Irritability is associated with anxiety and greater severity, but not bipolar spectrum features, in major depressive disorder.

OBJECTIVE: Irritability is common during major depressive episodes, but its clinical significance and overlap with symptoms of anxiety or bipolar disorder remains unclear. We examined clinical correlates of irritability in a confirmatory cohort of Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study participants with major depressive disorder (MDD). METHOD: Logistic regression was used to identify features associated with presence of irritability on the clinician-rated Inventory of Depressive Symptomatology. RESULTS: Of 2307 study participants, 1067(46%) reported irritability at least half the time during the preceding week; they were more likely to be female, to be younger, to experience greater depression severity and anxiety, and to report poorer quality of life, prior suicide attempts and suicidal ideation. Bipolar spectrum features were not more common among those with irritability. CONCLUSION: Irritable depression is not a distinct subtype of MDD, but irritability is associated with greater overall severity, anxiety comorbidity and suicidality.

Pretreatment frontal EEG and changes in suicidal ideation during SSRI treatment in major depressive disorder.

OBJECTIVE: We investigated frontal quantitative EEG (QEEG) as predictor of changes in suicidal ideation (SI) during SSRI treatment in major depressive disorder (MDD). METHOD: Eighty-two subjects meeting DSM-IV criteria for MDD entered an 8-week, prospective, open-label treatment with flexible dose SSRIs and completed at least 4 weeks of treatment. We assessed MDD severity with the 17-item Hamilton Depression Rating Scale (HAM-D-17); change in SI was measured with HAM-D item no. 3. We recorded four-channel EEGs (F7-Fpz, F8-Fpz, A1-Fpz, A2-Fpz) before treatment. RESULTS: During the first 4 weeks of treatment 9 (11%) subjects experienced worsening SI. Left-right asymmetry of combined theta + alpha power correlated significantly with change in SI from baseline, even when adjusting for changes in depression severity (HAM-D-17) and for the SSRI utilized. CONCLUSION: Frontal QEEG parameters before treatment may predict worsening SI during SSRI treatment in MDD.

African-American patients with cancer Talking About Clinical Trials (TACT) with oncologists during consultations: evaluating the efficacy of tailored health messages in a randomised controlled trial-the TACT study protocol.

INTRODUCTION: Low rates of accrual of African-American (AA) patients with cancer to therapeutic clinical trials (CTs) represent a serious and modifiable racial disparity in healthcare that impedes the development of promising cancer therapies. Suboptimal physician-patient consultation communication is a barrier to the accrual of patients with cancer of any race, but communication difficulties are compounded with AA patients. Providing tailored health messages (THM) to AA patients and their physician about CTs has the potential to improve communication, lower barriers to accrual and ameliorate health disparities. OBJECTIVE: (1) Demonstrate the efficacy of THM to increase patient activation as measured by direct observation. (2) Demonstrate the efficacy of THM to improve patient outcomes associated with barriers to AA participation. (3) Explore associations among preconsultation levels of: (A) trust in medical researchers, (B) knowledge and attitudes towards CTs, (C) patient-family member congruence in decision-making, and (D) involvement/information preferences, and group assignment. METHODS AND ANALYSIS: First, using established methods, we will develop THM materials. Second, the efficacy of the intervention is determined in a 2 by 2 factorial randomised controlled trial to test the effectiveness of (1) providing 357 AA patients with cancer with THM with 2 different 'depths' of tailoring and (2) either providing feedback to oncologists about the patients' trial THM or not. The primary analysis compares patient engaged communication in 4 groups preconsultation and postconsultation. ETHICS AND DISSEMINATION: This study was approved by the Virginia Commonwealth University Institutional Review Board. To facilitate use of the THM intervention in diverse settings, we will convene 'user groups' at 3 major US cancer centres. To facilitate dissemination, we will post all materials and the implementation guide in publicly available locations. TRIAL REGISTRATION NUMBER: NCT02356549.

Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction.

