Maintenance of therapeutic change: A usable evaluation design.

Specific strategies for improving maintenance of gains following initial treatment intervention have received relatively little attention. Effective methods for maintaining gains may differ from those needed to effect initial therapeutic change. A design for evaluating the cost-effectiveness of maintenance strategies is discussed, and some appropriate statistical analyses are suggested. This design is particularly suitable for use in ongoing treatment programs and individual practices where "no treatment" controls are impractical. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Natural history and prognosis of adenomatous hyperplasia and early hepatocellular carcinoma: multi-institutional analysis of 53 nodules followed up for more than 6 months and 141 patients with single early hepatocellular carcinoma treated by surgical resection or percutaneous ethanol injection

BACKGROUND: The natural history and posttherapeutic outcome of adenomatous hyperplasia and early hepatocellular carcinoma have rarely been analyzed. METHODS: Fifty-three hepatic tumors diagnosed as adenomatous hyperplasia or early hepatocellular carcinoma and followed up for more than 6 months and 141 patients with single early hepatocellular carcinoma treated by surgical resection or ethanol injection were collected retrospectively and analyzed. RESULTS: Some of the adenomatous hyperplasias developed to early and to advanced hepatocellular carcinoma. Tumors tended to grow faster in the order adenomatous hyperplasia, early hepatocellular carcinoma and advanced hepatocellular carcinoma, with respective mean (SD) tumor volume doubling times of 21.2 (10.7), 13.9 (11.7) and 6.0 (5.2) months. Overall survival rates at 5 years in 53 patients treated by surgery and 88 patients treated by ethanol injection were 89.6 and 71.9%, respectively. CONCLUSION: Progression of adenomatous hyperplasia and early HCC was confirmed pathologically. Early HCC was shown to have a good prognosis.     

Thymidylate synthase inhibition: a structure-based rationale for drug design

The effect of drugs in the fetus can be thought of in terms of the dose-response based on a knowledge of the general principles by which drug is transferred from the mother to the fetus. Fetal drug concentration, which determines the fetal response, is a function of the maternal concentration, the placental permeability, the fetal drug clearance, and differences in protein binding and ionization between the maternal and fetal plasma.     

A multidisciplinary approach to the early detection of ovarian carcinoma: rationale, protocol design, and early results

OBJECTIVE: This study was undertaken to determine the feasibility of currently available tests to detect ovarian cancer at a curable stage. By studying women at risk for the disease on the basis of their family histories of cancer, we hope to gain insight into the genetics and biologic characteristics of ovarian cancer. STUDY DESIGN: Asymptomatic women with a family history of cancer are interviewed by geneticists to obtain accurate pedigree and epidemiologic data. Screening tests including transvaginal ultrasonography, color Doppler imaging, CA 125 measurement, and other investigative biomarkers are performed between cycle days 3 and 8 and repeated biannually. RESULTS: A total of 597 women without symptoms were screened between July 1991 and June 1992. Cystic or complex adnexal masses were detected in 6.2% of patients. A pulsatile index value < 1.0 was measured in 80% of premenopausal patients and 24% of postmenopausal patients, whereas a resistance index value < 0.4 occurred in 12% of premenopausal and 3% of postmenopausal patients. A CA 125 level > 35 U/ml was found in 11.4% of the study participants. To date, one stage IA borderline ovarian tumor and one endometrial carcinoma have been found. CONCLUSIONS: Ovarian cancer screening needs to be investigated in a controlled fashion to determine means that will ultimately improve the survival from the disease.     

Early advanced hepatocellular carcinoma: evaluation of CT and MR appearance with pathologic correlation

PURPOSE: To determine the computed tomographic (CT) and magnetic resonance (MR) imaging appearances of early advanced hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty-seven surgically resected cases of early advanced HCC were studied with CT, CT during arterial portography, CT arteriography, and MR imaging. RESULTS: The sensitivity of standard CT (unenhanced, early, and late CT combined) for the detection of early advanced HCC was 81%, while that of standard MR imaging (T1- and T2-weighted MR imaging combined) was 83%. A nodule-in-nodule appearance was identified in approximately one-third to one-half of cases. Signal behavior of early and advanced components of early advanced HCC followed the expected behaviors of isolated early HCC and isolated advanced HCC, respectively. Tumor size was accurately estimated with standard CT and standard MR imaging. CONCLUSION: More research must be performed to ascertain whether any relationship exists between the different types of HCC and the clinical outcome.     

