RESUMEN
BACKGROUND: Percussion is derived from the Latin word to hear and to touch. Percussion of the abdomen is used to detect areas of tenderness, dullness within an area of tenderness suggestive of a mass, shifting dullness representing fluid or blood, splenic, hepatic and bladder enlargement, and free air in the peritoneum. Covered are abdominal signs of percussion attributed as medical eponyms from the time-period beginning in the mid-late nineteenth century. Described is historical information behind the sign, descriptions of the sign, and implication in modern clinical practice. DATA SOURCES: PubMed, Medline, online Internet word searches, textbooks, and references from other source text. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSION: Percussion signs defined as medical eponyms were important discoveries adopted by physicians prior to the advent of radiographs and other imaging and diagnostic techniques. The signs perfected during this time-period provided important clinical cues as to the presence of air within the peritoneum or rupture of the spleen.
Asunto(s)
Epónimos , Palpación/historia , Médicos/historia , Abdomen , Historia del Siglo XIX , HumanosRESUMEN
BACKGROUND: Percussion and auscultation are derived from the Latin words to touch and hear, respectively. Covered are abdominal percussion signs and ausculatory signs discovered from 1924 to 1980. Signs ascribed as medical eponyms pay homage to these physicians who provided new and unique insights into disease. DATA SOURCES: PubMed, Medline, online Internet word searches, textbooks, and references from other source text. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSION: Many of these signs have been discarded because of modern imaging and diagnostic techniques. When combined with a high clinical suspicion, positive results using percussion combined with palpation is a useful bedside technique in detecting splenic enlargement. Thus, some of these maneuvers remain important bedside techniques that skilled practitioners should master, and along with a meaningful history, provide relevant information to diagnosis. It is through learning about these signs that we gain a sense of humility on the difficulty physicians faced prior to the advent of techniques that now allow us an easier way to visualize and diagnose the underlying disease processes.
Asunto(s)
Epónimos , Palpación/historia , Percusión/historia , Médicos/historia , Historia del Siglo XX , HumanosRESUMEN
BACKGROUND: Abdominal palpation is an important clinical skill used by physicians to detect the cause of the underlying disease. Abdominal physical signs reported as medical eponyms are sometimes helpful in supporting or confirming clinical suspicion of a diagnosis. With the advent of advanced and rapid imaging techniques physicians often know the diagnosis prior to setting their hands on patients. Nevertheless, knowledge of these signs may still remain important in settings where imaging may not be readily available and importantly provide deeper insights into the mechanism of disease. In this paper, described are medical eponyms associated with abdominal palpation from the period 1907-1926. DATA SOURCES: PubMed, Medline, on-line Internet word searches, textbooks, and references from other source text were used as the data source. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSION: We describe brief historical background information about the physician who reported the sign, original description of the sign, and its clinical application and implication into today's medical practice.
Asunto(s)
Abdomen , Epónimos , Palpación/historia , Historia del Siglo XX , HumanosRESUMEN
BACKGROUND: An eponym in clinical medicine is an honorific term ascribed to a person(s) who may have initially discovered or described a device, procedure, anatomical part, treatment, disease, symptom, syndrome, or sign found on physical examination. Signs, although often lacking sufficient sensitivity and specificity, assist in some cases to differentiate and diagnose disease. With the advent of advanced technological tools in radiological imaging and diagnostic testing, the importance of inspection, the initial steps taught during the physical examination, is often overlooked or given only cursory attention. Nevertheless, in the era of evidence-based and cost-effective medicine, it becomes compelling, and we contend that a meticulously performed history and physical examination, applying the basic tenets of inspection, remains paramount prior to obtaining appropriate diagnostic tests. DATA SOURCES: PubMed, Medline, online Internet word searches and bibliographies from source text and textbooks. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSIONS: We describe the historical aspect, clinical application, and performance of medical eponymous signs of inspection found on physical examination during the 18th to 20th centuries.
Asunto(s)
Abdomen Agudo/historia , Medicina Clínica/historia , Epónimos , Examen Físico/historia , Abdomen Agudo/diagnóstico , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , HumanosRESUMEN
BACKGROUND: This paper describes medical eponyms associated with abdominal palpation from the period 1926-1976. Despite opposition by some, eponyms are a long standing tradition and widely used in medicine. The techniques may still be useful in some cases, assisting in the selection of an appropriate and cost-effective approach to patient care. In this piece, we cover signs named in honor of physicians who contributed to medicine by developing new palpatory techniques in an attempt to better diagnose disease of the abdominal wall, umbilicus, gallbladder, pancreas, and appendix. DATA SOURCES: PubMed, Medline, online Internet word searches, textbooks, and references from other source texts. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSION: We describe brief historical background information about the physician who reported the sign, original description of the sign, and its clinical application and implication into today's medical practice.
