Comparing tweet sentiments in megacities using machine learning techniques: In the midst of COVID-19.

COVID-19 was announced by the World Health Organization as a pandemic on March 11, 2020. Not only has COVID-19 struck the economy and public health, but it also has deep influences on people's feelings. Twitter, as an active social media, is a great database where we can investigate people's sentiments during this pandemic. By conducting sentiment analysis on Tweets using advanced machine learning techniques, this study aims to investigate how public sentiments respond to the pandemic from March 2 to May 21, 2020 in New York City, Los Angeles, London, and another six global mega-cities. Results showed that across cities, negative and positive Tweet sentiment clustered around mid-March and early May, respectively. Furthermore, positive sentiments of Tweets from New York City and London were positively correlated with stricter quarantine measures, although this correlation was not significant in Los Angeles. Meanwhile, Tweet sentiments of all three cities did not exhibit a strong correlation with new cases and hospitalization. Last but not least, we provide a qualitative analysis of the reasons behind differences in correlations shown above, along with a discussion of the polarizing effect of public policies on Tweet sentiments. Thus, the results of this study imply that Tweet sentiment is more sensitive to quarantine orders than reported statistics of COVID-19, especially in populous megacities where public transportation is heavily relied upon, which calls for prompt and effective quarantine measures during contagious disease outbreaks.

Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration.

BACKGROUND: People with chronic tetraplegia, due to high-cervical spinal cord injury, can regain limb movements through coordinated electrical stimulation of peripheral muscles and nerves, known as functional electrical stimulation (FES). Users typically command FES systems through other preserved, but unrelated and limited in number, volitional movements (eg, facial muscle activity, head movements, shoulder shrugs). We report the findings of an individual with traumatic high-cervical spinal cord injury who coordinated reaching and grasping movements using his own paralysed arm and hand, reanimated through implanted FES, and commanded using his own cortical signals through an intracortical brain-computer interface (iBCI). METHODS: We recruited a participant into the BrainGate2 clinical trial, an ongoing study that obtains safety information regarding an intracortical neural interface device, and investigates the feasibility of people with tetraplegia controlling assistive devices using their cortical signals. Surgical procedures were performed at University Hospitals Cleveland Medical Center (Cleveland, OH, USA). Study procedures and data analyses were performed at Case Western Reserve University (Cleveland, OH, USA) and the US Department of Veterans Affairs, Louis Stokes Cleveland Veterans Affairs Medical Center (Cleveland, OH, USA). The study participant was a 53-year-old man with a spinal cord injury (cervical level 4, American Spinal Injury Association Impairment Scale category A). He received two intracortical microelectrode arrays in the hand area of his motor cortex, and 4 months and 9 months later received a total of 36 implanted percutaneous electrodes in his right upper and lower arm to electrically stimulate his hand, elbow, and shoulder muscles. The participant used a motorised mobile arm support for gravitational assistance and to provide humeral abduction and adduction under cortical control. We assessed the participant's ability to cortically command his paralysed arm to perform simple single-joint arm and hand movements and functionally meaningful multi-joint movements. We compared iBCI control of his paralysed arm with that of a virtual three-dimensional arm. This study is registered with ClinicalTrials.gov, number NCT00912041. FINDINGS: The intracortical implant occurred on Dec 1, 2014, and we are continuing to study the participant. The last session included in this report was Nov 7, 2016. The point-to-point target acquisition sessions began on Oct 8, 2015 (311 days after implant). The participant successfully cortically commanded single-joint and coordinated multi-joint arm movements for point-to-point target acquisitions (80-100% accuracy), using first a virtual arm and second his own arm animated by FES. Using his paralysed arm, the participant volitionally performed self-paced reaches to drink a mug of coffee (successfully completing 11 of 12 attempts within a single session 463 days after implant) and feed himself (717 days after implant). INTERPRETATION: To our knowledge, this is the first report of a combined implanted FES+iBCI neuroprosthesis for restoring both reaching and grasping movements to people with chronic tetraplegia due to spinal cord injury, and represents a major advance, with a clear translational path, for clinically viable neuroprostheses for restoration of reaching and grasping after paralysis. FUNDING: National Institutes of Health, Department of Veterans Affairs.

Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification.