Definition of MI. Criteria for acute, evolving or recent MI. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: 1) Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following: a) ischemic symptoms; b) development of pathologic Qwaves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); or d) coronary artery intervention (e.g., coronary angioplasty). 2) Pathologic findings of an acute MI. Criteria for established MI. Any one of the following criteria satisfies the diagnosis for established MI: 1) Development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed. 2) Pathologic findings of a healed or healing MI.

Accumulation of radioiodinated 15-(p-iodophenyl)-6-tellurapentadecanoic acid in ischemic myocardium during acute coronary occlusion and reperfusion.

The myocardial uptake of 15-(p-iodophenyl)-6- tellurapentadecanoic acid ( TPDA ) was studied in dogs during coronary occlusion and after reperfusion. In eight dogs with a 3 hour occlusion (Group A) with (n = 5) and without (n = 3) 30 minutes of reperfusion, iodine-125 TPDA uptake correlated well with microsphere myocardial blood flow over a wide range of flow levels (n = 111, r = 0.94). In six dogs with a 20 minute occlusion of the left anterior descending coronary artery and 1 hour of reperfusion (Group B), iodine-125 TPDA uptake correlated equally well with myocardial blood flow (n = 37, r = 0.90). There was no difference between the slopes of regression lines for Groups A and B, indicating no release from the myocardium of radioiodinated TPDA . Dual radiolabeling of TPDA was employed in five Group A animals by intravenous injection of iodine-125 TPDA during coronary occlusion and iodine-131 TPDA after reperfusion. In 63 myocardial samples, microsphere reperfusion flow and iodine-131 TPDA uptake were closely correlated (r = 0.91). As with monovalent cations, at myocardial flows higher than control flows, iodine-131 TPDA uptake was flow-limited. It is concluded that: 1) radioiodinated TPDA accurately reveals severely ischemic areas of myocardium without myocardial release of the radionuclide in coronary occlusions lasting 20 to 180 minutes and followed by reperfusion, and 2) double radiolabeled TPDA allows assessment of both occlusion and reperfusion flows. This compound may find an application in the measurement of infarct size and the evaluation of interventional therapies in acute myocardial infarction.

Myocardial infarction with angiographically normal coronary arteries.

More than 30 years ago, when the techniques and indications for coronary arteriography were being defined, the entity of myocardial infarction with angiographically normal coronary arteries (MINC) was first reported. These first reports already noted that the few patients with MINC tended to be different from the much larger group of individuals with myocardial necrosis and coronary atherosclerosis. Since these early case reports and subsequent small collected series, there have been significant advances in our understanding of the pathophysiologic features of acute myocardial infarction. This review seeks to reexamine MINC in light of this new information.

Diastolic function of the heart in clinical cardiology.

During the last six years, there has been increased interest in the detection of abnormalities of left ventricular diastolic function in patients with heart disease. Before 1981, most studies on diastolic function were performed in the catheter laboratory using invasive techniques and complex methods. Recently, radionuclide angiograms and Doppler echocardiography have been employed to measure the dynamics of filling in normal individuals and in patients with heart disease. These methods are noninvasive, easy to perform, accurate, and reproducible. It is now clear that diastolic function may be altered globally and regionally, at rest and perhaps during exercise, in many patients with ischemic heart disease, hypertension, and hypertrophic cardiomyopathy. Interestingly, these diastolic abnormalities may even appear before systolic abnormalities are identified in these patients. Thus, diastolic abnormalities may permit assessment of presence of disease early in its evolution. Whether detection and quantitation of diastolic abnormalities will permit grading of disease severity or evaluation of therapeutic efficacy remains an important research question. At the present time, it appears that the decision to employ either radionuclide angiography or Doppler echocardiography for the assessment of diastolic abnormalities will depend on the local expertise to carry out the investigation. Both diagnostic modalities require standardization of accuracy and reproducibility with proper selection of control values from the appropriate populations of normal individuals. It is also important to remember that left ventricular diastolic abnormalities have to be identified after the elimination of the confounding influence of variables such as ejection fraction, heart rate, age, and preload (end-diastolic volume). Automation of the derivation of indexes of diastolic filling should provide an objective assessment of the dynamics of left ventricular filling. Although the value of measurement of diastolic filling in the individual patient remains controversial, we believe that the practice of cardiology is incomplete without consideration of the second half of cardiac function.