Asunto(s)
Abdomen Agudo/historia , Epónimos , Examen Físico/historia , Médicos/historia , Abdomen Agudo/diagnóstico , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Palpación/historia , Examen Físico/métodos , Estados UnidosRESUMEN
INTRODUCTION AND HYPOTHESIS: To determine the effectiveness of the muscarinic receptor antagonist solifenacin (VESIcare®) in the treatment of postvoid dribbling (PVD). METHODS: We carried out a multicenter, 12-week, double-blind, randomized, placebo-controlled, parallel design study. Between 2012 and 2015, a total of 118 women (age 18-89 years) with PVD at least twice/weekly, were randomized to receive solifenacin (5 mg; n = 58) or placebo (n = 60) once daily. The primary outcome was the percentage reduction in PVD episodes. Secondary outcomes included the percentage of patients with ≥50% reduction in PVD episodes and changes in quality of life. RESULTS: There were no differences in either the primary or secondary outcome variables. Subgroup analysis, based on those with more severe disease (>10 PVD episodes/week), showed a greater and significant percentage reduction in the frequency of PVD episodes per day (60.3% vs 32.1%; p = 0.035) and a higher percentage of patients showing ≥50% reduction in the frequency of PVD episodes with solifenacin (68.1% vs 45.8%; p = 0.0476). A significant solifenacin effect occurred at week 2 and continued through week 12 for the subgroup. For solifenacin, PVD reduction was the same for the entire cohort and subgroup, whereas for placebo, it was 10% lower in the subgroup, declining from 42% to 32%. CONCLUSION: There were no differences in PVD outcomes between the solifenacin and placebo groups. Solifenacin may play a role in treating women with the most severe symptoms. Because of the powerful placebo response seen in this study, behavior-based interventions may be useful for treating PVD.
Asunto(s)
Antagonistas Muscarínicos/uso terapéutico , Calidad de Vida/psicología , Succinato de Solifenacina/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Micción/efectos de los fármacos , Niño , Método Doble Ciego , Femenino , Humanos , Quinuclidinas , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/diagnóstico , Vejiga Urinaria Hiperactiva/psicologíaRESUMEN
BACKGROUND: Prior to the advent of modern imaging techniques, maneuvers were performed as part of the physical examination to further assess pathological findings or an acute abdomen and to further improve clinicians' diagnostic acumen to identify the site and cause of disease. Maneuvers such as changing the position of the patient, extremity, or displacing through pressure a particular organ or structure from its original position are typically used to exacerbate or elicit pain. Some of these techniques, also referred to as special tests, are ascribed as medical eponym signs. DATA SOURCES: PubMed, Medline, online Internet word searches, textbooks and references from other source text. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSION: These active and passive maneuvers of the abdomen, reported as medical signs, have variable performance in medical practice. The lack of diagnostic accuracy may be attributed to confounders such as the position of the organ, modification of the original technique, or lack of performance of the maneuver as originally intended.
Asunto(s)
Abdomen , Dolor Abdominal , Epónimos , Abdomen/patología , Abdomen/fisiopatología , Dolor Abdominal/clasificación , Dolor Abdominal/diagnóstico , Dolor Abdominal/patología , Dolor Abdominal/fisiopatología , HumanosRESUMEN
Flushing is the subjective sensation of warmth accompanied by visible cutaneous erythema occurring throughout the body with a predilection for the face, neck, pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are superficially located and in greatest numbers. Flushing can be present in either a wet or dry form depending upon whether neural-mediated mechanisms are involved. Activation of the sympathetic nervous system results in wet flushing, accompanied by diaphoresis, due to concomitant stimulation of eccrine sweat glands. Wet flushing is caused by certain medications, panic disorder and paroxysmal extreme pain disorder (PEPD). Vasodilator mediated flushing due to the formation and release of a variety of biogenic amines, neuropeptides and phospholipid mediators such as histamine, serotonin and prostaglandins, respectively, typically presents as dry flushing where sweating is characteristically absent. Flushing occurring with neuroendocrine tumors accompanied by gastrointestinal symptoms is generally of the dry flushing variant, which may be an important clinical clue to the differential diagnosis. A number of primary diseases of the gastrointestinal tract cause flushing, and conversely extra-intestinal conditions are associated with flushing and gastrointestinal symptoms. Gastrointestinal findings vary and include one or more of the following non-specific symptoms such as abdominal pain, nausea, vomiting, diarrhea or constipation. The purpose of this review is to provide a focused comprehensive discussion on the presentation, pathophysiology, diagnostic evaluation and management of those diseases that arise from the gastrointestinal tract or other site that may cause gastrointestinal symptoms secondarily accompanied by flushing. This review is divided into two parts given the scope of conditions that cause flushing and affect the gastrointestinal tract: Part 1 covers neuroendocrine tumors (carcinoid, pheochromocytomas, vasoactive intestinal polypeptide, medullary carcinoma of the thyroid), polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS), and conditions involving mast cells and basophils; while Part 2 covers dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications.
