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1.
RSC Adv ; 9(15): 8695-8699, 2019 Mar 12.
Article in English | MEDLINE | ID: mdl-35518684

ABSTRACT

We report a new synthetic route to a series of α-carboxynitrobenzyl photocaged l-aspartates for application in time-resolved structural biology. The resulting compounds were characterised in terms of UV/Vis absorption properties, aqueous solubility and stability, and photocleavage rates (τ = µs to ms) and quantum yields (φ = 0.05 to 0.14).

2.
Ther Innov Regul Sci ; 53(3): 403-411, 2019 05.
Article in English | MEDLINE | ID: mdl-30037308

ABSTRACT

BACKGROUND: Value demonstration in health care remains a challenge. This paper examines traditional approaches to pricing and the evolution of value-based pricing (VBP), and proposes a new framework for evidence-based valuation (EBV). The main objective of EBV is to estimate the value-based pricing range for the new medicine, identify key product attributes that drive value as perceived by various stakeholders, and then elucidate the requisite evidence to support those value claims. METHODS: EBV centers on a structured framework for estimating a drug's price based on its perceived value to various stakeholders. The EBV framework consists of identifying key value attributes that drive adoption of a drug in a given therapeutic area; gaining insights into stakeholder value considerations and evidence requirements; and quantifying stakeholders' perceptions of specific value attributes within pricing premiums. RESULTS: An example demonstrates the application of the EBV framework in a simplified manner for 3 drugs indicated for renal cell carcinoma, 3 drugs for prostate cancer, and 1 drug for melanoma. HTAs, published trial results, and publications archived in PubMed between 2005 and 2013 were analyzed to identify key value attributes. The following 5 attributes were considered: overall survival (OS), progression-free survival (PFS), population size, trial comparator, and adverse events. CONCLUSIONS: The method described offers a means to appraise pharmaceuticals in an environment increasingly focused on evidence-based medicine and value-based health care.


Subject(s)
Antineoplastic Agents/economics , Evidence-Based Medicine/economics , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Clinical Trials as Topic , Humans , Neoplasms/economics , Population Density , Survival Analysis , Treatment Outcome
3.
Pediatr Hematol Oncol ; 35(4): 288-296, 2018 May.
Article in English | MEDLINE | ID: mdl-30592246

ABSTRACT

Traditionally in hematopoietic stem cell transplant (HSCT), cyclosporine doses are individualized using cyclosporine trough concentrations (C0) while area under the concentration vs time curve (AUC) is used in solid organ transplant. AUC potentially has an important relationship with the development of acute graft-versus-host-disease (aGVHD). We conducted a prospective study to describe the relationship between severe (grade III-IV) aGVHD and cyclosporine AUC in pediatric HSCT recipients. Pediatric patients who underwent allogeneic myeloablative HSCT and scheduled to receive cyclosporine for aGVHD prophylaxis participated in this multicenter study. Cyclosporine doses were adjusted based on C0 according to each center's standard of care. Cyclosporine AUC was determined weekly until neutrophil engraftment or Day +42, whichever was later. Associations between severe aGVHD and cyclosporine AUC and other patient and treatment-related factors were evaluated. Of the 110 children enrolled, 97 were evaluable. Thirty-seven (38%) children developed aGVHD; 13 (13.4%) had severe aGVHD. On univariate analysis, there was no association between severe aGVHD and cyclosporine AUC at any time point before engraftment. Future research should focus on refinement of C0 targets for cyclosporine therapeutic drug monitoring in HSCT.


