Background & Goals: The wireless pH monitoring system such as the BRAVO pH system is a significan... more Background & Goals: The wireless pH monitoring system such as the BRAVO pH system is a significant advancement in the evaluation of patients with gastroesophageal reflux because of its potentially better tolerability and the ability to record data over a 48-hour period. The aim of our study was to evaluate safety, performance, tolerability, and day-today variability in acid reflux patterns using the BRAVO pH system. Methods: A total of 90 consecutive patients (48 men and 42 women) with persistent reflux symptoms underwent BRAVO pH capsule placement from October 2002 to August 2003 at a tertiary care hospital. The BRAVO pH capsule was deployed 6 cm proximal to the squamocolumnar junction under endoscopic guidance. The pH recordings over 48 hours were obtained after uploading data to a computer from the pager-like device that recorded pH signals from the BRAVO pH capsule. Results: Successful pH data over 48 hours was obtained in 90% of patients. Nearly two thirds of patients experienced a variety of symptoms ranging from a foreign body sensation to chest discomfort or pain. Four patients had severe chest pain, 3 of whom required endoscopic removal of the BRAVO pH capsule. In 74.4% of patients, number of reflux events as well as time (%) pH , 4 correlated from the first 24-hour period to the second 24-hour period. However, in 28% of patients, no predictable pattern of (%) time pH , 4 in the supine position was reproduced from one 24-hour period to the next 24-hour period. Conclusions: The BRAVO pH system appears a safe and effective method of recording esophageal acid exposure. It is an acceptable alternative for patients who are unwilling or unable to tolerate nasopharyngeal catheter-based pH studies, and it has a potential advantage of the 2-day recording period.
BACKGROUND: The indications for transfusion have never been evaluated in an adequately sized clin... more BACKGROUND: The indications for transfusion have never been evaluated in an adequately sized clinical trial. A pilot study was conducted to plan larger clinical trials. STUDY DESIGN AND METHODS: Hip fracture patients undergoing surgical repair who had postoperative hemoglobin levels less than 10 g per dL were randomly assigned to receive 1) symptomatic transfusion: that is, transfusion for symptoms of anemia or for a hemoglobin level that dropped below 8 g per dL or 2) threshold transfusion: that is, patients receive 1 unit of packed RBCs at the time of random assignment and as much blood as necessary to keep the hemoglobin level above 10 g per dL. Outcomes were 60-day mortality, morbidity, functional status, and place of residence. RESULTS: Among 84 eligible patients enrolled, mean ABBREVIATIONS: ASA =American Society of Anesthesiologists; CDC = Centers for Disease Control and Prevention; Hb = hemoglobin; MI = myocardial infarction; RBC(s) = red cell(s).
Background: Biliary disease commonly occurs in the elderly but there is limited data on ERCP in t... more Background: Biliary disease commonly occurs in the elderly but there is limited data on ERCP in the very old population. Aims/Methods: To evaluate endoscopic findings, interventions, success and complication rates of ERCP in patients $80 years (yr) of age in comparison to patients <80 yr old. All consecutive ERCPs performed between 2000-2002 at our institution were retrospectively reviewed for patients $80 yr and were compared to all ERCPs performed in the year 2000 in patients <80 yr. Results: 135 ERCPs were performed in 98 patients $80 yr (21 males, 77 females; mean age 84.6 6 0.5 yr). Clinical presentations were cholestasis (122), abdominal pain (71), acute pancreatitis (12), cholangitis (38), cholecystitis (14), and sepsis (3). Main endoscopic findings were common bile duct stones (64), stenosis by pancreatic cancer (20), cholangiocarcinoma (6), hepatocellular carcinoma (2), papillary adenoma (2), and benign stenosis (6). Stone extraction was successful on the first attempt in 59 cases, early re-ERCP was necessary in 8 patients for retained stones. In the <80 yr group 133 patients (59 males, 74 females; mean age 62.3 6 1.3 yr) underwent 175 ERCPs. Successful biliary cannulation was achieved in 86.7% in the $80 yr group vs 84.6% in the <80 yr group (p= 0.604) and sphincterotomies were performed in 61.5% vs 55.4% (p= 0.284), respectively. In the $80 yr group 27 plastic and 5 metal stents were inserted for malignancy (20) and benign disease (12) and in the <80 yr group as well 32 stents were used for benign (8) and malign (24) stenosis. The number of important chronic concomitant diseases was significantly higher in the older group (1.3 60.1 vs 0.9 6 0.08; p=0.006). There was no significant difference in the complication rate between the $80 and the <80 yr group (5.9 vs 2.9%; p=0.109; 3 vs 1 mild post-ERCP pancreatitis, 2 vs 1 bleedings, 2 vs 0 perforations, 1 vs 1 respiratory insufficiency during ERCP, and 1 vs 2 cholangitis, respectively). Conclusions: ERCP is a safe and effective intervention in the old as complication and success rates are comparable to younger patients although comorbidity is significantly higher.