Asunto(s)
Basófilos , Rubor/etiología , Enfermedades Gastrointestinales/etiología , Trastornos Leucocíticos/complicaciones , Mastocitosis/complicaciones , Tumores Neuroendocrinos/complicaciones , Síndrome POEMS/complicaciones , Dolor Abdominal/etiología , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/terapia , Tumor Carcinoide/complicaciones , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/terapia , Carcinoma Neuroendocrino/complicaciones , Carcinoma Neuroendocrino/diagnóstico , Carcinoma Neuroendocrino/terapia , Estreñimiento/etiología , Diarrea/etiología , Humanos , Trastornos Leucocíticos/diagnóstico , Trastornos Leucocíticos/terapia , Mastocitosis/diagnóstico , Mastocitosis/terapia , Náusea/etiología , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/terapia , Síndrome POEMS/diagnóstico , Síndrome POEMS/terapia , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Feocromocitoma/complicaciones , Feocromocitoma/diagnóstico , Feocromocitoma/terapia , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/terapia , Vipoma/complicaciones , Vipoma/diagnóstico , Vipoma/terapia , Vómitos/etiologíaRESUMEN
Flushing disorders with involvement of the gastrointestinal tract represent a heterogeneous group of conditions. In part 1 of this review series, neuroendocrine tumors (NET), mast cell activation disorders (MCAD), and hyperbasophilia were discussed. In this section we discuss the remaining flushing disorders which primarily or secondarily involve the gastrointestinal tract. This includes dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications. With the exception of paroxysmal pain disorders, panic disorders and some medications, these disorders presents with dry flushing. A detailed and comprehensive family, social, medical and surgical history, as well as recognizing the presence of other systemic symptoms are important in distinguishing the different disease that cause flushing with gastrointestinal symptoms.
Asunto(s)
Anafilaxia/complicaciones , Síndrome de Vaciamiento Rápido/complicaciones , Rubor/etiología , Enfermedades Gastrointestinales/etiología , Dolor/complicaciones , Recto/anomalías , Rosácea/complicaciones , Crisis Tiroidea/complicaciones , Consumo de Bebidas Alcohólicas/efectos adversos , Anafilaxia/diagnóstico , Anafilaxia/terapia , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/complicaciones , Síndrome de Vaciamiento Rápido/diagnóstico , Síndrome de Vaciamiento Rápido/terapia , Humanos , Hipertiroidismo/complicaciones , Hipertiroidismo/diagnóstico , Hipertiroidismo/terapia , Dolor/diagnóstico , Trastorno de Pánico/complicaciones , Trastorno de Pánico/diagnóstico , Trastorno de Pánico/terapia , Rosácea/diagnóstico , Rosácea/terapia , Crisis Tiroidea/diagnóstico , Crisis Tiroidea/terapiaRESUMEN
BACKGROUND: Abdominal palpation is a difficult skill to master in the physical examination. It is through the tactile sensation of touch that abdominal tenderness is detected and expressed through pain. Its findings can be used to detect peritonitis and other acute and subtle abnormalities of the abdomen. Some techniques, recognized as signs or medical eponyms, assist clinicians in detecting disease and differentiating other conditions based on location and response to palpation. Described in this paper are medical eponyms associated with abdominal palpation from the period 1876 to 1907. DATA SOURCES: PubMed, Medline, on-line Internet word searches, textbooks and references from other source text were used as the data source. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSION: We present brief historical background information about the physician who reported the sign, original description of the sign, and its clinical application and implication in today's medical practice.
