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We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.
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Antivirales , Antivirales/farmacología , Antivirales/química , Humanos , Animales , Proteínas 14-3-3/metabolismo , Complejos Multiproteicos/metabolismo , Interacciones Huésped-Patógeno/efectos de los fármacos , Línea CelularRESUMEN
We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease. One Sentence Summary: A host-targeted drug to treat all respiratory viruses without viral resistance development.
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BACKGROUND: The shift to value based total joint arthroplasty (TJA) reimbursement strategies has led to an increased focus on quality and the avoidance of poor outcomes. As a result, there has been greater encouragement for patients to undergo joint replacements in high volume centers of excellence. In this study, we examined the potential complications avoided if TJA procedure volume was shifted from poor quality (high incidence) facilities to high quality (low incidence) facilities within Hospital Referral Regions (HRRs). METHODS: Using Medicare 100% claims data linked to the Dartmouth Atlas of Health Care, we examined the clinical and cost benefits of shifting TJA procedures from low performing hospital to high performing hospitals within HRRs. RESULTS: Across all HRRs, we identified 1,878 cases of deep infection and 3,393 annual readmissions in the Medicare population that could have potentially been avoided, resulting in a mean cost savings of $41 million and $62 million, respectively, solely due to shifting procedure location from lower third performing hospitals to the upper third performing hospitals. CONCLUSIONS: Our study demonstrates that the incidence of deep infection and all-cause readmission varies widely among and within HRRs. Further, the potential reallocation of joint procedures from low quality facilities to high quality Centers of Excellence within an HRR could result in over $103 million in annual savings related to mitigated deep infections and readmissions.
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Artroplastia de Reemplazo de Cadera , Anciano , Ahorro de Costo , Bases de Datos Factuales , Humanos , Medicare , Readmisión del Paciente , Derivación y Consulta , Estados UnidosRESUMEN
Increased focus on reducing the cost of total knee arthroplasty (TKA) has driven greater interest in performing the procedure in an outpatient setting. This study used exact matching to compare clinical and economic outcomes following TKA in an outpatient vs rapid recovery inpatient setting. This study used a nationally representative commercial database. Patients were grouped into 2 cohorts: same-day outpatient TKA (surgery center or hospital outpatient) or short-stay inpatient TKA ("rapid recovery"; length of stay 1 day or less). Only patients discharged home under self-care or with health care were included. Exact 1:1 matching was performed on clinical and demographic characteristics to control for potential case-selection bias by choice of care setting. Prior to matching, 969 outpatients and 8101 rapid recovery inpatients met selection criteria. The outpatient cohort was younger (median age, 58 vs 61 years), predominantly female (56% vs 51%), and less comorbid (Charlson Comorbidity Index score of 0: 84.2% vs 74.0%) vs the rapid recovery cohort. Post-match, 863 patients were available in each cohort. The outpatient cohort exhibited a significantly lower incidence of opiate use (80.4% vs 90.7%; P<.001) and minor complications (2.8% vs 5.8%; P=.002). Incidence of major complications (5.2% vs 6.7%, P=.173) and 90-day readmissions (5.1% vs 7.3%, P=.064) were equivalent. The outpatient median 90-day episode payment was $6824 lower (22%) per patient ($24,749 vs $31,573, respectively; P<.001). This study suggests that among carefully selected patients undergoing outpatient TKA, outcomes are equivalent, if not improved, at a lower payor cost compared with a rapid recovery inpatient setting. [Orthopedics. 2020; 43(1):36-41.].
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Artroplastia de Reemplazo de Rodilla/efectos adversos , Pacientes Internos , Pacientes Ambulatorios , Readmisión del Paciente , Complicaciones Posoperatorias/etiología , Anciano , Bases de Datos Factuales , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Alta del PacienteRESUMEN
INTRODUCTION: This study examined whether recent nationwide declines in the incidence of transfusion following total joint arthroplasty were equal across inpatient facilities. METHODS: This analysis used the Premier database (2010 to 2015). Cohorts of primary total hip or knee arthroplasty (THA or TKA) and revision THA or TKA were defined. RESULTS: Among 1,013,024 patients who met selection criteria, the overall incidence of transfusion declined from 2010 through 2015 (primary THA: 22.1% to 7.1%; primary TKA: 18.1% to 3.2%; revision THA: 30.6% to 18.5%; and revision TKA: 19.8% to 9.8%; all P < 0.001). However, patients older than 65 years were associated with lower odds of transfusion relative to those younger than 65 years (P < 0.05 for three of four cohorts); smaller hospitals were associated with higher odds versus large hospitals (P < 0.05 all cohorts), and academic hospitals were associated with higher odds of transfusion versus community facilities (P < 0.05 for three of four cohorts). DISCUSSION: During this study period, a meaningful proportion of total joint arthroplasty procedures were performed at facilities with the most room to improve. Decreases in transfusion rates were dependent on specific hospital characteristics; these results may help direct targeted improvement initiatives. LEVEL OF EVIDENCE: Level III.
