Background/Purpose: Some Health Maintenance Organizations (HMO) limit access of their members to ... more Background/Purpose: Some Health Maintenance Organizations (HMO) limit access of their members to specialists to lower costs. The purpose of this study is to determine whether this policy affects the outcome of children with appendicitis. Methods: At a large academic medical center, children 17 years or younger with appendicitis were treated either by an HMO Adult General Surgical Service (group A)
At least 2 apparently independent mechanisms, microsatellite instability (MSI) and chromosomal in... more At least 2 apparently independent mechanisms, microsatellite instability (MSI) and chromosomal instability, are implicated in colorectal tumorigenesis. Their respective roles in predicting clinical outcomes of patients with T3N0 colorectal cancer remain unknown. Eighty-eight patients with a sporadic T3N0 colon or rectal adenocarcinoma were followed up for a median of 67 months. For chromosomal instability analysis, Ki-ras mutations were determined by single-strand polymerase chain reaction, and p53 protein staining was studied by immunohistochemistry. For MSI analysis, DNA was amplified by polymerase chain reaction at 7 microsatellite targets (BAT25, BAT26, D17S250, D2S123, D5S346, transforming growth factor receptor II, and BAX). Overall 5-year survival rate was 72%. p53 protein nuclear staining was detected in 39 patients (44%), and MSI was detected in 21 patients (24%). MSI correlated with proximal location (P <.001) and mucinous content (P <.001). In a multivariate analysis, p53 protein expression carried a significant risk of death (relative risk = 4.0, 95% CI = 1.6 to 10.1, P =.004). By comparison, MSI was not a statistically significant prognostic factor for survival in this group (relative risk = 2.2, 95% CI = 0.6 to 7.3, P =.21). p53 protein overexpression provides better prognostic discrimination than MSI in predicting survival of patients with T3N0 colorectal cancer. Although MSI is associated with specific clinicopathologic parameters, it did not predict overall survival in this group. Assessment of p53 protein expression by immunocytochemistry provides a simple means to identify a subset of T3N0 patients with a 4-times increased risk for death.
The specific performance of intrinsic laryngeal muscles has been difficult to evaluate, especiall... more The specific performance of intrinsic laryngeal muscles has been difficult to evaluate, especially in living subjects. To reproduce natural contractions, we artificially induced orderly recruitment of their innervating axons according to the size principle. In 5 dogs, both recurrent laryngeal nerves (RLNs) were stimulated with 50 through 10 Hz, 300 to 1000 microA currents while 600 Hz, 1000 to 0 microA decreasing blocking currents were administered. Surface electromyography electrodes placed on the thyroarytenoid, posterior cricoarytenoid, and lateral cricoarytenoid muscles were used to determine the amplitudes (in mA) of compound muscle action potentials. There was a highly statistically significant difference (P<.004) between the thyroarytenoideus which had the fastest rate of recruitment (8.38%), and posterior cricoarytenoideus, which had the slowest (4.81%). There was an intermediate recruitment rate (6.72%) of the lateral cricoarytenoideus, a divergence attributed to a more equal distribution in fast and slow types of myofibers and a smaller sample. We submit that RLN axons can be recruited in an orderly manner according to their sizes and that the rates are unique to the muscle classes they innervate. The parameters defining these contraction patterns may offer key information for laryngeal pacing.
Conversion rates following laparoscopic colorectal surgery vary widely between studies, and the o... more Conversion rates following laparoscopic colorectal surgery vary widely between studies, and the outcome of converted patients remains controversial. A comprehensive search of the English-language literature was updated until May 1999. Twenty-eight studies on 3232 patients were considered for analysis. The overall conversion rate was 15.38%. Seventy nine percent of the studies did not include a definition for conversion; in these studies, the conversion rate was significantly lower than in the series where a specific definition was considered (13.7% vs 18.9%, chi-square test, p < 0.001). Converted patients had a prolonged hospital stay (11.38 vs 7.41 days) and operative time (209 vs 189 min) in comparison with laparoscopically completed patients (95% confidence interval (CI), 1.70-4.00 and 35.90-37.10, respectively). The factors associated with an increased rate for conversion were left colectomy (Odds Ratio [OR] = 1.061), anterior resection of the rectum (OR = 1.088), diverticulitis (OR = 1.302), and cancer (OR = 2.944) (for each parameter, Wald chi-square value, p < 0.001). In nonrandomized studies, the rate of laparoscopically completed colorectal resections is close to 85%. Because converted patients have a distinct outcome, a clear definition of conversion is required to compare the results of randomized trials. Such trials should also consider a 20% rate of conversion when estimating the sample size for the desired power level. It is likely that converted patients will have a significant impact on the results of future clinical research in laparoscopic colorectal surgery.
The authors compared the changes in health care utilization and costs between a group of patients... more The authors compared the changes in health care utilization and costs between a group of patients with schizophrenia who started treatment with risperidone and a group that started treatment with olanzapine. A retrospective analysis was conducted of patients with schizophrenia who were given an initial prescription for risperidone or for olanzapine between March 1997 and March 1999. The change in utilization and cost of inpatient hospitalizations, outpatient clinic visits, medications, and total health care services from one year before to one year after initiation of treatment for the two groups was compared. The risperidone and olanzapine groups comprised 325 and 285 patients, respectively. Total health care costs declined by $1,536 on average for patients in the risperidone group and increased by $4,217 on average for patients in the olanzapine group after initiation of treatment. The difference was statistically significant, and it was largely due to drug and hospitalization costs. Drug costs for patients in the risperidone group underwent a smaller increase than those for patients in the olanzapine group ($991 versus $1,861). Hospitalization costs decreased by $4,011 for patients in the risperidone group and increased by $1,423 for those in the olanzapine group. Total health care costs declined for patients taking risperidone and increased for patients taking olanzapine after treatment was initiated.
