Figure 2 Schematic design of the PARMA study. Figure 3 Preliminary data from the PARMA study,

as presented at international meetings in 1992 and 1993. Figure 4 Overall survival of patients randomized to either high-dose therapy followed by transplantation or conventional therapy. ACUTE MYELOID LEUKEMIA (AML) Complete Remission Although it has been known for a long time that achieving a complete remission is the sine qua non for long-term survival, induction of remission has been fairly standardized over Inhibitors,research,lifescience,medical the past four decades. Standard induction for AML consists of 3 days of an anthracycline, usually TKI-258 solubility dmso daunorubicin, together with 7 days of cytarabine. The problem here relates to data

published in the late 1980s and the 1990s, which indicated that using virtually identical drug regimens the complete remission rate varied from 55% to 60% among the Southwest Oncology Group (SWOG) in the US, 65%–70% Inhibitors,research,lifescience,medical among the Eastern Cooperative Oncology Group (ECOG) in the US, 70%–75% in the Cancer and Leukemia Group B (CALGB) in the US, and 75%–85% in Medical Research Council (MRC) in Britain (Table 2). Despite these differences in the complete remission rate, the overall Inhibitors,research,lifescience,medical outcome for AML for younger adults is virtually identical in each of the major groups when evaluating for survival from diagnosis (Figure 5).7 The question still remained how these identical survival results could be achieved when there are such heterogeneous reports of the complete remission rates. Although not always clearly specified Inhibitors,research,lifescience,medical in the manuscripts, it was clear to practitioners that these discrepancies did not reflect an inherent difference in practice or responses within institutions. The explanation

here reflects a difference in the Inhibitors,research,lifescience,medical requirement or definition of a complete response such that, for example, in SWOG, patients needed to undergo central review at diagnosis and upon recovery of blood counts in order to confirm a complete remission. In ECOG, although central review was not required at the achievement of complete remission, final blood results needed to be performed at an ECOG-certified laboratory. This meant that Dichloromethane dehalogenase if a patient was discharged from the hospital, in apparent remission, but with a platelet count of 70,000/μL, and the confirmatory platelet count of over 100,000/μL required for the definition of complete remission was not performed at an ECOG-certified laboratory, such a patient could not be categorized as achieving complete remission (Table 3). Figure 5 Overall survival from diagnosis of patients younger than 60 years with acute myeloid leukemia. Table 2 AML—induction therapy—3 days of anthracycline and 7 days of cytarabine (“3+7”).

The extensive family and community networks of past Jewish

graduates also provided a supportive framework for Jewish students. Indeed, more than a quarter of all Jewish graduates in Padua came from just a dozen families. Figure 1 Rabbi Joseph Solomon Qandia Delmedigo (1591–1655) was a rabbi, author, physician, mathematician, and music theorist. He was a student in Padua in 1609–1610. THE UNIVERSITY Inhibitors,research,lifescience,medical OF PADUA The University of Padua was founded in 1222, and its Medical School opened in 1250. Its status under Venetian rule from the early fifteenth century and its freedom from papal influence gave it some characteristics which did not pertain elsewhere, such as making its own policy on the admission of students. The prosperity and stability of the Venetian republic created the conditions which made it possible for Jewish students to travel across Europe to study in Padua (Figure 2). Religious divisions in Europe did not prevent Protestant or Jewish students attending Inhibitors,research,lifescience,medical this PF-4708671 manufacturer nominally Catholic university,

with the first Jewish student graduating in 1409.14 Over the centuries it gained a reputation as a center of excellence for the quality of Inhibitors,research,lifescience,medical its teaching in its Medical School and in its other Faculties. Indeed, the Medical School was widely regarded as the best medical school in Europe. Foreign students, like William Harvey from England and many others from Britain and elsewhere in Europe, were drawn in large numbers because of the quality of the clinical teaching, rather than the formal lectures which were available in universities Inhibitors,research,lifescience,medical abroad.15 By the late sixteenth century students attended daily hospital rounds, and discussion of major cases, urine examination, feeling pulses, and attending autopsies were standard teaching methods.15 Figure 2 The extent of the Venetian Inhibitors,research,lifescience,medical Empire, its commercial colonies and shipping routes. Jews had been