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Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Transfusión Sanguínea/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Reoperación/estadística & datos numéricos , Anciano , Femenino , Hospitales/clasificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Oncoplastic breast surgery aims to optimize efficacy of surgical resection and cosmesis to maximize patient satisfaction; however, despite the benefits, oncoplastic techniques have not been widely adopted in the US. This study examined trends in the incidence of lumpectomy (partial mastectomy) with or without oncoplastic techniques from 2011 to 2016. METHODS: This was a retrospective analysis of claims from the Optum Clinformatics database (January 2010-March 2017). Female patients with no history of breast surgery in the prior year were categorized into three independent cohorts: isolated lumpectomy (Lx), lumpectomy with tissue transfer (LxTT), or lumpectomy with mammaplasty and/or mastopexy (LxMM). Oncoplastic techniques (in cohorts two and three) were performed at either time of the initial lumpectomy or during 90-day follow-up. RESULTS: Overall, 19,253 patients met the inclusion criteria (91.1% Lx, 5.2% LxTT, and 3.7% LxMM). Significantly fewer patients with Lx had a family history of breast cancer compared with patients with oncoplastic techniques (26.4% vs. 33.7% and 37.9%, respectively; p < 0.001). The incidence of Lx declined significantly from 2011 (92.9%) to 2016 (88.1%), while LxTT and LxMM increased from 4.2 to 7.2% and 2.8 to 4.7%, respectively (both p < 0.001). The greatest utilization of oncoplastic techniques was observed in the Pacific census division (19.2%), while lowest utilization was in the East South Central division (3.2%; p < 0.001). CONCLUSIONS: While increased adoption of oncoplastic techniques was observed, the compound annual growth rate remained below 10% and varied significantly by region. Further adoption of oncoplastic techniques is necessary to improve cosmetic outcomes and patient satisfaction following breast-conserving surgery.
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Neoplasias de la Mama/cirugía , Mamoplastia/tendencias , Mastectomía Segmentaria/tendencias , Adulto , Bases de Datos Factuales , Femenino , Gastos en Salud/estadística & datos numéricos , Humanos , Mamoplastia/efectos adversos , Mamoplastia/economía , Mastectomía Segmentaria/efectos adversos , Mastectomía Segmentaria/economía , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Estados UnidosRESUMEN
BACKGROUND: This study examined the correlation between publicly reported indicators of skilled nursing facility (SNF) quality and clinical outcomes after primary total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: This retrospective analysis used Medicare claims from the Centers for Medicare and Medicaid Services 100% Standard Analytic File (2014-2015) that were linked to SNF quality star ratings from the Centers for Medicare and Medicaid Services Nursing Home Compare database. Overall SNF rating and subcomponents of the rating were evaluated for correlation to 30-day and 90-day risk of readmission. Ratings were based upon a 5-star rating system (1 representing the lowest quality). Cox proportional hazards regressions controlled for age, race, census division, hospital location, comorbidities, and SNF length of stay. RESULTS: A total of 9418 SNFs, 58,064 TKA patients, and 26,837 THA patients met criteria. As SNF overall star rating increased from 1 to 5, incidence of all-cause 30-day readmission decreased from 6.4% to 5.0% for TKA (relative reduction [RR] 22%; P < .001) and from 9.1% to 6.2% for THA (RR 32%; P < .001). As nurse staffing rating increased, incidence of all-cause readmission decreased from 6.8% to 4.7% for the TKA cohort (30.9% RR; P < .001), and from 7.7% to 6.0% for the THA cohort (22.1% RR; P = .003). Regression analysis demonstrated that a higher star rating was associated with decreased risk of readmission (both cohorts P < .05). CONCLUSIONS: For patients undergoing TKA or THA, the overall SNF star rating, nurse staffing ratios, and physical therapy intensity were significantly correlated with risk of readmission within 30 days of SNF admission.
