-
D R Smith,
B Weinstock-Guttman,
J A Cohen,
X Wei,
C Gutmann,
R Bakshi,
M Olek,
L Stone,
S Greenberg,
D Stuart, J Orav,
W Stuart,
H Weiner
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the efficacy and safety of combination therapy with pulse cyclophosphamide given with methylprednisolone (MP) and interferon beta (IFNbeta)-Ia in multiple sclerosis (MS) patients with active disease during IFNbeta monotherapy.
This was a randomized, single-blind, parallel-group, multicenter trial in MS patients with a history of active disease during IFNbeta treatment. Patients were randomized to either cyclophosphamide 800 mg/m2 plus methylprednisolone 1 g IV (CY/MP) or methylprednisolone once a month for six months and then followed for an additional 18 months. All patients received three days of methylprednisolone 1 g IV at screening and 30 mcg IFNbeta-Ia IM weekly for the entire 24 months. The primary endpoint was change from baseline in the mean number of gadolinium-enhancing (Gd+) lesions. Secondary clinical endpoints included time to treatment failure.
Fifty-nine patients were randomized to treatment: 30 to CY/MP and 29 to MP Change from baseline in the number of Gd+ lesions was significantly different between treatment groups at three (P =0.01), six (P =0.04) and 12 months (P =0.02), with fewer lesions in the CY/MP group. The cumulative rate of treatment failure was significantly lower in the CY/MP group compared with the MP group (rate ratio =0.30; 95% confidence interval, 0.12-0.75; P =0.011). CY/MP treatment was well tolerated.
Combination therapy with CY/MP and IFNbeta-Ia decreased the number of Gd+ lesions and slowed clinical activity in patients with previously active disease on IFNbeta alone.
Multiple Sclerosis 11/2005; 11(5):573-82. · 4.26 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The use of a self-administered 10-Point Likert self-assessment quality of life scale was explored in a convenience sample of patients attending a brain tumor clinic. The original scale, developed by Priestman, was modified to be more brain-tumor specific. A total of 430 patients completed the scale at 535 different points of measurement. The patients had a variety of brain tumors ranging from meningiomas to high-grade gliomas. The Total Score of the original scale and the Modified Total Score of the brain-specific version were explored in relationship to patient demographics and available clinical characteristics: age, gender, severity of tumor, location of tumor, survival rates, prior surgery, radiation, radiosurgery, and chemotherapy. We also examined the relationship between sub-scales and these variables. On a scale of 10-100, the average Total Score was 67.83, not significantly different from the Modified Score. There were no differences between bilateral, midline, or left- versus right-sided lesions. Patients with the worst prognosis in terms of tumor type were 5-6 points lower in quality of life than patients with intermediate or relatively good prognosis. In a multiple regression model, adjusted for age, the overall score was related only to tumor severity and to gender, with women having significantly poorer functional status than men by 4 points. Both the Modified and Total Scores were significantly associated with higher mortality risk, and more specifically, poor scores on well-being, mood, physical function, house/job performance, self-care, concentration, and energy all predicted higher mortality risk. We suggest that the simplicity of this instrument may make it particularly useful for longitudinal assessment of quality of life in brain tumor patients.
Journal of Neuro-Oncology 12/2001; 55(2):121-31. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In a previous retrospective case-control study, hemoconcentration was associated with the development of pancreatic necrosis. The aim of the present study was to determine in a cohort study whether hemoconcentration is a marker for both organ failure and necrotizing pancreatitis. A cohort study was performed on patients admitted with acute pancreatitis from February 1996 to April 1997. Pancreatic necrosis was defined by findings on dynamic contrast-enhanced computed tomography scan or magnetic resonance imaging. Of 128 total patients with acute pancreatitis, 53 underwent computed tomography or magnetic resonance imaging. Eighteen of 53 had necrotizing pancreatitis. Logistic regression identified an admission hematocrit > or = 44% and a failure of admission hematocrit to decrease at 24 hours as the best binary predictors of necrotizing pancreatitis and organ failure. By 24 hours, 17 of 18 patients with necrotizing pancreatitis versus 11 of 35 with interstitial pancreatitis met one or the other criterion for necrosis (p < 0.001). By 24 hours, 13 of 15 with organ failure versus 36 of 104 without organ failure met one or the other criterion (p < 0.001). The negative predictive value by 24 hours was 96% for necrotizing pancreatitis and 97% for organ failure. Hemoconcentration with an admission hematocrit > or = 44% and/or failure of admission hematocrit to decrease at approximately 24 hours was associated with the development of necrotizing pancreatitis and organ failure. Patients who did not experience hemoconcentration were very unlikely to develop pancreatic necrosis or organ failure.