The future of academic medical centers in the United States: passing through the valley of the shadow of death.

The last 2 decades witnessed remarkable events in the life of academic medical centers (AMCs) in the United States. Twenty years ago, AMCs were thriving as the era of fee-for-service medicine came to a close: clinical departments were expanding, hiring new faculty members, purchasing new equipment as necessary, and funding research projects and protected research time with the abundant clinical revenues. The subsequent 20 years since that golden era came to a close witnessed teh disappearance of these expansionary trends. Departments have contracted, protected research time and start-up funds have declined precipitously, and many faculty members are infected with a sense of malaise and fear for the future.

Increasing frequency of staphylococcal infective endocarditis. Experience at a university hospital, 1981 through 1988.

To determine the characteristics of infective endocarditis in our hospital, we reviewed all patients with that diagnosis at the University of Massachusetts Medical Center, Worcester, between 1981 and 1988. Of 113 patients with infective endocarditis, 56 (50%) had staphylococcal endocarditis. Despite aggressive medical and surgical therapy, in-hospital mortality was 25%. Forty-five (80%) of the 56 cases of staphylococcal endocarditis involved Staphylococcus aureus with a mortality of 28% vs 9% in the non-S aureus group. Mortality was higher in patients with congestive heart failure (35%), atrioventricular block (45%), atrial fibrillation (42%), and prosthetic valve endocarditis (50%). Seventy-six percent of the patients with congestive heart failure required surgery. Patients with congestive heart failure and S aureus infection had a mortality of 45%. Thirty-six patients (64%) were alive at late follow-up (mean, 28.6 months). Mortality was highest (23%) during the first 3 months following diagnosis of staphylococcal endocarditis. Staphylococcal endocarditis represents an increasingly large proportion of patients with infectious endocarditis. Mortality rates remain high despite aggressive management of the patient's condition.

Recent trends in hospital mortality of acute myocardial infarction--the Worcester Heart Attack Study. Have improvements been realized for all age groups?

BACKGROUND: While age-related differences in patterns of care for acute myocardial infarction have been demonstrated, temporal trends in clinical outcome for patients in different age groups have not been carefully examined. METHODS: We analyzed data collected as part of an ongoing communitywide study of 5480 patients hospitalized with validated acute myocardial infarction in Worcester, Mass, during 7 selected years spanning a 15-year period (1975 through 1990). Patients were stratified into three age groups: less than 65 years (n = 2220), 65 through 74 years (n = 1595), and 75 years or older (n = 1665). Within each age group, the odds of in-hospital death were determined by study year, with adjustments for selected demographic, clinical, and hospital characteristics. RESULTS: For patients less than age 65 years, the odds of dying during the acute hospital phase of myocardial infarction were reduced for all study years relative to the reference year (1975), reaching their lowest level in 1990 (adjusted odds ratio [OR], 0.16; 95% confidence interval [CI], 0.06 to 0.48). For patients aged 65 through 74 years, the odds of dying declined among patients hospitalized in 1978 (adjusted OR, 0.71; 95% CI, 0.39 to 1.29) and 1981 (adjusted OR, 0.36; 95% CI, 0.19 to 0.66) but remained essentially unchanged during the subsequent study years through 1990. For patients 75 years of age or older, the odds of dying declined through 1984 (adjusted OR, 0.42; 95% CI, 0.25 to 0.72) but increased over the following study years: 1986, 1988, and 1990. CONCLUSIONS: While the risk of in-hospital death following acute myocardial infarction has recently declined for patients less than 65 years of age, improvements have not been realized for older age groups. Current patterns of management of acute myocardial infarction in older patients require reexamination.

The increased use of diagnostic procedures in patients with acute myocardial infarction. A community-wide perspective.