OBJECTIVES: The relationship of immune dysregulation and autoantibody production that may contribute to systemic lupus erythematosus (SLE) pathogenesis is unknown. This study evaluates the individual and combined contributions of autoantibodies, type I interferon (IFN-α) activity, and IFN-associated soluble mediators to disease development leading to SLE. METHODS: Serial serum specimens from 55 individuals collected prior to SLE classification (average timespan=4.3 years) and unaffected healthy controls matched by age (±5 years), gender, race and time of sample procurement were obtained from the Department of Defense Serum Repository. Levels of serum IFN-α activity, IFN-associated mediators and autoantibodies were evaluated and temporal relationships assessed by growth curve modelling, path analysis, analysis of covariance and random forest models. RESULTS: In cases, but not matched controls, autoantibody specificities and IFN-associated mediators accumulated over a period of years, plateauing near the time of disease classification (p<0.001). Autoantibody positivity coincided with or followed type II IFN dysregulation, preceding IFN-α activity in growth curve models, with elevated IFN-α activity and B-lymphocyte stimulator levels occurring shortly before SLE classification (p≤0.005). Cases were distinguished by multivariate random forest models incorporating IFN-γ, macrophage chemoattractant protein (MCP)-3, anti-chromatin and anti-spliceosome antibodies (accuracy 93% >4 years pre-classification; 97% within 2 years of SLE classification). CONCLUSIONS: Years before SLE classification, enhancement of the type II IFN pathway allows for accumulation of autoantibodies and subsequent elevations in IFN-α activity immediately preceding SLE classification. Perturbations in select immunological processes may help identify at-risk individuals for further clinical evaluation or participation in prospective intervention trials.

Dysregulation of innate and adaptive serum mediators precedes systemic lupus erythematosus classification and improves prognostic accuracy of autoantibodies.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a poorly understood preclinical stage of immune dysregulation and symptom accrual. Accumulation of antinuclear autoantibody (ANA) specificities is a hallmark of impending clinical disease. Yet, many ANA-positive individuals remain healthy, suggesting that additional immune dysregulation underlies SLE pathogenesis. Indeed, we have recently demonstrated that interferon (IFN) pathways are dysregulated in preclinical SLE. To determine if other forms of immune dysregulation contribute to preclinical SLE pathogenesis, we measured SLE-associated autoantibodies and soluble mediators in samples from 84 individuals collected prior to SLE classification (average timespan = 5.98 years), compared to unaffected, healthy control samples matched by race, gender, age (±5 years), and time of sample procurement. We found that multiple soluble mediators, including interleukin (IL)-5, IL-6, and IFN-γ, were significantly elevated in cases compared to controls more than 3.5 years pre-classification, prior to or concurrent with autoantibody positivity. Additional mediators, including innate cytokines, IFN-associated chemokines, and soluble tumor necrosis factor (TNF) superfamily mediators increased longitudinally in cases approaching SLE classification, but not in controls. In particular, levels of B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) were comparable in cases and controls until less than 10 months pre-classification. Over the entire pre-classification period, random forest models incorporating ANA and anti-Ro/SSA positivity with levels of IL-5, IL-6, and the IFN-γ-induced chemokine, MIG, distinguished future SLE patients with 92% (±1.8%) accuracy, compared to 78% accuracy utilizing ANA positivity alone. These data suggest that immune dysregulation involving multiple pathways contributes to SLE pathogenesis. Importantly, distinct immunological profiles are predictive for individuals who will develop clinical SLE and may be useful for delineating early pathogenesis, discovering therapeutic targets, and designing prevention trials.

Upper Extremity Assessment in Tetraplegia: The Importance of Differentiating Between Upper and Lower Motor Neuron Paralysis.

Scientific advances are increasing the options for improved upper limb function in people with cervical level spinal cord injury (SCI). Some of these interventions rely on identifying an aspect of paralysis that is not uniformly assessed in SCI: the integrity of the lower motor neuron (LMN). SCI can damage both the upper motor neuron and LMN causing muscle paralysis. Differentiation between these causes of paralysis is not typically believed to be important during SCI rehabilitation because, regardless of the cause, the muscles are no longer under voluntary control by the patient. Emerging treatments designed to restore upper extremity function (eg, rescue microsurgical nerve transfers, motor learning-based interventions, functional electrical stimulation) all require knowledge of LMN status. The LMN is easily evaluated using surface electrical stimulation and does not add significant time to the standard clinical assessment of SCI. This noninvasive evaluation yields information that contributes to the development of a lifetime upper extremity care plan for maximizing function and quality of life. Given the relative simplicity of this assessment and the far-reaching implications for treatment and function, we propose that this assessment should be adopted as standard practice for acute cervical SCI.

