Biomedical subjects

Jonathan J Shuster

Publications and source records attributed to Jonathan J Shuster.

At least 19 recordsLinked to original sources

PubMed2006

Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG).

The Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG) joined to form the Children's Oncology Group (COG) in 2000. This merger allowed analysis of clinical, biologic, and early response data predictive of event-free survival (EFS) in acute lymphoblastic leukemia (ALL) to develop a new classification system and treatment algorithm. From 11 779 children (age, 1 to 21.99 years) with newly diagnosed B-precursor ALL consecutively enrolled by the CCG (December 1988 to August 1995, n=4986) and POG (January 1986 to November 1999, n=6793), we retrospectively analyzed 6238 patients (CCG, 1182; POG, 5056) with informative cytogenetic data. Four risk groups were defined as very high risk (VHR; 5-year EFS, 45% or below), lower risk (5-year EFS, at least 85%), and standard and high risk (those remaining in the respective National Cancer Institute [NCI] risk groups). VHR criteria included extreme hypodiploidy (fewer than 44 chromosomes), t(9;22) and/or BCR/ABL, and induction failure. Lower-risk patients were NCI standard risk with either t(12;21) (TEL/AML1) or simultaneous trisomies of chromosomes 4, 10, and 17. Even with treatment differences, there was high concordance between the CCG and POG analyses. The COG risk classification scheme is being used for division of B-precursor ALL into lower- (27%), standard- (32%), high- (37%), and very-high- (4%) risk groups based on age, white blood cell (WBC) count, cytogenetics, day-14 marrow response, and end induction minimal residual disease (MRD) by flow cytometry in COG trials.

Adolescent↗

PubMed2006

Automated medication error studies with audit supplementation were effectively designed and analyzed by time series.

BACKGROUND AND OBJECTIVE: To provide researchers with an efficient yet methodologically robust method to design and analyze studies of the effectiveness of quality improvement interventions targeted at medical errors. METHODS: An interrupted time-series design was chosen. Error rates of a preintervention observational period are compared to those of an intervention period (interrupted by a brief transitional period not used in the analysis). Potential errors are flagged by computerized analysis. The positive predictive value of this automated method is established by targeted expert review of random samples of monthly admissions with flagged errors. The lengths of the preintervention and intervention observational periods and number of audits per month are determined via power and type I error analysis. The setting was a future study of electronic alert systems for errors related to nephrotoxic agents in a medium-sized hospital. RESULTS: Based on these methods, a study was deemed feasible to be conducted over a 38-month period, auditing 40 potential errors per month. CONCLUSION: A logistic monthly error process model with independent variables (1) time in months (same slope pre vs. postintervention), and (2) a discrete jump postintervention to assess the effect size, offers a flexible, easy-to-interpret way to attack this problem.

Decision Support Systems, Clinical↗

PubMed2006

Effectiveness of nesiritide on dialysis or all-cause mortality in patients undergoing cardiothoracic surgery.

BACKGROUND: Natriuretic peptides have been shown to have favorable renal effects. However, recent evidence suggests potential renal side effects in patients with congestive heart failure. HYPOTHESIS: This study examined the effect of nesiritide (human B-type natriuretic peptide) on hemodialysis or death in patients undergoing cardiothoracic surgery. METHODS: This retrospective cohort study included patients (n = 940) undergoing nontransplant adult cardiothoracic surgery between July 2001 and February 2004. Patients receiving nesiritide within 3 days after and not before surgery (n = 151) were compared with those not given nesiritide (n = 789) for incidence of hemodialysis or in-hospital death by Day 21 (HD/death). Patients with preexisting dialysis and intraoperative deaths were excluded. Forward inclusion multiple logistic regression was used based on published risk factors for HD/death. RESULTS: Of 940 patients (318 coronary artery bypass graft, 348 valve, and 274 thoracic aorta), 36 required dialysis and 60 patients died (HD/death; n = 77). Adjusted for significant confounders (gender, age, procedure, intra-aortic balloon, baseline serum creatinine mg/dl [SCr], 1 day % SCr increase), nesiritide showed a statistically nonsignificant HD/death reduction (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.29-1.17; p = 0.129) in the group as a whole. When stratified by baseline SCr, a significant benefit was noted in patients with SCr > 1.0 (OR, 0.35; 95% CI 0.14-0.87; p = 0.024), while no significant effect was found in patients with SCr < 1.0 (OR, 1.55; 95% CI 0.48-5.07, p = 0.465). CONCLUSIONS: Nesiritide appears promising in reducing the risk of dialysis or death in patients with SCr > 1.0 undergoing cardiothoracic surgery; however, no effect was noted with SCr < 1.0. This study provides strong rationale for a randomized trial.