Pancreas 05/2000; 20(4):367-72. · 2.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate women's health centers as alternatives to traditional internal medicine practices.
Cross-sectional mailed survey.
A women's health center and an internal medicine practice at each of three university-affiliated teaching hospitals.
There were 3,035 female patients randomly selected to receive a mailed survey after their office visits.
The survey asked for patient characteristics, patient satisfaction, and rates of gender-specific preventive health services. The survey response rate was 64% (1, 942/3,035). Patients at women's health centers were younger, more educated, had higher physical functioning but lower mental health functioning, and more of them were single and employed. Patient satisfaction was similar at the two types of practices, although patients at women's health centers were more satisfied with certain aspects of the patient-provider interaction. After adjusting for measured differences in patient characteristics and site, patients at women's health centers were more likely to receive discussions on hormone replacement therapy (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.1, 2.2) and dietary calcium (OR 1.3; 95% CI 1.1, 1. 6). They were also more likely to receive their gender-specific preventive health services from their primary care provider: breast examination (OR 2.0; 95% CI 1.5, 2.6), Pap smear (OR 2.4; 95% CI 1.9, 3.1), hormone replacement therapy discussion (OR 2.2; 95% CI 1.5, 3. 3), and dietary calcium discussion (OR 2.6; 95% CI 1.7, 3.9). These findings remained when the analyses were limited to patients of female providers only.
In this study, patients at women's health centers were more likely to receive gender-specific health prevention counseling than patients at internal medicine practices. Moreover, patients were more likely to receive their gender-specific preventive health services from their primary care providers.
Journal of General Internal Medicine 02/2000; 15(1):1-7. · 2.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of our study was to determine whether measurement of serum hematocrit during the first 24 h helps in distinguishing necrotizing from mild pancreatitis.
From May 1992 to June 1996, a case-control study was performed with cases of patients with necrotizing pancreatitis. We selected as a control the next patient admitted with mild pancreatitis.
There were 32 patients in each group. Logistic regression identified an admission hematocrit of > or = 47% and a failure of admission hematocrit to decrease at 24 h as the best binary risk factors for necrotizing pancreatitis. At admission, more patients with necrotizing pancreatitis than with mild pancreatitis had a hematocrit > or = 47% (11/32 vs 3/32; p = 0.03). At 24 h, 15 additional patients with necrotizing pancreatitis versus only one with mild pancreatitis showed no decrease in admission hematocrit (p < 0.01). Thus, by 24 h, 26 of 32 patients with necrotizing pancreatitis versus only four of 32 patients with mild pancreatitis met one or the other criterion (p < 0.01). The sensitivity and specificity at admission were 34% and 91%; at 24 h, 81% and 88%.
Hemoconcentration with an admission hematocrit > or = 47% or failure of admission hematocrit to decrease at approximately 24 h were strong risk factors for the development of pancreatic necrosis.
The American Journal of Gastroenterology 12/1998; 93(11):2130-4. · 7.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We performed a prospective observational study to examine the role of postoperative pain and its treatment on the development of postoperative delirium. Pain was measured in direct patient interviews using a visual analog scale (VAS) and was assessed for pain at rest, pain with movement, and maximal pain over the previous 24 h. Postoperative delirium was diagnosed during these interviews by using the confusion assessment method (CAM) and/or by using data from the medical record and the hospital's nursing intensity index. The method of postoperative analgesia, type of opioid, and cumulative opioid dose were also recorded. After controlling for known preoperative risk factors for delirium (age, alcohol abuse, cognitive function, physical function, serum chemistries, and type of surgery), higher pain scores at rest was associated with an increased risk of delirium over the first 3 postoperative days (adjusted risk ratio 1.20, P = 0.04). Pain with movement and maximal pain were not associated with delirium. Method of postoperative analgesia, type of opioid, and cumulative opioid dose were not associated with an increased risk of delirium. We conclude that more effective control of postoperative pain reduces the incidence of postoperative delirium. Implications: We performed daily interviews in a large population of patients undergoing noncardiac surgery to measure their level of pain and development of delirium. We found an association between higher pain levels at rest and the development of delirium. Our results suggest that better control of postoperative pain may reduce this serious complication.
Anesthesia & Analgesia 05/1998; 86(4):781-5. · 3.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To assess the correlation between cognitive dysfunction and disease burden in multiple sclerosis (MS) during a 1-year period.
The Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis was performed at entrance and 1 year. Patients underwent at least 20 proton density (range, 20-24) and T2-weighted axial magnetic resonance imaging (MRI) brain scans except for stable patients who were scanned monthly. Magnetic resonance imaging was evaluated using computer-automated, 3-dimensional volumetric analysis.
A research clinic of a university hospital.
Forty-four patients with MS of the following disease categories: relapsing-remitting (14), relapsing-remitting progressive (12), chronic progressive (13), and stable (5).
The relationships between scores on the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis and 2 MRI measures (total lesion volume and brain to intracranial cavity volume ratio) were assessed using linear regression. These MRI measures were also compared with cognitive status at 1 year using analysis of variance.
Overall, there was no decline in mean cognitive test performance during 1 year. Significant correlations were found between baseline neuropsychological test scores of nonverbal memory, information-processing speed, and attention and both MRI measures. Patients with chronic progressive MS demonstrated the strongest correlations. At 1 year, change in information-processing speed and attention correlated with change in total lesion volume. The mean increase in total lesion volume was 5.7 mL for 4 patients whose cognitive status worsened compared with 0.4 mL for 19 patients who improved and 0.5 mL for 21 patients who remained stable.
During a 1-year period mean cognitive performance did not worsen. Automated volumetric MRI measures of total lesion volume and brain to intracranial cavity volume ratio correlated with neuropsychological performance, especially in patients with chronic progressive MS. Worsening MRI lesion burden correlated with cognitive decline.
Archives of Neurology 09/1997; 54(8):1018-25. · 7.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to examine the extent and evolution of pain after common major surgical procedures and to establish correlates of three types of pain: pain at rest, pain with movement, and maximum pain over the previous 24 h. Patients completed a preoperative questionnaire to obtain data on age, gender, narcotic use, baseline level of pain, chronicity of pain, and level of anxiety. Patients were then interviewed on Postoperative Days 1, 2, and 3 to assess their pain on a scale of 0 (none) to 10 (worst imaginable). The mean pain score at rest was 2.6 on Postoperative Day 1 and decreased to 2.3 on Postoperative Day 3 (P = 0.06). The mean pain score with movement was 4.5 on Postoperative Day 1, which decreased to 4.2 on Postoperative Day 3 (P = 0.03). The mean maximum pain score over the previous 24 h was 6.3, which decreased to 5.6 (P = 0.0001). Preoperative narcotic use and high baseline preoperative pain, defined as a score > or = 4, were significantly (P < 0.05) associated with increased pain at rest, pain with movement, and maximum pain. Epidural analgesia was the only mode of analgesia significantly associated with both decreased postoperative pain at rest and decreased pain with movement (P < 0.05). These relatively high pain scores and minimum decreases in pain from Postoperative Days 1 to 3 emphasizes the need for more effective pain management continuing into the postoperative period to facilitate mobilization and recovery.
Anesthesia & Analgesia 08/1997; 85(1):117-23. · 3.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent research suggests that affective disorder is associated with increased mortality and physical morbidity, but the reasons for this association remain uncertain. This report describes a 50-year prospective study of 240 men evaluated from the time they were university students in 1940-1942. A family history of mental illness was obtained and the men's habits, psychological adjustment, and marital and occupational satisfaction were followed every 2 years and their objective physical health was tracked every 5 years until age 70. Twenty-five men were identified as having affective spectrum disorder prior to age 53. Of the variables studied, the presence of affective spectrum disorder was the most powerful predictor of poor psychosocial outcome at age 65 and one of the most powerful predictors of poor physical health. Alcohol abuse and cigarette abuse accounted for the observed increased rates of heart disease and cancer. When alcohol abuse, smoking, and suicide were controlled for, affective disorder made a significant contribution to physical morbidity by age 70, but not to mortality from natural causes. Affective spectrum disorder, even in an educated population without antisocial trends, carries a profound negative risk to late-life physical and social adjustment.
International Psychogeriatrics 02/1996; 8(1):13-32. · 2.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Quantitative angiography is the accepted method for measuring coronary luminal diameter. Electronic digital calipers have been used to assess arterial diameters in vasomotor function studies and after interventional procedures. However, careful validation of calipers against quantitative angiography has not been described.
