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1.
Eur J Clin Pharmacol ; 68(11): 1483-91, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22543981

RESUMO

PURPOSE: To test for associations between genetic polymorphisms of adrenergic receptors (AR) and other candidate genes and healthcare utilization in heart failure patients, taking into account other important factors, such as medication adherence. METHODS: One year-hospital utilization data were collected from 140 participants with heart failure, aged 50 years or older. Medication adherence was measured. Hospitalization and emergency department (ED) visits due to heart failure were used as healthcare outcomes. The genotypes of polymorphisms in six genes were determined: α(2C)-AR (ADRA2C), ß1-AR (ADRB1), ß2-AR (ADRB2), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and CYP4A11. Haplotypes for ADRB1 and ADRB2 were estimated. The genotype effects on healthcare outcomes were examined using log-linear regression models. RESULTS: Compared to ADRB1 Arg389 carriers, homozygous Gly389Gly carriers experienced fewer ED visits [incidence rate ratio (IRR) 0.07, 95 % confidence interval (CI) 0.01-0.54, P = 0.022]. Compared to ADRB2 homozygous Gly16Gly carriers, Arg16Gly carriers had fewer ED visits (IRR 0.23, 95 % CI 0.09-0.59, P = 0.006). Polymorphisms in ADRB1 as well as those in ADRB2 were in linkage disequilibrium, with three defining haplotypes, respectively. For ADRB2, the risk of hospitalizations and ED visits were relatively lower in Arg16/Gln27 carriers but relatively higher in homozygous Gly16/Gln27 carriers (P < 0.05). Compared to eNOS 894TT homozygous variants, 894GG and 894GT carriers had notably fewer ED visits (IRR 0.05, 95 % CI 0.01-0.25, P = 0.0013 and IRR 0.10, 95 % CI 0.02-0.42, P = 0.006, respectively). The other polymorphisms showed no association with healthcare outcomes. CONCLUSIONS: After controlling for demographics, functional status, and treatment adherence, polymorphisms in ADRB1, ADRB2 and eNOS are associated with healthcare outcomes in heart failure patients.


Assuntos
Insuficiência Cardíaca/genética , Insuficiência Cardíaca/terapia , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética , Idoso , Substituição de Aminoácidos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Seguimentos , Estudos de Associação Genética , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Heterozigoto , Hospitalização , Humanos , Indiana , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/metabolismo , Polimorfismo de Nucleotídeo Único , Receptores Adrenérgicos beta 1/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Método Simples-Cego
2.
BMC Cardiovasc Disord ; 12: 93, 2012 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-23092442

RESUMO

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may disrupt control of blood pressure in hypertensive patients and increase their risk of morbidity, mortality, and the costs of care. The objective of this study was to examine the association between incident use of NSAIDs and blood pressure in patients with hypertension. METHODS: We conducted a retrospective cohort study of adult hypertensive patients to determine the effects of their first prescription for NSAID on systolic blood pressure and antihypertensive drug intensification. Data were collected from an electronic medical record serving an academic general medicine practice in Indianapolis, Indiana, USA. Using propensity scores to minimize bias, we matched a cohort of 1,340 users of NSAIDs with 1,340 users of acetaminophen. Propensity score models included covariates likely to affect blood pressure or the use of NSAIDs. The study outcomes were the mean systolic blood pressure measurement after starting NSAIDs and changes in antihypertensive therapy. RESULTS: Compared to patients using acetaminophen, NSAID users had a 2 mmHg increase in systolic blood pressure (95% CI, 0.7 to 3.3). Ibuprofen was associated with a 3 mmHg increase in systolic blood pressure compared to naproxen (95% CI, 0.5 to 4.6), and a 5 mmHg increase compared to celecoxib (95% CI, 0.4 to 10). The systolic blood pressure increase was 3 mmHg in a subgroup of patients concomitantly prescribed angiotensin converting enzyme inhibitors or calcium channel blockers and 6 mmHg among those prescribed a beta-adrenergic blocker. Blood pressure changes in patients prescribed diuretics or multiple antihypertensives were not statistically significant. CONCLUSION: Compared to acetaminophen, incident use of NSAIDs, particularly ibuprofen, is associated with a small increase in systolic blood pressure in hypertensive patients. Effects in patients prescribed diuretics or multiple antihypertensives are negligible.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Acetaminofen/uso terapêutico , Analgésicos não Narcóticos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Celecoxib , Interações Medicamentosas , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Ibuprofeno/uso terapêutico , Indiana , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Naproxeno/uso terapêutico , Razão de Chances , Pontuação de Propensão , Pirazóis/uso terapêutico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sulfonamidas/uso terapêutico , Resultado do Tratamento
3.
Pharmacoepidemiol Drug Saf ; 19(11): 1194-8, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20842761

