RESUMEN
Shared decision-making (SDM) is the standard of care for patient or surrogates and their clinicians to arrive at a medical decision. Evidence suggests that SDM increases patients' understanding of their illness and satisfaction with their decision-making process. Dialysis patients often report the perception that they were passive participants in the decision to start dialysis, suggesting further opportunities for enhancing the application of SDM in decision-making with patients with kidney disease. The hallmark feature of SDM is sensitive, culturally- and equity-informed communication and effective partnership between patient or surrogate and clinician. In the process, the patient's personal expertise in the realm of their values and priorities is elicited, and the clinician's medical expertise is shared. The integration of this shared expertise then leads to an informed treatment decision. Frameworks such as the Serious Illness Conversation Guide and REMAP are guides for the SDM process, and communication tools and mnemonics can help facilitate SDM conversations. This paper will address SDM in nephrology practice, reviewing underlying supportive evidence, context, and timing for employing SDM in the trajectory of chronic kidney disease and acute kidney injury, special considerations in vulnerable populations to promote health equity, and communication tools and frameworks to facilitate the SDM process. By learning and applying these frameworks and tools, nephrology providers will be able to employ SDM in the management of kidney disease.
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Enfermedades Renales , Nefrología , Humanos , Promoción de la Salud , Diálisis Renal , ComunicaciónRESUMEN
Importance: There are limited data for the utility of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and death in adults with chronic kidney disease (CKD). Objective: To evaluate the association of statin use with all-cause mortality and major adverse cardiovascular events (MACE) among US veterans older than 65 years with CKD stages 3 to 4. Design, Setting, and Participants: This cohort study used a target trial emulation design for statin initiation among veterans with moderate CKD (stages 3 or 4) using nested trials with a propensity weighting approach. Linked Veterans Affairs (VA) Healthcare System, Medicare, and Medicaid data were used. This study considered veterans newly diagnosed with moderate CKD between 2005 and 2015 in the VA, with follow-up through December 31, 2017. Veterans were older than 65 years, within 5 years of CKD diagnosis, had no prior ASCVD or statin use, and had at least 1 clinical visit in the year prior to trial baseline. Eligibility criteria were assessed for each nested trial, and Cox proportional hazards models with bootstrapping were run. Analysis was conducted from July 2021 to October 2023. Exposure: Statin initiation vs none. Main Outcomes and Measures: Primary outcome was all-cause mortality; secondary outcome was time to first MACE (myocardial infarction, transient ischemic attack, stroke, revascularization, or mortality). Results: Included in the analysis were 14â¯828 veterans. Mean (SD) age at CKD diagnosis was 76.9 (8.2) years, 14â¯616 (99%) were men, 10â¯539 (72%) White, and 2568 (17%) Black. After expanding to person-trials and assessing eligibility at each baseline, there were 151â¯243 person-trials (14â¯685 individuals) of nonstatin initiators and 2924 person-trials (2924 individuals) of statin initiators included. Propensity score adjustment via overlap weighting with nonparametric bootstrapping resulted in covariate balance, with mean (SD) follow-up of 3.6 (2.7) years. The hazard ratio for all-cause mortality was 0.91 (95% CI, 0.85-0.97) comparing statin initiators to noninitiators. The hazard ratio for MACE was 0.96 (95% CI, 0.91-1.02). Results remained consistent in prespecified subgroup analyses. Conclusions and Relevance: In this target trial emulation of statin initiation in US veterans older than 65 years with CKD stages 3 to 4 and no prior ASCVD, statin initiation was significantly associated with a lower risk of all-cause mortality but not MACE. Results should be confirmed in a randomized clinical trial.