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Artroplastia de Reemplazo de Rodilla/rehabilitación , Readmisión del Paciente/estadística & datos numéricos , Instituciones de Cuidados Especializados de Enfermería/estadística & datos numéricos , Instituciones de Cuidados Especializados de Enfermería/normas , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/economía , Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Revisión de Utilización de Seguros/estadística & datos numéricos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Masculino , Medicare/economía , Medicare/estadística & datos numéricos , Readmisión del Paciente/economía , Indicadores de Calidad de la Atención de Salud/economía , Indicadores de Calidad de la Atención de Salud/estadística & datos numéricos , Estudios Retrospectivos , Instituciones de Cuidados Especializados de Enfermería/economía , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVES: Percutaneous core-needle biopsy (PCNB) is the standard of care to biopsy and diagnose suspicious breast lesions. Dependent on histology, many patients require additional open procedures for definitive diagnosis and excision. This study estimated the payer and patient out-of-pocket (OOP) costs, and complication risk, among those requiring at least 1 open procedure following PCNB. METHODS: This retrospective study used the Truven Commercial database (2009-2014). Women who underwent PCNB, with continuous insurance, and no history of cancer, chemotherapy, radiation, or breast surgery in the prior year were included. Open procedures were defined as open biopsy or lumpectomy. Study follow-up ended at chemotherapy, radiation, mastectomy, or 90 days-whichever occurred first. RESULTS: In total, 143 771 patients (mean age 48) met selection criteria; 85.1% underwent isolated PCNB, 12.4% one open procedure, and 2.5% re-excision. Incidence of complications was significantly lower among those with PCNB alone (9.2%) vs 1 open procedure (15.6%) or re-excision (25.3%, P < .001). Mean incremental commercial payments were US $13 190 greater among patients with 1 open procedure vs PCNB alone (US $17 125 vs US $3935, P < .001), and US $4767 greater with re-excision (US $21 892) relative to 1 procedure. Mean patient OOP cost was US $858 greater for 1 open procedure vs PCNB alone (US $1527 vs US $669), and US $247 greater for re-excision vs 1 procedure. CONCLUSIONS: A meaningful proportion of patients underwent open procedure(s) following PCNB which was associated with increased complication risk and costs to both the payer and the patient. These results suggest a need for technologies to reduce the proportion of cases requiring open surgery and, in some cases, re-excision.
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BACKGROUND: In the era of bundled payments, many hospitals are responsible for costs from admission through 90 days postdischarge. Although bundled episodes for hip fracture will have a separate target price for the bundle, little is known about the 90-day resource use burden for this patient population. METHODS: Using Medicare 100% Standard Analytic Files (2010-2014), we identified patients undergoing hemiarthroplasty or total hip arthroplasty (THA). Patients were aged 65 and older with admitting diagnosis of closed hip fracture, no concurrent fractures of the lower limb, and no history of hip surgery in the prior 12 months baseline. Continuous Medicare-only enrollment was required. Complications, resource use, and mortality from admission through 90 days following discharge (follow-up) were summarized. RESULTS: Four cohorts met selection criteria for analysis: (1) hemiarthroplasty diagnosis-related group (DRG) 469 (N = 19,634), (2) hemiarthroplasty DRG 470 (N = 77,744), (3) THA DRG 469 (N = 1686), and (4) THA DRG 470 (N = 9314). All-cause mortality during the study period was 51.6%, 29.5%, 48.1%, and 24.9% with mean 90-day costs of $28,952, $19,243, $29,763, and $18,561, respectively. Most of the patients waited 1 day from admission to surgery (41%-51%). Incidence of an all-cause complication was approximately 70% in each DRG 469 cohort and 14%-16% in each DRG 470 cohort. CONCLUSION: This study confirms patients with hip fracture are a costly subpopulation. Tailored care pathways to minimize post-acute care resource use are warranted for these patients.