RESUMO

BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors have been linked to cardiac death. The mechanism for this adverse effect appears to be by ischemic insult; however another mechanism could involve hyperkalemia. The objective of this study was to determine the effects of selective COX-2 inhibitors and non-selective nonsteroidal anti-inflammatory drugs (NSAIDs) on serum potassium concentration and the electrocardiogram. METHODS: A retrospective cohort study was conducted using propensity score matching of patients from an inner-city academic medical center at Indianapolis, Indiana. Two hundred and two patients prescribed selective COX-2 inhibitors were matched to 202 patients prescribed non-selective NSAIDs using propensity scores methods. Outcomes included change in serum potassium concentration from baseline and the risk of an abnormal electrocardiogram. RESULTS: Compared to patients prescribed non-selective NSAIDs, those prescribed a selective COX-2 inhibitor had a higher risk of serum potassium increase greater than 5 mEq/L (OR, 2.56; 95%CI, 1.03-6.36). However, patients prescribed selective COX-2 inhibitors had no greater risk of electrocardiogram abnormality (OR, 1.16; 95%CI, 0.74-1.82). CONCLUSIONS: Selective COX-2 inhibitors may have a greater risk of hyperkalemia than non-selective NSAIDs. This study was exploratory with small numbers of patients. Further studies are needed to confirm these results and any association with cardiovascular events.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Hiperpotassemia/induzido quimicamente , Centros Médicos Acadêmicos , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Eletrocardiografia , Feminino , Humanos , Hiperpotassemia/epidemiologia , Indiana/epidemiologia , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Estudos Retrospectivos
4.
Eur J Heart Fail ; 11(6): 542-50, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19380329

RESUMO

AIMS: Non-steroidal anti-inflammatory drugs have been associated with increased risk of congestive heart failure (CHF). We aimed to assess the impact of treatment with etoricoxib or diclofenac on risk of CHF relative to baseline risk factors. METHODS AND RESULTS: We performed a multivariate analysis of 34 701 patients with arthritis receiving etoricoxib 60 or 90 mg, or diclofenac 150 mg, daily for a mean of 18 months, to assess the incidence of confirmed, adjudicated CHF events resulting in emergency room visit or hospitalization. Analyses were performed using a Cox proportional hazard model to evaluate the hazard ratio (HR) between the levels of each risk marker for the incidence of CHF. Significant risk markers included history of CHF (HR: 6.69, 95% CI 3.59-12.47; P <0.0001), age > or = 65 years (2.56, 1.65-3.98; P <0.0001), and history of hypertension (1.83, 1.16-2.89; P = 0.0094) or diabetes (1.83, 1.15-2.94; P = 0.0116). Etoricoxib vs. diclofenac was a significant risk factor only when pooling the etoricoxib 90 mg cohorts (1.88; 1.13-3.10; P = 0.0143). Etoricoxib 60 mg did not significantly increase risk vs. diclofenac. CONCLUSION: History of CHF was highly associated with risk for CHF hospitalization. Hypertension, diabetes, and older age also increased risk modestly. There appeared to be a dose-related increase in CHF with etoricoxib compared with diclofenac, which reached statistical significance when the etoricoxib 90 mg groups (osteoarthritis and rheumatoid arthritis) were pooled.


Assuntos
Artrite/tratamento farmacológico , Diclofenaco/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Piridinas/efeitos adversos , Sulfonas/efeitos adversos , Idoso , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/efeitos adversos , Diclofenaco/administração & dosagem , Relação Dose-Resposta a Droga , Etoricoxib , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Piridinas/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , Sulfonas/administração & dosagem
5.
Ann Intern Med ; 146(10): 714-25, 2007 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-17502632

RESUMO

BACKGROUND: Patients with heart failure who take several prescription medications sometimes have poor adherence to their treatment regimens. Few interventions designed to improve adherence to therapy have been rigorously tested. OBJECTIVE: To determine whether a pharmacist intervention improves medication adherence and health outcomes compared with usual care for low-income patients with heart failure. DESIGN: Randomized, controlled trial conducted from February 2001 to June 2004. SETTING: University-affiliated, inner-city, ambulatory care practice. PATIENTS: 314 low-income patients 50 years of age or older with heart failure confirmed by their primary care physician. INTERVENTION: Patients were randomly assigned to intervention (39% [n = 122]) or usual care (61% [n = 192]) groups and were followed for 12 months. A pharmacist provided a 9-month multilevel intervention, with a 3-month poststudy phase. An interdisciplinary team of investigators designed the intervention to support medication management by patients who have low health literacy and limited resources. MEASUREMENTS: Primary outcomes were adherence, as measured by using electronic prescription monitors, and exacerbations requiring emergency department care or hospital admission. Secondary outcomes included health-related quality of life, patient satisfaction with pharmacy services, and total direct costs. RESULTS: During the 9-month intervention period, medication adherence was 67.9% and 78.8% in the usual care and intervention groups, respectively (difference, 10.9 percentage points [95% CI, 5.0 to 16.7 percentage points]). However, these salutary effects dissipated in the 3-month postintervention follow-up period, in which adherence was 66.7% and 70.6%, respectively (difference, 3.9 percentage points [CI, -5.9 to 6.5 percentage points]). Medications were taken on schedule 47.2% of the time in the usual care group and 53.1% of the time in the intervention group (difference, 5.9 percentage points [CI, 0.4 to 11.5 percentage points]), but this effect also dissipated at the end of the intervention (48.9% vs. 48.6%, respectively; difference, 0.3 percentage point [CI, -5.9 to 6.5 percentage points]). Emergency department visits and hospital admissions were 19.4% less (incidence rate ratio, 0.82 [CI, 0.73 to 0.93]) and annual direct health care costs were lower ($-2960 [CI, $-7603 to $1338]) in the intervention group. LIMITATIONS: Because electronic monitors were used to ascertain adherence, patients were not permitted to use medication container adherence aids. The intervention involved 1 pharmacist and a single study site that served a large, indigent, inner-city population of patients. Because the intervention had several components, intervention effects could not be attributed to a single component. CONCLUSIONS: A pharmacist intervention for outpatients with heart failure can improve adherence to cardiovascular medications and decrease health care use and costs, but the benefit probably requires constant intervention because the effect dissipates when the intervention ceases. ClinicalTrials.gov registration number: NCT00388622.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Cooperação do Paciente , Educação de Pacientes como Assunto , Assistência Farmacêutica/normas , Fármacos Cardiovasculares/efeitos adversos , Custos Diretos de Serviços , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Indiana , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Educação de Pacientes como Assunto/economia , Satisfação do Paciente , Assistência Farmacêutica/economia , Pobreza
6.
Acad Med ; 82(11): 1094-7, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17971698