Atrial fibrillation: overview of therapeutic trials

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia treated by physicians, and a plethora of therapeutic trials deal with selected aspects of its management. This overview attempts to categorize and summarize the available studies. A key to management of AF is a clinical classification schema that provides a framework for application of the available treatment modalities. Such a classification is provided. Antithrombotic trials have demonstrated the remarkable efficacy of warfarin and more modest effect of acetylsalicylic acid for prevention of stroke; these data are summarized. Cardioversion to restore sinus rhythm is an important aspect of management of AF, particularly of persistent and new onset AF. In this review pharmacological cardioversion is emphasized. The data concerning the use of various drugs for pharmacological cardioversion are reviewed. Many, but not all, agents have been shown to have efficacy in this regard, but efficacy with drugs is lower than that with electrical cardioversion and, in the case of amiodarone, may be delayed. For recurrent AF, the two major rhythm management approaches are maintenance of rhythm and heart rate control. Trials of pharmacological and nonpharmacological therapies for these purposes are reviewed and summarized. Management of AF is an active area of research, and the present review is intended as a foundation upon which new information can be added.     

Real-time evaluation of the effectiveness of microwave coagulation therapy for hepatocellular carcinoma using color Doppler imaging

The patient's insight in the course of a mental disease has recently become a matter of interest for psychiatrists. Various aspects of insight are examined, as well as the relationship between insight and different clinical variables. In the current study, we examined correlations between aspects of insight and intensity of psychopathological symptoms, occurrence of the various types of delusions, and the level of premorbid adjustment in patients with paranoid schizophrenia. We found significant relationships between poor insight and negative symptoms, thought-broadcasting, delusions of grandeur and sexual delusions, and worse premorbid adjustment in late adolescence and adulthood.     

PET evaluation of therapeutic limb perfusion in Merkel's cell carcinoma

An 87-yr-old woman diagnosed with recurrent Merkel's cell carcinoma was treated with therapeutic limb perfusion and underwent PET scanning with 18F-fluorodeoxyglucose (FDG). PET studies were obtained before and after treatment to determine the response to the intervention. A baseline whole-body study was obtained to assess the extent and degree of disease activity. This was followed by a repeat PET scan 2 mo. later after treatment with isolated limb chemotherapy with high-dose melphalan and tumor necrosis factor-alpha. The initial scan demonstrated multiple foci of high FDG uptake in the left calf, a left supraclavicular lesion and also detected concurrent keratinizing squamous cell metastasis in the right axilla. A repeat PET study showed complete metabolic resolution of the lesions in the left calf after treatment. FDG PET may be a useful technique for staging Merkel cell carcinoma and for assessing the tumor response after therapy of this rare tumor.     

Treatment preferences affect the therapeutic alliance: Implications for randomized controlled trials.

The influence of treatment preferences on the development of the therapeutic alliance was investigated. Seventy-five patients were followed while participating in a randomized controlled trial comparing supportive-expressive psychotherapy with sertraline or pill placebo in the treatment of major depressive disorder. Therapeutic alliance was assessed before treatment and at the 3rd, 5th, and 9th weeks of treatment. Among patients initially preferring psychotherapy, those receiving psychotherapy experienced increases in their alliance over time, whereas those receiving active medication or placebo experienced decreases. Among patients preferring pharmacotherapy, there were no differences in alliance development whether they received psychotherapy, active medication, or placebo. These relations were observed even when controlling for symptom severity. Thus, the congruence of patients' treatment preference and the treatment that they ultimately received influenced the development of the therapeutic alliance. Because alliance is a robust predictor of outcome, treatment preferences may need to be carefully considered in randomized controlled trial settings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Natural history of cancer of the kidney: iconographic follow-up