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Artroplastia de Reemplazo de Cadera/economía , Atención a la Salud/estadística & datos numéricos , Fracturas de Cadera/cirugía , Alta del Paciente/estadística & datos numéricos , Readmisión del Paciente/economía , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/mortalidad , Estudios de Cohortes , Costos y Análisis de Costo , Atención a la Salud/economía , Grupos Diagnósticos Relacionados/economía , Grupos Diagnósticos Relacionados/estadística & datos numéricos , Femenino , Fracturas del Cuello Femoral/cirugía , Gastos en Salud , Recursos en Salud , Hemiartroplastia , Lesiones de la Cadera/cirugía , Hospitalización , Hospitales , Humanos , Incidencia , Masculino , Medicare/economía , Análisis Multivariante , Readmisión del Paciente/estadística & datos numéricos , Huesos Pélvicos/cirugía , Estudios Retrospectivos , Atención Subaguda , Estados UnidosRESUMEN
BACKGROUND: Use of cardiac implantable electronic devices (CIEDs) is increasing. The incidence of bleeding-related complications during CIED procedures and the association with subsequent infection risk have been studied in trial settings but not in nonrandomized "real-world" populations. METHODS AND RESULTS: This retrospective database analysis of US insurance claims from the Truven MarketScan database (2009-2013) evaluated the incidence of bleeding complications during, or in the 30 days following, a CIED procedure and the association between bleeding and subsequent infection in days 31 to 365 of follow-up. This study identified 42 606 patients who had a primary or replacement CIED procedure and met all inclusion criteria. Incidence of bleeding ranged from 0.58% to 2.81% by type of pharmaceutical therapy. Incidence of infection during days 31 to 365 of follow-up was significantly higher among patients with a bleeding complication in the first 30 days versus those without (6.56% vs 1.24%, P<0.001), with results upheld in multivariate analysis (HR=2.97, 95% CI 1.94-4.54, P<0.001). CONCLUSIONS: This study provides a lower bound of the real-world incidence of bleeding complications following a CIED procedure within the coding limitations of an insurance claims database. Results confirm the association between bleeding in the pocket and risk of subsequent infection. Further research is needed to precisely identify the costs associated with bleeding in the pocket.
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Desfibriladores Implantables , Marcapaso Artificial , Hemorragia Posoperatoria/epidemiología , Implantación de Prótesis , Infección de la Herida Quirúrgica/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
AIM: To evaluate outcomes associated with use of a saline coupled bipolar sealer during open partial liver resection. METHODS: This retrospective analysis utilized the United States Premier™ insurance claims database (2010-2014). Patients were selected with codes for liver malignancy and partial hepatectomy or lobectomy. Cases were defined by use the saline-coupled bipolar sealer; controls had no use. A Propensity Score algorithm was used to match one case to five controls. A deviation-based cost modeling (DBCM) approach provided an estimate of cost-effectiveness. RESULTS: One hundred and forty-four cases and 720 controls were available for analysis. Patients in the case cohort received fewer transfusions vs controls (18.1% vs 29.4%, P = 0.007). In DBCM, more patients in the case cohort experienced "on-course" hospitalizations (53.5% vs 41.9%, P = 0.009). The cost calculation showed an average savings in total hospitalization costs of $1027 for cases vs controls. In multivariate analysis, cases had lower odds of receiving a transfusion (OR = 0.44, 95%CI: 0.27-0.71, P = 0.0008). CONCLUSION: Use of a saline-coupled bipolar sealer was associated with a greater proportion of patients with an "on course" hospitalization.