Acute Kidney Injury↗

PubMed2006

Neurocognitive findings in Prader-Willi syndrome and early-onset morbid obesity.

OBJECTIVES: To examine whether early-onset morbid obesity is associated with cognitive impairment, neuropathologic changes, and behavioral problems. STUDY DESIGN: This case-control study compared head MRI scans and cognitive, achievement, and behavioral evaluations of subjects with Prader-Willi syndrome (PWS), early-onset morbid obesity (EMO), and normal-weight sibling control subjects from both groups. Head MRI was done on 17 PWS, 18 EMO, and 21 siblings, and cognitive, achievement, and behavioral evaluations were done on 19 PWS, 17 EMO, and 24 siblings. RESULTS: The mean General Intellectual Ability score of the EMO group was 77.4 +/- 17.8; PWS, 63.3 +/- 14.2; and control subjects, 106.4 +/- 13.0. Achievement scores for the three groups were EMO, 78.7 +/- 18.8; PWS, 71.2 +/- 17.0; and control subjects, 104.8 +/- 17.0. Significant negative behaviors and poor adaptive skills were found in the EMO group. White matter lesions were noted on brain MRI in 6 subjects with PWS and 5 with EMO. None of the normal-weight control subjects had these findings. CONCLUSIONS: Individuals with EMO have significantly lower cognitive function and more behavioral problems than control subjects with no history of childhood obesity. Both EMO and PWS subjects have white matter lesions on brain MRI that have not previously been described.

Achievement↗

PubMed2006

Lung bioavailability of hydrofluoroalkane fluticasone in young children when delivered by an antistatic chamber/mask.

OBJECTIVE: To determine whether an antistatic valved holding chamber/mask improves lung bioavailability of hydrofluoroalkane (HFA) fluticasone in young children. STUDY DESIGN: Twelve patients, age 1 to 6 years, with well-controlled asthma were treated with an HFA fluticasone metered-dose inhaler (Flovent HFA) twice daily (440 microg/day). The drug was delivered by tidal breathing through conventional (AeroChamber Plus) and antistatic (AeroChamber MAX) valved holding chambers (VHCs) with masks in a randomized, crossover manner, each for 3 to 7 days. When adherence was 100% at home, blood was collected for measurement of steady-state fluticasone plasma concentration (FPC) 1 hour after the last dose was administered in the clinic. FPC indicates systemic exposure directly and airway delivery indirectly. It was measured by liquid chromatography-mass spectrometry. Data were analyzed by regression analysis. RESULTS: The mean +/- SD FPC was 107 +/- 30 pg/mL after conventional VHC and 186 +/- 134 pg/mL after the antistatic VHC (P = .03). In 5 patients (40%), the antistatic VHC increased FPC by >/= 100%, to potentially excessive levels in 4 of them; it had little effect in 7 patients. CONCLUSIONS: HFA fluticasone was delivered to the airways by both devices even though the patients could not inhale deeply and breath hold. The antistatic VHC variably increased lung bioavailability. To reduce systemic exposure, the dose should be weaned to the minimum required to maintain asthma control.

Administration, Inhalation↗

PubMed2006

Peripheral neuropathy in genetic mitochondrial diseases.

Peripheral neuropathy is an underrecognized but common occurrence in genetic mitochondrial disorders. To gain insight into the frequency and clinical presentation of this complication, nerve conduction studies were performed on 43 subjects with congenital lactic acidosis enrolled in a controlled clinical trial of oral dichloroacetate. Median and peroneal motor conduction studies and median and sural sensory conduction studies were performed on each patient. The mean amplitude of the peroneal motor nerve (P < 0.001) and the conduction velocities of the median (P < 0.001) and peroneal (P < 0.001) motor nerves were uniformly lower in our subjects than in healthy literature control subjects. There were no significant differences in sensory nerve conduction studies. A generalized reduction in motor nerve conduction velocity was the dominant electrophysiological abnormality in the patients in this study and was independent of age, sex, or congenital mitochondrial disorder. We postulate that cellular energy failure is the most likely common cause of peripheral neuropathy in patients with genetic mitochondrial diseases, owing to the high demand for adenosine triphosphate via aerobic carbohydrate metabolism by nerve tissue.

Acidosis, Lactic↗

PubMed2006

Ambulatory continuous interscalene nerve blocks decrease the time to discharge readiness after total shoulder arthroplasty: a randomized, triple-masked, placebo-controlled study.

