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1.
Pharmacoepidemiol Drug Saf ; 31(2): 141-148, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34363294

RESUMO

PURPOSE: Secondary hyperparathyroidism (SHPT) is common among dialysis patients, and calcimimetics are a mainstay of treatment. This study assessed whether cinacalcet use is associated with gastrointestinal bleeding in a large hemodialysis cohort. METHODS: A linked database of clinical records and medical claims for patients receiving hemodialysis in a large dialysis organization, 2007-2010, was used. A nested case-control study was performed among patients aged ≥18 years who had received hemodialysis for ≥90 days, had Medicare Parts A, B, and D coverage for ≥1 year, and had clinical evidence of SHPT (parathyroid hormone >300 pg/mL). Cases were those who experienced death or hospitalization caused by gastrointestinal bleeding. Each case was matched to up to four controls. Exposure was measured by any cinacalcet use, current use, past use, cumulative exposure days, and cumulative dosage. Conditional logistic models were used to assess the association. RESULTS: Of 48 437 patients included, 2570 experienced gastrointestinal bleeding events (2498 non-fatal, 72 fatal), and 2465 (2397 non-fatal, 68 fatal) were matched to 9500 controls; 17.2% of cases and 15.8% of controls had cinacalcet exposure and 11.1% of both cases and controls had current use. The adjusted odds ratios (95% CI) of gastrointestinal bleeding for any use, current use, and past use of cinacalcet were 1.04 (0.91-1.19), 0.97 (0.83-1.13), and 1.22 (0.99-1.50), respectively, with no use as the reference. CONCLUSION: The results do not suggest an elevated risk of gastrointestinal bleeding resulting in hospitalization or death for hemodialysis patients exposed to cinacalcet.


Assuntos
Hiperparatireoidismo Secundário , Medicare , Adolescente , Adulto , Idoso , Calcimiméticos/efeitos adversos , Cálcio , Estudos de Casos e Controles , Cinacalcete/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Humanos , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/epidemiologia , Hormônio Paratireóideo , Diálise Renal/efeitos adversos , Estados Unidos/epidemiologia
2.
Clin Nephrol ; 86 (2016)(11): 262-269, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27641053

RESUMO

;Aims: Standardized mortality and hospitalization ratios (SMRs, SHRs) are used to measure dialysis facility performance in the US, with adjustment for demographics and comorbid conditions derived from the end-stage renal disease (ESRD) Medical Evidence (ME) Report. Sensitivities are low for ME-based comorbidity, and levels of under-reporting may differ among facilities. We aimed to assess the effect of data inaccuracy on performance comparison. METHODS: Using the United States Renal Data System ESRD database, we included patients who initiated hemodialysis July 1 - December 31 in each of the years 2006 - 2010, had Medicare as primary payer, were aged ≥ 66 years, and had no prior transplant. Patients were followed from dialysis initiation to the earliest of death, transplant, modality change, or 1 year. SMRs and SHRs were calculated for for-profit/non-profit and rural/urban facilities for ME-based and claims-based comorbidity, separately. Cox models were used for expected number of deaths and piecewise Poison models for expected number of hospitalizations. Comorbidity agreement was measured by κ-statistic. Testing of differences between ME-based and claims-based SMRs/SHRs was performed by bootstrap. RESULTS: In all, 73,950 incident hemodialysis patients were included. κ-values for comorbidity agreement were low, < 0.5, except for diabetes (0.77). Percentages of claims-based comorbidity were similar for for-profit and non-profit facilities; ME-based comorbidity was lower for for-profit facilities. Differences between ME-based and claims-based SMRs/SHRs were statistically significant. Compared with ME-based SMRs/SHRs, claims-based ratios decreased 0.9/0.6% for for-profit and 1/0.7% for urban facilities and increased 3.4/2.8% for non-profit and 5.9/4.1% for rural facilities. CONCLUSIONS: Comorbidity data source may affect performance evaluation. The impact is larger for smaller groups.
.


Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Comorbidade , Confiabilidade dos Dados , Hospitalização/estatística & dados numéricos , Falência Renal Crônica/mortalidade , Diálise Renal/estatística & dados numéricos , Adulto , Idoso , Instituições de Assistência Ambulatorial/normas , Fatores de Confusão Epidemiológicos , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Medicare , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Diálise Renal/normas , Serviços de Saúde Rural/estatística & dados numéricos , Estados Unidos , Serviços Urbanos de Saúde/estatística & dados numéricos
3.
Am J Kidney Dis ; 65(1): 98-108, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25085647

RESUMO

BACKGROUND: Cardiovascular disease is a common cause of hospitalization in dialysis patients. Daily hemodialysis improves some parameters of cardiovascular function, but whether it associates with lower hospitalization risk is unclear. STUDY DESIGN: Observational cohort study using US Renal Data System data. SETTING & PARTICIPANTS: Medicare-enrolled daily (5 or 6 sessions weekly) home hemodialysis (HHD) patients initiating NxStage System One use from January 1, 2006, through December 31, 2009, and contemporary thrice-weekly in-center hemodialysis patients, matched 5 to 1. PREDICTOR: Daily HHD or thrice-weekly in-center hemodialysis. OUTCOMES & MEASUREMENTS: All-cause and cause-specific hospital admissions, hospital readmissions, and hospital days assessed from Medicare Part A claims. RESULTS: For 3,480 daily HHD and 17,400 thrice-weekly in-center hemodialysis patients in intention-to-treat analysis, the HR of all-cause admission for daily HHD versus in-center hemodialysis was 1.01 (95%CI, 0.98-1.03). Cause-specific admission HRs were 0.89 (95%CI, 0.86-0.93) for cardiovascular disease, 1.18 (95%CI, 1.13-1.23) for infection, 1.01 (95%CI, 0.93-1.09) for vascular access dysfunction, and 1.02 (95%CI, 0.99-1.06) for other morbidity. Regarding cardiovascular disease, first admission and readmission HRs for daily HHD versus in-center hemodialysis were 0.91 and 0.87, respectively. Regarding infection, first admission and readmission HRs were 1.35 and 1.03, respectively. Protective associations of daily HHD with heart failure and hypertensive disease were most pronounced, as were adverse associations of daily HHD with bacteremia/sepsis, cardiac infection, osteomyelitis, and vascular access infection. LIMITATIONS: Results may be confounded by unmeasured factors, including vascular access type; information about dialysis frequency, duration, and dose was lacking; causes of admission may be misclassified; results may not apply to patients without Medicare coverage. CONCLUSIONS: All-cause hospitalization risk was similar in daily HHD and thrice-weekly in-center hemodialysis patients. However, risk of cardiovascular-related admission was lower with daily HHD, and risk of infection-related admission was higher. More attention should be afforded to infection in HHD patients.


Assuntos
Doenças Cardiovasculares , Hemodiálise no Domicílio , Hospitalização/estatística & dados numéricos , Infecções , Falência Renal Crônica , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapia , Estudos de Coortes , Feminino , Hemodiálise no Domicílio/efeitos adversos , Hemodiálise no Domicílio/métodos , Hemodiálise no Domicílio/estatística & dados numéricos , Humanos , Infecções/epidemiologia , Infecções/etiologia , Infecções/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Assistência Médica/estatística & dados numéricos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
4.
BMC Nephrol ; 16: 41, 2015 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-25886282