Subject(s)
Cyclosporine/adverse effects , Graft vs Host Disease/etiology , Transplantation Conditioning/adverse effects , Adolescent , Child , Child, Preschool , Cyclosporine/therapeutic use , Female , Graft vs Host Disease/pathology , Hematopoietic Stem Cell Transplantation/methods , Humans , Infant , Infant, Newborn , Male , Prospective Studies , Transplantation Conditioning/methods
4.
Mar Pollut Bull ; 127: 512-523, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29475691

ABSTRACT

The response of oyster (Crassostrea virginica) hemocytes was studied following exposure to anatase nanoparticles (ca. 7.4nm), surface-coated rutile nanocomposites (UV-Titan M212, ca. 86nm) and bulk titanium dioxide (TiO2) particles (anatase and rutile crystalline forms; 0.4-0.5µm). Hemocytes were collected from oysters and exposed to one of the four particle types at concentrations of 0.1, 0.5, and 1.0mg/L under dark and environmentally-relevant light conditions for periods of two and four hours. Hemocyte mortality, phagocytosis, and reactive oxygen species (ROS) production were then evaluated using flow-cytometric assays. Bulk and nanoparticulate TiO2 had little effect on viability of oyster hemocytes or on production of ROS. Significant changes in phagocytosis occurred after exposure to anatase nanoparticles for 4h under dark conditions, and UV-Titan for 2h under light conditions. Results demonstrate that TiO2 particles (bulk or nanoscale) produce minimal effects on hemocyte biomarkers examined following acute, in vitro exposures.


Subject(s)
Crassostrea/drug effects , Environmental Monitoring/methods , Hemocytes/drug effects , Nanoparticles/toxicity , Titanium/toxicity , Water Pollutants, Chemical/toxicity , Animals , Cell Survival/drug effects , Crassostrea/cytology , Flow Cytometry , Hemocytes/metabolism , Phagocytosis/drug effects , Reactive Oxygen Species/metabolism , Surface Properties
5.
Mar Environ Res ; 110: 45-52, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26263835

ABSTRACT

The production rates of titanium dioxide (TiO2) nanoparticles for consumer products far exceed the pace at which research can determine the effects of these particles in the natural environment. Sedentary organisms such as suspension-feeding bivalves are particularly vulnerable to anthropogenic contaminants, such as nanoparticles, that enter coastal environments. The purpose of this work was to examine the ingestion, bioaccumulation, and depuration rates of TiO2 nanoparticles by two species of suspension-feeding bivalves, the blue mussel (Mytilus edulis) and the eastern oyster (Crassostrea virginica). Two representative TiO2 nanoparticles, UV-Titan M212 (Titan) and Aeroxide P25 (P25), were delivered to the animals either incorporated into marine snow or added directly to seawater at a concentration of 1.0 mg/L for exposure periods of 2 and 6 h. After feeding, the animals were transferred to filtered-seawater and allowed to depurate. Feces and tissues were collected at 0, 12, 24, 72, and 120 h, post-exposure, and analyzed for concentrations of titanium by inductively coupled plasma-mass spectrometry. Results indicated that the capture and ingestion (i.e., transfer to the gut) of TiO2 nanoparticles by both mussels and oysters was not dependent on the presence of marine snow, and weight-standardized clearance rates of bivalves exposed to TiO2 nanoparticles were not significantly different than those of unexposed control animals. Both species ingested about half of the nanoparticles to which they were exposed, and >90% of the nanoparticles were egested in feces within 12 h, post-exposure. The findings of this study demonstrate that mussels and oysters can readily ingest both Titan and P25 nanoparticles regardless of the form in which they are encountered, but depurate these materials over a short period of time. Importantly, bioaccumulation of Titan and P25 nanoparticles does not occur in mussels and oysters following exposures of up to 6 h.