A growing body of literature suggests that certain atypical antipsychotics, especially olanzapine... more A growing body of literature suggests that certain atypical antipsychotics, especially olanzapine and clozapine, may induce glucoregulatory dysfunction. We assessed the differences in risk of developing diabetes mellitus during treatment with olanzapine and risperidone by using patients treated with haloperidol and fluphenazine as control subjects in whom we would not expect to see an increased risk. We conducted a retrospective analysis of the Veteran's Integrated Service Network 10 Veterans Affairs (VA) database. Data for patients receiving olanzapine, risperidone, haloperidol, or fluphenazine from January 1, 1997-December 31, 2000, were included. Diabetes was defined as any health system encounter associated with the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis for diabetes (250.xx) or prescription for a hypoglycemic agent. Data of patients with markers for diabetes within 1 year before their index date, female patients, racial groups other than Caucasian or African-American, and patients receiving clozapine were not analyzed. We performed a Cox regression, with antipsychotic therapy as a time-dependent covariate. Other covariates considered for inclusion in the final model were number of days supply of antipsychotic drug, age, race, psychiatric diagnoses, substance abuse, lithium, valproic acid, and other typical or atypical antipsychotic agents. Data for 5837 patients were analyzed. Overall rate of developing diabetes in the study population was 6.3% (368 of 5837 patients). Olanzapine therapy was associated with a significantly higher risk of development of diabetes compared with risperidone (hazard ratio [HR] 1.37, 95% confidence interval 1.06-1.76, p=0.016) while controlling for race, age, diagnosis, substance abuse, lithium, valproic acid, and other atypical antipsychotic agents. No differences in the rate of developing diabetes were detected between fluphenazine and risperidone (HR 1.11, p=0.69), or haloperidol and risperidone (HR 0.89, p=0.41). Olanzapine was associated with a 37% (HR 1.37) increased risk of development of diabetes compared with risperidone in a VA population, even after adjusting for other factors associated with the development of diabetes and temporal exposure to study drug. Because of limitations associated with database research, prospective studies should be conducted to corroborate these findings.
Numerous studies suggest that the dihydropyridine calcium antagonists (DCAs) and nondihydropyridi... more Numerous studies suggest that the dihydropyridine calcium antagonists (DCAs) and nondihydropyridine calcium antagonists (NDCAs) have differential antiproteinuric effects. Proteinuria reduction is a correlate of the progression of renal disease. In an earlier systematic review, calcium antagonists were shown as effective antihypertensive drugs, but there was uncertainty about their renal benefits in patients with proteinuria and renal insufficiency. A systematic review was conducted to assess the differential effects of DCAs and NDCAs on proteinuria in hypertensive adults with proteinuria, with or without diabetes, and to determine whether these differential effects translate into altered progression of nephropathy. Studies included in the review had to be randomized clinical trials with at least 6 months of treatment, include a DCA or NDCA treatment arm, have one or more renal end points, and have been initiated after 1986. Summary data were extracted from 28 studies entered into two identical but separate databases, which were compared and evaluated by independent reviewers. The effects of each drug class on blood pressure (N= 1338) and proteinuria (N= 510) were assessed. After adjusting for sample size, study length, and baseline value, there were no statistically significant differences in the ability of either class of calcium antagonist to decrease blood pressure. The mean change in proteinuria was +2% for DCAs and -30% for NDCAs (95% CI, 10% to 54%, P= 0.01). Consistently greater reductions in proteinuria were associated with the use of NDCAs compared with DCAs, despite no significant differences in blood pressure reduction or presence of diabetes. This analysis supports (1) similar efficacy between subclasses of calcium antagonists to lower blood pressure, and (2) greater reductions in proteinuria by NDCAs compared to DCAs in the presence or absence of diabetes. Based on these findings, NDCAs, alone or in combination with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), are suggested as preferred agents to lower blood pressure in hypertensive patients with nephropathy associated with proteinuria.
Journal of Vascular and Interventional Radiology, 2014
To compare the durability of thoracic endovascular aortic repair (TEVAR) in two similar clinical ... more To compare the durability of thoracic endovascular aortic repair (TEVAR) in two similar clinical trials that used early- and later-generation stent grafts. Secondary procedures from the prospective, nonrandomized, multicenter, clinical trial databases of the test arm of the VALOR and VALOR II trials were analyzed at 3 years. Descriptive and statistical analyses were employed to compare the rate of and potential predictors for secondary procedures. A total of 127 and 96 patients were available for a minimum of 3 years of follow-up in the test arm of VALOR and VALOR II, respectively. By the first year after the index procedure, VALOR II patients were significantly less likely to have undergone a secondary procedure versus patients in the test arm of VALOR (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.01-0.63; P = .02), with most procedures performed for type I endoleak. Multivariate predictors at 3 years for the need for a secondary procedure in the VALOR test arm were maximum aneurysm diameter (P = .002) and aneurysm length (P = .01), both of which remained significant at the end of the study period. The estimated freedoms from secondary procedures in the VALOR test arm and VALOR II at 3 years were 85.1% (95% CI, 78.5%-89.8%) and 94.9% (95% CI, 88.8%-97.7%), respectively (P < .001). The rate of secondary procedures after TEVAR differed between the two cohorts, being substantially lower in the VALOR II trial at 1 year of follow-up. This finding suggests significant benefit from advances in some combination of operator experience, imaging systems, treatment planning, and device design.
Journal of the American College of Cardiology, 2002
We sought to assess the influence of peritransplant ischemia and fibrosis on the development of a... more We sought to assess the influence of peritransplant ischemia and fibrosis on the development of allograft vasculopathy, acute cellular rejection and long-term outcome. Allograft vasculopathy is a common long-term complication of cardiac transplantation. One of the potential risk factors is peritransplant allograft ischemia. One hundred forty heart transplant recipients had baseline and one-year intravascular ultrasound analysis done to assess the progression of allograft vasculopathy. Serial endomyocardial biopsies were evaluated for cellular rejection, vascular rejection, ischemia and fibrosis. Based on histology, patients were classified into one of the following groups: nonischemic (n = 32), ischemia (n = 24), fibrosis (n = 62) or vascular rejection (n = 22). Three-color flow cytometry crossmatching (FCXM) was used to assess donor-specific human lymphocyte antigens (HLA) sensitization. Long-term outcome of patients in each group was assessed by estimating incidence of graft failure or deaths over a seven-year follow up. Patients in the fibrosis group had the lowest incidence of donor-specific HLA sensitization (40%, p = 0.008) and lowest average episodes of cellular rejection (1.7 +/- 1.4, p = 0.04), but they had increased coronary vasculopathy progression (change in coronary intimal thickness = 0.59 +/- 0.28 mm, p < 0.0001) and poor seven-year event-free survival (49%, p = 0.01). The development of fibrosis after cardiac transplantation is associated with advanced coronary vasculopathy, although a low incidence of acute cellular rejection is noted, suggesting the presence of nonimmune mechanisms in mediating the pathogenesis of allograft vasculopathy.