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Aterosclerosis , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Insuficiencia Renal Crónica , Veteranos , Estados Unidos/epidemiología , Adulto , Masculino , Anciano , Humanos , Femenino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Estudios de Cohortes , Medicare , Aterosclerosis/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
Clinician-led conversations about future care priorities occur infrequently with end-stage renal disease (ESRD) patients on dialysis. This was a pilot study of structured serious illness conversations using the Serious Illness Conversation Guide (SICG) in a single dialysis clinic to assess acceptability of the approach and explore conversation themes and potential outcomes among patients with ESRD. Twelve individuals with ESRD on dialysis from a single outpatient dialysis clinic participated in this study. Participants completed a baseline demographics survey, engaged in a clinician-led structured serious illness conversation, and completed an acceptability questionnaire. Conversations were recorded, transcribed and thematically analyzed. The average age of participants was 68.8 years. The conversations averaged 20:53 in length. Ten participants (83%) felt that the conversation was held at the right time in their clinical course and eleven participants (91%) felt that it was worthwhile. Most participants (73%) reported neutral feelings about clinician use of a printed guide. Eleven participants (91%) reported no change in anxiety about their illness following the conversation, and five participants (42%) reported that the conversation increased their hopefulness about future quality of life. Thematic analysis revealed common perspectives on dialysis including that participants view in-center hemodialysis as temporary, compartmentalize their kidney disease, perceive narrowed life experiences and opportunities, and believe dialysis is their only option. This pilot study suggests that clinician-led structured serious illness conversations may be acceptable to patients with ESRD on dialysis. The themes identified can inform future serious illness conversations with dialysis patients.
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Fallo Renal Crónico , Diálisis Renal , Humanos , Anciano , Proyectos Piloto , Calidad de Vida , Comunicación , Fallo Renal Crónico/terapia , Enfermedad CríticaRESUMEN
BACKGROUND: Patients with kidney disease have notable unmet palliative care needs and represent an underserved population for specialty palliative care teams. INTERVENTION: We designed a specialty-aligned interprofessional palliative care service called KidneyPal that is aimed at improving delivery of palliative care to patients with kidney disease through focus groups and iterative improvement cycles. MEASURES: We iteratively measured the development of KidneyPal through clinical process metrics: percent of the inpatient nephrology census followed by KidneyPal, patient demographics, consult origin, clinician feedback, and self-reported team interventions. OUTCOMES: KidneyPal saw 314 unique patients from January 2019 to January 2021. The majority of consultations came from nephrology services though the source of consultation changed over time. We consulted on an average of 13.5% of the entire inpatient nephrology patient hospital census with highest involvement with patients on the inpatient nephrology hemodialysis service (mean of 29.9%). KidneyPal was rated highly by surveyed nephrology clinicians and provided high rates of psychosocial support and goals of care interventions. LESSONS LEARNED: The creation of KidneyPal led to us to serve a new cohort of patients with specialty palliative care. We grew over time to serve the full range of patients with kidney disease as defined by our nephrology service lines. We succeeded in doing so by embedding in nephrology and building relationships with those caring for people with kidney disease while tailoring our service and interventions over time.
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Enfermedades Renales , Nefrología , Humanos , Cuidados Paliativos , Derivación y Consulta , Diálisis RenalRESUMEN
BACKGROUND: Expanding specialty palliative care within complex health systems involves consideration of patients' unmet needs, clinicians' perceptions of palliative care, and the availability of palliative care resources. Prior to this quality improvement (QI) project, palliative care services in our health system primarily served oncology patients. INTERVENTION: We undertook a prospective strategic planning process that included executive sponsorship and engagement of institutional leaders and clinicians to help define which palliative care services were most needed by the health system. MEASURES: We interviewed and surveyed a broad range of clinicians including physicians, nurse practitioners, and social workers. OUTCOMES: The two most prominent themes that emerged from the stakeholder engagement process were clinicians' wish for specialty-aligned interprofessional palliative care teams and for expansion of nononcology palliative care access. CONCLUSION: Careful needs assessment and stakeholder engagement can result in goal-directed and data-driven expansion of palliative care services within tertiary health care systems.
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Enfermería de Cuidados Paliativos al Final de la Vida , Cuidados Paliativos , Humanos , Atención Terciaria de Salud , Estudios Prospectivos , Oncología MédicaRESUMEN
INTRODUCTION: Older patients with advanced chronic kidney disease (CKD) often are inadequately prepared to make informed decisions about treatments including dialysis and cardiopulmonary resuscitation. Further, evidence shows that patients with advanced CKD do not commonly engage in advance care planning (ACP), may suffer from poor quality of life, and may be exposed to end-of-life care that is not concordant with their goals. We aim to study the effectiveness of a video intervention on ACP, treatment preferences and other patient-reported outcomes. METHODS AND ANALYSIS: The Video Images about Decisions for Ethical Outcomes in Kidney Disease trial is a multi-centre randomised controlled trial that will test the effectiveness of an intervention that includes a CKD-related video decision aid followed by recording personal video declarations about goals of care and treatment preferences in older adults with advancing CKD. We aim to enrol 600 patients over 5 years at 10 sites. ETHICS AND DISSEMINATION: Regulatory and ethical aspects of this trial include a single Institutional Review Board mechanism for approval, data use agreements among sites, and a Data Safety and Monitoring Board. We intend to disseminate findings at national meetings and publish our results. TRIAL REGISTRATION NUMBER: NCT04347629.