Implanted neuroprosthesis for restoring arm and hand function in people with high level tetraplegia.

OBJECTIVE: To develop and apply an implanted neuroprosthesis to restore arm and hand function to individuals with high level tetraplegia. DESIGN: Case study. SETTING: Clinical research laboratory. PARTICIPANTS: Individuals with spinal cord injuries (N=2) at or above the C4 motor level. INTERVENTIONS: The individuals were each implanted with 2 stimulators (24 stimulation channels and 4 myoelectric recording channels total). Stimulating electrodes were placed in the shoulder and arm, being, to our knowledge, the first long-term application of spiral nerve cuff electrodes to activate a human limb. Myoelectric recording electrodes were placed in the head and neck areas. MAIN OUTCOME MEASURES: Successful installation and operation of the neuroprosthesis and electrode performance, range of motion, grasp strength, joint moments, and performance in activities of daily living. RESULTS: The neuroprosthesis system was successfully implanted in both individuals. Spiral nerve cuff electrodes were placed around upper extremity nerves and activated the intended muscles. In both individuals, the neuroprosthesis has functioned properly for at least 2.5 years postimplant. Hand, wrist, forearm, elbow, and shoulder movements were achieved. A mobile arm support was needed to support the mass of the arm during functional activities. One individual was able to perform several activities of daily living with some limitations as a result of spasticity. The second individual was able to partially complete 2 activities of daily living. CONCLUSIONS: Functional electrical stimulation is a feasible intervention for restoring arm and hand functions to individuals with high tetraplegia. Forces and movements were generated at the hand, wrist, elbow, and shoulder that allowed the performance of activities of daily living, with some limitations requiring the use of a mobile arm support to assist the stimulated shoulder forces.

Clinical Outcomes of "Paralyzed" Nerve Transfer for Treating Spinal Cord Injury: A Proof of Concept in a Human Model.

Functional electrical stimulation (FES) is an option to restore function in individuals after high cervical spinal cord injury (SCI) who have limited available options for tendon or nerve transfer. To be considered for FES implantation, patients must possess upper motor neuron (UMN) type denervation in potential recipient muscles, which can be confirmed by response to surface electrical stimulation during clinical evaluation. Lower motor neuron (LMN) denervated muscles will not respond to electrical stimulation and, therefore, are unavailable for use in an FES system. Previous animal studies have demonstrated that a "paralyzed" nerve transfer of a UMN-denervated motor branch to an LMN-denervated motor branch can restore electrical excitability in the recipient. In this study, we report the indications, surgical technique, and successful outcome (restoration of M3 elbow flexion) after the first "paralyzed" nerve transfer in a human patient.

Designing policy for Earth's urban future.

Global impacts of cities must be better conveyed to multilateral organizations.

Ticagrelor inverse agonist activity at the P2Y12 receptor is non-reversible versus its endogenous agonist adenosine 5´-diphosphate.

BACKGROUND AND PURPOSE: Ticagrelor is labelled as a reversible, direct-acting platelet P2Y12 receptor (P2Y12 R) antagonist that is indicated clinically for the prevention of thrombotic events in patients with acute coronary syndrome (ACS). As with many antiplatelet drugs, ticagrelor therapy increases bleeding risk in patients, which may require platelet transfusion in emergency situations. The aim of this study was to further examine the reversibility of ticagrelor at the P2Y12 R. EXPERIMENTAL APPROACH: Studies were performed in human platelets, with P2Y12 R-stimulated GTPase activity and platelet aggregation assessed. Cell-based bioluminescence resonance energy transfer (BRET) assays were undertaken to assess G protein-subunit activation downstream of P2Y12 R activation. KEY RESULTS: Initial studies revealed that a range of P2Y12 R ligands, including ticagrelor, displayed inverse agonist activity at P2Y12 R. Only ticagrelor was resistant to washout and, in human platelet and cell-based assays, washing failed to reverse ticagrelor-dependent inhibition of ADP-stimulated P2Y12 R function. The P2Y12 R agonist 2MeSADP, which was also resistant to washout, was able to effectively compete with ticagrelor. In silico docking revealed that ticagrelor and 2MeSADP penetrated more deeply into the orthosteric binding pocket of the P2Y12 R than other P2Y12 R ligands. CONCLUSION AND IMPLICATIONS: Ticagrelor binding to P2Y12 R is prolonged and more akin to that of an irreversible antagonist, especially versus the endogenous P2Y12 R agonist ADP. This study highlights the potential clinical need for novel ticagrelor reversal strategies in patients with spontaneous major bleeding, and for bleeding associated with urgent invasive procedures.