Journal of the American College of Cardiology, 1996
The REgression GRowth Evaluation Statin Study (REGRESS) is a two year double blind placebo contro... more The REgression GRowth Evaluation Statin Study (REGRESS) is a two year double blind placebo controlled prospective atherosclerosis regression study, pdmadly investigating pravastatin treatment effect by means of repeated quantitative coronary artsdngraphy (QCA) in a 885 male population with anglographicafly proven coronary artery disease. The differences between the means of the Mean Coronary ,?-~.=gment Diameter (MSD), and the medians of the Minimum Coronary Obstruction Diameter (MOD) showed a significant pravasfatin treatment effect (~MSD = 0.04 mm; p = 0.02); 8MOD = 0.06 mm; p = 0.001). With a six monthly interval, 255 patients received five B-:'nede ultrasound intima-media thickness (IMT) measurements of 16 prespedlied carotid and femoral artedal wall segments. Repeated Measurements ANOVA of the combined IM'I" data showed a significant pravastatin treatment effect on carotid and femoral IMT (p = 0,0024). The coronary and the padpheral treatment effects were correlated.
Journal of Stroke and Cerebrovascular Diseases, 1996
We sought to develop a risk profile that would predict worsening consciousness from edema after h... more We sought to develop a risk profile that would predict worsening consciousness from edema after hemispheric infarction. Charts were reviewed correlating initial computed tomography scan, neurologic examination, demographic features, and ischemic mechanism with worsening consciousness from massive edema after hemispheric infarction. An edema risk profile composed of two of three clinical factors (gaze preference, hemiplegia, or hemineglect) and evidence of acute cortical infarction on initial computed tomography scan highly correlated with the later development of worsening consciousness from edema. The edema risk profile correlated with worsening consciousness from edema after hemispheric infarction. The profile requires prospective verification before use for family counseling, for anticipatory care, and for randomizing patients in acute stroke trials aimed at controlling the formation and sequelae of edema after ischemic stroke.
Journal of Pediatric and Adolescent Gynecology, 2014
To examine the relationship between dietary intake and weight gain among adolescent females initi... more To examine the relationship between dietary intake and weight gain among adolescent females initiating depot medroxyprogesterone acetate (DMPA). Prospective observational study. Two urban Adolescent Medicine clinics. 45 postmenarchal females, age 12 to 21, enrolled after self-selecting to initiate DMPA. Participants received 150 mg DMPA intramuscularly every 12 weeks. Height, weight, and 24-hour dietary recall were collected at baseline, 3, 6, and 12 months. Body mass index (BMI) over time calculated as weight (kg)/height (m(2)). Associations between dietary variables and BMI were evaluated with repeated measures analysis of variance modeling. Mean chronological and gynecologic ages were 16.2 ± 1.5 and 4.2 ± 1.8 years, respectively. Mean BMI increased from 23.7 ± 5.3 to 25.3 ± 5.7 over 12 months. Average dietary intake included: 1781.4 ± 554.1 total kilocalories, 228.5 g ± 69.8 carbohydrates, 71.0 g ± 27.3 fat, and 61.0 g ± 20.2 protein. These diet measures were not associated with BMI over time. Dietary fiber, magnesium, and linoleic acid were inversely associated with increased BMI over time (P < .05) CONCLUSION: We found no evidence that general measures of diet (energy, carbohydrates, fat, and protein), as assessed by 24-hour recall, were predictive of weight gain on DMPA. Several nutrients abundant in foods that benefit overall health were inversely associated with increased BMI over time, suggesting that diet quality, rather than quantity, is a more important predictor of DMPA-associated weight gain.
Journal of Pediatric and Adolescent Gynecology, 2004
To examine the relationship between biochemical markers of bone metabolism and hormonal contracep... more To examine the relationship between biochemical markers of bone metabolism and hormonal contraception in adolescents. A prospective, observational design. The study was conducted in four adolescent health clinics in a large metropolitan area. The study population comprised healthy, postmenarcheal adolescent girls aged 12-18 initiating either medroxyprogesterone acetate (n=53) or an oral contraceptive (OC) containing 20 mug ethinyl estradiol/100 mug levonorgestrel (n=165) and those using no hormonal contraception (n=152). None. Serum bone specific alkaline phosphatase (BSAP), urinary deoxypyridinoline (DPD), and bone mineral density (BMD) at baseline and 12 months. At 12 month follow-up, serum BSAP levels were significantly higher (P < 0.05) in the control group (40.4 U/L +/- 1.03 SE), than in the DMPA group (35.2 U/L +/- 1.05 SE) and the OC group (35.5 U/L +/- 1.03 SE). There was a trend in urinary DPD levels to be higher (P=0.08) in the control group (9.9 nmol/mmol Cr +/- 1.03 SE) than in the DMPA group (9.1 +/- 1.05 SE) and the OC group (8.9 +/- 1.03 SE). No relationship was found between the biochemical markers and BMD at the lumbar spine or the femoral neck. Over 12 months, there was evidence of increased bone formation and resorption in the control group when compared to that in the DMPA and OC groups. This finding may indicate a suppression of bone metabolism in girls using DMPA or an OC containing 20 mug ethinyl estradiol/100 mug levonorgestrel.