A 29-year-old woman developed diplopia and ataxic gait. Neurological examination revealed total ophthalmoplegia, cerebellar ataxia, and areflexia. Muscle weakness in four limbs was also noted. We diagnosed the patient as having an overlap between Fisher's syndrome and Guillain-Barré syndrome. On day 5, she suddenly had flinging involuntary movements affecting the face and four extremities. Surface EMG recording revealed 1.5- 2 Hz rhythmic grouping discharges. The involuntary movements were considered as ballism. Brain CT and MRI could not detect any abnormal findings in subthalamic nucleus, but, electrophysiological findings revealed CNS lesions. Therefore, the clinical diagnosis also were Bickerstaff's brainstem encephalitis. She had high titer of IgG antibody to GQ 1b (1:64,000). Sera taken from patients with Fisher's syndrome, Guillain-Barré syndrome with ophthalmoparesis and Bickerstaff's brainstem encephalitis during the acute phases of these syndromes frequently have IgG antibody to GQ 1b ganglioside. It is concluded that some cases of acute ophthalmoparesis subsequent to infection or immunization may be categorized as autoimmune diseases. Hence, such disease which show external ophthalmoparesis may be designated the "anti-GQ 1 b IgG antibody syndrome". This is the first report on the patient with Guillain-Barré syndrome and the related disorders who showed ballism.     

Indication and limitation of hepatectomy for hepatocellular carcinoma

Hepatectomy for hepatocellular carcinoma (HCC) has become safer with recent advances in diagnostic methods, operative techniques and understanding of how to evaluate liver function. Hepatectomy is the treatment of choice for HCC provided that patients are selected carefully, because cure is possible with hepatectomy (some patients survive long without recurrence). However, the rate of recurrence after hepatectomy is high. Recurrences can arise because of either intrahepatic dissemination or factors that give rise to multicentric carcinoma, so one must decide the operative method, to prevent recurrence and the treatment if such occurs, based on the pathogenesis of HCC.     

Interconversion of stroke scales. Implications for therapeutic trials

BACKGROUND AND PURPOSE: Stroke scales are intended to measure stroke severity for the purpose of clinical trials. Scores have been used to determine trial entry, to compare patient groups within or between trials, or as a secondary end point. The use of scores as an end point in meta-analysis has not been validated, but such analyses have nevertheless been performed when equivocal results have been obtained using the main outcome measure. The different scale designs suggest that conversion of scores may not be possible. We sought to determine whether scores on different scales could be interconverted. METHODS: A single observer scored 433 consecutive admissions to an acute stroke unit on the Canadian Neurological Scale, the middle cerebral artery Neurological Score (or Orgogozo scale), and the National Institutes of Health stroke scale. Data were separated into training and test sets, and linear regression was used to model conversion between scales. Prediction errors were calculated. Strokes were subdivided according to the Oxfordshire Community Stroke Project classification, and coefficients of determination were calculated for different subtypes. RESULTS: Conversion between Canadian and middle cerebral artery Neurological scales was satisfactory (R2 = 94.7%), and prediction errors were acceptable (absolute prediction error, 5.0 +/- 5). Conversion from the National Institutes of Health scale was worse (R2 = 87.5% to Canadian and 89.0% to Neurological Score), and prediction errors were significantly greater (Neurological Score error, 8.7 +/- 7; Canadian Neurological Scale error, 8.5 +/- 7.3; P < .005 for both). Coefficients of determination for interconversion were significantly worse for dysphasic patients with total anterior circulation strokes than for other stroke types (P < .01). Reweighting the motor component of the National Institutes of Health scale improved coefficients of determination and reduced prediction errors, but prediction error for conversion to the Canadian scale remained significantly greater than other conversions (P = .001). CONCLUSIONS: The Canadian Neurological Scale and the middle cerebral artery Neurological Score may reliably be converted. The National Institutes of Health scale cannot be used to predict these scores reliably, even with reweighting of the motor score. Interconversion is poorest for patients with dysphasia and total anterior circulation strokes. These results suggest that there will be more general difficulty in interconverting scales that use different test items and weighting. Meta-analysis using sequential changes in averaged scores from various stroke scales is not valid.     