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Pérdida de Sangre Quirúrgica/prevención & control , Transfusión Sanguínea/estadística & datos numéricos , Carcinoma Hepatocelular/cirugía , Electrocirugia/métodos , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias/epidemiología , Lesión Renal Aguda/epidemiología , Adolescente , Adulto , Anciano , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Transfusión Sanguínea/economía , Estudios de Casos y Controles , Análisis Costo-Beneficio , Bases de Datos Factuales , Electrocirugia/economía , Femenino , Hepatectomía/economía , Hospitalización/economía , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/economía , Puntaje de Propensión , Estudios Retrospectivos , Adulto JovenRESUMEN
This study examined the correlation between patient comorbidity status, hospitalization length of stay (LOS), and cost for total knee arthroplasty (TKA), total hip arthroplasty (THA), and 1- to 3-level lumbar spinal fusion procedures. Using the Premier Perspective Database, adults older than 18 years who underwent primary unilateral TKA, THA, or spinal fusion between January 1, 2008, and June 30, 2014, were identified. Generalized linear models controlling for age, sex, region, hospital size, academic status, payor, and procedure year predicted the incremental total hospitalization cost among the sickest patients (Charlson Comorbidity Index [CCI] ≥3) vs healthy controls (CCI=0). The study cohort included 536,582 TKAs, 275,953 THAs, and 177,493 spinal fusion procedures. The percentages of patients with a CCI of 3 or greater were 5.4%, 4.7%, and 4.3%, for TKA, THA, and spinal fusion procedures, respectively. Mean (SD) LOS was longer by 0.9 (1.5), 1.4 (2.3), and 2.3 (3.8) days for patients with a CCI of 3 or greater vs 0 for TKA, THA, and spinal fusion procedures, respectively. Unadjusted total hospitalization costs were $17,512 for TKA, $18,915 for THA, and $32,932 for spinal fusion procedures; generalized linear models showed an incremental total hospitalization cost for CCI scores of 3 or greater of $2211, $3041, and $3922 vs CCI equal to 0 for each procedure type, respectively. Although representing a relatively small proportion of all patients undergoing elective orthopedic procedures, highly comorbid patients were associated with a greater total hospitalization cost burden. With the average patient comorbidity burden growing nationally, this study warrants further examination of improved standards of care for comorbid patients undergoing elective orthopedic procedures. [Orthopedics. 2016; 39(4):237-246.].
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Procedimientos Quirúrgicos Electivos/estadística & datos numéricos , Hospitalización/economía , Procedimientos Ortopédicos/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Comorbilidad , Bases de Datos Factuales , Procedimientos Quirúrgicos Electivos/economía , Femenino , Costos de Hospital , Hospitalización/estadística & datos numéricos , Humanos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Procedimientos Ortopédicos/economía , Estudios RetrospectivosRESUMEN
BACKGROUND: Inadvertent damage to leads for transvenous pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy defibrillators is an important complication associated with generator-replacement procedures. We sought to estimate the incidence and costs associated with transvenous lead damage following cardiac implantable electronic device replacement. METHODS AND RESULTS: Using the Truven Health Analytics MarketScan Commercial Research Database, we identified health care claims between 2009 and 2013 for lead damage following generator replacement. Patients were identified by claims with a procedure code for cardiac implantable electronic device replacement and then evaluated for 1 year. All follow-up visits for lead damage were identified, and incidence, risk factors, and hospitalization costs were determined. A total of 22 557 patients with pacemakers, 20 632 with implantable cardioverter-defibrillators, and 2063 with cardiac resynchronization therapy defibrillators met selection criteria. Incidence of lead damage was 0.46% for pacemaker replacement, 1.27% for implantable cardioverter-defibrillator replacement, and 1.94% for cardiac resynchronization therapy defibrillator replacement procedures (P<0.001). After adjusting for patient characteristics, patients with implantable cardioverter-defibrillators and cardiac resynchronization therapy defibrillators demonstrated risk of lead damage that was, respectively, double (hazard ratio 2.00, 95% CI 1.57-2.55) and >2.5 times (hazard ratio 2.58, 95% CI 1.73-3.83) that of patients with pacemakers. Lead revision or repair procedures were associated with increased inpatient hospitalization costs (mean $19 959 for pacemaker, $24 885 for implantable cardioverter-defibrillator, and $46 229 for cardiac resynchronization therapy defibrillator; P=0.048, Kruskal-Wallis test). CONCLUSIONS: These findings establish the first objective assessment of the incidence, risk factors, and economic burden of lead damage following cardiac implantable electronic device replacement in the United States. New care algorithms are warranted to avoid these events, which impose substantial burdens on patients, physicians, and payors.