Journal of Pediatric and Adolescent Gynecology, 2011
Since bone loss has been observed among adolescents on depot medroxyprogesterone acetate (DMPA), ... more Since bone loss has been observed among adolescents on depot medroxyprogesterone acetate (DMPA), a clinical population that commonly experiences weight gain, we were interested in examining the direct relationship between body weight and bone mineral density (BMD) in adolescents on DMPA as compared to those on oral contraceptive pills (OC) or on no hormonal contraception (control). Prospective, Longitudinal study. Four urban adolescent health clinics in a large metropolitan area. Postmenarcheal girls, age 12-18 years, selecting DMPA, OC or no hormonal contraception. At baseline, 6, 12, 18, and 24 months, all study participants underwent measurement of weight and BMD of the hip and spine. The correlation between weight and BMD, and the correlation between change in weight and change in BMD were assessed at each time point. Body weight was significantly (P < 0.05) positively correlated with femoral neck BMD and spine BMD at each time point regardless of contraceptive method. Change in body weight at 12 and 24 months was highly correlated with change in femoral neck BMD (P < 0.0001) for all treatment groups. No statistically significant correlation between change in weight and change in spine BMD was seen in the DMPA, OC, or control subjects at 12 or 24 months. Weight gain on DMPA may mitigate loss of BMD among adolescent users.
Craniotomy for resection of cerebral arterial venous malformation has been associated with postop... more Craniotomy for resection of cerebral arterial venous malformation has been associated with postoperative hypertension, which necessitates administration of large doses of antihypertensive medications to control blood pressure. Controlling blood pressure is essential because hypertensive episodes can lead to postoperative cerebral hemorrhage with increases in morbidity and mortality. We measured vasoactive peptide and catecholamine release in 13 patients who underwent resection of an arterial venous malformation and in a control group of 6 patients who presented for clipping of unruptured cerebral aneurysms. Plasma renin activity, angiotensin I and II, vasopressin, aldosterone, epinephrine, and norepinephrine levels were measured intraoperatively and for 36 h postoperatively. Analysis of variance was used to assess sample and group effects. A significant interaction between sample and groups was found for norepinephrine (p < 0.001) and renin (p = 0.002). Our data suggest that elevated plasma renin and norepinephrine levels are in part responsible for postoperative hypertension in patients undergoing resection of arterial venous malformations. Blocking the release of these hormones may help control blood pressure after surgery for removal of arterial venous malformations.
To examine hospitalisation rates and resource utilisation following initiation of risperidone lon... more To examine hospitalisation rates and resource utilisation following initiation of risperidone long-acting therapy (RLAT) among US veterans with schizophrenia. Encounter data were analysed from the Ohio Veterans Affairs (VA) Healthcare System. Adult patients (schizophrenia or schizoaffective disorder) with ≥1 medical or hospital visits with a diagnosis code of 295.xx, continuous enrolment from January 2003 through January 2006, and ≥4 injections of RLAT were selected. Analyses compared psychiatric-related resource utilisation pre- and post-exposure to RLAT; each patient served as his/her own control. The pre-exposure and post-exposure periods defined were equal in duration (e.g., a 6-month post-exposure period was matched with a 6-month pre-exposure period). Descriptive and comparative analyses (paired t tests, McNemar's test) were performed. Patients (n=106) were 51.9 years old (+/-10.2), male (93%), white (73%) and received on average 14 RLAT doses (+/-9.7; range, 4-47 injections) over 309 days (+/-196; range, 42-737 days). Most experienced a psychiatric-related hospitalisation prior to initiation; less than half experienced hospitalisation after initiation (75% vs. 42%; p<0.001). Relative to pre-initiation, fewer psychiatric-related hospitalisations (mean [SD] change, -0.8 [2.0]; p<0.001), shorter length of stay (-25 [63.6] days; p<0.001), fewer inpatient days/month (-3.1 [7.2] days) and one (2.8) additional outpatient visit/month (p<0.001) occurred post-initiation. The absence of a control group in this pre-/post comparison may have resulted in exposure to a regression to the mean effect. Also, this study evaluated only one cohort of patients in a VA healthcare setting. VA patients with schizophrenia and schizoaffective disorder treated with RLAT experienced fewer hospitalisations and psychiatric-related inpatient days following RLAT initiation. Further studies utilising a control group and in non-VA populations are warranted.
The Journal of Bone and Joint Surgery (American), 2005
Callison, J. Claiborne Jr.; Secic, Michelle; Fleisch, Sheryl B.; and Wright, Rick W., ,"Clinical ... more Callison, J. Claiborne Jr.; Secic, Michelle; Fleisch, Sheryl B.; and Wright, Rick W., ,"Clinical outcome at a minimum of five years after reconstruction of the anterior cruciate ligament.
Optimum treatment of the infected total knee arthroplasty has not been clearly established. To cl... more Optimum treatment of the infected total knee arthroplasty has not been clearly established. To clarify the efficacy of two-stage reimplantation, experience with 66 infected total knee arthroplasties in 64 patients who had been treated with 2-stage reimplantation total knee arthroplasty between September 1980 and October 1993 was reviewed. Of these, 55 knees in 54 patients were available for follow-up examinations at an average of 61.9 months (range, 28-146 months). The initial diagnoses were rheumatoid arthritis (14 knees) and osteoarthritis (41 knees). Reimplantation was successful in 80.0% of knees with low-virulence organisms (coagulase-negative Staphylococcus, Streptococcus), 71.4% with polymicrobial organisms, and 66.7% with high-virulence organisms (methicillin-resistant Staphylococcus aureus). Reimplantation was successful in 82% of patients with osteoarthritis and in 54% of patients with rheumatoid arthritis (P = .024). The success rate was 92% if infection occurred after primary arthroplasty but only 41% if after multiple previous knee operations (arthroscopy, osteotomy, or revision total knee arthroplasty) (P < .001).
The objective of this study was to examine body composition changes in adolescent girls initiatin... more The objective of this study was to examine body composition changes in adolescent girls initiating depot medroxyprogesterone acetate (DMPA), oral contraceptives, or no hormonal contraceptive method. At 6 months, DMPA resulted in significant increases in adiposity with concomitant decreases in lean body mass. Supplemental estrogen may lessen these DMPA effects. Ó
detection of ASCUS and LSIL. Although agreement between SC and CC samples was also only moderate ... more detection of ASCUS and LSIL. Although agreement between SC and CC samples was also only moderate for those with HR and LR types, there is no gold standard by which to determine which collection method is more accurate. Future studies will help to define this gold standard and clarify the role of HPV DNA self-testing in screening and management of adolescents.