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Planificación Anticipada de Atención , Insuficiencia Renal Crónica , Cuidado Terminal , Anciano , Humanos , Estudios Multicéntricos como Asunto , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal , Insuficiencia Renal Crónica/terapiaRESUMEN
BACKGROUND AND OBJECTIVES: AKI requiring KRT is associated with high mortality and utilization. We evaluated the use of an AKI Standardized Clinical Assessment and Management Plan (SCAMP) on patient outcomes, including mortality, hospital length of stay, and intensive care unit length of stay. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a 12-month controlled study in the intensive care units of a large academic tertiary medical center. We alternated use of the AKI-SCAMP with use of a "sham" control form in 4- to 6-week blocks. The primary outcome was risk of inpatient mortality. Prespecified secondary outcomes included 30- and 60-day mortality, hospital length of stay, and intensive care unit length of stay. Generalized estimating equations were used to estimate the effect of the AKI-SCAMP on mortality and length of stay. RESULTS: There were 122 patients in the AKI-SCAMP group and 102 patients in the control group. There was no significant difference in inpatient mortality associated with AKI-SCAMP use (41% versus 47% control). AKI-SCAMP use was associated with significantly reduced intensive care unit length of stay (mean, 8; 95% confidence interval, 8 to 9 days versus mean, 12; 95% confidence interval, 10 to 13 days; P<0.001) and hospital length of stay (mean, 25; 95% confidence interval, 22 to 29 days versus mean, 30; 95% confidence interval, 27 to 34 days; P=0.02). Patients in the AKI-SCAMP group were less likely to receive KRT in the context of physician-perceived treatment futility than those in the control group (2% versus 7%; P=0.003). CONCLUSIONS: Use of the AKI-SCAMP tool for AKI KRT was not significantly associated with inpatient mortality, but was associated with reduced intensive care unit length of stay, hospital length of stay, and use of KRT in cases of physician-perceived treatment futility. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Acute Kidney Injury Standardized Clinical Assessment and Management Plan for Renal Replacement Initiation, NCT03368183. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_07_CJN02060221.mp3.
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Lesión Renal Aguda/terapia , Algoritmos , Toma de Decisiones Clínicas , Terapia de Reemplazo Renal , Lesión Renal Aguda/mortalidad , Anciano , Femenino , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
CONTEXT: An important aspect of end-of-life care, place of death is understudied in advanced chronic (CKD) and end-stage kidney disease (ESKD). OBJECTIVE: We sought to examine trends and factors associated with where advanced CKD/ESKD patients die. METHODS: We conducted a retrospective cross-sectional study using mortality data from 2003 to 2017 for deaths attributed primarily to advanced CKD/ESKD in the United States. RESULTS: Between 2003 and 2017, 222,247 deaths were attributed to advanced CKD/ESKD. From 2003 to 2017, deaths occurring in hospitals declined from 56.0% (n = 5356) to 35.6% (n = 7764), whereas increases occurred in deaths at home (13.5% [n = 1292] to 24.3% [n = 5306]), nursing facilities (18.6% [n = 1776] to 19.3% [n = 4221]), and hospice facilities (0.3% [n = 29] to 13.4% [n = 2917]). Nonwhite race was associated with increased odds of hospital death (Black [OR = 1.59; 95% CI = 1.55, 1.62]; Native American [OR = 1.47; 95% CI = 1.32, 1.63]; Asian [OR = 1.43; 95% CI = 1.32, 1.55] and reduced odds of nursing facility (Black [OR = 0.622; 95% CI = 0.600, 0.645]; Native American [OR = 0.638; 95% CI = 0.572, 0.712]; Asian [OR = 0.574; 95% CI = 0.533, 0.619], or hospice facility death (Black [OR = 0.843; 95% CI = 0.773, 0.918]; Native American [OR = 0.380; 95% CI = 0.289, 0.500]; Asian [OR = 0.609; 95% CI = 0.502, 0.739]). Older age was associated with reduced odds of hospital death (≥85 [OR = 0.334; 95% CI = 0.312, 0.358]) and increased odds of home (≥85 [OR = 1.55; 95% CI = 1.43, 1.68]), nursing facility (≥85 [OR = 3.09; 95% CI = 2.76, 3.45]) or hospice facility death (≥85 [OR = 1.60; 95% CI = 1.49, 1.72]). CONCLUSIONS: Hospitals remain the most common place of death from advanced CKD/ESKD; however, the proportion of home, nursing facility, and hospice facility deaths have increased.