The Early Treatment Diabetic Retinopathy Study, a randomized clinical trial supported by the Nati... more The Early Treatment Diabetic Retinopathy Study, a randomized clinical trial supported by the National Eye Institute, was designed to assess the effect of photocoagulation and aspirin in 3711 patients with mild to severe nonproliferative or early proliferative diabetic retinopathy. Although the primary goal of the study was to evaluate the effect of photocoagulation and aspirin on diabetic retinopathy, the study also provided an opportunity to evaluate the effects of aspirin on the development of cataract. No evidence showed that aspirin use reduced the risk of development of cataract requiring extraction (4.1% vs 4.3% in patients assigned to aspirin or placebo treatment, respectively; Mantel-Cox P = .77; relative risk, 1.05; 99% confidence interval, 0.73 to 1.51). Aspirin use also did not reduce the risk of less extensive but visually significant lens opacities developing (29.6% vs 28.3%; Mantel-Cox P = .76; relative risk, 0.99; 99% confidence interval, 0.85 to 1.15). Early Treatment Diabetic Retinopathy Study results do not support the hypothesis that aspirin (at a dose of 650 mg/d) reduces the risk of cataract development in this diabetic population.
The seemingly inexorable decline in insulin independence after islet transplant alone (ITA) has r... more The seemingly inexorable decline in insulin independence after islet transplant alone (ITA) has raised concern about its clinical utility. We hypothesized that induction immunosuppression therapy determines durability of insulin independence. We analyzed the proportion of insulin-independent patients following final islet infusion in four groups of ITA recipients according to induction immunotherapy: University of Minnesota recipients given FcR nonbinding anti-CD3 antibody alone or T-cell depleting antibodies (TCDAb) and TNF-a inhibition (TNF-a-i) (group 1; n = 29); recipients reported to the Collaborative Islet Transplant Registry (CITR) given TCDAb+TNF-a-i (group 2; n = 20); CITR recipients given TCDAb without TNF-a-i (group 3; n = 43); and CITR recipients given IL-2 receptor antibodies (IL-2RAb) alone (group 4; n = 177). Results were compared with outcomes in pancreas transplant alone (PTA) recipients reported to the Scientific Registry of Transplant Recipients (group 5; n = 677). The 5-year insulin independence rates in group 1 (50%) and group 2 (50%) were comparable to outcomes in PTA (group 5: 52%; p>>0.05) but significantly higher than in group 3 (0%; p = 0.001) and group 4 (20%; p = 0.02). Induction immunosuppression was significantly associated with 5-year insulin independence (p = 0.03), regardless of maintenance immunosuppression or other factors. These findings support potential for long-term insulin independence after ITA using potent induction therapy, with anti-CD3 Ab or TCDAb+TNF-a-i.
Islet transplantation is an emerging treatment for T1D, in particular for those with long standin... more Islet transplantation is an emerging treatment for T1D, in particular for those with long standing disease experiencing severe hypoglycemia events (SHE). A phase 3 trial of islet transplantation in T1D complicated by SHE demonstrated &amp;amp;gt; 80% of islet recipients achieved HbA1c &amp;amp;lt; 7.0% and absence of SHE at 1 year. To better understand the long-term benefit for glycemic control and risk of immunosuppression to kidney function associated with islet transplantation vs. standard of care, we selected patients from CITR with at least one SHE in the year prior to transplant, and compared them to patients from T1DX with at least one SHE in the prior year and followed over 5 years. The cohorts from CITR (n = 58) and T1DX (n = 213) were aged 42 ± 9 and 43 ± 17 with disease duration 29 ± 10 and 26 ± 15 years (P &amp;amp;lt; 0.01) and experienced 5 ± 11 and 2 ± 1 SHE (P &amp;amp;lt; 0.01) in the year prior to baseline with HbA1c 7.3 ± 1.0 vs. 7.8 ± 1.5 (P &amp;amp;lt; 0.001). Mean HbA1c decreased to 6.3% vs. ranging 7.8-7.6% over 5 years (P &amp;amp;lt; 0.001), and the % experiencing recurrent SHE was less in CITR than T1DX (P &amp;amp;lt; 0.01), such that 78-77% vs. 23-28% met the primary endpoint of HbA1c &amp;amp;lt; 7.0% and absence of SHE (P &amp;amp;lt; 0.001). Insulin requirements were slightly less at baseline in CITR than T1DX (0.52 ± 0.14 vs. 0.64 ± 0.31 U/kg/d; P &amp;amp;lt; 0.001), and decreased to 0.06-0.17 vs. remaining 0.66-0.56 U/kg/d over 5 years (P &amp;amp;lt;0.001) with 80-48% insulin independent in CITR. GFR was 92 ± 17 and 90 ± 29 ml/min/1.73 m2 at baseline, and decreased to 83-78 vs. 87-81 ml/min/1.73 m2 over 5 years (P &amp;amp;lt; 0.001). These data demonstrate long-term durability of islet transplantation to achieve near-normal glycemic control in the absence of SHE more often than that observed with standard of care delivered by specialized diabetes practice. Initial reduction in GFR observed during the first-year post-transplant may be attributable to the initiation of immunosuppression, but was not associated with further decline during 5 year follow-up. Disclosure M.R. Rickels: None. N.C. Foster: None. C.M. Ballou: None. B.J. Hering: Other Relationship; Self; Diabetes-Free, Inc. R. Alejandro: None. R. Beck: Other Relationship; Self; Abbott Laboratories, Ascensia Diabetes Care, Bigfoot Biomedical, Dexcom, Inc., Insulet Corporation, Lilly Diabetes, Roche Diabetes Care, Tandem Diabetes Care. K. Miller: None. F.B. Barton: None. Funding National Institutes of Health; Leona M. and Harry B. Helmsley Charitable Trust