As part of a community-wide study examining time trends in the incidence and case-fatality rates of 3263 patients hospitalized with validated acute myocardial infarction (MI) during the years 1975, 1978, 1981, and 1984, we examined changes over time in the use of various noninvasive and invasive diagnostic tests during hospitalization for acute MI. In terms of the noninvasive procedures, exercise testing before hospital discharge increased from only 0.1% of patients in 1975 to 40.3% in 1984, while use of echocardiography (2.5%, 1975; 15.3%, 1984), Holter monitoring (1.0%, 1975; 34.0%, 1984), and radionuclide ventriculography (2.6%, 1975; 52.7%, 1984) also increased dramatically. Concerning the invasive procedures, use of coronary arteriography in patients with acute MI increased from 3.1% in 1975 to 9.8% in 1984. A more striking increase was noted in the use of pulmonary artery catheterization (7.2%, 1975; 19.9%, 1984). Examination of patient characteristics associated with the use of these tests demonstrated that the increased use of these diagnostic procedures was not due to changes in the clinical characteristics of patients hospitalized with acute MI; rather, it was the result of changes in physician practice patterns. If the practice patterns seen in this community-based study are similar to those seen throughout the United States, the charges for these diagnostic tests in 1984 are estimated to approach 600 million dollars. Given current interest in cost-containment and evaluation of clinical practices, these results suggest the need for further observational studies and clinical trials to assess the cost-effectiveness of these diagnostic tests. To assess the cost-effectiveness, it will be necessary to determine if the use of these tests improves the short-term or long-term prognosis of patients hospitalized with acute MI.

Multiple cholesterol emboli syndrome. Bowel infarction after retrograde angiography.

The two patients described in this article are among the first to have been diagnosed with extensive bowel infarction as a result of cholesterol embolization following cardiac catheterization. The presence of acute hypertension, renal insufficiency, livedo reticularis, and gangrenous skin changes are characteristic manifestations of the multiple cholesterol emboli syndrome. Additionally, gastrointestinal symptoms and melena may herald ischemia and infarction of the alimentary tract. Anticoagulation and thrombolytic therapy are relatively contraindicated in this syndrome and may, in fact, be a precipitating cause. The prognosis is usually poor; however, survival is possible with aggressive medical and surgical therapy, despite extensive infarction of the gastrointestinal tract and other organs. Prevention remains the most critical aspect of management of this potentially catastrophic illness.

Does aspirin consumption affect the presentation or severity of acute myocardial infarction?

BACKGROUND: While consumption of aspirin has been shown to decrease the occurrence of nonfatal cardiac events, the majority of studies have not demonstrated any impact of aspirin intake on cardiovascular mortality. The present population-based study explores the possibility that aspirin consumption affects the presentation and severity of acute myocardial infarction (AMI), and hence the likelihood of clinical detection. METHODS: We monitored the use of aspirin before admission for 2114 patients with a validated diagnosis of AMI in 16 hospitals in the Worcester, Mass, metropolitan area during 1986, 1988, and 1990. The AMIs were characterized as Q wave vs non-Q wave and large (peak creatine kinase levels more than five times normal) vs small (peak creatine kinase levels less than two times normal). RESULTS: A total of 332 patients (16%) with validated AMI took aspirin before hospital admission. Nearly 65% of aspirin users had non-Q wave AMIs, compared with 49% of nonaspirin users. Thirty percent of aspirin users sustained small AMIs, compared with 22% of nonaspirin users. These findings persisted after stratifying for previous AMI, history of coronary disease, receipt of thrombolytic therapy, and exclusion of early hospital deaths. Using multivariable regression models to control for age, gender, previous evidence of coronary disease, and use of other medications, prior aspirin consumption remained independently associated with AMI type (non-Q-wave AMI) and smaller infarct size. CONCLUSION: Aspirin consumption appears to modify the presentation of AMI, increasing the likelihood that the infarct will be of the small, non-Q-wave variety.

Gender differences in the treatment of patients with acute myocardial infarction. A multihospital, community-based perspective.