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Cuidados Paliativos al Final de la Vida , Hospitales para Enfermos Terminales , Fallo Renal Crónico , Anciano , Estudios Transversales , Humanos , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
The Advancing American Kidney Health (AAKH) Initiative aims to promote high-value patient-centered care by improving access to and quality of treatment options for kidney failure. The 3 explicit goals of the initiative are to reduce the incidence of kidney failure, increase the number of available kidneys for transplantation, and increase transplantation and home dialysis. To ensure a patient-centered movement toward home dialysis modalities, actionable principles of palliative care, including systematic communication and customized treatment plans, should be incorporated into this policy. In this perspective, we describe 2 opportunities to strengthen the patience-centeredness of the AAKH Initiative through palliative care: (1) serious illness conversations should be required for all dialysis initiations in the End-Stage Renal Disease Treatment Choices model, and (2) conservative kidney management should be counted as a home modality alongside peritoneal dialysis and home hemodialysis. A serious illness conversation can help clinicians discern whether a patient's goals and values are best respected by a home dialysis modality or whether a nondialytic strategy such as conservative kidney management should be considered. An intensive and careful patient- and family-centered selection process will be necessary to ensure that no patient is pressured to forego conventional dialysis.
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Fallo Renal Crónico/terapia , Cuidados Paliativos/métodos , Atención Dirigida al Paciente/métodos , Calidad de Vida , Diálisis Renal , Humanos , Estados UnidosRESUMEN
BACKGROUND: Percutaneous coronary intervention (PCI) use is low in the setting of stable symptomatic angina in individuals with advanced chronic kidney disease (CKD) despite high cardiovascular risk in this population, and PCI is frequently deferred out of concern for precipitating dialysis therapy. Whether this is appropriate is uncertain, and patient-centered data comparing the relative risks and benefits of continued medical therapy versus PCI in patients with advanced CKD and stable angina are scarce. STUDY DESIGN: Decision analysis. SETTING & POPULATION: Hypothetical cohort of individuals with advanced CKD (stages 4-5 with estimated glomerular filtration rates ≤ 20mL/min/1.73m2) and stable angina. MODEL, PERSPECTIVE, & TIMELINE: A Markov model with a Monte Carlo simulation through 12 cycles, that is, 3 years of 3-month intervals, with 10,000 microsimulations predicted mean quality-adjusted life-years. INTERVENTION: PCI first, medical management, or dialysis (hemodialysis [HD]) followed by PCI. OUTCOMES: Outcomes modeled were progression to HD therapy (for those not assigned to the preemptive HD strategy), catheter infection, and death. RESULTS: Our analysis showed mean quality-adjusted life-years of 1.103 ± 0.69 for PCI first, 1.088±0.70 for medical management, and 0.670±0.58 for HD followed by PCI. Probabilistic sensitivity analysis found PCI as the preferred strategy > 60% of the time. LIMITATIONS: Values for probabilities and utilities were estimated and/or derived from multiple sources that were not uniform in their populations in terms of age, comorbid condition burden, and degree of kidney failure, and several simplifying assumptions were made. CONCLUSIONS: Our analysis demonstrates that quality-adjusted life expectancy is similar for the PCI first and medical management strategies in patients with advanced CKD with stable angina and that the decision depends on patient preferences other than those incorporated in our model. Both strategies are superior to preemptive dialysis.