associated with some of the earliest European universities, and while there had been occasional Jewish medical students at other Italian universities it was only in Padua where, despite regulations to the contrary, Jews managed to qualify as physicians from the early fifteenth century and on a regular and continuing basis in the subsequent out centuries.16 While encountering petty anti-Jewish prejudices, usually in the form of fines or other financial impositions during their course of study, the opportunity offered by Padua was not equaled elsewhere in Europe before the end of the seventeenth century. Elsewhere in Italy and beyond, equal opportunities for Jewish medical students had to wait for more enlightened times. A few Jews were admitted to degrees in Siena during the seventeenth century and just a few at various times in Naples, Bologna, Rome, and Pisa, while in Livorno Jews were only admitted to medical studies in 1738. Jewish medical students first appeared at the University of Padua in the early fifteenth century, and numbers grew gradually.

In the United States, the incidence of adenocarcinoma has risen, while squamous

cell carcinoma has declined. It is now recognized in the AJCC staging system that these two histologies can carry different clinical outcomes (2). Institutional preferences and patient characteristics will often guide the management, as there are data to support multiple approaches for locally advanced esophageal cancer including upfront chemoradiation therapy (CRT) with or without surgery, perioperative chemotherapy, adjuvant radiation or chemoradiation. Surgery generally remains a mainstay in management of localized esophageal cancer, but as a single modality results in unacceptably Inhibitors,research,lifescience,medical high rates of local relapse and poor long-term survival rates, leading to the integration of radiation therapy and chemotherapy as neoadjuvant or adjuvant modalities. The results of many studies have led to mixed results; therefore, there is no consensus about the optimal management Inhibitors,research,lifescience,medical of these patients. There is a growing recognition that even in well clinically stage ultrasound T2

N0 esophageal cancer, between 20-25% may be upstaged to have pathologic T3 and/or node positive disease. Hence, these patients would often be referred Inhibitors,research,lifescience,medical for postoperative therapy. This review, while addressing the different sequencing of multimodality therapy, aims to focus mostly on how best to manage patients in the postoperative setting. Definitive chemoradiotherapy Along the lines of definitive management of esophageal

cancer, it is important to discuss the RTOG 8501 trial which was instrumental in Inhibitors,research,lifescience,medical defining the superiority of chemoradiation over radiation therapy (3). The trial randomized patients to 64 Gy alone (n=60) to 50 Gy with concurrent cisplatin and 5-FU (n=61) for a total of 4 courses of chemotherapy. Overall survival at 2 years increased from 10% with radiation alone to 38% in the combined therapy group (p=0.001). Distant and local recurrences were also reduced in the Inhibitors,research,lifescience,medical chemoradiation group. An update of this study showed that the 5-year survival rate with CRT was 27% compared to 0% with radiation alone (4). Approximately 85% of these patients had squamous histology. Of note, the 2010 NCCN guidelines recommend that T1 node positive or T2-T4 4-Aminobutyrate aminotransferase Nx esophageal cancer cases be treated with definitive chemoradiation or preoperative chemoradiation (50-50.4 Gy) followed by either esophagectomy (preferred) or observation for those achieving a complete clinical response, or for those with INK1197 in vitro persistent local disease, either esophagectomy (preferred) or palliative treatment. It is recommended adenocarcinoma of the distal esophagus or GEJ be treated with preoperative chemotherapy followed by esophagectomy.

28 Thus, it seems reasonable to conclude that the hypersecretion of Cortisol in patients with VX-689 concentration depression or dementia may at least be partly a consequence of an increased activation of the HPA axis by AVP. Additional evidence for the change in the functional activity of the pituitary gland is provided by the finding that the adrenals and the pituitary are enlarged in those with depression,29,30 Inhibitors,research,lifescience,medical these changes being associated with a hypersecretion of CRF.31 Furthermore, the density of the CRF receptors in the

frontal cortex are reduced, presumably as a consequence of the hypersecretion of CRF.32,33 The hypersecretion of CRF would appear to be a state, rather than a trait, marker of depression.34 If hypercortisolemia is a common feature Inhibitors,research,lifescience,medical of major depression and some types of dementia, it would be anticipated that immunosuppression would