RESUMO

BACKGROUND: Cinacalcet reduces parathyroid hormone (PTH) levels in patients receiving hemodialysis, but no non-experimental studies have evaluated the association between changes in PTH levels following cinacalcet initiation and clinical outcomes. We assessed whether short-term change in PTH levels after first cinacalcet prescription could serve as a surrogate marker for improvements in longer-term clinical outcomes. METHODS: United States Renal Data System data were linked with data from a large dialysis organization. We created a point prevalent cohort of adult hemodialysis patients with Medicare as primary payer who initiated cinacalcet November 1, 2004-February 1, 2007, and were on cinacalcet for ≥ 40 days. We grouped patients into quartiles of PTH change after first cinacalcet prescription. We used Cox proportional hazard modeling to evaluate associations between short-term PTH change and time to first composite event (hospitalization for cardiovascular events or mortality) within 1 year. Overall models and models stratified by baseline PTH levels were adjusted for several patient-related factors. RESULTS: For 2485 of 3467 included patients (72%), PTH levels decreased after first cinacalcet prescription; for 982 (28%), levels increased or were unchanged. Several characteristics differed between PTH change groups, including age and mineral-and-bone-disorder laboratory values. In adjusted models, we did not identify an association between greater short-term PTH reduction and lower composite event rates within 1 year, overall or in models stratified by baseline PTH levels. CONCLUSIONS: Short-term change in PTH levels after first cinacalcet prescription does not appear to be a useful surrogate for longer-term improvements in cardiovascular or survival risk.


Assuntos
Cinacalcete/uso terapêutico , Hiperparatireoidismo Secundário/tratamento farmacológico , Falência Renal Crônica/terapia , Hormônio Paratireóideo/sangue , Diálise Renal/efeitos adversos , Adulto , Idoso , Análise de Variância , Estudos de Coortes , Bases de Dados Factuais , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/mortalidade , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/efeitos dos fármacos , Prognóstico , Modelos de Riscos Proporcionais , Diálise Renal/métodos , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos
5.
Am J Nephrol ; 37(4): 389-98, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23548469

RESUMO

BACKGROUND/AIMS: Data describing real-world use and effectiveness of cinacalcet are limited. We aimed to characterize predictors of treatment and changes in secondary hyperparathyroidism (SHPT) biochemistry after cinacalcet initiation. METHODS: We studied 25,250 in-center hemodialysis patients from a large dialysis provider, alive through November 2004, with no prior cinacalcet prescription. Patients were followed until initiation of cinacalcet, censoring, death, or July 31, 2007. Initiators were further followed for dose titration and discontinuation. Predictors of these events were evaluated using Cox proportional hazards modeling. Biochemical parameters and other SHPT medication use were compared between baseline, pre-initiation, and post-initiation time points. RESULTS: Over an average of 1.25 years of follow-up, 30% of patients initiated cinacalcet therapy. Between baseline and initiation (mean of 386 days), parathyroid hormone (PTH) and phosphorus levels increased 78 and 7%, respectively, in these patients. After adjustment, cinacalcet initiation was associated with higher SHPT severity, younger age, African-American race, higher phosphorus levels, and more comorbidity. Within 1 month of initiation, median PTH was reduced by 15-30% and phosphorus by 3-5%. Reductions were sustained or increased over 12 months, depending on initiating PTH level and whether dose up-titration occurred. Discontinuation was common, although many patients reinitiated. CONCLUSIONS: A substantial proportion of patients experienced SHPT progression and initiated cinacalcet treatment. Reductions in biochemistry varied by disease severity and whether doses were titrated.


Assuntos
Hiperparatireoidismo Secundário/tratamento farmacológico , Naftalenos/uso terapêutico , Diálise Renal , Vitamina D/administração & dosagem , Adolescente , Adulto , Idoso , Cálcio/sangue , Cinacalcete , Feminino , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/sangue , Fósforo/sangue , Estados Unidos , Adulto Jovem
6.
Am J Nephrol ; 38(2): 104-14, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23899621

