉTHODOLOGIE: La moyenne des coûts médicaux directs sur un an a été estimée à l'inclusion pour l'ensemble de la cohorte et pour chaque catégorie d'IRC du KDIGO. Les coûts ont également été classés selon les caractéristiques démographiques et cliniques des patients à l'inclusion, et par types de soins (soins en néphrologie et en cardiologie). RÉSULTATS: Dans la cohorte étudiée, la moyenne des coûts cumulatifs non ajustés sur un an s'établissait à 14 634 $ CA par patient (médiane: 3 672 $; Q1: 1 496 $ et Q3: 10 221 $), et davantage pour les patients présentant des comorbidités, un faible DFGe ou une grave albuminurie. Les coûts des soins en santé rénale et cardiovasculaire pour l'ensemble de la cohorte s'élevaient respectivement à 230 $ (1,6 % du montant total) et 720 $ (4,9 % du montant total) par personne. Ces coûts augmentaient considérablement pour les patients présentant un faible DFGe (<15 ml/min/1,73 m2) à l'inclusion, soit en moyenne 14 169 $ (32,3 % du montant total) en santé rénale et 2 395 $ (5,5 % du montant total) en santé cardiovasculaire. LIMITES: L'estimation ne tient compte que du coût des soins prodigués aux patients, et non des coûts assumés par les patients ou leurs proches. L'analyse n'incluant pas les montants pour les patients non atteints d'IRC, nous n'avons pas été en mesure d'évaluer les coûts différentiels associés à la maladie. CONCLUSION: Nous avons constaté que les patients atteints d'IRC, même s'ils n'étaient pas dialysés à l'inclusion, engendraient des coûts de santé plus élevés (plus de deux fois le coût par personne au Canada en 2015) avec une association graduelle de ceux-ci à la gravité de l'IRC. Nos résultats peuvent orienter les évaluations de coût actuelles et futures pour l'ensemble du spectre de l'IRC, notamment l'estimation des économies potentielles qui pourraient résulter d'interventions visant la prévention de l'insuffisance rénale ou le ralentissement de son évolution.

Cost-effectiveness of home blood pressure telemonitoring and case management in the secondary prevention of cerebrovascular disease in Canada.

Home blood pressure (BP) telemonitoring and pharmacist case management reduce BP, but cost-effectiveness assessments are mixed. We examined the incremental cost-effectiveness of this intervention vs usual care in Canadians with cerebrovascular disease. A Markov decision model cost-utility analysis examining community-residing, high-risk patients with a recent nondisabling cerebrovascular event was created. A lifetime time horizon and health care payer perspective were used. Achieved BP, future cardiovascular risks, and attendant consequences on quality-adjusted life years and Canadian dollar costs were modeled. BP telemonitoring was assumed to occur for 3 months, then quarterly. Life tables were used to determine overall mortality, adjusted by cardiovascular disease mortality. Relative efficacies of intervention-associated BP lowering, resource use, and costs were obtained from Canadian published literature. Reduction in systolic BP of 9.7 mmHg was used in the base case; subsequently, robust sensitivity analyses were conducted. The results showed that, over the lifetime horizon, telemonitoring with case management led to net health care savings of $1929 Canadian and increased per-patient QALYs by 0.83. These findings were robust to sensitivity analysis, with the intervention remaining dominant or highly cost-effective. Increasing telemonitoring costs by 50% still resulted in the intervention being dominant; if the costs of telemonitoring plus case management were 2-3 times base case cost, incremental cost-effectiveness was $1200-$4700 per quality-adjusted life year gained. In conclusion, home BP telemonitoring and pharmacist case management poststroke lowered costs and improved QALYs. Strategies and funding for broad implementation of this dominant strategy should be implemented.

Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S. pneumoniae.

Pneumonia remains the single leading cause of childhood death worldwide. Despite the commercial availability of multiple pneumococcal conjugate vaccines (PCVs), high dosage cost and supply shortages prevent PCV delivery to much of the developing world. The current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine development. The 13-valent pneumococcal conjugate vaccine (PCV-13) investigated in this research incorporated serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Pneumococcal polysaccharides (PnPSs) and CRM197 carrier protein were produced and purified in-house, and used to prepare PnPS-CRM conjugates using unique, cyanide-free, in vacuo glycation conjugation methods. In vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free protein. In vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13, Prevnar®13 (Pfizer, USA). A boost dose was provided to all groups post-dose 1 at t = 14 days. Post-dose 2 results at t = 28 days showed that all 13 serotypes in PnuVax's PCV-13 were boostable. Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes, with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose 2. As a result, the novel polysaccharide-protein conjugates developed in this work are highly promising for use in human PCV development. The in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.

Economic evaluation of frequent home nocturnal hemodialysis based on a randomized controlled trial.

Provider and patient enthusiasm for frequent home nocturnal hemodialysis (FHNHD) has been renewed; however, the cost-effectiveness of this technique is unknown. We performed a cost-utility analysis of FHNHD compared with conventional hemodialysis (CvHD; 4 hours three times per week) from a health payer perspective over a lifetime horizon using patient information from the Alberta NHD randomized controlled trial. Costs, including training costs, were obtained using microcosting and administrative data (CAN$2012). We determined the incremental cost per quality-adjusted life year (QALY) gained. Robustness was assessed using scenario, sensitivity, and probabilistic sensitivity analyses. Compared with CvHD (61% in-center, 14% satellite, and 25% home dialysis), FHNHD led to incremental cost savings (-$6700) and an additional 0.38 QALYs. In sensitivity analyses, when the annual probability of technique failure with FHNHD increased from 7.6% (reference case) to ≥19%, FHNHD became unattractive (>$75,000/QALY). The cost/QALY gained became $13,000 if average training time for FHNHD increased from 3.7 to 6 weeks. In scenarios with alternate comparator modalities, FHNHD remained dominant compared with in-center CvHD; cost/QALYs gained were $18,500, $198,000, and $423,000 compared with satellite CvHD, home CvHD, and peritoneal dialysis, respectively. In summary, FHNHD is attractive compared with in-center CvHD in this cohort. However, the attractiveness of FHNHD varies by technique failure rate, training time, and dialysis modalities from which patients are drawn, and these variables should be considered when establishing FHNHD programs.

Surface-active copolymer formation stabilizes PEG droplets and bubbles in silicone foams.

Large increases in viscosity are not normally observed when insoluble liquid polymers are mixed in the absence of a compatibilizing agent: the liquids separate into bulk phases. Mixing propyl- or allyl-modified oligo(ethylene glycol)(PEG), but not the parent hydroxy-terminated oligo(ethylene glycol), with silicone pre-elastomers led a sharp increase in viscosity that preceded the onset of cure. Only in the case of allyl-modified PEG, however, did a low density, closed cell silicone foam form that, in addition to trapped bubbles, contained dispersed PEG droplets. Rheological studies demonstrate that the origins of the viscosity build lie in the formation, shortly after mixing, of organo-PEG stabilized droplets that act as fillers within the silicone pre-elastomers. Similar viscosity builds were not observed with hydroxy-terminated oligo(ethylene glycol). Although the propyl-modified PEG led initially to large viscosity increases, its ability to stabilize bubbles was comparably limited. The surface activity of the propyl- and allyl-PEG compounds themselves facilitates the formation of a colloidal dispersion within the silicone. However, the key to the observed foamed product is the in situ platinum-catalyzed hydrosilylation of the allyl group, prior to or concomitant with silicone cure, leading to PEG-silicone copolymers that are able to stabilize both dispersed PEG droplets and bubbles.