Subject(s)
Crassostrea/metabolism , Metal Nanoparticles/analysis , Mytilus edulis/metabolism , Titanium/metabolism , Water Pollutants, Chemical/metabolism , Animals , Connecticut , Environmental Monitoring
6.
Ann Epidemiol ; 25(8): 613-619.e2, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25935710

ABSTRACT

PURPOSE: Prescription drug overdose (PDO) deaths are a critical public health problem in the United States. This study aims to assess the association between emergency department (ED) utilization patterns in a cohort of ED patients and the risk of subsequent unintentional PDO mortality. METHODS: Using data from the New York Statewide Planning and Research Cooperative System for 2006-2010, a nested case-control design was used to examine the relationship between ED utilization patterns in New York State residents of age 18-64 years and subsequent PDO death. RESULTS: The study sample consisted of 2732 case patients who died of PDO and 2732 control ED patients who were selected through incidence density sampling. With adjustment for demographic characteristics, and diagnoses of pain, substance abuse, and psychiatric disorders, the estimated odds ratios of PDO death relative to one ED visit or less in the previous year were 4.90 (95% confidence interval [CI]: 4.50-5.34) for those with two ED visits, 16.61 (95% CI: 14.72-18.75) for those with three ED visits, and 48.24 (95% CI: 43.23-53.83) for those with four ED visits or more. CONCLUSIONS: Frequency of ED visits is strongly associated with the risk of subsequent PDO death. Intervention programs targeting frequent ED users are warranted to reduce PDO mortality.


Subject(s)
Drug Overdose/mortality , Emergency Service, Hospital/statistics & numerical data , Prescription Drugs/poisoning , Adolescent , Adult , Case-Control Studies , Death , Female , Health Care Surveys , Humans , Male , Middle Aged , New York/epidemiology , Prescription Drugs/administration & dosage , Risk Factors , Substance-Related Disorders/epidemiology , Young Adult
7.
Microb Ecol ; 65(4): 920-1, 2013 May.
Article in English | MEDLINE | ID: mdl-23052928

ABSTRACT

This piece is being submitted as a short commentary for the special edition on Oceans and Human Health (OHH). It is written from the perspective of a student who has attended all three biennial Gordon Research Conferences and Seminars on OHH beginning in 2008.


Subject(s)
Marine Biology/education , Public Health , Science/organization & administration , Congresses as Topic , Group Processes , Humans , Oceans and Seas , Public Health/education , Science/education
8.
Ther Innov Regul Sci ; 47(3): 306-311, 2013 May.
Article in English | MEDLINE | ID: mdl-30231435

ABSTRACT

Taking treatments from bench to bedside, or bench to community, requires a viable pathway connecting molecular science to global need through public and private research funding, clinical development, drug marketing, and policy making. In this paper, the authors present a systematic analysis of the effectiveness of translating basic science into reduced global burden of disease as a proxy for systemic public health impact. They pose a compound research question: Is the current drug development pipeline aligned with current and future global burden of disease, and, if not, where do the disconnections occur?

10.
Cancer ; 116(16): 3924-33, 2010 Aug 15.
Article in English | MEDLINE | ID: mdl-20626016

ABSTRACT

BACKGROUND: Children undergoing stem cell transplant (SCT) experience high levels of somatic distress and mood disturbance. This trial evaluated the efficacy of complementary therapies (massage, humor therapy, relaxation/imagery) for reducing distress associated with pediatric SCT. METHODS: Across 4 sites, 178 pediatric patients scheduled to undergo SCT were randomized to a child-targeted intervention involving massage and humor therapy, the identical child intervention plus a parent intervention involving massage and relaxation/imagery, or standard care. Randomization was stratified by site, age, and type of transplant. The interventions began at admission and continued through SCT Week +3. Primary outcomes included patient and parent reports of somatic distress and mood disturbance obtained weekly from admission through Week +6 using the Behavioral, Affective, and Somatic Experiences Scales. Secondary outcomes included length of hospitalization, time to engraftment, and usage of narcotic analgesic and antiemetic medications. RESULTS: A mixed model approach was used to assess longitudinal trends of patient and parent report outcomes and to test differences between groups on these measures. Significant changes across time were observed on all patient and parent report outcomes. However, no significant differences between treatment arms were found on the primary outcomes. Similarly, no significant between-group differences were noted on any of the medical variables as secondary outcomes. CONCLUSIONS: Results of this multisite trial failed to document significant benefits of complementary interventions in the pediatric SCT setting.