be a common feature of these conditions. However, it is apparent that both immunosuppression (for example, of natural killer cell [NKC] activity) and immune activation (for example, macrophage activation) are common features of depression. One possible explanation is that an increased vulnerability to environmental stress, which is a Inhibitors,research,lifescience,medical common feature of both depression and dementia,35 elicits a bidirectional, homeostatic interaction between the endocrine and immune systems. Thus, CRF has been associated with humoral activation that results in an increased release of Inhibitors,research,lifescience,medical proinflammatory cytokines. By activating the HPA axis, proinflammatory cytokines not only further release CRF, but also lead to glucocorticoid resistance, thereby impairing the regulatory feedback mechanism. Conversely, the increase in the concentration of plasma Cortisol, together with the increased sympathetic activity that is a normal feature of the stress response, suppresses NKC and T-cell replication. There is evidence that activation of the β-adrenoceptors on the NKC membrane, and which results in the decrease in activity of the NKCs, occurs Inhibitors,research,lifescience,medical independently of the activation of the HPA axis.35 Clearly the interaction between the immune system and the HPA axis is both complex and interdependent.

In the past 20 years, attention has focused on changes in the hypothalamic-pituitary-adrenal axis, together with the biogenic amine neurotransmitters noradrenaline, serotonin, and, to a lesser extent, dopamine.36,37 More recently, however, it has become apparent that both major depression and chronic stress PD184352 (CI-1040) result in more persistent structural changes in the brain as a consequence of the decrease in the synthesis of neurotrophic factors, such as BDNF and the antiapoptotic factor bcl-2.38 These changes are attributed to the chronic increase in brain glucocorticoids that arise due to the desensitization of central glucocorticoid type 2 receptors that occur as a consequence of the reduction in the inhibitory feedback mechanism.

5% dextrose peritoneal dialysis solution for 90 minutes. The coliseum technique was used. For gastrointestinal malignancies, mitomycin C (10-12.5 mg/m2) was

used. For mesothelioma and ovarian malignancies, cisplatin (50 mg/m2) and doxorubicin (15 mg/m2) or mitomycin C (10-12.5 mg/m2) were employed. Early postoperative intraperitoneal chemotherapy was postoperatively administered in accordance with previously defined guidelines (4). Anaesthesia At our institution, the indication for intraoperative RBC transfusion was a hemoglobin concentration <80 g/L and/or signs of anaemia (sinus tachycardia with a heart rate of >100 per minute, a systolic blood pressure Inhibitors,research,lifescience,medical of <100 mmHg, urine output of <30 mL/hr due to ongoing blood loss). To minimise unnecessary blood loss we have focused on maintaining normothermia and optimimizing acid-base balance. In the operating theatre, forced warm air blankets were applied and the head was covered

with a heat reflecting cap. All fluids and blood Inhibitors,research,lifescience,medical products were infused via fluid warming devices. Acidosis was managed by resuscitation and mechanical ventilation. Our response to fluid resuscitation and coagulopathy Inhibitors,research,lifescience,medical in patients expected to require an extensive procedure because of high volume disease has changed since June, 2006. Previously, we followed the standard resuscitation strategy with an emphasis on crystalloid and RBC administration to improve cardiac output and oxygen delivery. Procoagulant factors (FFP,

cryoprecipitate, platelets) were transfused in response to abnormal coagulation laboratory parameters, hypotension unresponsive to crystalloid administration, transfusion >6 units or obvious Inhibitors,research,lifescience,medical microvascular bleeding. Since June 2006, a protocol driven approach has been adopted which involves the early and aggressive administration of procoagulant factors Inhibitors,research,lifescience,medical (particularly FFP) to prevent rather than treat coagulopathy. In particular it was deemed not necessary to wait for laboratory results before initiating administration of procoagulants. Procoagulant factors were organized to be available from the outset of surgery and were given such that the ratio of FFP:RBC administered exceeded much 1:1, even through the early intraoperative period. Moreover, a fluid restriction strategy was pursued to minimize dilutional coagulopathy. The Mdm2 inhibitor rationale behind this change in strategy was multifactorial. Firstly, recent data from trauma surgery has shown that current resuscitation strategies severely underestimate the degree of coagulopathy during surgery. Secondly, our own experience showed that waiting for laboratory results before administering procoagulant factors often resulted in marked coagulation defects and significant blood loss, which could be reduced with a pre-emptive strategy.