Difluorinated thromboxane A2 reveals crosstalk between platelet activatory and inhibitory pathways by targeting both the TP and IP receptors.

BACKGROUND AND PURPOSE: Thromboxane A2 (TXA2) is a prostanoid produced during platelet activaton, important in enhancing platelet reactivity by activation of TP receptors. However, due to the short half-life, studying TXA2 signalling is challenging. To enhance our understanding of TP receptor-mediated platelet biology, we therefore synthesised mono and difluorinated TXA2 analogues and explored their pharmacology on heterologous and endogenously expressed TP receptor function. EXPERIMENTAL APPROACH: Platelet functional and signalling responses were studied using aggregometry, Ca2+ mobilisation experiments and immunoblotting and compared with an analogue of the TXA2 precursor prostaglandin H2, U46619. Gαq/Gαs receptor signalling was determined using a bioluminescence resonance energy transfer (BRET) assay in a cell line overexpression system. KEY RESULTS: BRET studies revealed that F-TXA2 and F2-TXA2 promoted receptor-stimulated TP receptor G-protein activation similarly to U46619. Unexpectedly, F2-TXA2 caused reversible aggregation in platelets, whereas F-TXA2 and U46619 induced sustained aggregation. Blocking the IP receptor switched F2-TXA2-mediated reversible aggregation into sustained aggregation. Further BRET studies confirmed F2-TXA2-mediated IP receptor activation. F2-TXA2 rapidly and potently stimulated platelet TP receptor-mediated protein kinase C/P-pleckstrin, whereas IP-mediated protein kinase A/P-vasodilator-stimulated phosphoprotein was more delayed. CONCLUSION AND IMPLICATIONS: F-TXA2 is a close analogue to TXA2 used as a selective tool for TP receptor platelet activation. In contrast, F2-TXA2 acts on both TP and IP receptors differently over time, resulting in an initial wave of TP receptor-mediated platelet aggregation followed by IP receptor-induced reversibility of aggregation. This study reveals the potential difference in the temporal aspects of stimulatory and inhibitory pathways involved in platelet activation.

Preoperative evaluation of nerve transfer recipients after spinal cord injury using stimulated manual muscle testing.

Nerve transfer after spinal cord injury has become increasingly popular. Accurate preoperative identification of lower motor neuron involvement in potential recipient nerves is critical. Electrodiagnostic testing has been shown to correlate with intraoperative findings; however, it is time-consuming, costly and may not be readily available. Stimulated manual muscle testing is an alternative diagnostic approach. It is inexpensive and easily done by the surgeon or therapist in the office; however, correlation with intraoperative stimulation has not been reported. A retrospective review was conducted for patients who underwent nerve transfer for tetraplegia with recorded preoperative stimulated manual muscle testing and intraoperative stimulation results. Nine patients including 37 nerve transfers were included. Of the 37 nerve transfers, 36 were accurately graded preoperatively by stimulated manual muscle testing. Stimulated manual muscle testing had a sensitivity of 89%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 97%. This study supports stimulated manual muscle testing for preoperative distinction between upper versus lower motor neuron injuries.Level of evidence: IV.

How do density, employment and transit affect the prevalence of COVID-19 pandemic? A study of 3,141 counties across the United States.