Background. This report summarizes the primary efficacy and the safety outcomes of islet transpla... more Background. This report summarizes the primary efficacy and the safety outcomes of islet transplantation reported to the NIDDK and JDRF funded Collaborative Islet Transplant Registry (CITR), currently the most comprehensive collection of human-to-human islet transplant data. Methods. CITR collects and monitors comprehensive data on allogeneic islet transplantation in North America, Europe, and Australia since 1999. Results. As of April 2008, the CITR registry comprised 325 adult recipients of 649 islet infusions derived from 712 donors. At 3 years post-first infusion, 23% of islet-alone recipients were insulin independent (IIՆ2 weeks), 29% were insulin dependent with detectable C-peptide, 26% had lost function, and 22% had missing data. Seventy percent achieved II at least once, of whom 71% were still II 1 year later and 52% at 2 years. Higher number of infusions, greater number of total islet equivalents infused, lower pretransplant HbA 1c levels, processing centers related to the transplant center, and larger islet size are factors that favor the primary outcomes. Protocols with daclizumab or etanercept during induction had higher rates of II and lower rates of function loss, which endorse the current approaches. Infusion-related adverse event incidence was 0.71 events/person-year (EPY) in year 1, whereas immunosuppression-related adverse event incidence was 0.87 EPY, both declining to less than 0.21 EPY thereafter. Conclusions. Clinical islet transplantation needs to be evaluated using the most clinically relevant endpoints such as glucose stabilization and severe hypoglycemia prevention. The cumulative results of the registry confirm the inarguably positive impact of islet transplantation on metabolic control in T1 diabetes.
CUTE CHEST SYNDROME AND painful episodes are the most common precedents of death in adults with s... more CUTE CHEST SYNDROME AND painful episodes are the most common precedents of death in adults with sickle cell anemia (SCA). 1 A randomized, doubleblinded, placebo-controlled trial, the
MSH is a randomized, placebo-controlled clinical trial of hydroxyurea to prevent sickle cell cris... more MSH is a randomized, placebo-controlled clinical trial of hydroxyurea to prevent sickle cell crises. The primary end point is the occurrence of painful crises. Analysis of this primary end point must accommodate the occurrence of multiple crises in each patient and the termination of followup for some patients due to death or other severe adverse clinical outcomes, as well as loss to follow-up. Simulation studies will be presented to evaluate alternate statistical tests for primary end point analyses in the MSH. These include: (1) calculation of individual crisis rates for each patient by dividing the number of crises by the patient's follow-up time, with a test for difference in mean crisis rate (ignoring deaths) according to treatment; (2) Wilcoxon or van der Waerden rank tests of differences between patients dying before the end of follow-up assigned the worst ranks; and, (3) extensions of the log rank test.
... Ward Hagar, MD Adult Sickle Cell Program Children's Hospital and Research Center at Oakl... more ... Ward Hagar, MD Adult Sickle Cell Program Children's Hospital and Research Center at Oakland Oakland, Calif 1. Steinberg MH, Barton F, Castro O, et al. ... Dean Anthony Lee, MD, PhD Brigitta U. Mueller, MD Department of Pediatrics Baylor College of Medicine Houston, Tex ...
During the procedure, the following data were recorded: total induction time (start of anesthesia... more During the procedure, the following data were recorded: total induction time (start of anesthesia to endoscope insertion), total induction drug(s) dose, total procedure time
This multicenter study compared health-related quality of life (HRQOL) and family function of ped... more This multicenter study compared health-related quality of life (HRQOL) and family function of pediatric liver transplant recipients to those of healthy children to determine if this population differed from a healthy population and to distinguish which pretransplant and posttransplant factors impact HRQOL and family function. HRQOL data from 102 patients achieving 2-year survival were collected with the Infant Toddler Quality of Life Instrument or the Child Health Questionnaire Parent Form 50 parent surveys. Family functioning was assessed with the Family Assessment Device (FAD) completed by each participant's family members. Demographic and clinical information were retrieved from the Studies of Pediatric Liver Transplant database. Recipients 5 years of age and older scored lower than a normative sample in physical health (P Ͻ 0.001), general health (P Ͻ 0.001), parental emotional impact (P Ͻ 0.001), and disruption of family activities (P Ͻ 0.001). Younger children, 2 to 5 years of age, scored lower than controls in global health (P ϭ 0.004) and general health perceptions (P Ͻ 0.001) but did not differ in subscales measuring physical and psychosocial outcomes. Univariate analysis among the subscales identified demographic but not clinical variables as significant predictors of HRQOL. Mean scores of FAD scales were below published thresholds indicating healthy family functioning. As reported in previous studies, parents of older recipients reported higher levels of stress, although their level of family function appears normal. Significant associations were also observed between FAD scores and demographic variables, suggesting that further investigation of the impact of race, parental marital status, and socioeconomic status on the patient rehabilitation process is needed.