RESUMO

In 2000, leaders at Indiana University School of Medicine (IUSM) consciously set out to incorporate professionalism into the culture of the school. The dean of IUSM offers his personal perspective of the state of professionalism at his institution before the culture change, explaining the inspiration for the leadership's efforts toward pursuing a culture of professionalism. The author describes specific actions taken at IUSM to foster professionalism, including crafting a Core Values and Guiding Principles document that explicitly stated the institution's ideals and that was circulated to and eventually approved in 2001 by every member of the IUSM faculty, graduate trainees, and student body; explicitly incorporating professionalism into faculty recruiting and student admissions processes; integrating professionalism into the IUSM curriculum; and employing a Relationship-Centered Care Initiative, which encourages members of the IUSM community to acknowledge and reflect on their personal experiences as caregivers, to cultivate an appreciation for what is best about medicine. To underscore the importance of the culture change, IUSM leadership have been involved in every step of the process and have committed to rewarding professional behavior among faculty members. The author encourages other institutions to strive for similar culture change to promote professionalism across medicine.


Assuntos
Educação de Graduação em Medicina/organização & administração , Cultura Organizacional , Competência Profissional , Pessoal Administrativo , Docentes de Medicina , Humanos , Indiana , Liderança , Critérios de Admissão Escolar , Faculdades de Medicina/organização & administração
7.
J Am Heart Assoc ; 6(10)2017 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-28982672

RESUMO

BACKGROUND: Loop diuretics are highly natriuretic but their short duration of action permits postdiuretic sodium retention, which limits salt loss unless dietary salt is severely restricted. We tested the hypothesis that a more prolonged duration of action would enhance salt loss. METHODS AND RESULTS: Ten healthy participants were crossed over between 20 mg of oral immediate-release or extended-release (ER) torsemide while consuming a fixed diet with 300 mmol·d-1 of Na+. Compared with immediate-release, plasma torsemide after ER was 59% lower at 1 to 3 hours but 97% higher at 8 to 10 hours as a result of a >3-fold prolongation of time to maximal plasma concentrations. The relationship of natriuresis to log torsemide excretion showed marked hysteresis, but participants spent twice as long with effective concentrations of torsemide after ER, thereby enhancing diuretic efficiency. Compared with immediate-release, ER torsemide did not reduce creatinine clearance and increased fluid (1634±385 versus 728±445 mL, P<0.02) and Na+ output (98±15 versus 42±17 mmol, P<0.05) despite an 18% reduction in exposure. Neither formulation increased K+ excretion. CONCLUSIONS: Torsemide ER prolongs urine drug levels, thereby increasing the time spent with effective drug concentrations, reduces postdiuretic Na+ retention, and moderates a fall in glomerular filtration rate. It caused significant Na+ loss even during very high salt intake. Thus, a short duration of action limits salt loss with loop diuretics. These conclusions warrant testing in subjects with edema and heart failure.