Previous research has explored the effect of the built environment on the spread of the coronavirus disease (COVID-19) pandemic. This study extends the existing literature by examining the relationship between pandemic prevalence and density, employment, and transit factors at the county level. Using multilinear spatial-lag regressions and time series clustering analyses on the Smart Location Database encompassing 3141 counties in the United States, our findings reveal the following: (1) Density, employment, and transit variables yield heterogeneous effects to infection rate, death rate, and mortality rate. (2) Pedestrian-oriented road density is positively correlated to the prevalence of COVID-19, every 0.011 miles/acre increase is associated with 1% increase in the infection rate. (3) A consistent negative correlation is observed between jobs per household and infection rate, while a decrease in unemployment rate leads to an increase in the death rate. (4) The results from time series analysis suggest that areas characterized by low auto-oriented intersection density but high pedestrian-oriented road density are more susceptible to the impacts of pandemics. This highlights the need to prioritize pandemic prevention efforts in the suburban and rural areas with low population density, as emphasized in existing literature emphasized.

Treatment of hemophagocytic lymphohistiocytosis with alemtuzumab in systemic lupus erythematosus.

Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder characterized by cytokine dysregulation and uncontrolled activation of T lymphocytes and macrophages. It is categorized as primary when associated with specific genetic mutations or secondary when associated with infections, malignancies, or autoimmune disorders. Clinical features of HLH include unexplained fever, hepatosplenomegaly, pancytopenia, and severe hyperferritinemia. Treatment of primary HLH has become standardized based on the HLH-2004 protocol using cyclosporine, etoposide, and dexamethasone with or without intrathecal methotrexate followed by hematopoietic stem cell transplantation. Treatment of secondary HLH is directed at control of the underlying condition. If unsuccessful, cytotoxic agents such as those in HLH-2004, steroids, intravenous γ-globulin, or targeted immune therapy have been used. Immunotherapy targeting CD52 expressed on immune effector cells of HLH is a rational therapeutic approach in patients too ill for traditional cytotoxic chemotherapy. We describe the successful use of alemtuzumab to treat HLH due to systemic lupus erythematosus.

Surgical restoration of arm and hand function in people with tetraplegia.

Improved hand and arm function is the most sought after function for people living with a cervical spinal cord injury (SCI). Surgical techniques have been established to increase upper extremity function for tetraplegics, focusing on restoring elbow extension, wrist movement, and hand opening and closing. Additionally, more innovative treatments that have been developed (implanted neuroprostheses and nerve transfers) provide more options for improving function and quality of life. One of the most important steps in the process of restoring upper extremity function in people with tetraplegia is identifying appropriate candidates - typically those with American Spinal Injury Association (ASIA) motor level C5 or greater. Secondary complications of SCI can pose barriers to restoring function, particularly upper extremity spasticity. A novel approach to managing spasticity through high-frequency alternating currents designed to block unwanted spasticity is being researched at the Cleveland FES Center and may improve the impact of reconstructive surgery for these individuals. The impact of these surgeries is best measured within the framework of the World Health Organization's International Classification of Function, Disability and Health. Outcome measures should be chosen to reflect changes within the domains of body functions and structures, activity, and participation. There is a need to strengthen the evidence in the area of reconstructive procedures for people with tetraplegia. Research continues to advance, providing more options for improved function in this population than ever before. The contribution of well-designed outcome studies to this evidence base will ultimately help to address the complications surrounding access to the procedures.

Improving hand function after spinal cord injury.

Nerve transfer surgery has expanded reconstructive options for restoring upper extremity function following spinal cord injury. By adding new motor donors to the pool already available through tendon transfers, the effectiveness of treatment should improve. Planning which procedures and in which order to perform, along with their details must be delineated. To meet these demands, refined diagnostics are needed, along with awareness of the remaining challenges to restore intrinsic muscle function and to address spasticity and its consequences. This article summaries recent advances in surgical reanimation of upper extremity motor control, together with an overview of the development of neuro-prosthetic and neuromodulation techniques to modify recovery or substitute for functional losses after spinal cord injuries.

Targeted idiotype-fusion DNA vaccines for human multiple myeloma: preclinical testing.