BACKGROUND: A continuous interscalene nerve block (CISB) may be used to provide analgesia after shoulder arthroplasty. Therefore, inpatient stays may be shortened if CISB (1) provides adequate analgesia without intravenous opioids and (2) improves shoulder mobilization. This study investigated the relationship between ambulatory CISB and the time to reach three discharge criteria after shoulder arthroplasty. METHODS: Preoperatively, patients received a CISB. All patients received a perineural 0.2% ropivacaine infusion from surgery until 06:00 the following morning, at which time they were randomly assigned either to continue perineural ropivacaine or to switch to normal saline. The primary endpoint was the time from the end of surgery until three discharge criteria were attained (adequate analgesia, independence from intravenous analgesics, and tolerance to 50% of shoulder motion targets). Patients were discharged home as early as the afternoon after surgery with their CISB using a portable infusion pump. RESULTS: Patients receiving perineural ropivacaine (n = 16) attained all three discharge criteria in a median (10th-90th percentiles) of 21 (16-41) h, compared with 51 (37-90) h for those receiving perineural normal saline (n = 13, P < 0.001). Unlike patients receiving perineural ropivacaine, patients receiving perineural normal saline often required intravenous morphine, but still experienced a higher degree of pain and tolerated less external rotation. CONCLUSIONS: An ambulatory CISB considerably decreases the time until readiness for discharge after shoulder arthroplasty, primarily by providing potent analgesia that permits greater passive shoulder movement and the avoidance of intravenous opioids. Additional research is required to define the appropriate subset of patients and assess the incidence of complications associated with earlier discharge.

Aged↗

PubMed2006

Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children.

OBJECTIVE: Open-label studies indicate that oral dichloroacetate (DCA) may be effective in treating patients with congenital lactic acidosis. We tested this hypothesis by conducting the first double-blind, randomized, control trial of DCA in this disease. METHODS: Forty-three patients who ranged in age from 0.9 to 19 years were enrolled. All patients had persistent or intermittent hyperlactatemia, and most had severe psychomotor delay. Eleven patients had pyruvate dehydrogenase deficiency, 25 patients had 1 or more defects in enzymes of the respiratory chain, and 7 patients had a mutation in mitochondrial DNA. Patients were preconditioned on placebo for 6 months and then were randomly assigned to receive an additional 6 months of placebo or DCA, at a dose of 12.5 mg/kg every 12 hours. The primary outcome results were (1) a Global Assessment of Treatment Efficacy, which incorporated tests of neuromuscular and behavioral function and quality of life; (2) linear growth; (3) blood lactate concentration in the fasted state and after a carbohydrate meal; (4) frequency and severity of intercurrent illnesses and hospitalizations; and (5) safety, including tests of liver and peripheral nerve function. OUTCOME: There were no significant differences in Global Assessment of Treatment Efficacy scores, linear growth, or the frequency or severity of intercurrent illnesses. DCA significantly decreased the rise in blood lactate caused by carbohydrate feeding. Chronic DCA administration was associated with a fall in plasma clearance of the drug and with a rise in the urinary excretion of the tyrosine catabolite maleylacetone and the heme precursor delta-aminolevulinate. CONCLUSIONS: In this highly heterogeneous population of children with congenital lactic acidosis, oral DCA for 6 months was well tolerated and blunted the postprandial increase in circulating lactate. However, it did not improve neurologic or other measures of clinical outcome.

Acidosis, Lactic↗

PubMed2005

Diagnostics for assumptions in moderate to large simple clinical trials: do they really help?

In this article, primarily we look at a case study, where prior to conducting the major efficacy analysis, one performs a diagnostic test for assumptions, and acts upon the result if the diagnostic test rejects the assumptions. Specifically, we show by an example that a hybrid approach of using a diagnostic test for equality of variance in a two-sample t-test situation can adversely affect, rather than protect, the operating characteristics of the study. If this kind of hybrid approach fails in such a simple setting, analysts should be very cautious about using hybrid approaches in more complex analyses of efficacy. Secondarily, we present rationale as to why the classical tests (or slightly modified versions) can be viewed as asymptotically non-parametric, and can actually be more robust against failure of assumptions than rank tests. Readers are cautioned that this illustration is limited to efficacy analysis, and is not meant as a criticism of other analyses, such as modelling or exploratory ones.

Analysis of Variance↗

PubMed2005

Assessment of cervical antibody concentrations fails to enhance the value of cervical length as a predictor of preterm delivery.