Assuntos
Rim/efeitos dos fármacos , Natriurese/efeitos dos fármacos , Eliminação Renal/efeitos dos fármacos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacocinética , Sulfonamidas/farmacocinética , Adulto , Área Sob a Curva , Creatinina/urina , Estudos Cross-Over , Preparações de Ação Retardada , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Voluntários Saudáveis , Humanos , Índia , Rim/metabolismo , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Cloreto de Sódio na Dieta/efeitos adversos , Cloreto de Sódio na Dieta/urina , Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Torasemida , Adulto Jovem
8.
Circulation ; 105(11): 1348-53, 2002 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-11901047

RESUMO

BACKGROUND: Adenosine may adversely affect renal function via its effects on renal arterioles and tubuloglomerular feedback, but effects of adenosine blockade in humans receiving furosemide and ACE inhibitors is unknown. METHODS AND RESULTS: This was a randomized, double-blind, ascending-dose, crossover study evaluating 3 doses of BG9719 in 63 patients with congestive heart failure. Patients received placebo or 1 of 3 doses of BG9719 on 1 day and the same medication plus furosemide on a separate day. Renal function and electrolyte and water excretion were assessed. BG9719 alone caused an increase in urine output and sodium excretion (P<0.05). Although administration of furosemide alone caused a large diuresis, addition of BG9719 to furosemide increased diuresis, which was significant at the 0.75-microg/mL concentration. BG9719 alone improved glomerular filtration rate (GFR) at the 2 lower doses. Furosemide alone caused a decline in GFR. When BG9719 was added to furosemide, however, creatinine clearance remained at baseline at the 2 lower doses. CONCLUSIONS: In patients with congestive heart failure on standard therapy, including ACE inhibitors, BG9719 increased both urine output and GFR. In these same patients, furosemide increased urine output at the expense of decreased GFR. When BG9719 was given in addition to furosemide, urine volume additionally increased and there was no deterioration in GFR. A1 adenosine antagonism might preserve renal function while simultaneously promoting natriuresis during treatment for heart failure.


Assuntos
Diurese/efeitos dos fármacos , Diuréticos/efeitos adversos , Furosemida/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Antagonistas de Receptores Purinérgicos P1 , Xantinas/uso terapêutico , Idoso , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Creatinina/sangue , Creatinina/urina , Estudos Cross-Over , Diuréticos/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Combinação de Medicamentos , Eletrólitos/urina , Feminino , Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Sódio/urina , Urinálise , Xantinas/sangue
9.
Clin Pharmacol Ther ; 77(5): 437-50, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15900289

RESUMO

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) and can thereby reduce renal function, especially with respect to solute excretion and renal perfusion. AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] is a COX-inhibiting nitric oxide donator. Donation of nitric oxide by AZD3582 could preserve blood flow and thereby counteract the deleterious effects of COX inhibition in the gastrointestinal tract and possibly in other organ systems, including the kidney. The aim of this single-dose study was to assess the hypothesis that AZD3582 would not adversely affect renal function compared with NSAIDs. METHODS: In a parallel, randomized, double-blind fashion, a total of 60 healthy subjects (age range, 20-44 years) received 2 single doses of 750 mg AZD3582, 1500 mg AZD3582, 50 mg rofecoxib, 500 mg naproxen, or placebo (n = 12 per group). The first dose was given after a 5-day normal-sodium diet (150 mmol/d), and the second was given after a consecutive 3-day low-sodium diet (10 mmol/d). Urinary sodium excretion during normal sodium intake and glomerular filtration rate (GFR) (assessed by iohexol clearance) during sodium depletion were the primary variables measured. RESULTS: Urinary sodium excretion was reduced in all active treatment groups (maximal reduction of approximately 11 mmol/h during normal sodium intake, P < .05 versus placebo for all groups). GFR was also reduced in all active treatment groups. In sodium-depleted subjects, the mean (SD) maximal reduction in GFR during 0 to 6 hours for 750 mg AZD3582, 1500 mg AZD3582, 50 mg rofecoxib, and 500 mg naproxen was 28.1 mL/min (13.5 mL/min), 33.7 mL/min (23.3 mL/min), 25.2 mL/min (29.2 mL/min), and 41.7 mL/min (30.7 mL/min), respectively, with a statistically significant difference between 500 mg naproxen and placebo. Relative changes in sodium excretion and GFR were similar during normal sodium intake and sodium depletion during active treatment. CONCLUSION: The renal effects of 750 mg and 1500 mg AZD3582 were similar to those of 500 mg naproxen and 50 mg rofecoxib. Thus the potential for nitric oxide donation to create a renal-sparing agent was not found for AZD3582.


Assuntos
Inibidores de Ciclo-Oxigenase/farmacocinética , Lactonas/farmacocinética , Naftalenos/farmacocinética , Naproxeno/farmacocinética , Doadores de Óxido Nítrico/farmacocinética , Sulfonas/farmacocinética , Adulto , Área Sob a Curva , Pressão Sanguínea/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/metabolismo , Dieta Hipossódica , Método Duplo-Cego , Esquema de Medicação , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Iohexol , Lactonas/administração & dosagem , Lactonas/sangue , Masculino , Naftalenos/administração & dosagem , Naftalenos/sangue , Naproxeno/administração & dosagem , Naproxeno/sangue , Doadores de Óxido Nítrico/administração & dosagem , Doadores de Óxido Nítrico/metabolismo , Potássio/urina , Renina/sangue , Renina/efeitos dos fármacos , Sódio/sangue , Sódio/urina , Sulfonas/administração & dosagem , Sulfonas/sangue
10.
Clin Pharmacol Ther ; 77(3): 189-201, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15735613