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Dispositivos de Terapia de Resincronización Cardíaca/economía , Terapia de Resincronización Cardíaca/economía , Desfibriladores Implantables/economía , Remoción de Dispositivos/economía , Cardioversión Eléctrica/economía , Costos de Hospital , Falla de Prótesis , Anciano , Anciano de 80 o más Años , Terapia de Resincronización Cardíaca/efectos adversos , Bases de Datos Factuales , Remoción de Dispositivos/efectos adversos , Cardioversión Eléctrica/efectos adversos , Cardioversión Eléctrica/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: This study evaluated the factors and costs associated with discharge destination and readmission, within 90 days of surgery, for primary or revision total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: This retrospective database analysis used health care claims from the Truven MarketScan Database (2009-2013). Patients were selected if aged ≥18 years, with continuous health plan enrollment from 3-month baseline through 3-month follow-up. Logistic regression and Cox proportional hazard models were used to analyze factors associated with discharge destination and risk of readmission. Total 90-day costs were calculated for different patient pathways of care, dependent on complications, discharge destination, and readmission status. RESULTS: A total of 323,803 primary TKA, 25,354 revision TKA, 159,390 primary THA, and 17,934 revision THA cases met selection criteria. All-cause complications occurred in 2.5%, 37.2%, 2.6%, and 35.0% of each cohort. Complications, transfusions, and length of stay ≥3 days were associated with greater odds of discharge to home with home health services or skilled nursing facility (SNF) vs home under self-care (P < .001 all cohorts), whereas discharge to home with home health services or SNF was associated with greater risk of readmission (P < .05 for all cohorts except one). The ratio of total 90-day costs for the highest- (revision, SNF, readmission) vs lowest-cost (primary, home under self-care, no readmission) care pathways ranged from 1.8 to 2.2. CONCLUSION: As Medicare payment policy for total joint arthroplasty shifts toward bundling, an awareness of factors associated with outlier costs will be requisite to remain profitable.
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Artroplastia de Reemplazo de Cadera/economía , Artroplastia de Reemplazo de Rodilla/economía , Readmisión del Paciente/economía , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Costos de la Atención en Salud , Humanos , Tiempo de Internación , Modelos Logísticos , Masculino , Medicare , Persona de Mediana Edad , Alta del Paciente , Periodo Posoperatorio , Modelos de Riesgos Proporcionales , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Instituciones de Cuidados Especializados de Enfermería , Estados UnidosRESUMEN
BACKGROUND: This study evaluated the comparative risk of autologous and allogenic blood transfusion, inhospital complications, and incremental total hospitalization costs for primary unilateral, simultaneous bilateral, and revision total knee arthroplasty (TKA) procedures. METHODS: Using the Premier Perspective database, we identified adults who underwent primary unilateral, simultaneous bilateral, or revision TKA procedures. Logistic regression, controlling for patient and hospital characteristics, was used to determine the risk of autologous or allogeneic blood transfusion. Controlling for the same factors, generalized linear models predicted incremental total hospitalization cost associated with transfusion. RESULTS: Between January 2008 and June 2014, 513,558 primary unilateral, 33,977 bilateral, and 32,494 revision TKA patients met selection criteria. The overall percentage receiving a transfusion was 14.1% for unilateral, 36.3% for bilateral, and 20.0% for revision procedures. Logistic regression showed patients aged >65 years, female gender, Northeastern location, large hospitals, and higher Charlson score to be significantly associated with higher transfusion risk. Although overall risk of transfusion decreased over the study period, patients with Charlson score ≥3 were at 2.27 (primary unilateral), 1.88 (bilateral), and 2.44 (revision) greater odds of transfusion compared with healthy controls (Charlson score = 0). Generalized linear models showed an incremental total hospitalization cost among those receiving a transfusion of $2477, $4235, and $8594, respectively, compared with those without transfusion. CONCLUSIONS: Transfusion risk remains a significant burden in select patient populations and procedures. The incremental cost of receiving a transfusion is significant, including not only direct costs but also staff time and increased hospital resource use.
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Artroplastia de Reemplazo de Rodilla/economía , Transfusión Sanguínea , Hospitalización/economía , Medición de Riesgo/métodos , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/métodos , Bases de Datos Factuales , Femenino , Recursos en Salud , Costos de Hospital , Humanos , Tiempo de Internación , Modelos Logísticos , Masculino , Persona de Mediana Edad , Reoperación/economía , Estudios RetrospectivosRESUMEN
PURPOSE: The impact of correcting elevated International Normalized Ratio (INR) values on inhospital mortality in patients with warfarin-associated major bleeding is presented. METHODS: Using patient information from the database of a large U.S. health system, a retrospective analysis was conducted to (1) evaluate inpatient practice patterns in correcting INR elevations among patients hospitalized with warfarin-related intracranial hemorrhage (ICH) or non-ICH bleeding and (2) test the hypothesis that achieving INR correction, defined as an INR of ≤1.5, at any point during the hospital stay is correlated with lower inhospital mortality. Cox proportional hazards models were constructed to assess predictors of inhospital death. RESULTS: Among the 354 patients who met the study selection criteria, INR correction was achieved in 87.9% overall (92.5% and 85.5% of patients with ICH and non-ICH bleeds, respectively). Patients whose elevated INR values were corrected had significantly lower inhospital death rates than those with uncorrected elevations: 15.3% versus 55.6% (p = 0.010) among patients with ICH and 2.0% versus 11.8% (p = 0.017) among those with non-ICH bleeds. After adjusting for baseline demographics and comorbidities, the correlation between failure to correct INR elevations and increased mortality risk was significant only for patients with ICH (hazard ratio, 8.04; 95% confidence interval, 2.07-31.18; p = 0.003). CONCLUSION: Results of this study indicated that correction of elevated INR values was associated with a lower likelihood of inhospital death among warfarin-treated patients hospitalized for ICH or non-ICH major bleeding.