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NH... more This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The use of hydroxyurea, a cytotoxic agent, to decrease the frequency of painful crises in patients with sickle cell anemia. Patients assigned to hydroxyurea received an initial dose of 15 mg per kilogram of body weight per day, and the dose was increased by 5 mg per kilogram of body weight per day every 12 weeks, unless marrow depression (indicated by a neutrophil count below 2,000 per cubic millimetre, a reticulocyte or platelet count below 80,000 per cubic millimetre, or a haemoglobin level below 4.5 g per decilitre) was present. If marrow depression occurred, treatment was stopped until blood counts recovered. Treatment was then resumed at a dose that was 2.5 mg/kg lower than the dose associated with marrow depression, starting a new 12-week cycle. Type of intervention Palliative care and secondary prevention. Economic study type Cost-effectiveness analysis. Study population Patients enrolled in the study had sickle cell anemia, were at least 18 years old, had had at least 3 painful crises the previous year and were not chronic users of large amounts of opiate analgesics. Patients known to have sickle cell-beta^+-thalassemia and sickle cell-beta^o-thalassemia were excluded, but those with sickle cell-alpha-thalassemia were included. If patients had received transfusions, hemolysates of their red cells could not contain more than 15% hemoglobin A at the time treatment began. Other reasons for exclusion from the study included pregnancy, known narcotic or regular consumption of more than 30 oxycodone capsules (or the equivalent) every two weeks, participation in a long-term programme of transfusion, concurrent treatment with another potential antisickling agent, pretreatment blood counts that could not be distinguished from levels considered to indicate marrow depression, a history of stroke during the preceding six years, prior hydroxyurea therapy, and the presence of antibody to the human immunodeficiency virus (HIV). Setting The setting was a hospital. The economic analysis was carried out in the USA.
In the wake of reports of falsified data in one of the trials of the National Surgical Adjuvant P... more In the wake of reports of falsified data in one of the trials of the National Surgical Adjuvant Project for Breast and Bowel Cancer supported by the National Cancer Institute, clinical trials came under close scrutiny by the public, the press, and Congress. Questions were asked about the quality and integrity of the collected data and the analyses and conclusions of trials. In 1995, the leaders of the Society for Clinical Trials (the Chair of the Policy Committee, Dr. David DeMets, and the President of the Society, Dr. Sylvan Green) asked two members of the Society (Dr. Genell Knatterud and Dr. Frank Rockhold) to act as co-chairs of a newly formed subcommittee to discuss the issues of data integrity and auditing. In consultation with Drs. DeMets and Green, the co-chairs selected other members (Ms. Franca Barton, Dr. C.E. Davis, Dr. Bill Fairweather, Dr. Stephen George, Mr. Tom Honohan, Dr. Richard Mowery, and Dr. Robert O&#39;Neill) to serve on the subcommittee. The subcommittee considered &quot;how clean clinical trial data should be, to what extent auditing procedures are required, and who should conduct audits and how often.&quot; During the initial discussions, the subcommittee concluded that data auditing was insufficient to achieve data integrity. Accordingly, the subcommittee prepared this set of guidelines for standards of quality assurance for multicenter clinical trials. We include recommendations for appropriate action if problems are detected.
OBJECTIVE To determine C-peptide measures and levels associated with positive glycemic control... more OBJECTIVE To determine C-peptide measures and levels associated with positive glycemic control outcomes following islet transplantation (ITx) in type 1 diabetes. RESEARCH DESIGN AND METHODS We evaluated Collaborative Islet Transplant Registry (CITR) Islet-Alone recipients with pre-transplant C-peptide <0.1 nmol/L and mean follow up of 4.6±1.1 years (n=677). Area under the curve of receiver-operator characteristics (ROC-AUC) were used to evaluate predictive value of fasting and stimulated glucose and C-peptide measures for 7 primary outcomes: a) absence of severe hypoglycemic events (ASHE); b) HbA1c<7.0%; c) HbA1c<7.0% & ASHE; d) HbA1c≤6.5%; e) HbA1c≤6.5% & ASHE; f) insulin independence; and g) ASHE, HbA1c≤6.5% & insulin independence (the optimal outcome). Measures with the highest ROC-AUC were selected for determination of optimal cut points. RESULTS Fasting C-peptide was highly predictive for ASHE (ROC-AUC=0.906; optimal cut point=0.070 nmol/L), and the optimal outcome ...