OBJECTIVE: As part of a community-wide study examining temporal trends in the incidence and survival rates of acute myocardial infarction, we examined differences between the sexes in overall utilization rates and changes over time, therein, of various therapies used in the management of acute myocardial infarction. DESIGN: Nonconcurrent prospective study. PATIENTS: Three thousand three hundred sixty-one men and 2119 women hospitalized with validated acute myocardial infarction in 16 hospitals in the Worcester, Mass, metropolitan area during 1975, 1978, 1981, 1984, 1986, 1988, and 1990. RESULTS: After controlling, by means of a logistic regression analysis, for a variety of patient-related factors that could affect physician prescribing patterns, women were significantly more likely to receive diuretics during hospitalization for acute myocardial infarction, whereas men were significantly more likely to receive antiplatelet agents, lidocaine, and other antiarrhythmic agents. No statistically significant differences were seen between men and women with regard to the use of anticoagulants, beta-blockers, calcium channel blockers, digoxin, nitrates, and thrombolytic agents. Marked increases over time (1975 through 1990) were seen in the use of anticoagulants, antiplatelet agents, beta-blockers, lidocaine, and nitrates in each of the sexes, while declines were seen in the use of digoxin and diuretics. Use of thrombolytic therapy increased between 1986 and 1990, whereas use of calcium channel blockers decreased over this period for both men and women. CONCLUSIONS: The results of this multihospital, population-based, observational study suggest that physician practice patterns in the pharmacologic treatment of men and women hospitalized with acute myocardial infarction are very similar.

Superior vena cava syndrome. Its association with indwelling balloon-tipped pulmonary artery catheters.

The placement of flow-directed pulmonary artery catheters has become a routine procedure in hospitals throughout the country. There have been scattered reports of complications associated with their placement, but in general, if it is done under proper conditions, it is associated with low morbidity and mortality. Recently, there have been questions raised regarding the thrombogenicity of these catheters. We report three cases of superior vena cava syndrome associated with the use of indwelling pulmonary artery catheters that we have encountered and a review of experience of others.

Neurophysiological studies of sensory gating in mania: comparison with schizophrenia.

The action of central nervous system mechanisms involved in sensory gating was assessed in acutely psychotic manic patients. An early positive component of the auditory average evoked response, recorded at the vertex 50 msec after a click stimulus, was studied. Stimuli were delivered at 10-sec intervals to establish a base-line response. Sensory gating mechanisms were then tested using a conditioning-testing paradigm to assess the change in response to a second stimulus following the first at either 0.5-, 1.0- or 2.0-sec intervals. A similar paradigm had been used previously to assess deficits in this function in acute and chronic schizophrenics. We found a deficit in sensory gating in acutely manic patients. similar to that found in schizophrenics, although the variability in response was more marked in the manic patients. We followed these patients during their treatment on lithium carbonate and found a return of these neuronal functions towards normal values which corresponded to their clinical improvement. A series of stable euthymic bipolar patients were found to have responses indistinguishable from normal controls. The data suggest that deficits in neuronal gating functions, similar to those found in schizophrenia, can be seen during acute mania but these deficits return to normal as the acute psychosis abates.

Major depressive subtypes and treatment response.

The purpose of this study was to investigate the relationships between depressive subtypes and response to fluoxetine treatment in a large cohort of outpatients. We studied 294 outpatients with major depressive disorder who were then treated with fluoxetine 20 mg/day for 8 weeks. Treatment outcome was evaluated with the Hamilton Depression Rating Scale (HDRS)-17, the Clinical Global Impressions-Severity, and with the HDRS-8; the latter is proposed to be a relatively more specific measure of depression severity than the HDRS-17. We assessed the relationships between degree of treatment response and several depressive subtypes (melancholic, atypical, hostile, and anxious depression, double depression, and depression with comorbid personality disorders), after adjusting for baseline depression severity. We found that nonanxious depressives (patients without any comorbid anxiety disorder) improved slightly but significantly more during treatment than anxious depressives on all outcome measures. Melancholic depression was associated with slightly less improvement on the HDRS-17 only, whereas the other subtypes of depression were not associated with differences in treatment outcome.

Patterns of axis I comorbidity in early-onset versus late-onset major depressive disorder.