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Angina Estable/etiología , Angina Estable/terapia , Técnicas de Apoyo para la Decisión , Intervención Coronaria Percutánea , Insuficiencia Renal Crónica/complicaciones , Humanos , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Índice de Severidad de la EnfermedadRESUMEN
Dialysis-dependent ESRD is a serious illness with high disease burden, morbidity, and mortality. Mortality in the first year on dialysis for individuals over age 75 years old approaches 40%, and even those with better prognoses face multiple hospitalizations and declining functional status. In the last month of life, patients on dialysis over age 65 years old experience higher rates of hospitalization, intensive care unit admission, procedures, and death in hospital than patients with cancer or heart failure, while using hospice services less. This high intensity of care is often inconsistent with the wishes of patients on dialysis but persists due to failure to explore or discuss patient goals, values, and preferences in the context of their serious illness. Fewer than 10% of patients on dialysis report having had a conversation about goals, values, and preferences with their nephrologist, although nearly 90% report wanting this conversation. Many nephrologists shy away from these conversations, because they do not wish to upset their patients, feel that there is too much uncertainty in their ability to predict prognosis, are insecure in their skills at broaching the topic, or have difficulty incorporating the conversations into their clinical workflow. In multiple studies, timely discussions about serious illness care goals, however, have been associated with enhanced goal-consistent care, improved quality of life, and positive family outcomes without an increase in patient distress or anxiety. In this special feature article, we will (1) identify the barriers to serious illness conversations in the dialysis population, (2) review best practices in and specific approaches to conducting serious illness conversations, and (3) offer solutions to overcome barriers as well as practical advice, including specific language and tools, to implement serious illness conversations in the dialysis population.
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Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Fallo Renal Crónico/terapia , Nefrólogos/psicología , Relaciones Médico-Paciente , Calidad de Vida , Diálisis Renal , Factores de Edad , Anciano , Toma de Decisiones Clínicas , Comunicación , Comorbilidad , Femenino , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/psicología , Masculino , Participación del Paciente , Pronóstico , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVES: Protein and potassium intake and the resulting diet-dependent net acid load may affect kidney stone formation. It is not known whether protein type or net acid load is associated with risk of kidney stones. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We prospectively examined intakes of protein (dairy, nondairy animal, and vegetable), potassium, and animal protein-to-potassium ratio (an estimate of net acid load) and risk of incident kidney stones in the Health Professionals Follow-Up Study (n=42,919), the Nurses' Health Study I (n=60,128), and the Nurses' Health Study II (n=90,629). Multivariable models were adjusted for age, body mass index, diet, and other factors. We also analyzed cross-sectional associations with 24-hour urine (n=6129). RESULTS: During 3,108,264 person-years of follow-up, there were 6308 incident kidney stones. Dairy protein was associated with lower risk in the Nurses' Health Study II (hazard ratio for highest versus lowest quintile, 0.84; 95% confidence interval, 0.73 to 0.96; P value for trend <0.01). The hazard ratios for nondairy animal protein were 1.15 (95% confidence interval, 0.97 to 1.36; P value for trend =0.04) in the Health Professionals Follow-Up Study and 1.20 (95% confidence interval, 0.99 to 1.46; P value for trend =0.06) in the Nurses' Health Study I. Potassium intake was associated with lower risk in all three cohorts (hazard ratios from 0.44 [95% confidence interval, 0.36 to 0.53] to 0.67 [95% confidence interval, 0.57 to 0.78]; P values for trend <0.001). Animal protein-to-potassium ratio was associated with higher risk (P value for trend =0.004), even after adjustment for animal protein and potassium. Higher dietary potassium was associated with higher urine citrate, pH, and volume (P values for trend <0.002). CONCLUSIONS: Kidney stone risk may vary by protein type. Diets high in potassium or with a relative abundance of potassium compared with animal protein could represent a means of stone prevention.