RESUMO

BACKGROUND/AIMS: African-Americans with end-stage renal disease receiving dialysis have more severe secondary hyperparathyroidism than Whites. We aimed to assess racial differences in clinical use of cinacalcet. METHODS: This retrospective cohort study used data from DaVita, Inc., for 45,589 prevalent hemodialysis patients, August 2004, linked to Centers for Medicare & Medicaid Services data, with follow-up through July 2007. Patients with Medicare as primary payer, intravenous vitamin D use, or weighted mean parathyroid hormone (PTH) level >150 pg/ml at baseline (August 1-October 31, 2004) were included. Cox proportional hazard modeling was used to evaluate race and other demographic and clinical characteristics as predictors of cinacalcet initiation, titration, and discontinuation. RESULTS: Of 16,897 included patients, 7,674 (45.4%) were African-American and 9,223 (54.6%) were white; 53.2% of cinacalcet users were African-American. Cinacalcet was prescribed for 47.7% of African-Americans and 34.5% of Whites, and for a greater percentage of African-Americans at higher doses at each PTH strata. After covariate adjustment, African-Americans were more likely than Whites to receive cinacalcet prescriptions (hazard ratio 1.17, p < 0.001). The direction and magnitude of this effect appeared to vary by age, baseline PTH, and calcium, and by elemental calcium use. African-Americans were less likely than Whites to have prescriptions discontinued and slightly more likely to undergo uptitration (hazard ratio 1.09, 95% confidence interval 0.995-1.188), but this relationship lacked statistical significance. CONCLUSION: Cinacalcet is prescribed more commonly and at higher initial doses for African-Americans than for Whites to manage secondary hyperparathyroidism.


Assuntos
Negro ou Afro-Americano , Calcimiméticos/uso terapêutico , Disparidades em Assistência à Saúde , Falência Renal Crônica/etnologia , Falência Renal Crônica/terapia , Naftalenos/uso terapêutico , Diálise Renal/métodos , Adolescente , Adulto , Idoso , Centers for Medicare and Medicaid Services, U.S. , Cinacalcete , Feminino , Humanos , Falência Renal Crônica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/uso terapêutico , Modelos de Riscos Proporcionais , Qualidade da Assistência à Saúde , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Vitamina D/uso terapêutico , População Branca , Adulto Jovem
7.
Kidney Int ; 78(6): 578-89, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20555319

RESUMO

Secondary hyperparathyroidism (SHPT) affects a significant number of hemodialysis patients, and metabolic disturbances associated with it may contribute to their high mortality rate. As patients with lower serum calcium, phosphorus, and parathyroid hormone are reported to have improved survival, we tested whether prescription of the calcimimetic cinacalcet to hemodialysis patients with SHPT improved their survival. We prospectively collected data on hemodialysis patients from a large provider beginning in 2004, a time coincident with the commercial availability of cinacalcet hydrochloride. This information was merged with data in the United States Renal Data System to determine all-cause and cardiovascular mortality. Patients included in the study received intravenous (i.v.) vitamin D therapy (a surrogate for the diagnosis of SHPT). Of 19,186 patients, 5976 received cinacalcet and all were followed from November 2004 for up to 26 months. Unadjusted and adjusted time-dependent Cox proportional hazards modeling found that all-cause and cardiovascular mortality rates were significantly lower for those treated with cinacalcet than for those without calcimimetic. Hence, this observational study found a significant survival benefit associated with cinacalcet prescription in patients receiving i.v. vitamin D. Definitive proof, however, of a survival advantage awaits the performance of randomized clinical trials.


Assuntos
Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/mortalidade , Naftalenos/uso terapêutico , Calcimiméticos/uso terapêutico , Doenças Cardiovasculares/mortalidade , Cinacalcete , Estudos de Coortes , Bases de Dados Factuais , Avaliação de Medicamentos , Humanos , Falência Renal Crônica/epidemiologia , Estudos Prospectivos , Diálise Renal , Taxa de Sobrevida , Vitamina D/uso terapêutico
8.
Clin J Am Soc Nephrol ; 11(8): 1413-1421, 2016 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-27269611