Asunto(s)
Abdomen/patología , Abdomen/fisiopatología , Epónimos , Palpación/historia , Historia del Siglo XIX , Historia del Siglo XX , HumanosRESUMEN
PURPOSE: The Healthy Work Place (HWP) study investigated methods to improve clinicians' dissatisfaction and burnout. The purpose of this paper is to identify factors that influenced study enrollment and completion and assess effects of initial clinic site enrollment rates on clinician outcomes, including satisfaction, burnout, stress and intent to leave practice. DESIGN/METHODOLOGY/APPROACH: In total, 144 primary care clinicians (general internists, family physicians, nurse practitioners and physician assistants) at 14 primary care clinics were analyzed. FINDINGS: In total, 72 clinicians enrolled in the study and completed the first survey (50 percent enrollment rate). Of these, 10 did not complete the second survey (86 percent completion rate). Gender, type, burnout, stress and intervention did not significantly affect survey completion. Hence, widespread agreement about most moral/ethical issues (72 percent vs 22 percent; p=0.0060) and general agreement on treatment methods (81 percent vs 50 percent; p=0.0490) were reported by providers that completed both surveys as opposed to just the initial survey. Providers with high initial clinic site enrollment rates (=50 percent providers) obtained better outcomes, including improvements in or no worsening of satisfaction (odds ratio (OR)=19.16; p=0.0217) and burnout (OR=6.24; p=0.0418). SOCIAL IMPLICATIONS: More providers experiencing workplace agreement completed the initial and final surveys, and providers at sites with higher initial enrollment rates obtained better outcomes including a higher rate of improvement or no worsening of job satisfaction and burnout. ORIGINALITY/VALUE: There is limited research on clinicians' workplace and other factors that influence their participation in survey-based studies. The findings help us to understand how these factors may affect quality of data collecting and outcome. Thus, the study provides us insight for improvement of quality in primary care.
Asunto(s)
Agotamiento Profesional/epidemiología , Satisfacción en el Trabajo , Atención Primaria de Salud , Encuestas y Cuestionarios/estadística & datos numéricos , Lugar de Trabajo/psicología , Ética Médica , Femenino , Personal de Salud/psicología , Humanos , Masculino , Mejoramiento de la Calidad/organización & administración , Factores SexualesRESUMEN
BACKGROUND: Administrative data are frequently used to identify venous thromboembolism (VTE) for research and quality reporting. However, the validity of these codes, particularly in outpatients, has not been well-established. OBJECTIVE: To determine how well International Classification of Diseases, Ninth Revision (ICD-9) codes for VTE predict chart-confirmed acute VTE in inpatient and outpatients. PATIENTS AND METHODS: We selected 4642 adults with an incident ICD-9 diagnosis of VTE between years 2004 and 2010 from the Cardiovascular Research Network Venous Thromboembolism cohort study. Medical charts were reviewed to determine validity of events. Positive predictive values (PPVs) of ICD-9 codes were calculated as the number of chart-validated VTE events divided by the number with specific VTE codes. Analyses were stratified by VTE type [pulmonary embolism (PE), deep venous thrombosis (DVT)], code position (primary, secondary), and setting [hospital/emergency department (ED), outpatient]. RESULTS: The PPV for any diagnosis of VTE was 64.6% for hospital/ED patients and 30.9% for outpatients. Primary diagnosis codes from hospital/ED patients were more likely to represent acute VTE than secondary diagnosis codes (78.9% vs. 44.4%, P<0.001). Primary hospital/ED codes for PE and lower extremity DVT had higher PPV than for upper extremity DVT (89.1%, 74.9%, and 58.1%, respectively). Outpatient codes were poorly predictive of acute VTE: 28.0% for PE and 53.6% for lower extremity DVT. CONCLUSIONS: ICD-9 codes for VTE obtained from outpatient encounters or from secondary diagnosis codes do not reliably reflect acute VTE. More accurate ways of identifying VTE in outpatients are needed before these codes can be adopted for research or policy purposes.
Asunto(s)
Pacientes Internos , Pacientes Ambulatorios , Indicadores de Calidad de la Atención de Salud , Tromboembolia Venosa/diagnóstico , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Validación como Asunto , Trombosis de la Vena/diagnósticoRESUMEN
Hospitalized patients are at risk of venous thromboembolism (VTE) and prophylaxis is often suboptimal due to difficulty in identifying at-risk patients. Simple and validated risk-assessment models (RAMs) are available to assist clinicians in identifying patients who have a high risk for developing VTE. Despite the well-documented association of immobility with increased risk of thrombosis, immobility is not consistently defined in clinical studies. We conducted a systematic review of published VTE RAMs and used objective criteria to determine how the term immobility is defined in RAMs. We identified 17 RAMs with six being externally validated. The concept of immobility is vaguely described in different RAMs, impacting the validity of these models in clinical practice. The wide variability in defining mobility in RAMs precluded its accurate clinical application, further limiting generalization of published RAMs. Externally validated RAMs with clearly defined qualitative or quantitative terms of immobility are needed to assess VTE risk in real-time at the point-of-care.