OBJECTIVES: A homodimeric fusion DNA vaccine targeting idiotype (Id) to antigen-presenting cells (APC) induced robust tumor protection in a mouse model of multiple myeloma (MM). Similar Id vaccine molecules were generated for four patients with MM with three main objectives: (i) do the vaccine molecules induce bona fide anti-Id immune responses in mice? (ii) does targeting of the vaccine molecules to APC enhance immune responses? (iii) can anti-Id antibodies, generated as by-product in vaccinated mice, be used to establish sensitive assays for complete remission (CR) prior to patient vaccination? METHODS: Chimeric vaccine molecules targeting patient Id to mouse major histocompatibility complex (MHC) class II molecules were genetically constructed for four patients with MM. RESULTS: DNA vaccination of mice with chimeric vaccines targeting patient Id to mouse MHC class II molecules elicited antibodies specific for the patient's myeloma protein. Targeting MHC class II greatly enhanced anti-Id responses. Mouse anti-Id antibodies were used to establish myeloma protein-specific enzyme-linked immunosorbent assays (ELISAs) that were between 75 and 1500 times more sensitive than conventional serum protein electrophoresis and immunofixation. CONCLUSIONS: These results pave the way for testing targeted DNA Id vaccines in patients in CR. Id- and patient-specific ELISA could be established affording evaluation of CR depth beyond current serological methods.

Cost-effectiveness of lanthanum carbonate in the treatment of hyperphosphatemia in chronic kidney disease before and during dialysis.

OBJECTIVES: Hyperphosphatemia is a common and harmful condition in patients with chronic kidney disease (CKD). We determined the cost-effectiveness of the noncalcium-based phosphate binder lanthanum carbonate (LC) as second-line treatment of hyperphosphatemia after therapy failure with calcium-based binders (CB). METHODS: Two CKD populations were modeled: 1) predialysis CKD patients and 2) incident dialysis patients. Patients not responding to CB with a serum phosphate (SP) level >5.5 mg/dl received a trial with LC. Patients not responding to LC (SP >4.6 mg/dl) returned to CB treatment. Patient-level data were obtained from clinical trials in predialysis and dialysis. Time-dependent, life-long Markov models (discounting at 3.5% annually) were developed, using a UK National Health Service perspective. RESULTS: The health gains with second-line LC treatment compared to CB treatment were 44 and 56 quality-adjusted life-years (QALYs) for the predialysis and incident dialysis populations, respectively. Second-line LC was a cost-saving strategy in the predialysis population because of the cost-savings of delayed CKD progression. Second-line LC was cost-effective at £6900 (90% probability interval: £5800-£8300) per QALY gained in the dialysis population. Results were robust to plausible variations in other model parameters; inclusion of future unrelated dialysis costs had a large influence on cost-effectiveness estimates. CONCLUSIONS: Second-line treatment with LC is associated with considerable clinical benefits and good value for money in CKD, irrespective of dialysis status. These results support Kidney Disease Outcomes Quality Initiative guidelines to treat CKD patients with hyperphosphatemia irrespective of dialysis status.

Cost-effectiveness of lanthanum carbonate versus sevelamer hydrochloride for the treatment of hyperphosphatemia in patients with end-stage renal disease: a US payer perspective.

OBJECTIVE: To assess the cost-effectiveness of lanthanum carbonate (LC) versus sevelamer hydrochloride (SH) as a treatment for hyperphosphatemia in end-stage renal disease (ESRD) patients. METHODS: A Markov model was developed to estimate health outcomes; quality-adjusted life years (QALYs) and life-years saved (LYS), as well as associated costs. The model incorporated patient-level data from a randomized head-to-head crossover study that compared the reduction of serum phosphorus using LC and SH for 4 weeks each. The model included patients previously treated with calcium-based binders. Both the intent-to-treat (ITT) population and the cohort of patients who completed treatment in both periods of the study (i.e., completer population) were assessed. The baseline risks of cardiovascular disease (CVD), all-cause mortalities for CVD, and non-CVD patients were derived from a large US renal database. Patient outcomes were modeled for 10 years, and incremental cost-effectiveness ratios (ICERs) were calculated for LC relative to SH. Deterministic and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the base-case model. RESULTS: For the ITT population, the ICERs of LC versus SH were $24,724/QALY and $15,053/LYS, respectively (in US dollars). When the completer population was considered, the ICERs of LC versus SH were $15,285/QALY and $9,337/LYS (Table 2), respectively. The PSA indicated 61.9% and 85.8% probabilities for ITT and completer populations of LC being cost-effective at the $50,000/QALY willingness-to-pay threshold, respectively. CONCLUSION: LC is a cost-effective strategy compared with SH in the treatment of ESRD patients with hyperphosphatemia who were previously treated with calcium-based binders. Sensitivity analyses demonstrated the robustness of the pharmacoeconomic model.