A structural rationale for the design of water soluble peptide-derived neurokinin-1 antagonists

Molecular models of a pharmacophore for NK1 neurokinin antagonists and of ligand-receptor complexes for the human NK1 G protein-coupled receptor are presented. The models develop a structural rationale for the discovery of the recently described highly potent peptidomimetic NK1 antagonists S18523 and S19752 which were designed to be water soluble. Water solubility was conferred on these compounds by introduction of an anionic butyl-tetrazole substituent on the scaffold of dipeptide-derived NK1 antagonist analogues. The models provide convincing evidence that the anionic butyl-tetrazole moieties of S18523 and S19752 protrude outside the membrane-spanning domain of the receptor and do not interfere significantly with the core of the antagonist binding site. It is emphasized that this result could only be obtained through the combination of the two modelling approaches. The result suggest a general way to modify the transport properties of the peptidomimetic antagonists without altering the receptor-binding interaction, and it outlines the potential of including the combination of pharmacophore models and crude models of receptor-ligand complexes early in the drug design process.     

The Sleep Heart Health Study: design, rationale, and methods

The Sleep Heart Health Study (SHHS) is a prospective cohort study designed to investigate obstructive sleep apnea (OSA) and other sleep-disordered breathing (SDB) as risk factors for the development of cardiovascular disease. The study is designed to enroll 6,600 adult participants aged 40 years and older who will undergo a home polysomnogram to assess the presence of OSA and other SDB. Participants in SHHS have been recruited from cohort studies in progress. Therefore, SHHS adds the assessment of OSA to the protocols of these studies and will use already collected data on the principal risk factors for cardiovascular disease as well as follow-up and outcome information pertaining to cardiovascular disease. Parent cohort studies and recruitment targets for these cohorts are the following: Atherosclerosis Risk in Communities Study (1,750 participants), Cardiovascular Health Study (1,350 participants), Framingham Heart Study (1,000 participants), Strong Heart Study (600 participants), New York Hypertension Cohorts (1,000 participants), and Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study (900 participants). As part of the parent study follow-up procedures, participants will be surveyed at periodic intervals for the incidence and recurrence of cardiovascular disease events. The study provides sufficient statistical power for assessing OSA and other SDB as risk factors for major cardiovascular events, including myocardial infarction and stroke.     

Natural history and evaluation of ST segment changes and MB CK release in acute myocardial infarction

The experimental evidence relating ST segment elevation in the electrocardiogram to the progress and extent of ischaemic myocardial damage is discussed. There are difficulties in applying this to patients: the reproducibility of praecordial mapping was tested using a multiple analysis of variance. This showed that factors such as time after the onset of myocardial infarction and posture can affect measurements of sigmaST elevation significantly. There was a pattern of changes in segmaST elevation and of changes in plasma MB CK activity in a group of patients with uncomplicated anterior infarction. A significant byt weak correlation was found between sigmaST elevation in the first hour and the total MB CK activity released into the plasma, but not at any other time. The use of sigmaST elevation as a measure of the extent of ischaemic damage is unreliable. In 5 patients with a variety of complications of acute anterior infarction, changes in sigmaST elevation werr significantly different from the uncomplicated group, and MB CK release profiles suggested further necrosis. The pattern and time course of ST segment changes may be of use in assessing the progress of ischaemic myocardial damage.     

A trial of the synthetic malaria vaccine SPf66 in Tanzania: rationale and design

By using acetyl strophanthidin (AS) 0.2 mumol/L, the delayed after-depolarization (DAD) was induced in sheep cardiac Purkinje fibers and recorded with intra-cellular microelectrode. When beta-adrenoceptor was blocked by propranolol 1.0 mumol/L, phenylephrine 1.0 mumol/L increased the amplitude of DAD from 8.1 +/- 2.2 mV to 9.5 +/- 2.8 mV, prolonged the duration of DAD from 240 +/- 47 ms to 273 +/- 47 ms (n = 13, P < 0.01) and increased the up rising velocity of DAD from 0.039 +/- 0.023 V/s to 0.051 +/- 0.026 V/s (n = 13, P < 0.05). The DAD occurred earlier for 30 +/- 47 ms to preceding action potential (n = 13, P < 0.05). When triggered action potentials were induced by norepinephrine 1.0 mumol/L on the basis of DAD, propranolol 1.0 mumol/L could suppress the triggered beats while phentolamine 1.8 mumol/L showed little effect. The above results indicate that excitation of alpha-receptor had only slight augmentation effect on DAD. However, for the triggered activity induced by DAD, the inhibitory effect of beta-blockers are stronger than that of alpha-blockers.