We have no data to address this issue, which may be a focus of future studies. The CCI has some conceptually common items with other measures (feeling as if the situation was unreal, CI994 emotional numbness and fear) and some related phenomena (feeling emotionally stuck and sensory impressions). It would be pretentious to address this as convergent validity, but the commonalities are great enough to warrant studying the relationship between the CCI, the IES and the PTSS-10. The correlations with these stress measures Inhibitors,research,lifescience,medical were significant, indicating that the CCI can be used as a predictor for posttraumatic

stress after injuries. It might have been interesting to assess the convergent validity with other measures of peritraumatic responses like the Peritraumatic Distress Inventory (PDI). However, Inhibitors,research,lifescience,medical the main focus of this study was the sensory perception. The assessments at two time points made it possible to study changes in perceived threat during the casualty chain. The level of perceived threat was moderately but significantly higher at the scene of the injury than in the hospital, but there

was a stronger explained variance measured Inhibitors,research,lifescience,medical in hospital. The mean score of dissociation and perceptions were quite similar at both measurement points. Measuring the responses in hospital seems to be sufficient in identifying those at risk of developing posttraumatic stress. Strengths and Limitations Inhibitors,research,lifescience,medical The CCI showed strong internal consistency and a two-factor scale, despite the fact that the participants were drawn from a physically injured population with a broad range of stress symptoms. Accordingly, the instrument can be used in conscious patients admitted in the ER following a physical incident to see who may be at risk for subsequent posttraumatic stress. It examined a large sample from a region surrounding the capital of Norway. The duration of the threat was assessed by questions about the scene of the injury and

Inhibitors,research,lifescience,medical about the participants’ stay in the hospital. The participants completed the questionnaires some weeks after their accident. The time of assessment (weeks after the accident) raise questions regarding the CCI’s ability to identify patients at risk. Even though a recall bias may be present, those with symptoms after some weeks are most likely at greater risk for symptoms also at a later stage. Analysis showed no significant difference in others stress score (IES) between patients answering close to the accident compared to those answering several weeks after the event. This may confirm that the ability to remember feelings and responses in certain situations should not be underestimated. In the pilot study, patients were assessed within a few days post trauma while admitted to hospital. For most patients the self-assessment was difficult at this time point. Some were sleepy, some stressed and some were cognitively not able to concentrate. This was a major reason for postal assessment after discharge.

While it will therefore continue to need refinement, the Directory is a key tool for rational service development in children’s palliative care. Competing interests The authors declare that they have no competing interests. Authors’ contributions RH conceived of the study, supervised the data collection and wrote the manuscript. MD carried out the data collection. RH, RHastings, MD and JN all developed the Directory itself, making amendments in various iterations. All authors

participated in development of the final manuscript and have seen and approved the submitted draft. Pre-publication history The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1472-684X/12/43/prepub #CYT387 keyword# Acknowledgement The authors would like to thank Ms. Sonjia Ezergailis, Research Inhibitors,research,lifescience,medical Nurse at Children’s Hospice UK (now Together for Short Lives) who gathered diagnostic data from the children’s hospices, and all the data managers who participated. This project was part funded by Welsh Office of Research and Development (WORD), grant number ReF06/2/237.
In England and Wales, the annual death rate is around 1% [1]. In high income countries,

most people die in old age; in England between 2008 and 2010, 66.7% of Inhibitors,research,lifescience,medical people who died were over the age of 75 and 36.2% were over the age 85 [2]. Three main end of life decline trajectories Inhibitors,research,lifescience,medical have been identified [3]; short period of decline typical of cancer (21%); long-term limitations with intermittent serious episodes typical of organ failure (21%); and prolonged dwindling typical of frail elderly people and people with dementia (20%). Additionally, 15% of

people die suddenly and 24% die following other, varied trajectories. While dying is not always associated with pain or suffering, people who are dying Inhibitors,research,lifescience,medical can suffer isolation, grief, anxiety and depression [4]. Carers of people who are dying, or those who are bereaved, may suffer from illnesses including depression [5] or complicated grief [6] and may feel isolated as people around them fail to offer support. A recent systematic literature review revealed that people throughout the world share core ideals of a ‘good death’ [7], which include being free of pain and other symptoms, being with friends and family, not being no a burden, being listened to, being able to decide about medical treatments [8] and being treated with respect. In some studies ‘having one’s affairs in order’ was highlighted as important, while religion or spirituality was important to some people [9-11]. Many people would like to be cared for at home during their final illness [12-14]. ‘Having one’s affairs in order’ necessarily requires preparation which might also assist people to have other end of life care wishes met.