RESUMO

BACKGROUND AND OBJECTIVES: Fractures are a major source of morbidity and mortality in patients receiving dialysis. We sought to determine whether rates of fractures and tendon ruptures vary geographically. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the US Renal Data System were used to create four yearly cohorts, 2007-2010, including all eligible prevalent patients on hemodialysis in the United States on January 1 of each year. A secondary analysis comprising patients in a large dialysis organization conducted over the same period permitted inclusion of patient-level markers of mineral metabolism. Patients were grouped into 10 regions designated by the Centers for Medicare and Medicaid Services and divided by latitude into one of three bands: south, <35°; middle, 35° to <40°; and north, ≥40°. Poisson regression was used to calculate unadjusted and adjusted region-level rate ratios for events. RESULTS: Overall, 327,615 patients on hemodialysis were included. Mean (SD) age was 61.8 (15.0) years old, 52.7% were white, and 55.0% were men. During 716,962 person-years of follow-up, 44,014 fractures and tendon ruptures occurred, the latter being only 0.3% of overall events. Event rates ranged from 5.36 to 7.83 per 100 person-years, a 1.5-fold rate difference across regions. Unadjusted region-level rate ratios varied from 0.83 (95% confidence interval, 0.81 to 0.85) to 1.20 (95% confidence interval, 1.18 to 1.23), a 1.45-fold rate difference. After adjustment for a wide range of case mix variables, a 1.33-fold variation in rates remained. Rates were higher in north and middle bands than the south (north rate ratio, 1.18; 95% confidence interval, 1.13 to 1.23; middle rate ratio, 1.13; 95% confidence interval, 1.10 to 1.17). Latitude explained 11% of variation, independent of region. A complementary analysis of 87,013 patients from a large dialysis organization further adjusted for circulating mineral metabolic parameters and protein energy wasting yielded similar results. CONCLUSIONS: Rates of fractures vary geographically in the United States dialysis population, even after adjustment for known patient characteristics. Latitude seems to contribute to this phenomenon, but additional analyses exploring whether other factors might influence variation are warranted.


Assuntos
Fraturas Ósseas/epidemiologia , Falência Renal Crônica/terapia , Diálise Renal/estatística & dados numéricos , Traumatismos dos Tendões/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Ruptura , Análise Espaço-Temporal , Estados Unidos/epidemiologia , Adulto Jovem
9.
Shock ; 19(4): 321-7, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12688542

RESUMO

Lipopolysaccharide (LPS) stimulation of macrophages or monocytes is believed to occur via a serum- and CD14-dependent signaling pathway via toll-like receptor 4 (TLR4). We sought to determine whether serum and/or CD14 are required for LPS to induce the endotoxin-tolerant state in human monocytes. LPS treatments were performed in the presence or absence of an anti-CD14 monoclonal antibody and with or without fetal bovine serum. Endotoxin tolerance was assessed after an 18-h exposure (pretreatment) to 10 ng/mL of LPS. Medium was discarded and cells were challenged with activating (1-1000 ng/mL) doses of LPS. LPS-stimulated tumor necrosis factor (TNF) secretion into culture supernatants was determined after 5 h by ELISA and p44/p42 ERK kinase activation was measured after 30 min by Western blot. Statistical analysis was by ANOVA. LPS induced endotoxin-tolerance with a significant inhibition of LPS-stimulated TNF secretion and less p44/p42 ERK kinase activation. When LPS-stimulation of naïve (nontolerant) monocytes was performed in medium with anti-CD14 antibody or without serum, there was marked blunting of TNF release. However, LPS pretreatment in medium without serum or in medium containing anti-CD14 antibody resulted in changes in monocyte activation and function characteristic of endotoxin tolerance. LPS-stimulated p44/p42 ERK kinase activation and TNF release were diminished whether or not anti-CD14 antibody was present during LPS pretreatment. LPS-stimulated TNF secretion and p44/p42 ERK kinase activation require the presence of serum and are inhibited by anti-CD14 antibody. Our findings suggest that LPS induces endotoxin tolerance in human monocytic cells via a pathway that does not require serum or cell surface CD14.