Background & Goals: The wireless pH monitoring system such as the BRAVO pH system is a significan... more Background & Goals: The wireless pH monitoring system such as the BRAVO pH system is a significant advancement in the evaluation of patients with gastroesophageal reflux because of its potentially better tolerability and the ability to record data over a 48-hour period. The aim of our study was to evaluate safety, performance, tolerability, and day-today variability in acid reflux patterns using the BRAVO pH system. Methods: A total of 90 consecutive patients (48 men and 42 women) with persistent reflux symptoms underwent BRAVO pH capsule placement from October 2002 to August 2003 at a tertiary care hospital. The BRAVO pH capsule was deployed 6 cm proximal to the squamocolumnar junction under endoscopic guidance. The pH recordings over 48 hours were obtained after uploading data to a computer from the pager-like device that recorded pH signals from the BRAVO pH capsule. Results: Successful pH data over 48 hours was obtained in 90% of patients. Nearly two thirds of patients experienced a variety of symptoms ranging from a foreign body sensation to chest discomfort or pain. Four patients had severe chest pain, 3 of whom required endoscopic removal of the BRAVO pH capsule. In 74.4% of patients, number of reflux events as well as time (%) pH , 4 correlated from the first 24-hour period to the second 24-hour period. However, in 28% of patients, no predictable pattern of (%) time pH , 4 in the supine position was reproduced from one 24-hour period to the next 24-hour period. Conclusions: The BRAVO pH system appears a safe and effective method of recording esophageal acid exposure. It is an acceptable alternative for patients who are unwilling or unable to tolerate nasopharyngeal catheter-based pH studies, and it has a potential advantage of the 2-day recording period.
BACKGROUND: The indications for transfusion have never been evaluated in an adequately sized clin... more BACKGROUND: The indications for transfusion have never been evaluated in an adequately sized clinical trial. A pilot study was conducted to plan larger clinical trials. STUDY DESIGN AND METHODS: Hip fracture patients undergoing surgical repair who had postoperative hemoglobin levels less than 10 g per dL were randomly assigned to receive 1) symptomatic transfusion: that is, transfusion for symptoms of anemia or for a hemoglobin level that dropped below 8 g per dL or 2) threshold transfusion: that is, patients receive 1 unit of packed RBCs at the time of random assignment and as much blood as necessary to keep the hemoglobin level above 10 g per dL. Outcomes were 60-day mortality, morbidity, functional status, and place of residence. RESULTS: Among 84 eligible patients enrolled, mean ABBREVIATIONS: ASA =American Society of Anesthesiologists; CDC = Centers for Disease Control and Prevention; Hb = hemoglobin; MI = myocardial infarction; RBC(s) = red cell(s).
Background: Biliary disease commonly occurs in the elderly but there is limited data on ERCP in t... more Background: Biliary disease commonly occurs in the elderly but there is limited data on ERCP in the very old population. Aims/Methods: To evaluate endoscopic findings, interventions, success and complication rates of ERCP in patients $80 years (yr) of age in comparison to patients <80 yr old. All consecutive ERCPs performed between 2000-2002 at our institution were retrospectively reviewed for patients $80 yr and were compared to all ERCPs performed in the year 2000 in patients <80 yr. Results: 135 ERCPs were performed in 98 patients $80 yr (21 males, 77 females; mean age 84.6 6 0.5 yr). Clinical presentations were cholestasis (122), abdominal pain (71), acute pancreatitis (12), cholangitis (38), cholecystitis (14), and sepsis (3). Main endoscopic findings were common bile duct stones (64), stenosis by pancreatic cancer (20), cholangiocarcinoma (6), hepatocellular carcinoma (2), papillary adenoma (2), and benign stenosis (6). Stone extraction was successful on the first attempt in 59 cases, early re-ERCP was necessary in 8 patients for retained stones. In the <80 yr group 133 patients (59 males, 74 females; mean age 62.3 6 1.3 yr) underwent 175 ERCPs. Successful biliary cannulation was achieved in 86.7% in the $80 yr group vs 84.6% in the <80 yr group (p= 0.604) and sphincterotomies were performed in 61.5% vs 55.4% (p= 0.284), respectively. In the $80 yr group 27 plastic and 5 metal stents were inserted for malignancy (20) and benign disease (12) and in the <80 yr group as well 32 stents were used for benign (8) and malign (24) stenosis. The number of important chronic concomitant diseases was significantly higher in the older group (1.3 60.1 vs 0.9 6 0.08; p=0.006). There was no significant difference in the complication rate between the $80 and the <80 yr group (5.9 vs 2.9%; p=0.109; 3 vs 1 mild post-ERCP pancreatitis, 2 vs 1 bleedings, 2 vs 0 perforations, 1 vs 1 respiratory insufficiency during ERCP, and 1 vs 2 cholangitis, respectively). Conclusions: ERCP is a safe and effective intervention in the old as complication and success rates are comparable to younger patients although comorbidity is significantly higher.