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Proteínas en la Dieta , Encuestas Epidemiológicas , Cálculos Renales/epidemiología , Potasio en la Dieta , Adulto , Animales , Calcio/orina , Ácido Cítrico/orina , Productos Lácteos , Femenino , Estudios de Seguimiento , Humanos , Concentración de Iones de Hidrógeno , Incidencia , Masculino , Persona de Mediana Edad , Ácido Oxálico/orina , Estudios Prospectivos , Estados Unidos/epidemiología , Ácido Úrico/orina , Urinálisis , VerdurasRESUMEN
OBJECTIVE: To determine factors influencing outcome for patients with gestational trophoblastic disease (GTD) from throughout the world. STUDY DESIGN: Physicians known to treat GTD were sent a questionnaire. RESULTS: There were 32 responses from 17 countries, totaling 26,153 patients. Of 14,093 patients with complete mole 20.6% developed trophoblastic neoplasia, and 5.7% died. There were 10,230 patients with partial mole, of whom 6.5% received therapy for neoplasia. There were 548 patients with post-term pregnancy choriocarcinoma, of whom 13.4% died. Of 137 patients with placental site trophoblastic tumor 16.1% died. The remaining 1,165 patients did not fit into a designated diagnostic category. The mortality rate for 2,818 patients with GTD primarily treated at a trophoblast center was 2.1%, as compared with 8% among 1,854 patients referred after failure of primary treatment (p < 0.01). CONCLUSION: Patients treated by physicians experienced in the management of trophoblastic disease have better results and survival.
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Enfermedad Trofoblástica Gestacional/terapia , Coriocarcinoma/diagnóstico , Coriocarcinoma/mortalidad , Coriocarcinoma/terapia , Competencia Clínica , Femenino , Enfermedad Trofoblástica Gestacional/diagnóstico , Enfermedad Trofoblástica Gestacional/mortalidad , Humanos , Mola Hidatiforme/diagnóstico , Mola Hidatiforme/mortalidad , Mola Hidatiforme/terapia , Embarazo , Encuestas y Cuestionarios , Resultado del Tratamiento , Tumor Trofoblástico Localizado en la Placenta/diagnóstico , Tumor Trofoblástico Localizado en la Placenta/mortalidad , Tumor Trofoblástico Localizado en la Placenta/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/mortalidad , Neoplasias Uterinas/terapiaAsunto(s)
Reanimación Cardiopulmonar/métodos , Computadoras de Mano , Arteria Femoral/diagnóstico por imagen , Paro Cardíaco/terapia , Monitoreo Fisiológico/instrumentación , Pulso Arterial , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Arteria Femoral/fisiología , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Estudios Prospectivos , Reproducibilidad de los Resultados , UltrasonografíaRESUMEN
BACKGROUND: Uracil mustard and 5-fluorouracil (UM-FU) combination chemotherapy was used as one of the earliest combination chemotherapies in ovarian carcinoma from 1964 to 1971 at Yale New Haven Medical Center. METHODS: UM-FU was offered to patients with stage III and IV, histologically verified, ovarian carcinoma. Uracyl mustard was administered orally--1 mg/ kg, daily. 5-Fluorouracyl was administered every four weeks at 5 mg/kg for five days by intravenous infusion. RESULTS: Of a total 185 patients with ovarian cancer, 76 received UM-FU. Thirty-five patients had measurable disease. Fifteen (42%) showed objective response lasting three to 95 months, with decrease in size of masses and disappearance of ascites or hydrothorax. Their survival from diagnosis to death was 41 months. Twenty patients showed no response; their mean survival was 18 months. Three of the 76 patients who received UM-FU developed acute nonlymphocytic leukemia. CONCLUSION: UM-FU was effective in controlling ascites and hydrothorax and diminished intraabdominal masses. The discovery of adriamycin and then platinum led to more effective therapy and the use of uracil mustard was superseded. It is no longer available. The experience reported is of historic interest.
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Antineoplásicos/historia , Protocolos de Quimioterapia Combinada Antineoplásica/historia , Carcinoma/historia , Fluorouracilo/historia , Neoplasias Ováricas/historia , Mostaza de Uracilo/historia , Adulto , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma/tratamiento farmacológico , Carcinoma/patología , Femenino , Fluorouracilo/administración & dosificación , Historia del Siglo XX , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Mostaza de Uracilo/administración & dosificaciónRESUMEN
Semi-dry grasslands in the European Alps have been increasingly fragmented over the last 150 years. Few studies have investigated the implications of landscape configuration for genetic structure and gene flow among remnant habitat patches. Conservation management of semi-dry grassland plants rarely accounts for possible effects of major landscape elements, such as forest patches, as barriers to gene flow and dispersal via seed and pollen, despite their potential importance for biodiversity conservation. Using 1416 individuals from 61 sampling sites across 2 valleys in South-Eastern Switzerland and Amplified fragment length polymorphism (AFLP) fingerprints, we applied a spatial strip and a circle approach to determine the impact of different landscape elements on genetic differentiation in the semi-dry grassland herb Trifolium montanum (mountain clover). Overall genetic differentiation among sampling sites was low (overall F ST = 0.044). Forest area had no effect on gene flow at the landscape scale, but area of semi-dry grassland, the potential habitat of T. montanum, road area, and altitude influenced genetic differentiation among sampling sites. The observed pattern of genetic differentiation suggests that a future increase in forest area, due to land use abandonment, at least in the short term, are unlikely to directly impact patterns of genetic variation in T. montanum.