Subject(s)
Complementary Therapies , Parents , Stem Cell Transplantation/adverse effects , Stress, Psychological/therapy , Adolescent , Child , Female , Humans , Laughter Therapy , Length of Stay , Male , Massage
11.
Transl Res ; 156(2): 91-7, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20627193

ABSTRACT

To assess complete remission before subjecting nongermline metastatic retinoblastoma patients to an autologous peripheral stem cell transplant, we tested for patient-specific retinoblastoma tumor suppressor gene (RB1) mutant alleles in cerebrospinal fluid (CSF) and bone marrow. In 1 child with CSF and 1 with bone marrow metastases, allele-specific polymerase chain reaction (AS-PCR) detected the biallelic RB1 mutations specific to their tumors. The tumor of Child A was homozygous for R251X, and in Child B, it was homozygous for R358X. In Child A, the R251X mutation was detected in mutant controls diluted to 1:12,800 but not in CSF samples, corroborating clinical remission after chemotherapy. In Child B's bone marrow, AS-PCR for R358X was strongly positive at the detection of relapse, and subsequent bone marrow samples corroborated clinical remission after chemotherapy. No mutant tumor RB1 alleles were detected in their harvested peripheral blood stem cells. Both children were deemed suitable candidates for supralethal-dosage consolidation chemotherapy followed by autologous peripheral stem cell rescue of the bone marrow aimed at curing their metastatic retinoblastoma. When Child A recurred, the mutant tumor RB1 allele was detected 3.5 months before conventional pathology detected retinoblastoma tumor cells in the CSF. Assaying tumor-specific RB1 mutations complements cytological and immunohistochemical assessment of retinoblastoma involvement of CSF and bone marrow. Tumor cells can be detected in numbers lower than possible by conventional methods. An early diagnosis of relapse may allow an early institution of new therapy. A prospective international multicenter trial of the rare patients with metastatic retinoblastoma would assess the role of molecular monitoring in surveillance for minimal residual disease and recurrence.


Subject(s)
Mutation , Retinal Neoplasms/genetics , Retinoblastoma Protein/genetics , Retinoblastoma/genetics , Biopsy , Bone Marrow/pathology , Bone Marrow Transplantation , Bone Neoplasms/pathology , Cerebrospinal Fluid/metabolism , Child , Child, Preschool , Eye Enucleation , Female , Humans , Infant , Neoplasm Metastasis/genetics , Polymerase Chain Reaction , Radiography , Retinal Neoplasms/diagnostic imaging , Retinal Neoplasms/pathology , Retinal Neoplasms/surgery , Retinoblastoma/diagnostic imaging , Retinoblastoma/pathology , Retinoblastoma/surgery , Stem Cell Transplantation
12.
Pediatr Transplant ; 14(3): 377-82, 2010 May.
Article in English | MEDLINE | ID: mdl-19793223

ABSTRACT

Approximately 10% of children with ALL present at diagnosis with VHR for relapse if treated with chemotherapy alone. They may benefit from allogeneic HSCT in CR1. We have reviewed the outcome of this population in our institution. Forty-three patients (median age: 8.9 yr) with VHR ALL in CR1 underwent HSCT from October 1994 to April 2006. VHR features included Philadelphia chromosome (n = 17), induction failure (n = 9), hypodiploidy (n = 6), MLL gene rearrangement (n = 5), and others (n = 6). All patients received TBI (1200 cGy) with either CY and/or etoposide. Stem cell source was unrelated (n = 24) and related (n = 19). Incidence of grade III-IV acute GVHD and chronic extensive GVHD were 25% and 16%, respectively. Twelve patients relapsed (eight received related HSCT). Eleven patients died due to transplant-related mortality (eight received unrelated HSCT). For a median follow up of 39 months (range 11-110), the event free survival and OS were 0.49 (95% CI: 0.31-0.67) and 0.53 (CI: 0.44-0.71), respectively. Outcomes of children with VHR ALL receiving HSCT in CR1 remain unsatisfactory. Relapse, mainly after related HSCT, and TRM, mainly after unrelated HSCT, continue to be major problems.