Background/Purpose: Some Health Maintenance Organizations (HMO) limit access of their members to ... more Background/Purpose: Some Health Maintenance Organizations (HMO) limit access of their members to specialists to lower costs. The purpose of this study is to determine whether this policy affects the outcome of children with appendicitis. Methods: At a large academic medical center, children 17 years or younger with appendicitis were treated either by an HMO Adult General Surgical Service (group A)
At least 2 apparently independent mechanisms, microsatellite instability (MSI) and chromosomal in... more At least 2 apparently independent mechanisms, microsatellite instability (MSI) and chromosomal instability, are implicated in colorectal tumorigenesis. Their respective roles in predicting clinical outcomes of patients with T3N0 colorectal cancer remain unknown. Eighty-eight patients with a sporadic T3N0 colon or rectal adenocarcinoma were followed up for a median of 67 months. For chromosomal instability analysis, Ki-ras mutations were determined by single-strand polymerase chain reaction, and p53 protein staining was studied by immunohistochemistry. For MSI analysis, DNA was amplified by polymerase chain reaction at 7 microsatellite targets (BAT25, BAT26, D17S250, D2S123, D5S346, transforming growth factor receptor II, and BAX). Overall 5-year survival rate was 72%. p53 protein nuclear staining was detected in 39 patients (44%), and MSI was detected in 21 patients (24%). MSI correlated with proximal location (P <.001) and mucinous content (P <.001). In a multivariate analysis, p53 protein expression carried a significant risk of death (relative risk = 4.0, 95% CI = 1.6 to 10.1, P =.004). By comparison, MSI was not a statistically significant prognostic factor for survival in this group (relative risk = 2.2, 95% CI = 0.6 to 7.3, P =.21). p53 protein overexpression provides better prognostic discrimination than MSI in predicting survival of patients with T3N0 colorectal cancer. Although MSI is associated with specific clinicopathologic parameters, it did not predict overall survival in this group. Assessment of p53 protein expression by immunocytochemistry provides a simple means to identify a subset of T3N0 patients with a 4-times increased risk for death.
The specific performance of intrinsic laryngeal muscles has been difficult to evaluate, especiall... more The specific performance of intrinsic laryngeal muscles has been difficult to evaluate, especially in living subjects. To reproduce natural contractions, we artificially induced orderly recruitment of their innervating axons according to the size principle. In 5 dogs, both recurrent laryngeal nerves (RLNs) were stimulated with 50 through 10 Hz, 300 to 1000 microA currents while 600 Hz, 1000 to 0 microA decreasing blocking currents were administered. Surface electromyography electrodes placed on the thyroarytenoid, posterior cricoarytenoid, and lateral cricoarytenoid muscles were used to determine the amplitudes (in mA) of compound muscle action potentials. There was a highly statistically significant difference (P<.004) between the thyroarytenoideus which had the fastest rate of recruitment (8.38%), and posterior cricoarytenoideus, which had the slowest (4.81%). There was an intermediate recruitment rate (6.72%) of the lateral cricoarytenoideus, a divergence attributed to a more equal distribution in fast and slow types of myofibers and a smaller sample. We submit that RLN axons can be recruited in an orderly manner according to their sizes and that the rates are unique to the muscle classes they innervate. The parameters defining these contraction patterns may offer key information for laryngeal pacing.
Conversion rates following laparoscopic colorectal surgery vary widely between studies, and the o... more Conversion rates following laparoscopic colorectal surgery vary widely between studies, and the outcome of converted patients remains controversial. A comprehensive search of the English-language literature was updated until May 1999. Twenty-eight studies on 3232 patients were considered for analysis. The overall conversion rate was 15.38%. Seventy nine percent of the studies did not include a definition for conversion; in these studies, the conversion rate was significantly lower than in the series where a specific definition was considered (13.7% vs 18.9%, chi-square test, p < 0.001). Converted patients had a prolonged hospital stay (11.38 vs 7.41 days) and operative time (209 vs 189 min) in comparison with laparoscopically completed patients (95% confidence interval (CI), 1.70-4.00 and 35.90-37.10, respectively). The factors associated with an increased rate for conversion were left colectomy (Odds Ratio [OR] = 1.061), anterior resection of the rectum (OR = 1.088), diverticulitis (OR = 1.302), and cancer (OR = 2.944) (for each parameter, Wald chi-square value, p < 0.001). In nonrandomized studies, the rate of laparoscopically completed colorectal resections is close to 85%. Because converted patients have a distinct outcome, a clear definition of conversion is required to compare the results of randomized trials. Such trials should also consider a 20% rate of conversion when estimating the sample size for the desired power level. It is likely that converted patients will have a significant impact on the results of future clinical research in laparoscopic colorectal surgery.
The authors compared the changes in health care utilization and costs between a group of patients... more The authors compared the changes in health care utilization and costs between a group of patients with schizophrenia who started treatment with risperidone and a group that started treatment with olanzapine. A retrospective analysis was conducted of patients with schizophrenia who were given an initial prescription for risperidone or for olanzapine between March 1997 and March 1999. The change in utilization and cost of inpatient hospitalizations, outpatient clinic visits, medications, and total health care services from one year before to one year after initiation of treatment for the two groups was compared. The risperidone and olanzapine groups comprised 325 and 285 patients, respectively. Total health care costs declined by $1,536 on average for patients in the risperidone group and increased by $4,217 on average for patients in the olanzapine group after initiation of treatment. The difference was statistically significant, and it was largely due to drug and hospitalization costs. Drug costs for patients in the risperidone group underwent a smaller increase than those for patients in the olanzapine group ($991 versus $1,861). Hospitalization costs decreased by $4,011 for patients in the risperidone group and increased by $1,423 for those in the olanzapine group. Total health care costs declined for patients taking risperidone and increased for patients taking olanzapine after treatment was initiated.