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Ambiente , Trifolium/genética , Ecosistema , Evolución Molecular , Flujo Génico , Variación Genética , Genética de Población , Geografía , Densidad de Población , SuizaRESUMEN
BACKGROUND: Several biomarkers of metabolic acidosis, including lower plasma bicarbonate, have been associated with prevalent hypertension in cross-sectional studies. We sought to examine prospectively whether lower plasma bicarbonate is associated with incident hypertension. METHODS: We conducted a prospective case-control study nested within the Nurses' Health Study II. Plasma bicarbonate was measured in 695 nonobese women without hypertension at time of blood draw who subsequently developed hypertension during 6 years of follow-up. Control subjects were matched to case subjects according to age, race, time and day of blood draw, and day of menstrual cycle. We used unconditional logistic regression to generate odds ratios (ORs) for development of hypertension by quintile of baseline plasma bicarbonate. RESULTS: After adjusting for matching factors, body mass index, family history of hypertension, plasma creatinine, and dietary and lifestyle factors, higher plasma bicarbonate was associated with lower odds of developing hypertension across quintiles (P for linear trend = 0.04). Those in the highest compared with the lowest quintile of plasma bicarbonate had 31% lower odds of developing hypertension (OR = 0.69; 95% confidence interval = 0.48-0.99). Further adjustment for diet-estimated net endogenous acid production, plasma insulin, 25-hydroxyvitamin D, and uric acid did not alter these findings. CONCLUSIONS: Our case-control study is consistent with a modest association between higher plasma bicarbonate and reduced odds of developing hypertension among nonobese women, although our findings are of borderline statistical significance. Further research is required to confirm this finding as part of a larger prospective cohort study and to elucidate the mechanism for this relation.
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Bicarbonatos/sangre , Hipertensión/sangre , Hipertensión/epidemiología , Enfermeras y Enfermeros/estadística & datos numéricos , Adulto , Biomarcadores/sangre , Boston/epidemiología , Tampones (Química) , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/diagnóstico , Incidencia , Persona de Mediana Edad , Prevalencia , Estudios ProspectivosRESUMEN
BACKGROUND AND OBJECTIVES: Lower urinary citrate excretion is a risk factor for nephrolithiasis and associated with metabolic acidosis and higher prevalence of hypertension and insulin resistance. This study sought to quantify the independent predictors of urinary citrate excretion in population-based cohorts. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cross-sectional study of 2561 individuals from the Health Professionals Follow-Up Study and Nurses' Health Studies I and II who provided two 24-hour urine collections was conducted. Dietary data were ascertained from the semiquantitative food frequency questionnaire. Lifestyle and disease data were derived from responses to biennial questionnaires. Multivariable linear regression was used to quantify the predictors of urinary citrate excretion. RESULTS: After adjusting for age, urinary creatinine, dietary, and other factors, higher intake of nondairy animal protein (per 10 g/d; -20 mg/d; 95% confidence interval [-29 to -11]), higher body mass index (per 1 kg/m(2); -4 mg/d; [-6 to -2]), and history of nephrolithiasis (-57 mg/d; [-79 to -36]), hypertension (-95 mg/d; [-119 to -71]), gout (-104 mg/d; [-155 to -54]), and thiazide use (-34 mg/d; [-68 to -1]) were independently associated with lower 24-hour urinary citrate excretion. Higher intake of potassium (per 1000 mg/d; 53 mg/d; [33 to 74]), higher urinary sodium (per 100 mEq/d; 56 mg/d; [31 to 80]), and history of diabetes (61 mg/d; [21 to 100]) were independently associated with higher citrate excretion. CONCLUSIONS: Several dietary and lifestyle factors and medical conditions are independently associated with urinary citrate excretion.