Subject(s)
Hematopoietic Stem Cell Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Recurrence , Remission Induction , Risk Factors , Survival Rate , Transplantation Conditioning/methods , Treatment Outcome
13.
Ophthalmic Genet ; 30(3): 121-6, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19941416

ABSTRACT

OBJECTIVE: Cerebrospinal fluid (CSF) metastasis is the most difficult type of retinoblastoma metastasis to cure, even with bone marrow transplant. Most metastatic retinoblastoma cells express P-glycoprotein causing multidrug resistance (MDR). P-glycoprotein-rich blood vessels form blood-brain and blood-eye barriers, inhibit drug entry into central nervous system (CNS) and eyes. High-dose craniospinal radiation is too morbid for treatment of young children. To cure CSF metastasis without radiation, we designed an intensive multimodality chemotherapy regimen. METHOD: After left eye enucleation, a 4-month-old boy with bilateral International Intraocular Retinoblastoma Classification Group E eyes and CSF metastasis was treated with 7-cycle high-dose carboplatin and etoposide, standard-dose vincristine, and high-dose/short-infusion cyclosporine to inhibit P-glycoprotein. Intraventricular drugs, non-substrate of P-glycoprotein (cytarabine), or less susceptible to MDR (topotecan), contributed to treatment of the metastasis. On achieving complete response, he was consolidated with supralethal-dosage carboplatin, etoposide, and cyclophosphamide, and his bone marrow rescued with autologous cord blood stem cells. RESULTS: Following 1-cycle systemic chemotherapy and 2-dose intraventricular chemotherapy, the CSF metastasis cleared. The right eye tumor regressed completely. The patient remains in remission 8.3 years after diagnosis and 7.8 years post-transplant. CONCLUSION: Intensive multimodality chemotherapy can cure CSF metastasis in retinoblastoma without incurring extreme morbidity from craniospinal radiation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/therapy , Cerebrospinal Fluid , Cord Blood Stem Cell Transplantation , Retinal Neoplasms/therapy , Retinoblastoma/therapy , Carboplatin/administration & dosage , Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/secondary , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Etoposide/administration & dosage , Eye Enucleation , Humans , Infant , Male , Prognosis , Retinal Neoplasms/cerebrospinal fluid , Retinal Neoplasms/pathology , Retinoblastoma/cerebrospinal fluid , Retinoblastoma/secondary , Transplantation, Autologous , Treatment Outcome , Vincristine/administration & dosage
14.
Ann Pharmacother ; 43(4): 767-71, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19318596

ABSTRACT

OBJECTIVE: To report a case of calcineurin-induced pain syndrome (CIPS) in a child undergoing his second hematopoietic stem cell transplant (HSCT). CASE SUMMARY: A 6.1-year-old child received cyclosporine and methotrexate for acute graft-versus-host disease (aGVHD) prophylaxis after his first HSCT for acute myeloblastic leukemia. Amlodipine was given for the treatment of hypertension. Symptoms of CIPS were not observed. After the second HSCT at the age of 6.7 years, the child received cyclosporine (target trough whole blood cyclosporine concentration range 150-200 microg/L), starting on day -3, and mycophenolate mofetil for aGVHD prophylaxis. With the first cyclosporine dose, the patient complained of leg pain that was most severe during the cyclosporine infusion. Analgesic agents and a change from intravenous to oral administration of cyclosporine were ineffective in controlling the pain. Magnetic resonance imaging findings on day 10 showed periosteal soft tissue changes and mild bone marrow edema of the femora and tibiae. Tacrolimus was substituted for cyclosporine on day 20; on day 21 amlodipine was initiated to manage hypertension. Trough whole blood tacrolimus concentrations ranged from 1.7 to 6.2 microg/L. Pain was reduced in severity by day 29 and completely resolved once tacrolimus was discontinued on day 42. In this case, CIPS was considered to be probably associated with cyclosporine according to the Naranjo probability scale. DISCUSSION: CIPS is hypothesized to result from calcineurin-induced vascular changes that disturb bone perfusion and permeability, leading to intraosseous vasoconstriction and bone marrow edema. In our patient, symptoms were most acute during the infusion, when whole blood cyclosporine concentrations were likely to be the highest. Our patient's symptoms were resolved when tacrolimus was substituted for cyclosporine and amlodipine was initiated. CONCLUSIONS: Interventions aimed at reducing pain associated with CIPS may include the initiation of calcium-channel blocker therapy and conversion to an alternative calcineurin inhibitor.