The Early Treatment Diabetic Retinopathy Study, a randomized clinical trial supported by the Nati... more The Early Treatment Diabetic Retinopathy Study, a randomized clinical trial supported by the National Eye Institute, was designed to assess the effect of photocoagulation and aspirin in 3711 patients with mild to severe nonproliferative or early proliferative diabetic retinopathy. Although the primary goal of the study was to evaluate the effect of photocoagulation and aspirin on diabetic retinopathy, the study also provided an opportunity to evaluate the effects of aspirin on the development of cataract. No evidence showed that aspirin use reduced the risk of development of cataract requiring extraction (4.1% vs 4.3% in patients assigned to aspirin or placebo treatment, respectively; Mantel-Cox P = .77; relative risk, 1.05; 99% confidence interval, 0.73 to 1.51). Aspirin use also did not reduce the risk of less extensive but visually significant lens opacities developing (29.6% vs 28.3%; Mantel-Cox P = .76; relative risk, 0.99; 99% confidence interval, 0.85 to 1.15). Early Treatment Diabetic Retinopathy Study results do not support the hypothesis that aspirin (at a dose of 650 mg/d) reduces the risk of cataract development in this diabetic population.
The seemingly inexorable decline in insulin independence after islet transplant alone (ITA) has r... more The seemingly inexorable decline in insulin independence after islet transplant alone (ITA) has raised concern about its clinical utility. We hypothesized that induction immunosuppression therapy determines durability of insulin independence. We analyzed the proportion of insulin-independent patients following final islet infusion in four groups of ITA recipients according to induction immunotherapy: University of Minnesota recipients given FcR nonbinding anti-CD3 antibody alone or T-cell depleting antibodies (TCDAb) and TNF-a inhibition (TNF-a-i) (group 1; n = 29); recipients reported to the Collaborative Islet Transplant Registry (CITR) given TCDAb+TNF-a-i (group 2; n = 20); CITR recipients given TCDAb without TNF-a-i (group 3; n = 43); and CITR recipients given IL-2 receptor antibodies (IL-2RAb) alone (group 4; n = 177). Results were compared with outcomes in pancreas transplant alone (PTA) recipients reported to the Scientific Registry of Transplant Recipients (group 5; n = 677). The 5-year insulin independence rates in group 1 (50%) and group 2 (50%) were comparable to outcomes in PTA (group 5: 52%; p>>0.05) but significantly higher than in group 3 (0%; p = 0.001) and group 4 (20%; p = 0.02). Induction immunosuppression was significantly associated with 5-year insulin independence (p = 0.03), regardless of maintenance immunosuppression or other factors. These findings support potential for long-term insulin independence after ITA using potent induction therapy, with anti-CD3 Ab or TCDAb+TNF-a-i.
Islet transplantation is an emerging treatment for T1D, in particular for those with long standin... more Islet transplantation is an emerging treatment for T1D, in particular for those with long standing disease experiencing severe hypoglycemia events (SHE). A phase 3 trial of islet transplantation in T1D complicated by SHE demonstrated &amp;amp;gt; 80% of islet recipients achieved HbA1c &amp;amp;lt; 7.0% and absence of SHE at 1 year. To better understand the long-term benefit for glycemic control and risk of immunosuppression to kidney function associated with islet transplantation vs. standard of care, we selected patients from CITR with at least one SHE in the year prior to transplant, and compared them to patients from T1DX with at least one SHE in the prior year and followed over 5 years. The cohorts from CITR (n = 58) and T1DX (n = 213) were aged 42 ± 9 and 43 ± 17 with disease duration 29 ± 10 and 26 ± 15 years (P &amp;amp;lt; 0.01) and experienced 5 ± 11 and 2 ± 1 SHE (P &amp;amp;lt; 0.01) in the year prior to baseline with HbA1c 7.3 ± 1.0 vs. 7.8 ± 1.5 (P &amp;amp;lt; 0.001). Mean HbA1c decreased to 6.3% vs. ranging 7.8-7.6% over 5 years (P &amp;amp;lt; 0.001), and the % experiencing recurrent SHE was less in CITR than T1DX (P &amp;amp;lt; 0.01), such that 78-77% vs. 23-28% met the primary endpoint of HbA1c &amp;amp;lt; 7.0% and absence of SHE (P &amp;amp;lt; 0.001). Insulin requirements were slightly less at baseline in CITR than T1DX (0.52 ± 0.14 vs. 0.64 ± 0.31 U/kg/d; P &amp;amp;lt; 0.001), and decreased to 0.06-0.17 vs. remaining 0.66-0.56 U/kg/d over 5 years (P &amp;amp;lt;0.001) with 80-48% insulin independent in CITR. GFR was 92 ± 17 and 90 ± 29 ml/min/1.73 m2 at baseline, and decreased to 83-78 vs. 87-81 ml/min/1.73 m2 over 5 years (P &amp;amp;lt; 0.001). These data demonstrate long-term durability of islet transplantation to achieve near-normal glycemic control in the absence of SHE more often than that observed with standard of care delivered by specialized diabetes practice. Initial reduction in GFR observed during the first-year post-transplant may be attributable to the initiation of immunosuppression, but was not associated with further decline during 5 year follow-up. Disclosure M.R. Rickels: None. N.C. Foster: None. C.M. Ballou: None. B.J. Hering: Other Relationship; Self; Diabetes-Free, Inc. R. Alejandro: None. R. Beck: Other Relationship; Self; Abbott Laboratories, Ascensia Diabetes Care, Bigfoot Biomedical, Dexcom, Inc., Insulet Corporation, Lilly Diabetes, Roche Diabetes Care, Tandem Diabetes Care. K. Miller: None. F.B. Barton: None. Funding National Institutes of Health; Leona M. and Harry B. Helmsley Charitable Trust