The mean age was higher among users of both medications than users of neither (61.2 vs. 54.1, P<0.0001). There was a difference between the groups in terms of gender breakdown (P=0.01), racial breakdown (P=0.04), BMI (P=0.002), presence of diabetes (P<0.0001) and hypertension (P<0.0001). Medication users and non-users did not differ in any other factors. Table 6 shows the association between users of both medications Inhibitors,research,lifescience,medical and colonoscopy findings, adjusted for age, sex, race, BMI, diabetes, hypertension and

smoking or alcohol use. Compared to non-users of either medication, those who used both had an increased risk for having two or more adenomas (OR =2.56, 95% CI: 1.21, 5.39, P=0.01). No associations were seen between any other colonoscopy findings and aspirin use in the total population. In the Hispanic population, compared to non-users of either medication, those who used both had an increased risk for having two or more adenomas (OR =19.04, 95% CI: 1.30, 280.09, P=0.03), adenoma present in the distal colon (OR =5.75, 95% CI:

1.64, 20.21, P=0.01) and Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical largest adenoma in distal colon (OR =5.75, 95% CI: 1.64, 20.21, P=0.01). No other associations were seen in the Hispanic population. Table 5 Demographics of aspirin and statin users and non-users undergoing colonoscopy Table 6 Association between aspirin and statin use and colonoscopy findings in total population and Hispanics Inhibitors,research,lifescience,medical Discussion To our knowledge this is the first study assessing aspirin and statin use in a Hispanic population. We found that statin use was not associated with any colonoscopy findings, though aspirin use increased the risk for two or more adenomas and adenoma in the proximal colon in our total population, but did not see the

same results when restricting the analysis to Hispanics. An increased risk for two or more adenomas was also seen in the total population for users of both statins and aspirin. In Hispanics, use of both medications was associated with two or more adenomas, adenoma present in the distal colon and largest adenoma in distal colon. There have been many trials discussing Inhibitors,research,lifescience,medical the Saracatinib price relationship between aspirin/non-steroidal anti-inflammatory drugs (NSAIDs) and colorectal adenoma/carcinomas in predominant white patient populations. One recent meta-analysis combined four randomized double-blinded placebo trials that evaluated aspirin and prevention of CRA. The results showed that aspirin users had a pooled risk Metalloexopeptidase ratio of 0.83 (95% CI: 0.72, 0.96) for any adenoma, with an absolute risk reduction of 6.7% compared to placebo (6). They concluded that aspirin is effective for the prevention of CRA in patients with a history of these lesions. There have also been studies looking specifically at NSAIDS and colon cancer. Patients taking 200mg BID of Celecoxib had a reduced rate of sporadic CRA (RR: 0.67, 95% CI: 0.59, 0.77), while those taking 400 mg BID also had a reduced risk of sporadic CRA (RR: 0.55, 95% CI: 0.48, 0.64) (7).

The patient-centred subscale of the questionnaire tapped into patient-related factors that

may influence psychiatrists’ prescription patterns. Questions in this subscale included patients and relatives’ acceptance of LAIs, which we hypothesised would significantly affect prescribing patterns. Patient preferences have been found to influence clinicians’ tendency to prescribe LAIs [Patel and David, 2005; Patel et al. 2009; Heres et al. 2011]. We also noted that psychiatrists who prescribed LAIs less frequently were more likely to believe that depots were coercive. This alludes to the negative ‘image’ of LAIs [Mahadun and Marshall, 2008] which is likely to adversely affect LAI utilisation Inhibitors,research,lifescience,medical and promote stigma [Patel et al. 2010b]. In contrast to a similar study among psychiatrists in the UK [Patel et al. 2010a], we observed a significant relationship between psychiatrists’