Subject(s)
Cyclosporine/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Reflex Sympathetic Dystrophy/chemically induced , Calcium Channel Blockers/therapeutic use , Child , Hematopoietic Stem Cell Transplantation/methods , Humans , Male , Pain/chemically induced , Pain/diagnosis , Pain/drug therapy , Reflex Sympathetic Dystrophy/diagnosis , Reflex Sympathetic Dystrophy/drug therapy
15.
Pediatr Blood Cancer ; 52(5): 683-5, 2009 May.
Article in English | MEDLINE | ID: mdl-19156855

ABSTRACT

Several factors unique to Fanconi anemia (FA) limit the success of allogeneic hematopoietic stem cell transplantation (HSCT) in this population. In this report, we describe a multi-center pilot study of five consecutive FA patients with high-risk features for transplant prepared with fludarabine, without radiation. Four patients engrafted quickly, experienced minimal toxicity and are well at 43-65 months post-transplant. One patient had a C-mismatched unrelated donor transplant and had unsustained engraftment. This fludarabine based regimen without radiation was safe and effective for four high-risk patients, suggesting that eliminating radiation should be further studied as an approach to HSCT in children with FA.


Subject(s)
Fanconi Anemia/surgery , Hematopoietic Stem Cell Transplantation , Transplantation Conditioning/methods , Vidarabine/analogs & derivatives , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Graft Survival/drug effects , Humans , Male , Pilot Projects , Radiation , Risk Factors , Transplantation, Homologous , Treatment Outcome , Vidarabine/pharmacology
16.
Contraception ; 78(1): 36-41, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18555816

ABSTRACT

BACKGROUND: The study was conducted to assess outcomes among women using the levonorgestrel-releasing intrauterine system (LNG-IUS). STUDY DESIGN: The data were collected via a retrospective claims database analysis of 152 women. Two nested cohorts were further distinguished based on length of follow-up: two and three continuous years (n=73 and n=29, respectively). RESULTS: Over 90% had a single insertion, and fewer than 4% experienced an LNG-IUS-related complication. Thirteen percent of women experienced menorrhagia in the year preceding insertion; this figure dropped to 12.5%, 1.2% and 0% in the 1, 2 and 3 years postinsertion. Mean number of gynecology-related visits decreased from four to two in the overall cohort, from seven to four in the cohort with 2 years of follow-up and from nine to four in the cohort with 3 years of follow-up. CONCLUSION: LNG-IUS use prevented pregnancy in all patients and was associated with decreased vaginal bleeding starting in the second year postinsertion.