Background. This report summarizes the primary efficacy and the safety outcomes of islet transpla... more Background. This report summarizes the primary efficacy and the safety outcomes of islet transplantation reported to the NIDDK and JDRF funded Collaborative Islet Transplant Registry (CITR), currently the most comprehensive collection of human-to-human islet transplant data. Methods. CITR collects and monitors comprehensive data on allogeneic islet transplantation in North America, Europe, and Australia since 1999. Results. As of April 2008, the CITR registry comprised 325 adult recipients of 649 islet infusions derived from 712 donors. At 3 years post-first infusion, 23% of islet-alone recipients were insulin independent (IIՆ2 weeks), 29% were insulin dependent with detectable C-peptide, 26% had lost function, and 22% had missing data. Seventy percent achieved II at least once, of whom 71% were still II 1 year later and 52% at 2 years. Higher number of infusions, greater number of total islet equivalents infused, lower pretransplant HbA 1c levels, processing centers related to the transplant center, and larger islet size are factors that favor the primary outcomes. Protocols with daclizumab or etanercept during induction had higher rates of II and lower rates of function loss, which endorse the current approaches. Infusion-related adverse event incidence was 0.71 events/person-year (EPY) in year 1, whereas immunosuppression-related adverse event incidence was 0.87 EPY, both declining to less than 0.21 EPY thereafter. Conclusions. Clinical islet transplantation needs to be evaluated using the most clinically relevant endpoints such as glucose stabilization and severe hypoglycemia prevention. The cumulative results of the registry confirm the inarguably positive impact of islet transplantation on metabolic control in T1 diabetes.
CUTE CHEST SYNDROME AND painful episodes are the most common precedents of death in adults with s... more CUTE CHEST SYNDROME AND painful episodes are the most common precedents of death in adults with sickle cell anemia (SCA). 1 A randomized, doubleblinded, placebo-controlled trial, the
MSH is a randomized, placebo-controlled clinical trial of hydroxyurea to prevent sickle cell cris... more MSH is a randomized, placebo-controlled clinical trial of hydroxyurea to prevent sickle cell crises. The primary end point is the occurrence of painful crises. Analysis of this primary end point must accommodate the occurrence of multiple crises in each patient and the termination of followup for some patients due to death or other severe adverse clinical outcomes, as well as loss to follow-up. Simulation studies will be presented to evaluate alternate statistical tests for primary end point analyses in the MSH. These include: (1) calculation of individual crisis rates for each patient by dividing the number of crises by the patient's follow-up time, with a test for difference in mean crisis rate (ignoring deaths) according to treatment; (2) Wilcoxon or van der Waerden rank tests of differences between patients dying before the end of follow-up assigned the worst ranks; and, (3) extensions of the log rank test.
... Ward Hagar, MD Adult Sickle Cell Program Children's Hospital and Research Center at Oakl... more ... Ward Hagar, MD Adult Sickle Cell Program Children's Hospital and Research Center at Oakland Oakland, Calif 1. Steinberg MH, Barton F, Castro O, et al. ... Dean Anthony Lee, MD, PhD Brigitta U. Mueller, MD Department of Pediatrics Baylor College of Medicine Houston, Tex ...
During the procedure, the following data were recorded: total induction time (start of anesthesia... more During the procedure, the following data were recorded: total induction time (start of anesthesia to endoscope insertion), total induction drug(s) dose, total procedure time
This multicenter study compared health-related quality of life (HRQOL) and family function of ped... more This multicenter study compared health-related quality of life (HRQOL) and family function of pediatric liver transplant recipients to those of healthy children to determine if this population differed from a healthy population and to distinguish which pretransplant and posttransplant factors impact HRQOL and family function. HRQOL data from 102 patients achieving 2-year survival were collected with the Infant Toddler Quality of Life Instrument or the Child Health Questionnaire Parent Form 50 parent surveys. Family functioning was assessed with the Family Assessment Device (FAD) completed by each participant's family members. Demographic and clinical information were retrieved from the Studies of Pediatric Liver Transplant database. Recipients 5 years of age and older scored lower than a normative sample in physical health (P Ͻ 0.001), general health (P Ͻ 0.001), parental emotional impact (P Ͻ 0.001), and disruption of family activities (P Ͻ 0.001). Younger children, 2 to 5 years of age, scored lower than controls in global health (P ϭ 0.004) and general health perceptions (P Ͻ 0.001) but did not differ in subscales measuring physical and psychosocial outcomes. Univariate analysis among the subscales identified demographic but not clinical variables as significant predictors of HRQOL. Mean scores of FAD scales were below published thresholds indicating healthy family functioning. As reported in previous studies, parents of older recipients reported higher levels of stress, although their level of family function appears normal. Significant associations were also observed between FAD scores and demographic variables, suggesting that further investigation of the impact of race, parental marital status, and socioeconomic status on the patient rehabilitation process is needed.