Asunto(s)
Hospitalización , Hipocinesia , Modelos Cardiovasculares , Tromboembolia Venosa , Humanos , Hipocinesia/complicaciones , Hipocinesia/epidemiología , Hipocinesia/terapia , Factores de Riesgo , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/terapiaRESUMEN
Superficial vein thrombosis (SVT) may be associated with complications such as venous thromboembolism (VTE) and recurrent SVT. The purpose of this study was to explore risk factors among patients with a first isolated episode of SVT (index SVT) involving upper and lower extremities and to estimate the prevalence of VTE complications within 1 year of index SVT. Retrospective chart review of electronic records at Marshfield Clinic in Wisconsin identified 381 subjects with a first isolated SVT diagnosis (male/female: 170/211; median age 59.4 years). Patients were stratified based on whether they did (n = 44; 11.5 %) or did not (n = 337; 88.5 %) experience VTE complications and whether they did (n = 25; 6.6 %) or did not (n = 356; 93.4 %) experience pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 1 year of index SVT. There were 49 complications among 44 patients; these included DVT (n = 18, 36.7 %), propagation of SVT (n = 18, 36.7 %), PE (n = 9, 18.4 %), new SVT at different location (n = 3, 6.1 %), and recurrent SVT (n = 1, 2.0 %). Univariate analysis of all VTE complications identified seven potential risk factors and similar analysis of PE/DVT complications identified eight potential risk factors, with six common risk factors identified in both analyses. Multivariate analysis identified indwelling venous catheter 30 days prior to SVT (p = 0.044), cancer history with treatment in the previous year (p = 0.001), and non-surgical trauma 7 days prior to SVT (p < 0.001) as independent risk factors for PE/DVT complications. Independent risk factors identified in the current study may convey greater risk for VTE complications, especially PE/DVT, following an initial isolated SVT episode.
Asunto(s)
Embolia Pulmonar/etiología , Tromboembolia Venosa/etiología , Trombosis de la Vena/complicaciones , Catéteres de Permanencia/efectos adversos , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Heridas y Lesiones/complicacionesRESUMEN
BACKGROUND: Warfarin is an oral anticoagulant used in the long-term treatment/prevention of venothromboembolic disease. Patients undergoing elective surgical and non-surgical procedures may require temporary warfarin discontinuation followed by reinitiation after their procedure. Because little information is available regarding best methods for warfarin reinitiation, we investigated current practices to inform management decisions. METHODS: Subjects were required to have a known and stable warfarin dose prior to discontinuation, which was operationalized by requiring, within 7-days prior to discontinuation, that they have at least one INR in therapeutic range (2.0-3.5), no INR(s) out of range, and no more than a 15% change in warfarin dose. Stable dose prior to discontinuation was defined as the average daily dose received in the 7 days immediately prior to discontinuation. Reinitiation dose was defined as the average daily dose received in the first 3 days after warfarin was restarted. Subjects were divided into three groups based on whether they received approximately the same, a higher, or a lower dose at reinitiation and were also grouped by calendar time into three distinct periods that reflected differing levels of availability of electronic and patient care data that may impact reinitiation dose decisions. These groupings facilitated analyses and descriptions of trends in reinitiation dosing and supported other analyses, including tests for association between dose group and selected subject demographic, clinical, medication and hospitalization measures. All study data were abstracted from Marshfield Clinic electronic patient care and administrative databases and electronic patient care databases from Ministry St. Joseph's Hospital (Marshfield, WI). RESULTS: We identified 205 subjects with warfarin temporarily discontinued between 1994 and 2012: 99 subjects in same dose group, 32 subjects in the low group, and 74 subjects in the high group. Because relatively wide differences were observed in the proportion of same dose subjects during more recent years (2007-2012) compared to earlier years (54% vs 35%), we focused our analyses on this recent period, which included 140 subjects. Review of physician notes and other documents yielded virtually no information about reasons for reinitiation dose decisions. In addition, tests for association between reinitiation dose group and subject demographic, clinical, medication and hospital measures were uniformly uninformative. CONCLUSIONS: We observed varied dosing strategies for reinitiating patients on warfarin and, in more recent years, an apparent trend toward reinitiating patients on the same dose. However we could not associate dosing strategy with specific patient demographic, clinical, medication or hospital factors. Many factors influence whether a physician reinitiates a patient at a different dose than his/her prior stable warfarin dose. However, in the absence of clinical indications for modification, we believe patients with a previously established effective dose should be reinitiated at that same dose following temporary warfarin discontinuation.