RESUMO

OBJECTIVE: Data from electronic dosing monitors and published pharmacokinetic parameters were used to derive medication adherence measures for immediate-release metoprolol and examine their association with health care utilization of outpatients aged 50 years or older with heart failure. METHODS: We used a 1-compartment model and published population pharmacokinetic parameters to estimate mean plasma metoprolol concentrations for patients treated for 6 to 12 months. In the absence of directly measured plasma concentrations, we calculated the intended mean plasma concentration (Cp'(ave)) under the assumption of perfect adherence to the prescribed dose and frequency of administration. Projected mean plasma concentrations (Cp(ave)) were estimated by use of data from recorded dosing times. In addition to taking adherence (percentage of dose taken) and scheduling adherence (percentage of doses taken on schedule), we calculated the deviation from the intended exposure (DeltaCp(ave) = Cp'(ave) - Cp(ave)) and the proportion of intended exposure achieved by the patient (Cp(ave) /Cp'(ave)). We assessed the association between the adherence measures and the numbers of emergency department visits and hospital admissions experienced by the patients. RESULTS: Patients (N = 80) were aged 62 +/- 8 years. Mean DeltaCp(ave) and Cp(ave)/Cp'(ave) were 7.9 ng/mL (SD, 10.7) and 0.6 (SD, 0.3), respectively. Log-linear models adjusted for patient functional status indicated that greater deviation from the intended metoprolol exposure (DeltaCp(ave)) was associated with increased numbers of emergency department visits ( P < .0001) and hospital admissions (P < .0001). A higher proportion of intended exposure (Cp(ave) /Cp'(ave)) corresponded to a reduced number of emergency department visits (P = .0204) and hospital admissions (P = .0093). Taking adherence was univariately associated with both emergency department visits and hospital visits (P < .0001 and P = .0010, respectively). Scheduling adherence was associated with the number of emergency department visits (P = .0181) but not with the number of hospital admissions (P = .1602). Model selection procedures consistently chose the proposed measures over taking adherence and scheduling adherence. CONCLUSION: Deviation from the intended exposure and proportion of intended exposure achieved by the patient are valid adherence measures for immediate-release metoprolol and are associated with health care utilization. The potential utility of these measures for other beta-adrenergic antagonists and perhaps other cardiovascular drugs should be investigated.


Assuntos
Serviços de Saúde para Idosos/estatística & dados numéricos , Insuficiência Cardíaca/tratamento farmacológico , Metoprolol/farmacologia , Cooperação do Paciente/estatística & dados numéricos , Idoso , Algoritmos , Fármacos Cardiovasculares/classificação , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Formas de Dosagem , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Insuficiência Cardíaca/classificação , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Metoprolol/uso terapêutico , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Farmacocinética
11.
West J Nurs Res ; 27(8): 977-93; discussion 994-9, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16275694

RESUMO

Patients with heart failure are required to comply with a medication regimen and dietary sodium restrictions. The objectives of this study were to determine the most frequently perceived benefits of and barriers to compliance with medication and dietary sodium restrictions and evaluate the relevancy of these scale items for testing in tailored intervention studies. Data were collected as part of two studies that evaluated the psychometric properties of two questionnaires. The most frequently identified benefit of medication compliance was decreasing the chance of being hospitalized, and the most commonly reported barrier was disruption of sleep. Patients were knowledgeable about the benefits of compliance with dietary sodium restrictions, and the poor taste of food on the low sodium diet was the most common barrier. Heart failure patients perceive benefits of and barriers to compliance with therapeutic regimens that are likely to be amenable to tailored interventions designed to enhance compliance.


Assuntos
Dieta Hipossódica/psicologia , Tratamento Farmacológico/psicologia , Insuficiência Cardíaca/psicologia , Cooperação do Paciente/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Dieta Hipossódica/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Análise Fatorial , Feminino , Preferências Alimentares/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Necessidades e Demandas de Serviços de Saúde , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Pesquisa Metodológica em Enfermagem , Psicometria , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos do Sono-Vigília/induzido quimicamente , Inquéritos e Questionários/normas , Paladar
12.
Am J Med ; 116(7): 443-50, 2004 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-15047033

RESUMO

BACKGROUND: Heart failure disproportionately affects older adults for whom multiple medications are prescribed to prevent exacerbations and hospitalization. To target interventions effectively, it is important to understand the association of medication acquisition with health care utilization and costs. METHODS: We used electronic medical records from an urban public health care system to identify patients aged >/=50 years who had a diagnosis of heart failure. We assessed the association between inappropriate or appropriate medication supplies and hospitalization and costs using multivariable analyses that adjusted for demographic characteristics, prior health care use, health status, and insurance status. RESULTS: Total health care costs for treating 1554 patients with heart failure from 1996 to 2000 were 36.6 million dollars (in 2000 dollars). Less than a third of patients received appropriate medication supplies (between 90% and 110% of the supplies needed) annually. Compared with patients with appropriate supplies, the odds of hospitalization were greater among those with undersupplies (odds ratio [OR] = 3.1; 95% confidence interval [CI]: 2.3 to 4.2; P <0.0001) or oversupplies (OR = 2.0; 95% CI: 1.7 to 2.4; P <0.0001). Total costs were 25% higher for patients with undersupplies (95% CI: 8% to 46%; P = 0.004) and 18% higher for those with oversupplies (95% CI: 7% to 30%; P = 0.0009) than for those with appropriate supplies. CONCLUSION: Among adults with heart failure, inappropriate medication supplies were associated with increased hospitalization and higher costs. Monitoring medication supplies from electronic medical records may be a useful component of programs aiming to improve care while managing costs.