We used digital calipers and quantitative angiography to measure 517 arterial diameters (88 nonstenotic segments) in 24 transplant patients undergoing vasomotor function studies with acetylcholine and nitroglycerin, 20 stenoses in 14 patients with coronary artery disease, and 15 stenoses in 15 patients before and after excimer laser-facilitated coronary angioplasty and at 6 months' follow-up. In nonstenotic arterial segments ranging in size from 0.6 to 3.5 mm, calipers overestimated diameters measured by quantitative angiography by 0.29 +/- 0.21 mm (mean +/- SD) (limits of agreement, -0.13 to 0.71 mm). However, when the vasomotor responses were expressed as percent diameter change, the two methods did not differ significantly (-1 +/- 10%; limits of agreement, -21% to 19%). In the 35 stenoses measured before intervention and 30 stenoses measured after intervention, calipers and quantitative angiography differed by 3 +/- 9% (limits of agreement, -15% to 21%) across a range of stenosis severity (11% to 80%). Repeat caliper measurements by the same observer of the percent diameter change in the transplant patients and the percent stenosis in the coronary artery disease patients led to standard deviations of the differences of 9.3% and 7.6%, respectively. Two different observers recorded percent diameter change and percent stenosis that differed with standard deviations of 9.6% and 7.8%, respectively.
Quantitative angiography and electronic digital calipers produce similar relative changes in arterial diameters and percent stenosis in a broad range of severities. Digital calipers thus are a rapid and convenient alternative to computerized quantitative angiography in certain research studies and clinical practice of assessing stenosis severity.
Circulation 11/1993; 88(4 Pt 1):1724-9. · 14.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To assess the degree of intraobserver and interobserver variability in endometriosis staging using the revised American Fertility Society (AFS) classification of endometriosis.
Videotapes of laparoscopies of 20 patients with endometriosis were each scored twice by five observers.
The reproductive endocrine unit of a tertiary care, university-affiliated hospital.
Five subspecialty-certified reproductive endocrinologists.
None.
Variability in assigned score was measured for each of the five components of the AFS classification, as well as total scores and stage of endometriosis.
There was considerable variability in the scores assigned to each videotape, both by the same observer and by different observers. The grand total score, which ranged from 0 to 90, varied with an SD of 13.44 when a single patient was rated twice by the same observer and varied with an SD of 17.12 when a single patient was rated by two different observers. Among individual components of the score, the greatest variability occurred in endometriosis of the ovary and cul-de-sac obliteration, with less variability observed for peritoneum endometriosis and for ovarian and tubal adhesions. Comparison of intraobserver and interobserver scores resulted in a change in endometriosis stage in 38% and 52% of patients, respectively. There were statistically significant differences in mean endometriosis scores among the observers in four of the five anatomic categories examined.
Intraobserver and interobserver variability was high for ovarian endometriosis and cul-de-sac subscores using the revised AFS classification of endometriosis.
Fertility and Sterility 06/1993; 59(5):1015-21. · 3.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ischemia on ambulatory electrocardiographic monitoring has been shown to adversely affect short-term prognoses in patients with unstable angina, after myocardial infarction, and with chronic stable angina.
In this long-term study, we followed 138 patients (mean age, 59 +/- 9 years) with chronic stable angina and positive exercise tests for cardiac events (e.g. death, myocardial infarction, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery). In 105 patients, ambulatory electrocardiographic monitoring was performed after all antianginal medication was withheld for 48 hours. In 26 patients, the diagnostic tests were repeated while on their usual medication. In addition to the 105 patients, 33 patients had their monitoring performed only while on their usual medication. During 37 +/- 17 months of follow-up, there were nine deaths, nine myocardial infarctions, and 35 revascularization procedures. In patients monitored off medication, Cox survival analysis showed that the occurrence of ischemia on electrocardiographic monitoring was the most significant predictor of death and myocardial infarction in the subsequent 2 years (p = 0.02) and all adverse events for 5 years (p = 0.009). Patients who were monitored on medication and did not have ischemia (n = 18) appeared to have more adverse events than patients who had no ischemia while being monitored off medication (n = 43).
Asymptomatic ischemia on ambulatory electrocardiographic monitoring in patients with stable angina predicts death and myocardial infarction for 2 years and all adverse events for 5 years. Monitoring performed while on medication may show no ischemia; however, this may not indicate low risk of future coronary events.