Subject(s)
Family Planning Services/methods , Intrauterine Devices, Medicated , Levonorgestrel/administration & dosage , Menorrhagia/therapy , Adult , Cohort Studies , Female , Humans , Levonorgestrel/therapeutic use , Middle Aged , Norethindrone/administration & dosage , Norethindrone/therapeutic use , Progesterone/administration & dosage , Progesterone/therapeutic use , Retrospective Studies
17.
Crit Care ; 12(2): R60, 2008.
Article in English | MEDLINE | ID: mdl-18442375

ABSTRACT

INTRODUCTION: Patients requiring prolonged acute mechanical ventilation (PAMV) represent one-third of those who need mechanical ventilation, but they utilize two-thirds of hospital resources devoted to mechanical ventilation. Measures are needed to optimize the efficiency of care in this population. Both duration of intensive care unit stay and mechanical ventilation are associated with anemia and increased rates of packed red blood cell (pRBC) transfusion. We hypothesized that transfusions among patients receiving PAMV are common and associated with worsened clinical and economic outcomes. METHODS: A retrospective analysis of a large integrated claims database covering a 5-year period (January 2000 to December 2005) was conducted in adult patients receiving PAMV (mechanical ventilation for >/= 96 hours). The incidence of pRBC transfusions was examined as the main exposure variable, and hospital mortality served as the primary outome, with hospital length of stay and costs being secondary outcomes. RESULTS: The study cohort included 4,344 hospitalized patients receiving PAMV (55% male, mean age 61.5 +/- 16.4 years). Although hemoglobin level upon admission was above 10 g/dl in 75% of patients, 67% (n = 2,912) received at least one transfusion, with a mean of 9.1 +/- 12.0 units of pRBCs transfused per patient over the course of hospitalization. In regression models adjusting for confounders, exposure to pRBCs was associated with a 21% increase in the risk for hospital death (95% confidence interval [CI] = 1.00 to 1.48), and marginal increases in length of stay (6.3 days, 95% CI = 5.1 to 7.6) and cost ($48,972, 95% CI = $45,581 to $52,478). CONCLUSION: Patients receiving PAMV are at high likelihood of being transfused with multiple units of blood at relatively high hemoglobin levels. Transfusions independently contribute to increased risk for hospital death, length of stay, and costs. Reducing exposure of PAMV patients to blood may represent an attractive target for efforts to improve quality and efficiency of health care delivery in this population.


Subject(s)
Anemia/etiology , Anemia/therapy , Blood Transfusion/statistics & numerical data , Critical Illness/therapy , Respiration, Artificial , Chi-Square Distribution , Comorbidity , Female , Humans , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Male , Middle Aged , Regression Analysis , Respiration, Artificial/adverse effects , Retrospective Studies , Statistics, Nonparametric , Treatment Outcome
18.
Br J Haematol ; 140(2): 214-7, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18028482

ABSTRACT

This retrospective cohort study aimed at determining whether overweight children undergoing allogeneic stem cell transplantation (SCT) had inferior overall survival compared with children who were not overweight. Children >/=2 years of age who received allogeneic SCT were included. Overweight was defined as a body mass index >/= 95th percentile; 54/325 (17%) children were overweight. Overall survival at 5 years was significantly inferior at 46.6 +/- 7.3% in the overweight group compared with 59.5 +/- 3.2% in the non-overweight group (P = 0.02). Our study demonstrated that overweight children who undergo allogeneic SCT had inferior survival compared with children who were not overweight.


Subject(s)
Hematopoietic Stem Cell Transplantation , Overweight/complications , Adolescent , Anthropometry/methods , Body Mass Index , Child , Child, Preschool , Epidemiologic Methods , Female , Humans , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/therapy , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prognosis , Treatment Outcome
19.
Ophthalmology ; 115(1): 11-7, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17475331