Assuntos
Fármacos Cardiovasculares/economia , Fármacos Cardiovasculares/uso terapêutico , Custos de Medicamentos , Custos de Cuidados de Saúde , Serviços de Saúde/economia , Serviços de Saúde/estatística & dados numéricos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/economia , Antagonistas Adrenérgicos beta/economia , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/economia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antiarrítmicos/economia , Antiarrítmicos/uso terapêutico , Diuréticos/economia , Diuréticos/uso terapêutico , Prescrições de Medicamentos/economia , Feminino , Insuficiência Cardíaca/epidemiologia , Hospitalização/economia , Humanos , Indiana/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Receptores de Angiotensina/uso terapêutico , Fatores de Risco , Saúde da População Urbana
13.
Semin Arthritis Rheum ; 32(3 Suppl 1): 33-42, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12528072

RESUMO

The purpose of this review is to provide an overview of the effect of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-specific-2 inhibitors (coxibs) on renal function. Both COX isoforms (COX-1 and COX-2) constitutively are expressed in the adult mammalian kidney and contribute to the biosynthesis of prostaglandins (PGs). Inhibition of COX activity in the kidney by NSAIDs has relatively mild consequences in healthy individuals, but can lead to serious adverse events in patients whose renal function is PG dependent. Most studies have reported transient decreases in sodium excretion upon initiation of therapy with either traditional NSAIDs or coxibs. In patients whose renal function is dependent on prostanoids, both nonselective NSAIDs and coxibs can affect the glomerular filtration rate. Changes in renal function may result in hypertension and edema. Several studies have compared the effects of traditional NSAIDs, celecoxib, and rofecoxib on blood pressure and incidence of edema, but the results have not been consistent, as the trials used different clinical models and study designs. No trials to date have been performed with rigorous study designs that allow meaningful drug comparisons at comparably effective doses. In consequence, patients who are at risk for adverse renal events should be monitored with the same caution when receiving coxibs as when receiving treatment with nonselective NSAIDs. They include patients with congestive heart failure or renal or hepatic disease, as well as those of advanced age receiving therapy with diuretics or angiotensin-converting enzyme (ACE) inhibitors.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase/efeitos adversos , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/fisiopatologia , Humanos , Rim/fisiopatologia , Nefropatias/fisiopatologia , Testes de Função Renal
14.
Pharmacotherapy ; 23(3): 326-32, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12627931

RESUMO

STUDY OBJECTIVE: To determine the relationship between adherence to diuretic therapy and health care utilization. DESIGN: Prospective, observational study. SETTING: University-affiliated medical center. PATIENTS: Forty-two patients with heart failure. INTERVENTION: Electronic monitoring of adherence to diuretic therapy (percentage of diuretic prescription container openings) and to scheduling (percentage of container openings within a specific time). MEASUREMENTS AND MAIN RESULTS: All patients were prescribed a diuretic, most commonly furosemide (88%). Patients varied widely in adherence to therapy (mu = 72% +/- 30%) and to scheduling (mu = 43% +/- 30%). Education was a predictor of drug-taking adherence (p=0.0062) but not of scheduling adherence. Log-linear models revealed that poor scheduling adherence was associated with increased cardiovascular-related hospitalizations (chi2 11.63, p=0.0006) and predicted more heart failure-related hospitalizations (chi2 4.04, p=0.0444). In contrast, neither measure was significantly associated with cardiovascular- or heart failure-related emergency department visits. We found a moderate correlation between scheduling adherence and taking adherence (r = 0.6513). CONCLUSION: Patients taking a greater proportion of diuretic agents on schedule may decrease the risk of cardiovascular- and heart failure-related hospitalizations. If these findings are confirmed by a larger study, interventions to improve adherence and patient health outcomes should consider the timing of doses as well as the number of daily doses of a diuretic.