Circulation 06/1991; 83(5):1598-604. · 14.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We examined immune function and changes in T cell populations over a 1-year period in a series of progressive multiple sclerosis (MS) patients treated with different regimens of cyclophosphamide/ACTH as part of the Northeast Multiple Sclerosis Treatment Group. Our studies were designed to determine the effect of different cyclophosphamide/ACTH regimens on T cell populations and functional immune assays and to determine whether immune measures could be identified to predict which patients responded favorably to treatment. Cyclophosphamide/ACTH infusions significantly decreased the proportion of peripheral blood CD4+ T cells at 2, 6 and 12 months following treatment while there was a tendency for increased CD8 expression. This was associated with significant decreases of CD4/CD8 ratios at 2, 6 and 12 months following treatment compared to pretreatment. No changes in CD3+ T cells were observed while there were increased percentages of CDw26 (Ta1) positive and IL-2 positive T cells following treatment. The only T cell populations predictive of improvement were percentages of either CD3+ or CD4+ cells where increased percentages of either these populations at 2 months following cyclophosphamide/ACTH infusions were associated with improvement at both 6 and 12 months. In terms of functional immune measures, we found that cyclophosphamide/ACTH treatment decreased the level of proliferation in the allogeneic mixed lymphocyte reaction (MLR) at 2 months and of spontaneous proliferation of mononuclear cells at 12 months following therapy. Changes in spontaneous proliferation were predictive of clinical improvement at 12 months in that subjects with improved scores on the disability status scale (DSS) had decreases in spontaneous proliferation at 12 months as compared to pretreatment, whereas those stable or worse did not change significantly. Thus, our studies have demonstrated specific alterations in immune function following immunosuppression with cyclophosphamide/ACTH and suggest that certain immune measures may be linked to a positive clinical response and thus associated with disease progression in MS.
Journal of Neuroimmunology 06/1991; 32(2):149-58. · 2.96 Impact Factor
-
Clinical research 01/1991; 38(4):686-93.
-
[show abstract]
[hide abstract]
ABSTRACT: We compared the performance of 50 multiple sclerosis (MS) patients and 35 normal controls on a variety of memory tasks to determine the nature and severity of memory deficits in the MS patients and the proportion of patients affected. We also determined the relationship between memory and other cognitive functions, demographic factors, disease characteristics, depression, and psychoactive medication. We found significant differences between patients and controls on almost all memory tests. Patterns of learning, effects of interference, and improvement with cuing were similar for both groups. Thirty percent of patients showed severe memory impairment, 30% were moderately impaired, and 40% were mildly or not impaired. Memory dysfunction was related to impairment of other cognitive functions, lower socioeconomic status, chronic progressive type of MS, and use of antianxiety medication, but not to severity of disability, duration of MS symptoms or depression.
Journal of Clinical and Experimental Neuropsychology 09/1990; 12(4):566-86. · 2.13 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Nine of 50 MS patients became hypomanic or manic during treatment with ACTH or prednisone. Symptoms did not occur with every drug exposure and were more common with ACTH. Patients at risk were identified by episodes of major depression before and after the onset of MS and by family histories of depression or alcoholism.
Neurology 11/1988; 38(10):1631-4. · 8.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: One hundred sixty-four patients with chronic progressive multiple sclerosis (MS) have been treated with a regimen of high-dose IV cyclophosphamide and ACTH over the past 6 years. Their status was reviewed to determine complications associated with treatment, dosage of medication used to induce a remission, factors which may predict a response to therapy, and subsequent course following treatment. One year following initial treatment, 81% of patients were improved or stabilized. Reprogression occurred in 69% of patients at a mean time of 17.6 months. Fifty-eight patients who initially stabilized after treatment and then reprogressed were treated a second time. One year after retreatment, 70% of these patients were improved or stabilized. Alopecia, nausea and vomiting, and minor infections were the most frequent complications. There were no deaths associated with treatment, the complication rate did not change with multiple treatments, and no late complications have yet been observed. Improvement tended to occur in younger patients with shorter disease duration. Although this treatment regimen is generally well tolerated and can favorably affect the course of chronic progressive MS in a majority of patients, a single treatment does not induce a permanent remission, and some form of maintenance treatment or retreatment is required. Current treatment programs involve testing a modified induction regimen and periodic outpatient booster injections to maintain remission.
Neurology 08/1988; 38(7 Suppl 2):9-14. · 8.31 Impact Factor
-
Annals of the New York Academy of Sciences 02/1988; 540:535-6. · 3.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Standardized interview techniques, diagnostic criteria, and rating scales were used to assess 50 moderately disabled multiple sclerosis (MS) patients. Fifty-four percent met lifetime Research Diagnostic Criteria for major depression, with a significant increase in the rate from before to after the onset of MS symptoms. The MS patients were significantly more depressed than other medical patients described in the literature. Major depressions were associated with steroid-treated exacerbations and a history of major depression. Symptoms of depression may be easily confused with those of MS, resulting in inadequate diagnosis and treatment.
General Hospital Psychiatry 12/1987; 9(6):426-34. · 2.74 Impact Factor