BACKGROUND: This study of a large clinical sample of depressed patients examined whether childhood onset as compared with adult onset Major Depressive Disorder (MDD) would confer a greater risk for Axis I comorbidity and whether childhood onset MDD would also differ from adult onset MDD in the pattern of comorbid disorders. METHODS: We examined lifetime co-occurrence of Axis I disorders among 381 adult outpatients with MDD by Structured Clinical Interview for DSM-III-R-Patient Edition (SCID-P). Subjects were divided into childhood onset (n = 47), adolescent onset (n = 101) and adult onset (n = 233) MDD groups. RESULTS: We found that the two early-onset groups exhibited significantly increased rates of Axis I comorbidity. The childhood onset group accounted for a disproportionately high percentage of depressed adults with two or more comorbid Axis I disorders. Social and simple phobias and alcohol abuse/dependence were significantly more prevalent among individuals with childhood onset MDD than among individuals with adult onset MDD. Alcohol abuse/dependence, but not anxiety disorders, was significantly more prevalent among adolescent onset than adult onset MDD groups. Panic, generalized anxiety, obsessive-compulsive and somatoform disorders were equally distributed across MDD onset groups. Comorbid disorders were much more likely to have followed onset of MDD among individuals with childhood compared with adult onset, except for social phobia which more frequently preceded the depression. The relative ordering among the comorbid conditions with respect to whether they followed or preceded MDD did not vary notably across the three age of onset groups. CONCLUSIONS: We conclude that early-onset MDD is associated with an increased density of Axis I comorbidity that seems to be limited to specific disorders.

Signal transduction by platelet adenylate cyclase: alterations in depressed patients may reflect impairment in the coordinated integration of cellular signals (coincidence detection).

BACKGROUND: Adenylate cyclase (AC) responds to distinct but coincident signals from the agonist-stimulated G-protein Gs and the inhibitory G-protein Gi by generating a greater output signal-to-noise ratio--i.e., agonist-stimulated to basal ratio (fold-stimulation)--through coincidence detection than that generated by a single input (Gs) alone. Such coincidence detection by murine brain AC was found to be enhanced during chronic antidepressant treatment with imipramine. METHODS: We examined and compared the basal, agonist-stimulated, and guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) or AlF4 ion postreceptor-stimulated AC activities in mononuclear leukocytes and platelets from the same blood specimens obtained from depressed patients (n = 27) and control subjects (n = 19). RESULTS: In all subjects, the differences (delta GTP gamma S or delta AlF4) between postreceptor measures of AC in mononuclear leukocytes (where AC is regulated by Gs but not by Gi) and platelets (where AC is regulated by both Gs and Gi) were highly significant. In controls, the relationships between delta GTP gamma S or delta AlF4 and basal, agonist-stimulated, and the fold-stimulation of agonist-stimulated platelet AC resembled the regulation of AC by Gi in model-membrane systems. Comparable relationships between delta GTP gamma S or delta AlF4 and basal, agonist-stimulated, and the fold-stimulation of agonist-stimulated platelet AC activities were not observed in depressed patients. CONCLUSIONS: Our results suggest that in controls, platelet AC enzyme activity is determined (in part) by the coordinated integration of signals from Gs and Gi through coincidence detection, while such coincidence detection by platelet AC may be impaired in patients with depressive disorders.

Strengthening clinical effectiveness trials: equipoise-stratified randomization.

As psychiatric practice patterns evolve to take advantage of the growing list of treatments with proven efficacy, research studies with broader aims will become increasingly important. Randomized trials may need to accommodate multiple treatment options. In completely randomized designs, patients are assigned at random to one of the options, requiring that patients and clinicians find each of the options acceptable. In "clinician's choice" designs, patients are randomized to a small number of broad strategies and the choice of specific option within the broad strategy is left up to the clinician. The clinician's choice design permits some scope to patient and clinician preferences, but sacrifices the ability to make randomization-based comparisons of specific options. We describe a new approach, which we call the "equipoise stratified" design, that merges the advantages and avoids the disadvantages of the other two designs for clinical trials. The three designs are contrasted, using the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression trial as an example.