Assuntos
Diuréticos/uso terapêutico , Serviços de Saúde/estatística & dados numéricos , Insuficiência Cardíaca/tratamento farmacológico , Cooperação do Paciente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
15.
J Pain Symptom Manage ; 23(4 Suppl): S15-20; discussion S21-3, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11992745

RESUMO

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used. These agents are associated with adverse renal effects caused by the reduction in synthesis of renal prostaglandins through inhibition of cyclooxygenase (COX). Both isoforms of COX, COX-1 and COX-2, are expressed in the kidney in constitutive and inducible forms. It is assumed therefore that the COX-2-selective inhibitors, rofecoxib and celecoxib, would have an effect on renal function similar to that of nonselective NSAIDs. Several studies have evaluated this issue, although they have different study models and some have design flaws that limit their interpretation. Therefore, conclusions should be based on the pattern of observed effects rather than on individual data. These studies suggest that both celecoxib and rofecoxib can cause sodium retention and decrease glomerular filtration rate (GFR) to a similar extent as nonselective NSAIDs in patients at risk for adverse renal effects. Consequently, the same precautions regarding renal risk that are followed for nonselective NSAIDs should be used when selective COX-2 inhibitors are administered.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase/efeitos adversos , Isoenzimas/fisiologia , Nefropatias/induzido quimicamente , Prostaglandina-Endoperóxido Sintases/fisiologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/uso terapêutico , Edema/induzido quimicamente , Humanos , Hipertensão Renal/induzido quimicamente , Rim/efeitos dos fármacos , Rim/enzimologia , Proteínas de Membrana , Prostaglandinas/fisiologia
16.
Am J Geriatr Pharmacother ; 2(1): 36-43, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15555477

RESUMO

BACKGROUND: Adults aged > or =50 years often have multiple chronic diseases requiring multiple medications. However, even drugs with well-documented benefits are often not taken as prescribed, for a variety of reasons. OBJECTIVE: The objective of this article was to provide background information about medication adherence and its measurement, the development of the conceptual model for use in adherence research, and supportive intervention strategies such as pharmaceutical care by pharmacists to improve chronic medication use in older adults. METHODS: English-language literature published from 1990 to 2000 was searched on MEDLINE, International Pharmaceutical Abstracts, and AARP Ageline using the terms aged, heart failure, CHF, adherence, chronic heart failure, compliance, and related terms. The authors used their personal files and libraries to obtain seminal literature and textbooks published before 1990. RESULTS: Although the cognitive processes needed to manage and take medications decline with aging, the number of prescription and nonprescription medications consumed increases. Other factors such as vision, hearing, health literacy, disability, and social and financial resources may all complicate the ability of older adults to adhere to the pharmacologic prescription. CONCLUSIONS: Many factors are associated with medication adherence and related health outcomes in older adults. Therefore, strategies to improve adherence will need to be multidimensional, including improvements in pharmacy services that consider age-related factors (eg, declining cognitive and physical functions) as well as a variety of environmental and social factors.


Assuntos
Envelhecimento/psicologia , Tratamento Farmacológico , Avaliação de Resultados em Cuidados de Saúde , Cooperação do Paciente , Idoso , Prescrições de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Medicamentos sem Prescrição , Cooperação do Paciente/psicologia , Assistência Farmacêutica , Fatores Socioeconômicos
17.
Am J Geriatr Pharmacother ; 2(1): 53-65, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15555479

RESUMO

BACKGROUND: Medications can improve the functioning and health-related quality of life of patients with chronic heart failure (CHF) and reduce morbidity, mortality, and costs of treatment. However, patients may not adhere to therapy. Patients with complex medication regimens and low health literacy are at risk for nonadherence. OBJECTIVE: The primary goal of this project is to develop and assess a multilevel pharmacy-based program to improve patient medication adherence and health outcomes for elderly CHF patients with low health literacy. METHODS: In this 4-year, controlled trial, patients aged 50 years with a diagnosis of CHF who are being treated at Wishard Health Services (Indianapolis, Indiana) are randomly assigned to pharmacist intervention or usual care. Intervention patients receive 9 months of pharmacist support and 3 months of postintervention follow-up. The intervention involves a pharmacist providing verbal and written education, icon-based labeling of medication containers, and therapeutic monitoring. The pharmacist identifies patients' barriers to appropriate drug use, coaches them on overcoming these barriers, and coordinates medication use issues with their primary care providers. Daily updates of relevant monitoring data are delivered via an electronic medical record system and stored in a personal computer system designed to support pharmacist monitoring and facilitate documentation of interventions. To measure medication adherence objectively, electronic monitoring lids are used on all CHF medications for patients in both study groups. Other assessments include self-reported medication adherence, results of echocardiography (eg, ejection fraction), brain natriuretic peptide concentrations, and health-related quality of life. Health services utilization, refill adherence, and cost data derive from electronic medical records. After completion of this study, the data can be used to assess the effectiveness and cost-effectiveness of our intervention. RESULTS: One hundred twenty-two patients have been assigned to receive the intervention and 192 to receive usual care. CONCLUSIONS: Our study aims to improve patients' knowledge and self-management of their medication and to improve medication monitoring in a multilevel pharmacy-based intervention. By doing so, we intend that the intervention will improve the health outcomes of elderly patients with CHF.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Cooperação do Paciente , Idoso , Doença Crônica , Comunicação , Rotulagem de Medicamentos , Educação em Farmácia , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Educação de Pacientes como Assunto , Assistência Farmacêutica , Farmacêuticos , Médicos , Papel Profissional
18.
Sports Health ; 4(5): 377-83, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23016110