A growing body of literature suggests that certain atypical antipsychotics, especially olanzapine... more A growing body of literature suggests that certain atypical antipsychotics, especially olanzapine and clozapine, may induce glucoregulatory dysfunction. We assessed the differences in risk of developing diabetes mellitus during treatment with olanzapine and risperidone by using patients treated with haloperidol and fluphenazine as control subjects in whom we would not expect to see an increased risk. We conducted a retrospective analysis of the Veteran's Integrated Service Network 10 Veterans Affairs (VA) database. Data for patients receiving olanzapine, risperidone, haloperidol, or fluphenazine from January 1, 1997-December 31, 2000, were included. Diabetes was defined as any health system encounter associated with the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis for diabetes (250.xx) or prescription for a hypoglycemic agent. Data of patients with markers for diabetes within 1 year before their index date, female patients, racial groups other than Caucasian or African-American, and patients receiving clozapine were not analyzed. We performed a Cox regression, with antipsychotic therapy as a time-dependent covariate. Other covariates considered for inclusion in the final model were number of days supply of antipsychotic drug, age, race, psychiatric diagnoses, substance abuse, lithium, valproic acid, and other typical or atypical antipsychotic agents. Data for 5837 patients were analyzed. Overall rate of developing diabetes in the study population was 6.3% (368 of 5837 patients). Olanzapine therapy was associated with a significantly higher risk of development of diabetes compared with risperidone (hazard ratio [HR] 1.37, 95% confidence interval 1.06-1.76, p=0.016) while controlling for race, age, diagnosis, substance abuse, lithium, valproic acid, and other atypical antipsychotic agents. No differences in the rate of developing diabetes were detected between fluphenazine and risperidone (HR 1.11, p=0.69), or haloperidol and risperidone (HR 0.89, p=0.41). Olanzapine was associated with a 37% (HR 1.37) increased risk of development of diabetes compared with risperidone in a VA population, even after adjusting for other factors associated with the development of diabetes and temporal exposure to study drug. Because of limitations associated with database research, prospective studies should be conducted to corroborate these findings.
Numerous studies suggest that the dihydropyridine calcium antagonists (DCAs) and nondihydropyridi... more Numerous studies suggest that the dihydropyridine calcium antagonists (DCAs) and nondihydropyridine calcium antagonists (NDCAs) have differential antiproteinuric effects. Proteinuria reduction is a correlate of the progression of renal disease. In an earlier systematic review, calcium antagonists were shown as effective antihypertensive drugs, but there was uncertainty about their renal benefits in patients with proteinuria and renal insufficiency. A systematic review was conducted to assess the differential effects of DCAs and NDCAs on proteinuria in hypertensive adults with proteinuria, with or without diabetes, and to determine whether these differential effects translate into altered progression of nephropathy. Studies included in the review had to be randomized clinical trials with at least 6 months of treatment, include a DCA or NDCA treatment arm, have one or more renal end points, and have been initiated after 1986. Summary data were extracted from 28 studies entered into two identical but separate databases, which were compared and evaluated by independent reviewers. The effects of each drug class on blood pressure (N= 1338) and proteinuria (N= 510) were assessed. After adjusting for sample size, study length, and baseline value, there were no statistically significant differences in the ability of either class of calcium antagonist to decrease blood pressure. The mean change in proteinuria was +2% for DCAs and -30% for NDCAs (95% CI, 10% to 54%, P= 0.01). Consistently greater reductions in proteinuria were associated with the use of NDCAs compared with DCAs, despite no significant differences in blood pressure reduction or presence of diabetes. This analysis supports (1) similar efficacy between subclasses of calcium antagonists to lower blood pressure, and (2) greater reductions in proteinuria by NDCAs compared to DCAs in the presence or absence of diabetes. Based on these findings, NDCAs, alone or in combination with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), are suggested as preferred agents to lower blood pressure in hypertensive patients with nephropathy associated with proteinuria.
Journal of Vascular and Interventional Radiology, 2014
To compare the durability of thoracic endovascular aortic repair (TEVAR) in two similar clinical ... more To compare the durability of thoracic endovascular aortic repair (TEVAR) in two similar clinical trials that used early- and later-generation stent grafts. Secondary procedures from the prospective, nonrandomized, multicenter, clinical trial databases of the test arm of the VALOR and VALOR II trials were analyzed at 3 years. Descriptive and statistical analyses were employed to compare the rate of and potential predictors for secondary procedures. A total of 127 and 96 patients were available for a minimum of 3 years of follow-up in the test arm of VALOR and VALOR II, respectively. By the first year after the index procedure, VALOR II patients were significantly less likely to have undergone a secondary procedure versus patients in the test arm of VALOR (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.01-0.63; P = .02), with most procedures performed for type I endoleak. Multivariate predictors at 3 years for the need for a secondary procedure in the VALOR test arm were maximum aneurysm diameter (P = .002) and aneurysm length (P = .01), both of which remained significant at the end of the study period. The estimated freedoms from secondary procedures in the VALOR test arm and VALOR II at 3 years were 85.1% (95% CI, 78.5%-89.8%) and 94.9% (95% CI, 88.8%-97.7%), respectively (P < .001). The rate of secondary procedures after TEVAR differed between the two cohorts, being substantially lower in the VALOR II trial at 1 year of follow-up. This finding suggests significant benefit from advances in some combination of operator experience, imaging systems, treatment planning, and device design.
Journal of the American College of Cardiology, 2002
We sought to assess the influence of peritransplant ischemia and fibrosis on the development of a... more We sought to assess the influence of peritransplant ischemia and fibrosis on the development of allograft vasculopathy, acute cellular rejection and long-term outcome. Allograft vasculopathy is a common long-term complication of cardiac transplantation. One of the potential risk factors is peritransplant allograft ischemia. One hundred forty heart transplant recipients had baseline and one-year intravascular ultrasound analysis done to assess the progression of allograft vasculopathy. Serial endomyocardial biopsies were evaluated for cellular rejection, vascular rejection, ischemia and fibrosis. Based on histology, patients were classified into one of the following groups: nonischemic (n = 32), ischemia (n = 24), fibrosis (n = 62) or vascular rejection (n = 22). Three-color flow cytometry crossmatching (FCXM) was used to assess donor-specific human lymphocyte antigens (HLA) sensitization. Long-term outcome of patients in each group was assessed by estimating incidence of graft failure or deaths over a seven-year follow up. Patients in the fibrosis group had the lowest incidence of donor-specific HLA sensitization (40%, p = 0.008) and lowest average episodes of cellular rejection (1.7 +/- 1.4, p = 0.04), but they had increased coronary vasculopathy progression (change in coronary intimal thickness = 0.59 +/- 0.28 mm, p < 0.0001) and poor seven-year event-free survival (49%, p = 0.01). The development of fibrosis after cardiac transplantation is associated with advanced coronary vasculopathy, although a low incidence of acute cellular rejection is noted, suggesting the presence of nonimmune mechanisms in mediating the pathogenesis of allograft vasculopathy.