Assuntos
Endotoxinas/farmacologia , Sangue Fetal/fisiologia , Receptores de Lipopolissacarídeos/fisiologia , Lipopolissacarídeos/farmacologia , Monócitos/efeitos dos fármacos , Animais , Anticorpos Monoclonais/farmacologia , Bovinos , Tolerância a Medicamentos , Ativação Enzimática/efeitos dos fármacos , Humanos , Receptores de Lipopolissacarídeos/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Monócitos/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
Surgery ; 133(5): 538-46, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12773982

RESUMO

BACKGROUND: Increased systemic levels of inflammatory mediators are seen after open abdominal operations. Macrophages that are exposed to lipopolysaccharide secrete cytokines. Peritoneal macrophages normally reside in a pO(2) of 40 mm Hg. We hypothesize that exposure of lipopolysaccharide-stimulated macrophages to "non-physiologic" pO(2) augments cytokine secretion. METHOD: Murine macrophages were preconditioned to a pO(2) of 40 mm Hg for 24 hours. The medium then was discarded and exchanged for a medium containing a pO(2) of 40, 150, or 440 mm Hg. Macrophages were incubated in the desired pO(2) for 6 and 24 hours while stimulated with lipopolysaccharide (0 to 100 ng/mL). The effect of pO(2) was compared. Supernatant tumor necrosis factor (TNF) and interleukin-6 were measured with enzyme-linked immunosorbent assay. Statistics were performed with analysis of variance. RESULTS: We found dose-dependent lipopolysaccharide-stimulated TNF and interleukin-6 production with macrophages incubated at physiologic pO(2). Higher pO(2) did not stimulate TNF and interleukin-6 in the absence of lipopolysaccharide. However, a pO(2) of 150 and 440 mm Hg significantly (P <.05) increased lipopolysaccharide-stimulated TNF and interleukin-6 production versus 45 mm Hg. CONCLUSION: Our data suggest synergy between increased pO(2) and lipopolysaccharide for macrophage TNF and interleukin-6 production. Similar pO(2) elevations may occur with an open peritoneum or high supplemental O(2). Cytokines from peritoneal macrophages may contribute to the increased systemic inflammation after open operations.


Assuntos
Citocinas/metabolismo , Hiperóxia/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/metabolismo , Animais , Células Cultivadas , Meios de Cultura/química , Relação Dose-Resposta a Droga , Interleucina-6/biossíntese , Lipopolissacarídeos/administração & dosagem , Macrófagos Peritoneais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oxigênio/metabolismo , Pressão Parcial , Fator de Necrose Tumoral alfa/biossíntese
11.
Surg Infect (Larchmt) ; 4(2): 171-80, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12906717

RESUMO

BACKGROUND: In vitro pretreatment of human monocytes with lipopolysaccharide (LPS) induces "endotoxin tolerance" with blunted TNF and IL-6 release to rechallenge with LPS. The pro-inflammatory cytokines TNF and IL-6 are important mediators in sepsis. A high IL-6 concentration has been used as a marker of infection severity, but IL-6 may also have beneficial effects as an acute-phase protein. We sought to address two questions: (a) What is the relationship between TNF and IL-6 release? (b) Is the clinical outcome different for intensive care unit (ICU) patients with ex vivo characteristics of endotoxin tolerance (low levels of ex vivo LPS-stimulated cytokine release)? MATERIALS AND METHODS: Heparinized whole blood was obtained from 62 surgical ICU patients and 15 control subjects and incubated for 3 h at 37 degrees C in the presence or absence of 10 ng/mL LPS. Concentrations of TNF and IL-6 were measured in plasma samples using an enzyme-linked immunosorbent assay (pg/mL). Clinical data on ICU length of stay (LOS), ventilator days, white blood cell count (WBC), and documented clinical infection were obtained by chart review. Outcome parameters for patients with low ex vivo LPS-stimulated cytokine release (low = IL-6 < 3000 pg/mL and TNF <2100 pg/mL) were compared to patients with Normal/High concentrations of cytokines. RESULTS: Cytokines were essentially undetectable in ICU patients or controls without LPS stimulation, however a range of values was measured for LPS-stimulated release in both ICU patients (IL-6, 7847 +/- 857 pg/mL; TNF, 4390 +/- 457 pg/mL) and controls (IL-6, 7704 +/- 793 pg/mL; TNF, 6706 +/- 715 pg/mL). There were no differences in age between High/Normal concentrations of cytokines compared to the Low cytokine group, however there were significant differences in WBC, cytokine concentrations, ICU LOS, incidence of clinical infection, and mortality. The Low group also required an average of 6.9 more days of mechanical ventilation (p < 0.05). LPS-stimulated TNF release seemed to correlate better with the observed mortality than did IL-6 release. CONCLUSION: The data suggest that ICU patients with characteristics of endotoxin tolerance (low LPS-stimulated cytokine release capacity) have significantly poorer clinical outcomes. Ex vivo LPS-stimulated whole blood cytokine production may be useful to identify ICU patients with severe sepsis.