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Anticoagulantes/efectos adversos , Transfusión de Componentes Sanguíneos/métodos , Hemorragia/inducido químicamente , Warfarina/efectos adversos , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Hemorragia/terapia , Mortalidad Hospitalaria , Humanos , Relación Normalizada Internacional , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/terapia , Tiempo de Internación , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Estados UnidosAsunto(s)
Interferón beta/administración & dosificación , Interferón beta/uso terapéutico , Programas Controlados de Atención en Salud , Esclerosis Múltiple/tratamiento farmacológico , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/uso terapéutico , Humanos , Inyecciones Intramusculares , Interferón beta-1a , Evaluación de Resultado en la Atención de SaludRESUMEN
While no curative treatment exists for multiple sclerosis (MS), several disease-modifying therapies (DMTs) have been developed to reduce relapse rates, slow disability progression, and modify the overall disease course. However, because of the chronic nature of the disease, long-term therapy adherence can be challenging for some patients with MS. Low adherence to DMTs has been shown to be associated with higher rates of disease relapses and progression as well as with an increase in medical resource utilization. As new MS treatments are developed, a comprehensive understanding of current adherence rates and the impact of adherence on clinical and economic outcomes is of particular interest. Our objective was to conduct a review of the published literature to evaluate rates of adherence to DMTs in MS and the impact of adherence on both clinical and economic outcomes from the patient and payer perspectives. Systematic literature searches were conducted using MEDLINE, EMBASE, and the Cochrane Central Register for Controlled Trials. Studies were limited to those completed on human subjects, written in the English language, and published between May 1, 2001, and May 1, 2011. Additional inclusion criteria required that studies involve a population of patients with MS, utilize the administration of DMTs, and report a measurement of adherence. Studies reporting persistence measures (e.g., treatment discontinuation rates) or rates of switching between DMTs (with no other measure of adherence reported) were excluded if they did not also assess adherence. Among the 24 studies meeting inclusion criteria, adherence to DMTs ranged from 41% to 88%. Weighted mean adherence rates were higher for intramuscular (IM) interferon beta-1a (IFNß-1a) administered once a week (69.4%), and subcutaneous (SC) IFNß-1b administered every other day (63.8%) than for SC IFNß-1a administered 3 times a week (58.4%) and glatiramer acetate administered daily (56.8%). There was a numerically greater risk of MS relapse or disease progression among patients nonadherent to therapy versus adherent patients, with findings statistically significant in 2 of 4 studies. Additionally, 2 studies showed statistically significant reductions in inpatient or emergency room utilization and total MS-related medical costs among patients adherent to therapy compared with nonadherent patients. Higher patient out-of-pocket copayments and coinsurance were significantly associated with lower adherence to DMTs, while the use of interventional or disease therapy management programs were associated with improved adherence. Lack of medication adherence remains a problem among patients with MS. Improvements in adherence have the potential to improve patient and payer burden in terms of improved clinical outcomes and lower nonpharmacy medical resource utilization.