Journal of the American College of Cardiology, 1996
The REgression GRowth Evaluation Statin Study (REGRESS) is a two year double blind placebo contro... more The REgression GRowth Evaluation Statin Study (REGRESS) is a two year double blind placebo controlled prospective atherosclerosis regression study, pdmadly investigating pravastatin treatment effect by means of repeated quantitative coronary artsdngraphy (QCA) in a 885 male population with anglographicafly proven coronary artery disease. The differences between the means of the Mean Coronary ,?-~.=gment Diameter (MSD), and the medians of the Minimum Coronary Obstruction Diameter (MOD) showed a significant pravasfatin treatment effect (~MSD = 0.04 mm; p = 0.02); 8MOD = 0.06 mm; p = 0.001). With a six monthly interval, 255 patients received five B-:'nede ultrasound intima-media thickness (IMT) measurements of 16 prespedlied carotid and femoral artedal wall segments. Repeated Measurements ANOVA of the combined IM'I" data showed a significant pravastatin treatment effect on carotid and femoral IMT (p = 0,0024). The coronary and the padpheral treatment effects were correlated.
Journal of Stroke and Cerebrovascular Diseases, 1996
We sought to develop a risk profile that would predict worsening consciousness from edema after h... more We sought to develop a risk profile that would predict worsening consciousness from edema after hemispheric infarction. Charts were reviewed correlating initial computed tomography scan, neurologic examination, demographic features, and ischemic mechanism with worsening consciousness from massive edema after hemispheric infarction. An edema risk profile composed of two of three clinical factors (gaze preference, hemiplegia, or hemineglect) and evidence of acute cortical infarction on initial computed tomography scan highly correlated with the later development of worsening consciousness from edema. The edema risk profile correlated with worsening consciousness from edema after hemispheric infarction. The profile requires prospective verification before use for family counseling, for anticipatory care, and for randomizing patients in acute stroke trials aimed at controlling the formation and sequelae of edema after ischemic stroke.
Journal of Pediatric and Adolescent Gynecology, 2014
To examine the relationship between dietary intake and weight gain among adolescent females initi... more To examine the relationship between dietary intake and weight gain among adolescent females initiating depot medroxyprogesterone acetate (DMPA). Prospective observational study. Two urban Adolescent Medicine clinics. 45 postmenarchal females, age 12 to 21, enrolled after self-selecting to initiate DMPA. Participants received 150 mg DMPA intramuscularly every 12 weeks. Height, weight, and 24-hour dietary recall were collected at baseline, 3, 6, and 12 months. Body mass index (BMI) over time calculated as weight (kg)/height (m(2)). Associations between dietary variables and BMI were evaluated with repeated measures analysis of variance modeling. Mean chronological and gynecologic ages were 16.2 ± 1.5 and 4.2 ± 1.8 years, respectively. Mean BMI increased from 23.7 ± 5.3 to 25.3 ± 5.7 over 12 months. Average dietary intake included: 1781.4 ± 554.1 total kilocalories, 228.5 g ± 69.8 carbohydrates, 71.0 g ± 27.3 fat, and 61.0 g ± 20.2 protein. These diet measures were not associated with BMI over time. Dietary fiber, magnesium, and linoleic acid were inversely associated with increased BMI over time (P < .05) CONCLUSION: We found no evidence that general measures of diet (energy, carbohydrates, fat, and protein), as assessed by 24-hour recall, were predictive of weight gain on DMPA. Several nutrients abundant in foods that benefit overall health were inversely associated with increased BMI over time, suggesting that diet quality, rather than quantity, is a more important predictor of DMPA-associated weight gain.
Journal of Pediatric and Adolescent Gynecology, 2004
To examine the relationship between biochemical markers of bone metabolism and hormonal contracep... more To examine the relationship between biochemical markers of bone metabolism and hormonal contraception in adolescents. A prospective, observational design. The study was conducted in four adolescent health clinics in a large metropolitan area. The study population comprised healthy, postmenarcheal adolescent girls aged 12-18 initiating either medroxyprogesterone acetate (n=53) or an oral contraceptive (OC) containing 20 mug ethinyl estradiol/100 mug levonorgestrel (n=165) and those using no hormonal contraception (n=152). None. Serum bone specific alkaline phosphatase (BSAP), urinary deoxypyridinoline (DPD), and bone mineral density (BMD) at baseline and 12 months. At 12 month follow-up, serum BSAP levels were significantly higher (P < 0.05) in the control group (40.4 U/L +/- 1.03 SE), than in the DMPA group (35.2 U/L +/- 1.05 SE) and the OC group (35.5 U/L +/- 1.03 SE). There was a trend in urinary DPD levels to be higher (P=0.08) in the control group (9.9 nmol/mmol Cr +/- 1.03 SE) than in the DMPA group (9.1 +/- 1.05 SE) and the OC group (8.9 +/- 1.03 SE). No relationship was found between the biochemical markers and BMD at the lumbar spine or the femoral neck. Over 12 months, there was evidence of increased bone formation and resorption in the control group when compared to that in the DMPA and OC groups. This finding may indicate a suppression of bone metabolism in girls using DMPA or an OC containing 20 mug ethinyl estradiol/100 mug levonorgestrel.