personal dislike for injections Inhibitors,research,lifescience,medical and higher mean scores on the patient-centred subscale. This might suggest that respondents who disliked injections would tend to prescribe them less, believing that patients may dislike injections themselves. Studies examining the attitudes of patients and their caregivers in developing countries towards LAIs and factors Inhibitors,research,lifescience,medical influencing LAI prescribing are needed. One wonders whether erroneous beliefs about the potency of parenteral medications over oral medications might positively influence acceptance of LAIs. Furthermore, methods by which medication choice can best be offered need further exploration as high illiteracy rates Inhibitors,research,lifescience,medical and low earning power are commonplace. Conclusion This study reveals that senior Inhibitors,research,lifescience,medical trainees and consultant psychiatrists in Selleckchem Tacedinaline Nigeria report a high utilisation rate for LAIs. Although they hold positive views about LAIs, their knowledge concerning LAIs was only fair and should be updated. Although it was mostly agreed that LAIs significantly reduced relapse rates, patient-centred factors were found to be significant in influencing prescribing rates for

LAIs. Acknowledgments The authors would like to thank Dr B. Ola and Dr J. Abdulmalik for their assistance with the collection of data. Footnotes Funding: This research received of no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflict of interest statement: The authors declare no conflicts of interest in preparing this article. Contributor Information Bawo O. James, Federal Psychiatric Hospital, Ugbowo Lagos Road, Benin City, 30001, Nigeria. Joyce O. Omoaregba, Federal Psychiatric Hospital, Benin City, Nigeria. Kingsley M. Okonoda, Jos University Teaching Hospital, Jos, Nigeria. Edebi U. Otefe, Neuropsychiatric Hospital Aro, Abeokuta, Nigeria. Maxine X. Patel, Kings College London, London, UK.

g., CK-MB, troponin) is reasonable in the first 24 hours after CABG, and cTn is preferred to CK-MB as the optimal indicator of myonecrosis.13 Additional Considerations The 2012 task force included new sections pertinent to myocardial injury and MI in patients undergoing EPO906 manufacturer cardiac and non-cardiac procedures, in critically-ill patients, and in patients with heart failure.2 These sections

emphasized the risk of myocardial necrosis due to regional ischemia or direct trauma in certain cardiovascular procedures, including transcatheter aortic valve replacement (TAVR) or mitral clip. In the absence of supporting evidence, the task force recommended using the same criteria for an MI diagnosis in patients undergoing TAVR. Inhibitors,research,lifescience,medical Caution is advised against mislabeling myocardial necrosis Inhibitors,research,lifescience,medical associated with the ablation of arrhythmias as MI. In accordance with the 2008-2009 revision of the WHO definition of MI,14 the third global MI task force also differentiated between recurrent MI and reinfarction.2 Reinfarction describes an acute MI occurring within 28

days of an incident or recurrent MI. The Inhibitors,research,lifescience,medical 2012 task force did not recommend CK-MB measurements in these patients but, rather, serial cTn measurements, with the reinfarction diagnosis established when a ≥20% increase in cTn values is observed. If characteristics of MI occur after 28 days following an incident MI, it is considered to be a recurrent MI. The 2012 task force also recommends the routine monitoring of cardiac biomarkers in high-risk patients both prior to and 48–72 hours after major noncardiac surgery, but it

does not define high-risk surgical procedures.2 In general, major vascular surgery (aortic/peripheral vascular surgery with reported perioperative cardiac risk >5%) is considered a high- risk or Inhibitors,research,lifescience,medical major surgery.15 Conclusion In summary, the Third Universal Definition of Myocardial Infarction consensus document incorporates patient symptoms, ECG changes, the highly sensitive cTn biochemical markers, and information gleaned from various imaging techniques into comprehensive, Inhibitors,research,lifescience,medical clinically oriented, and reproducible definitions of MI. Funding Statement Funding/Support: Dr Bozkurt receives grant funding from the National Institutes of Health and from Forest Pharmaceuticals. Footnotes Conflict of Interest Disclosure: The authors have completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict GBA3 of Interest Statement and none were reported.
Introduction There are growing numbers of adults with congenital heart disease (CHD), and the role of cardiac magnetic resonance (CMR) imaging is continually expanding in this patient population.1 The majority of these patients have undergone surgical repairs in childhood, and lifelong follow-up is recommended.2 Serial imaging of adults with CHD is important to monitor for interval changes, as many adults with CHD do not recognize subtle changes in exercise capacity.