ABSTRACT

PURPOSE: To evaluate total and condition-related charges incurred by blind patients in a managed care population in the United States and compare total charges with those of a matched nonblind cohort. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with blindness (N = 10 796) and a 1:1 matched cohort of nonblind patients were selected from a managed care claims database. All study subjects were required to be > or =18 years old at diagnosis (blind patients) or enrollment (nonblind patients) and to have had > or =1 years of continuous follow-up. METHODS: Total and pharmacy-related direct medical charges in the first year of follow-up were calculated for both blind and nonblind cohorts. Among blind patients, condition-related charges, charge per treated person, and charge breakdown by age group were calculated. For patients with follow-up extending past 1 year, total charges (both cohorts) and condition-related charges (blind cohort only) were assessed and annualized. Mean and median charges were assessed for blind and nonblind patients within each stratum of matched covariates; a multivariate linear regression assessed the statistical significance of the difference in charges between the 2 cohorts. MAIN OUTCOME MEASURES: Total health care charges in the first year of follow-up and condition-related health care charges in the first year of follow-up for blind patients. RESULTS: For the blind population (mean age, 52 years [standard deviation (SD), 17.5]), the total mean and median health care charges per person in the first year were $20,677 (SD, $48,835) and $6854, respectively. Total mean and median health care charges per nonblind patient in the first year were $13,321 (SD, $40,059) and $3778, respectively. Condition-related charges among blind patients were substantially lower than total charges, with mean and median charges per person of $4565 (SD, $17,472) and $371, respectively. After adjusting for covariates, blind patients had significantly higher total health care charges in the first year of follow-up than nonblind patients (P<0.0001). Costs of the blind did not differ substantially from costs of the normally sighted in subsequent years of follow-up. CONCLUSION: This study demonstrates the substantial direct cost burden of blindness during the first year of follow-up in a managed care population.


Subject(s)
Blindness/economics , Cost of Illness , Direct Service Costs , Managed Care Programs/economics , Visually Impaired Persons , Aged , Databases, Factual , Female , Health Services Research , Humans , Male , Middle Aged , Retrospective Studies , United States
20.
Ophthalmology ; 115(4): 633-638.e4, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17716736

ABSTRACT

OBJECTIVES: To determine the total and condition-related direct health care charges of patients with ocular hypertension (OH) or primary open-angle glaucoma (POAG) and identify factors that affect these charges. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with OH (n = 36 767) and POAG (n = 72 412) with > or =1 year of continuous enrollment during calendar years 1998 through 2005 in a nationally representative, multimanaged health plan database (PharMetrics). METHODS: First year total health care and condition-related charges were calculated. Subsequently multivariate linear regression models determined the impact of ophthalmic condition (OH or POAG), age, index year, gender, geographic region, payer mix, product type, treatment with glaucoma medication, ocular comorbidities, and systemic comorbidities on these charges. MAIN OUTCOME MEASURES: Per-person per year first-year total health care and ocular condition-related charges in United States dollars, adjusted for multiple covariates. RESULTS: Patients with POAG had significantly higher adjusted total and condition-related health care charges during the first year of follow-up than patients with OH in multivariable analysis ($2070 vs. $1990, P<0.0001 and $556 vs. $322 P<0.0001, respectively). Females and older patients had higher total health care charges compared with males and younger patients ($586 or 28.3% more; P<0.0001 and $27 per year or 0.8% per year more; P<0.0001, respectively). However, neither gender nor age were strong determinants of condition-related charges (P = 0.13 and P = 0.052, respectively). Index year, region, payer, and product types significantly dictated both total and disease-related charges. Patients with ocular comorbid conditions, including cataracts, cataract surgery, diabetic retinopathy, and blindness, had significantly higher total and condition-related health care charges than patients without these conditions (P<0.0001). CONCLUSION: Total and condition-related health care charges are considerable for patients with OH and POAG. These data identify several factors that dictate these charges.


Subject(s)
Fees and Charges , Glaucoma, Open-Angle/therapy , Health Care Costs , Ocular Hypertension/therapy , Age Factors , Aged , Cohort Studies , Comorbidity , Databases, Factual , Eye Diseases/epidemiology , Female , Follow-Up Studies , Glaucoma, Open-Angle/epidemiology , Humans , Linear Models , Male , Managed Care Programs , Middle Aged , Ocular Hypertension/epidemiology , Retrospective Studies , Sex Factors , United States
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