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NH... more This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The use of hydroxyurea, a cytotoxic agent, to decrease the frequency of painful crises in patients with sickle cell anemia. Patients assigned to hydroxyurea received an initial dose of 15 mg per kilogram of body weight per day, and the dose was increased by 5 mg per kilogram of body weight per day every 12 weeks, unless marrow depression (indicated by a neutrophil count below 2,000 per cubic millimetre, a reticulocyte or platelet count below 80,000 per cubic millimetre, or a haemoglobin level below 4.5 g per decilitre) was present. If marrow depression occurred, treatment was stopped until blood counts recovered. Treatment was then resumed at a dose that was 2.5 mg/kg lower than the dose associated with marrow depression, starting a new 12-week cycle. Type of intervention Palliative care and secondary prevention. Economic study type Cost-effectiveness analysis. Study population Patients enrolled in the study had sickle cell anemia, were at least 18 years old, had had at least 3 painful crises the previous year and were not chronic users of large amounts of opiate analgesics. Patients known to have sickle cell-beta^+-thalassemia and sickle cell-beta^o-thalassemia were excluded, but those with sickle cell-alpha-thalassemia were included. If patients had received transfusions, hemolysates of their red cells could not contain more than 15% hemoglobin A at the time treatment began. Other reasons for exclusion from the study included pregnancy, known narcotic or regular consumption of more than 30 oxycodone capsules (or the equivalent) every two weeks, participation in a long-term programme of transfusion, concurrent treatment with another potential antisickling agent, pretreatment blood counts that could not be distinguished from levels considered to indicate marrow depression, a history of stroke during the preceding six years, prior hydroxyurea therapy, and the presence of antibody to the human immunodeficiency virus (HIV). Setting The setting was a hospital. The economic analysis was carried out in the USA.
In the wake of reports of falsified data in one of the trials of the National Surgical Adjuvant P... more In the wake of reports of falsified data in one of the trials of the National Surgical Adjuvant Project for Breast and Bowel Cancer supported by the National Cancer Institute, clinical trials came under close scrutiny by the public, the press, and Congress. Questions were asked about the quality and integrity of the collected data and the analyses and conclusions of trials. In 1995, the leaders of the Society for Clinical Trials (the Chair of the Policy Committee, Dr. David DeMets, and the President of the Society, Dr. Sylvan Green) asked two members of the Society (Dr. Genell Knatterud and Dr. Frank Rockhold) to act as co-chairs of a newly formed subcommittee to discuss the issues of data integrity and auditing. In consultation with Drs. DeMets and Green, the co-chairs selected other members (Ms. Franca Barton, Dr. C.E. Davis, Dr. Bill Fairweather, Dr. Stephen George, Mr. Tom Honohan, Dr. Richard Mowery, and Dr. Robert O&#39;Neill) to serve on the subcommittee. The subcommittee considered &quot;how clean clinical trial data should be, to what extent auditing procedures are required, and who should conduct audits and how often.&quot; During the initial discussions, the subcommittee concluded that data auditing was insufficient to achieve data integrity. Accordingly, the subcommittee prepared this set of guidelines for standards of quality assurance for multicenter clinical trials. We include recommendations for appropriate action if problems are detected.
OBJECTIVE To determine C-peptide measures and levels associated with positive glycemic control... more OBJECTIVE To determine C-peptide measures and levels associated with positive glycemic control outcomes following islet transplantation (ITx) in type 1 diabetes. RESEARCH DESIGN AND METHODS We evaluated Collaborative Islet Transplant Registry (CITR) Islet-Alone recipients with pre-transplant C-peptide <0.1 nmol/L and mean follow up of 4.6±1.1 years (n=677). Area under the curve of receiver-operator characteristics (ROC-AUC) were used to evaluate predictive value of fasting and stimulated glucose and C-peptide measures for 7 primary outcomes: a) absence of severe hypoglycemic events (ASHE); b) HbA1c<7.0%; c) HbA1c<7.0% & ASHE; d) HbA1c≤6.5%; e) HbA1c≤6.5% & ASHE; f) insulin independence; and g) ASHE, HbA1c≤6.5% & insulin independence (the optimal outcome). Measures with the highest ROC-AUC were selected for determination of optimal cut points. RESULTS Fasting C-peptide was highly predictive for ASHE (ROC-AUC=0.906; optimal cut point=0.070 nmol/L), and the optimal outcome ...
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