Journal of Pediatric and Adolescent Gynecology, 2011
Since bone loss has been observed among adolescents on depot medroxyprogesterone acetate (DMPA), ... more Since bone loss has been observed among adolescents on depot medroxyprogesterone acetate (DMPA), a clinical population that commonly experiences weight gain, we were interested in examining the direct relationship between body weight and bone mineral density (BMD) in adolescents on DMPA as compared to those on oral contraceptive pills (OC) or on no hormonal contraception (control). Prospective, Longitudinal study. Four urban adolescent health clinics in a large metropolitan area. Postmenarcheal girls, age 12-18 years, selecting DMPA, OC or no hormonal contraception. At baseline, 6, 12, 18, and 24 months, all study participants underwent measurement of weight and BMD of the hip and spine. The correlation between weight and BMD, and the correlation between change in weight and change in BMD were assessed at each time point. Body weight was significantly (P < 0.05) positively correlated with femoral neck BMD and spine BMD at each time point regardless of contraceptive method. Change in body weight at 12 and 24 months was highly correlated with change in femoral neck BMD (P < 0.0001) for all treatment groups. No statistically significant correlation between change in weight and change in spine BMD was seen in the DMPA, OC, or control subjects at 12 or 24 months. Weight gain on DMPA may mitigate loss of BMD among adolescent users.
Craniotomy for resection of cerebral arterial venous malformation has been associated with postop... more Craniotomy for resection of cerebral arterial venous malformation has been associated with postoperative hypertension, which necessitates administration of large doses of antihypertensive medications to control blood pressure. Controlling blood pressure is essential because hypertensive episodes can lead to postoperative cerebral hemorrhage with increases in morbidity and mortality. We measured vasoactive peptide and catecholamine release in 13 patients who underwent resection of an arterial venous malformation and in a control group of 6 patients who presented for clipping of unruptured cerebral aneurysms. Plasma renin activity, angiotensin I and II, vasopressin, aldosterone, epinephrine, and norepinephrine levels were measured intraoperatively and for 36 h postoperatively. Analysis of variance was used to assess sample and group effects. A significant interaction between sample and groups was found for norepinephrine (p < 0.001) and renin (p = 0.002). Our data suggest that elevated plasma renin and norepinephrine levels are in part responsible for postoperative hypertension in patients undergoing resection of arterial venous malformations. Blocking the release of these hormones may help control blood pressure after surgery for removal of arterial venous malformations.
To examine hospitalisation rates and resource utilisation following initiation of risperidone lon... more To examine hospitalisation rates and resource utilisation following initiation of risperidone long-acting therapy (RLAT) among US veterans with schizophrenia. Encounter data were analysed from the Ohio Veterans Affairs (VA) Healthcare System. Adult patients (schizophrenia or schizoaffective disorder) with ≥1 medical or hospital visits with a diagnosis code of 295.xx, continuous enrolment from January 2003 through January 2006, and ≥4 injections of RLAT were selected. Analyses compared psychiatric-related resource utilisation pre- and post-exposure to RLAT; each patient served as his/her own control. The pre-exposure and post-exposure periods defined were equal in duration (e.g., a 6-month post-exposure period was matched with a 6-month pre-exposure period). Descriptive and comparative analyses (paired t tests, McNemar's test) were performed. Patients (n=106) were 51.9 years old (+/-10.2), male (93%), white (73%) and received on average 14 RLAT doses (+/-9.7; range, 4-47 injections) over 309 days (+/-196; range, 42-737 days). Most experienced a psychiatric-related hospitalisation prior to initiation; less than half experienced hospitalisation after initiation (75% vs. 42%; p<0.001). Relative to pre-initiation, fewer psychiatric-related hospitalisations (mean [SD] change, -0.8 [2.0]; p<0.001), shorter length of stay (-25 [63.6] days; p<0.001), fewer inpatient days/month (-3.1 [7.2] days) and one (2.8) additional outpatient visit/month (p<0.001) occurred post-initiation. The absence of a control group in this pre-/post comparison may have resulted in exposure to a regression to the mean effect. Also, this study evaluated only one cohort of patients in a VA healthcare setting. VA patients with schizophrenia and schizoaffective disorder treated with RLAT experienced fewer hospitalisations and psychiatric-related inpatient days following RLAT initiation. Further studies utilising a control group and in non-VA populations are warranted.
The Journal of Bone and Joint Surgery (American), 2005
Callison, J. Claiborne Jr.; Secic, Michelle; Fleisch, Sheryl B.; and Wright, Rick W., ,"Clinical ... more Callison, J. Claiborne Jr.; Secic, Michelle; Fleisch, Sheryl B.; and Wright, Rick W., ,"Clinical outcome at a minimum of five years after reconstruction of the anterior cruciate ligament.
Optimum treatment of the infected total knee arthroplasty has not been clearly established. To cl... more Optimum treatment of the infected total knee arthroplasty has not been clearly established. To clarify the efficacy of two-stage reimplantation, experience with 66 infected total knee arthroplasties in 64 patients who had been treated with 2-stage reimplantation total knee arthroplasty between September 1980 and October 1993 was reviewed. Of these, 55 knees in 54 patients were available for follow-up examinations at an average of 61.9 months (range, 28-146 months). The initial diagnoses were rheumatoid arthritis (14 knees) and osteoarthritis (41 knees). Reimplantation was successful in 80.0% of knees with low-virulence organisms (coagulase-negative Staphylococcus, Streptococcus), 71.4% with polymicrobial organisms, and 66.7% with high-virulence organisms (methicillin-resistant Staphylococcus aureus). Reimplantation was successful in 82% of patients with osteoarthritis and in 54% of patients with rheumatoid arthritis (P = .024). The success rate was 92% if infection occurred after primary arthroplasty but only 41% if after multiple previous knee operations (arthroscopy, osteotomy, or revision total knee arthroplasty) (P < .001).
The objective of this study was to examine body composition changes in adolescent girls initiatin... more The objective of this study was to examine body composition changes in adolescent girls initiating depot medroxyprogesterone acetate (DMPA), oral contraceptives, or no hormonal contraceptive method. At 6 months, DMPA resulted in significant increases in adiposity with concomitant decreases in lean body mass. Supplemental estrogen may lessen these DMPA effects. Ó
detection of ASCUS and LSIL. Although agreement between SC and CC samples was also only moderate ... more detection of ASCUS and LSIL. Although agreement between SC and CC samples was also only moderate for those with HR and LR types, there is no gold standard by which to determine which collection method is more accurate. Future studies will help to define this gold standard and clarify the role of HPV DNA self-testing in screening and management of adolescents.
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