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Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/psicología , Cooperación del Paciente/psicología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/economía , Costo de Enfermedad , Progresión de la Enfermedad , Vías de Administración de Medicamentos , Esquema de Medicación , Servicio de Urgencia en Hospital/estadística & datos numéricos , Acetato de Glatiramer , Hospitalización , Humanos , Interferón beta-1a , Interferon beta-1b , Interferón beta/administración & dosificación , Interferón beta/economía , Esclerosis Múltiple/economía , Péptidos/administración & dosificación , Péptidos/economía , RecurrenciaRESUMEN
We present an unconventional approach to antiviral drug discovery, which is used to identify potent small molecules against rabies virus. First, we conceptualized viral capsid assembly as occurring via a host-catalyzed biochemical pathway, in contrast to the classical view of capsid formation by self-assembly. This suggested opportunities for antiviral intervention by targeting previously unappreciated catalytic host proteins, which were pursued. Second, we hypothesized these host proteins to be components of heterogeneous, labile, and dynamic multi-subunit assembly machines, not easily isolated by specific target protein-focused methods. This suggested the need to identify active compounds before knowing the precise protein target. A cell-free translation-based small molecule screen was established to recreate the hypothesized interactions involving newly synthesized capsid proteins as host assembly machine substrates. Hits from the screen were validated by efficacy against infectious rabies virus in mammalian cell culture. Used as affinity ligands, advanced analogs were shown to bind a set of proteins that effectively reconstituted drug sensitivity in the cell-free screen and included a small but discrete subfraction of cellular ATP-binding cassette family E1 (ABCE1), a host protein previously found essential for HIV capsid formation. Taken together, these studies advance an alternate view of capsid formation (as a host-catalyzed biochemical pathway), a different paradigm for drug discovery (whole pathway screening without knowledge of the target), and suggest the existence of labile assembly machines that can be rendered accessible as next-generation drug targets by the means described.
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Antivirales/farmacología , Interacciones Huésped-Patógeno/efectos de los fármacos , Virus de la Rabia/efectos de los fármacos , Virus de la Rabia/fisiología , Proteínas Virales/fisiología , Secuencia de Aminoácidos , Animales , Sistema Libre de Células , Chlorocebus aethiops , Descubrimiento de Drogas , Interacciones Huésped-Patógeno/fisiología , Humanos , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Proteínas de la Nucleocápside/química , Proteínas de la Nucleocápside/genética , Proteínas de la Nucleocápside/fisiología , Dominios y Motivos de Interacción de Proteínas , Virus de la Rabia/genética , Células Vero , Proteínas Virales/química , Proteínas Virales/genética , Ensamble de Virus/efectos de los fármacosRESUMEN
BACKGROUND: Chronic hepatitis C virus (HCV) may progress to advanced liver disease (ALD), including decompensated cirrhosis and/or hepatocellular carcinoma (HCC). ALD can lead to significant clinical and economic consequences, including liver transplantation. This study evaluated the health care costs associated with ALD among HCV infected patients in a Medicaid population. METHODS: Using Florida Medicaid claims data, cases were patients with at least 1 diagnosis of HCV or prescription therapy for HCV (ribavirin plus interferon, peginterferon, or interferon alfacon-1) prior to an incident ALD-related diagnosis ("index event") between 1999 and 2007. ALD-related conditions included decompensated cirrhosis, HCC, or liver transplant. A cohort of HCV patients without ALD (comparison group subjects) were matched 1-to-1 based on age, sex, and race. Baseline and follow-up were the 12 months prior to and following index, respectively; with both periods allowing for a maximum one month gap in eligibility. For both case and comparison patient cohorts, per-patient-per-eligible month (PPPM) costs were calculated as total Medicaid paid amount for each patient over their observed number of eligible months in follow-up, divided by the patient's total number of eligible months. A generalized linear model (GLM) was constructed controlling for age, race, Charlson score, alcoholic cirrhosis, and hepatitis B to explore all-cause PPPM costs between study groups. The final study group included 1,193 cases and matched comparison patients (mean age: 49 years; 45% female; 54% white, 23% black, 23% other). RESULTS: The majority of ALD-related diagnoses were for decompensated cirrhosis (92%), followed by HCC (6%) and liver transplant (2%). Cases had greater comorbidity (mean Charlson score: 3.1 vs. 2.3, P < 0.001). All-cause inpatient use up to 1-year following incident ALD diagnosis was significantly greater among cases with ALD (74% vs. 27%, P < 0.001). In the GLM, cases had 2.39 times greater total adjusted mean all-cause PPPM costs compared to the comparison group ($4,956 vs. $1,735 respectively; P < 0.001). Among cases, mean total unadjusted ALD-related costs were $1,356 PPPM, which were largely driven by inpatient costs ($1,272). CONCLUSIONS: Our results suggest that among patients diagnosed with HCV, the incremental costs of developing ALD are substantial, with inpatient stays as the main driver of these increased costs.