RESUMO

Ketorolac tromethamine (Toradol(®)) is a non-steroidal anti-inflammatory drug that has potent analgesic and anti-inflammatory properties. It can be administered orally, intravenously, intramuscularly, or via a nasal route. Ketorolac injections have been used for several years in the National Football League (NFL), in both the oral and injectable forms, to treat musculoskeletal injuries and to prevent post-game soreness. In an attempt to determine the appropriate use of this medication in NFL players, the NFL Team Physician Society appointed a Task Force to consider the best available evidence as to how ketorolac should be used for pain management in professional football players. These treatment recommendations were established based on the available medical literature taking into consideration the pharmacokinetic properties of ketorolac, its accepted indications and contraindications, and the unique clinical challenges of the NFL. The Task Force recommended that 1) ketorolac should only be administered under the direct supervision and order of a team physician; 2) ketorolac should not be used prophylactically as a means of reducing anticipated pain either during or after participation in NFL games or practices and should be limited to those players diagnosed with an injury or condition and listed on the teams' injury report; 3) ketorolac should be given in the lowest effective therapeutic dose and should not be used in any form for more than 5 days; 4) ketorolac should be given in its oral preparation under typical circumstances; 5) ketorolac should not be taken concurrently with other NSAIDs or by those players with a history of allergic reaction to ketorolac, other NSAIDs or aspirin; and 6) ketorolac should not be used by a player with a history of significant gastrointestinal bleeding, renal compromise, or a past history of complications related to NSAIDs.

19.
Cardiovasc Ther ; 30(6): 342-50, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21884017

RESUMO

INTRODUCTION: The increased thrombotic cardiovascular (CV) risk in trials of cyclo-oxygenase-2 (COX-2) inhibitors versus placebo, and the apparent similar risk with nonsteroidal antiinflammatory drugs (NSAIDs), may be related to their potential to elevate blood pressure (BP). AIMS: We evaluated the relationship between baseline BP and change in BP on CV events (CVEs) in patients receiving NSAIDs or COX-2 inhibitors in the prospective randomized, double-blind, Multinational Etoricoxib and Diclofenac Arthritis Long-term Program (N = 34,701) comparing etoricoxib 60 or 90 mg or diclofenac 150 mg daily for a mean duration of 18 months. The main outcome measure was confirmed thrombotic CVEs. The Antiplatelet Trialists' Collaboration endpoint, all-cause mortality, CV/congestive heart failure (CHF) mortality, and CHF incidence were similarly evaluated. RESULTS: We found that baseline systolic BP (SBP) was associated with significantly higher risk of all events (P < 0.001). Baseline diastolic BP (DBP) was inversely and significantly associated with risk of all events (P < 0.001 to P = 0.016) except CV/CHF mortality (P = 0.054). There was no significant differential effect between etoricoxib and diclofenac in relation to CVEs, except for confirmed CHF, for which the risk was significantly higher with etoricoxib (P = 0.019). Only CHF risk (P = 0.020 for both SBP and DBP change), but not thrombotic endpoints, was significantly associated with change in BP from months 0 to 4. These findings were not meaningfully altered after covariate adjustment for baseline CV risk. CONCLUSIONS: Baseline BP, but not change in BP, was significantly associated with risk of thrombotic CVEs through 18 months. The CV risk of COX-2s and NSAIDs did not appear to be related to the BP-elevating effects of these agents, although such analyses, i.e., from randomized controlled trials, are unable to definitively exclude such a relationship.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Diclofenaco/administração & dosagem , Piridinas/efeitos adversos , Sulfonas/efeitos adversos , Trombose/induzido quimicamente , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite/tratamento farmacológico , Peso Corporal , Comorbidade , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Diclofenaco/uso terapêutico , Método Duplo-Cego , Etoricoxib , Feminino , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Piridinas/uso terapêutico , Grupos Raciais , Medição de Risco , Sulfonas/uso terapêutico , Trombose/epidemiologia
20.
Semin Nephrol ; 31(6): 483-94, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22099505

RESUMO

All diuretics except spironolactone exert their effects from the lumen of the nephron. Thus, to exert an effect, they must reach the urine. Pharmacokinetics (PK) describes this access. Different edematous disorders can affect access to this site of action and therein affect response to a diuretic. In addition, once a diuretic reaches the site of action, a response ensues. The characteristics of this response that can be affected by a patient's clinical condition are described by the pharmacodynamics (PD) of a diuretic. To understand the mechanisms of abnormal response to a diuretic one must dissect its PK and PD in different edematous disorders. For example, in patients with renal insufficiency, the mechanism of poor diuretic response is PK. In contrast, in patients with cirrhosis or in those with congestive heart failure, it is PD. In patients with nephrotic syndrome, both PK and PD are operative. These different mechanisms mandate differences in therapeutic strategy, as explained in this article.


Assuntos
Diuréticos/uso terapêutico , Diuréticos/farmacocinética , Diuréticos/farmacologia , Edema/tratamento farmacológico , Edema/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/metabolismo , Insuficiência Renal/tratamento farmacológico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacocinética , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacologia , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico
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