Assuntos
Interleucina-6/biossíntese , Lipopolissacarídeos/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Adulto , Cuidados Críticos , Humanos , Técnicas In Vitro , Interleucina-6/imunologia , Lipopolissacarídeos/sangue , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/imunologia
12.
Clin J Am Soc Nephrol ; 4(2): 354-60, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19129318

RESUMO

BACKGROUND AND OBJECTIVES: Cinacalcet was introduced in mid-2004 to treat secondary hyperparathyroidism in dialysis patients. We aimed to characterize adult patients who received cinacalcet prescriptions and to determine (1) dosage titration and effects on laboratory values, active intravenous vitamin D use, and phosphate binder prescriptions and (2) percentage who achieved National Kidney Foundation Kidney Disease Outcomes Quality Initiative targets for serum parathyroid hormone, calcium, and phosphorus and experienced biochemical adverse effects. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This observational study evaluated 45,487 prevalent patients from a dialysis organization database linked with the Centers for Medicare and Medicaid Services End-Stage Renal Disease database. Patient characteristics, laboratory values (albumin, parathyroid hormone, calcium, phosphorus), intravenous vitamin D, and oral medication (cinacalcet, phosphate binders) prescriptions were evaluated for cinacalcet patients. RESULTS: By June 2006, almost 32% of patients had received cinacalcet prescriptions. Mean baseline corrected calcium was 9.8 mg/dl and phosphorus was 6.3 mg/dl, and median parathyroid hormone was 577 pg/ml, versus 9.5 mg/dl, 5.3 mg/dl, and 215 pg/ml, respectively, for noncinacalcet patients. Patients with cinacalcet prescriptions for > or =6 mo had corrected calcium reduced by 4.2%, phosphorus by 7.0%, and parathyroid hormone by 29.9% by 12 mo. More cinacalcet patients attained Kidney Disease Outcomes Quality Initiative targets with less hyperparathyroidism, hypercalcemia, and hyperphosphatemia but more hypoparathyroidism and hypocalcemia. Over 12 mo, vitamin D use and use consistency increased, phosphate binder dosages increased, and mean cinacalcet daily dosage reached 55 mg. CONCLUSIONS: Patients with cinacalcet prescriptions exhibited more severe hyperparathyroidism and hyperphosphatemia than noncinacalcet patients. Positive effects were less dramatic than in Phase III clinical trials, possibly as a result of modest, slow dosage titration.


Assuntos
Biomarcadores/sangue , Hiperparatireoidismo Secundário/tratamento farmacológico , Falência Renal Crônica/terapia , Naftalenos/uso terapêutico , Avaliação de Processos e Resultados em Cuidados de Saúde , Padrões de Prática Médica/tendências , Diálise Renal , Adolescente , Adulto , Cálcio/sangue , Centers for Medicare and Medicaid Services, U.S. , Cinacalcete , Bases de Dados como Assunto , Prescrições de Medicamentos , Quimioterapia Combinada , Uso de Medicamentos , Revisão de Uso de Medicamentos , Feminino , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , Hormônio Paratireóideo/sangue , Fósforo/sangue , Guias de Prática Clínica como Assunto , Diálise Renal/efeitos adversos , Diálise Renal/estatística & dados numéricos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Vitamina D/uso terapêutico , Adulto Jovem
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