OBJECTIVE: The purpose of this study was to determine if cervical fluid antibody concentrations can enhance the value of cervical length in predicting risk of preterm delivery. STUDY DESIGN: We obtained cervical fluid samples with preweighed cellulose wicks from a prospective cohort of women 23 to 32 weeks' gestation with signs and symptoms of preterm labor and intact membranes. Total immunoglobulin A and G (IgA and IgG) concentrations were determined by enzyme-linked immunosorbent assay. Bacterial vaginosis was diagnosed by Gram stain, and cervical length was measured with endovaginal ultrasound. RESULTS: For subjects with term (n = 77) and preterm (n = 24) deliveries, median IgA and IgG concentrations were 736 vs 643 microg/mL (P = .33) and 1528 vs 1769 microg/mL (P = .85). For subjects with normal flora (n = 71), intermediate flora (n = 14), and bacterial vaginosis (n = 16), median IgA and IgG concentrations were 717, 624, and 774 microg/mL (P = .90) and 1383, 1553, and 2731 microg/mL (P = .02). In a forward stepwise logistic regression model, cervical length was the only factor associated with preterm delivery (P < .001). CONCLUSION: Measuring the concentrations of IgA and IgG in cervical fluid does not enhance the value of cervical length in predicting risk of preterm delivery.

Adult↗

PubMed2005

The methylenetetrahydrofolate reductase 677C->T polymorphism and dietary folate restriction affect plasma one-carbon metabolites and red blood cell folate concentrations and distribution in women.

Whether folate status and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism interact to affect methionine-cycle metabolite concentrations is uncertain. We evaluated the effects of dietary folate restriction on relations among folate status indices and plasma concentrations of methionine cycle metabolites in women with the MTHFR 677 C/C and T/T genotypes. Healthy, normohomocysteinemic women (n = 18; 20-30 y old) of adequate B vitamin status, and equally divided according to MTHFR 677C-->T genotype (9 C/C and 9 T/T) were recruited. Folate status indices and methionine cycle metabolites were measured in blood samples collected at baseline and after 7 wk of dietary folate restriction (115 microg dietary folate equivalents/d). Significant negative correlations between plasma total homocysteine concentrations and total or 5-methyl folate concentrations (P = 0.041 and 0.023, respectively) in RBCs were found only in T/T subjects. Formylated folates were detected in RBCs of T/T subjects only, and their abundance was predictive of plasma total homocysteine concentration despite no significant alteration by folate restriction. Plasma concentrations of S-adenosylmethionine and S-adenosylhomocysteine were not significantly affected by dietary folate restriction and the MTHFR 677 T/T genotype. In conclusion, plasma total homocysteine concentrations in subjects with the MTHFR 677 T/T genotype were inversely related to 5-methyl folate concentrations and directly related to formylated folate concentrations in RBCs, even though the latter were not significantly affected by moderate folate restriction.

Amino Acid Substitution↗

PubMed2005

Homocysteine synthesis is elevated but total remethylation is unchanged by the methylenetetrahydrofolate reductase 677C->T polymorphism and by dietary folate restriction in young women.

The effects of folate status and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism on the kinetics of homocysteine metabolism are unclear. We measured the effects of dietary folate restriction on the kinetics of homocysteine remethylation and synthesis in healthy women (20-30 y old) with the MTHFR 677 C/C or T/T genotypes (n = 9/genotype) using i.v. primed, constant infusions of [(13)C(5)]methionine, [3-(13)C]serine, and [(2)H(3)]leucine before and after 7 wk of dietary folate restriction (115 mug dietary folate equivalents/d). Dietary folate restriction significantly reduced folate status ( approximately 65% reduction in serum folate) in both genotypes. Total remethylation flux was not affected by dietary folate restriction, the MTHFR 677C-->T polymorphism, or their combination. However, the percentage of remethylation from serine was reduced approximately 15% (P = 0.031) by folate restriction in C/C subjects. Further, homocysteine synthesis rates of T/T subjects and folate-restricted C/C subjects were twice that of C/C subjects at baseline. In conclusion, elevated homocysteine synthesis is a cause of mild hyperhomocysteinemia in women with marginal folate status, particularly those with the MTHFR 677 T/T genotype.

Adult↗

PubMed2005

The effect of propofol on thermal pain perception.

We studied the effect of propofol, a widely used sedative-hypnotic drug, on pain perception. Eighteen subjects received propofol in two sedative concentrations that were balanced and randomized in order. Painful (45 degrees C, 47 degrees C, and 49 degrees C) stimulation temperatures were presented in random order, and nonpainful 31 degrees C stimuli were presented on alternate trials. We used a target-controlled infusion and chose effect site concentrations of 0.5 mug/mL for mild sedation and 1.0 mug/mL for moderate sedation. Using a visual analog scale, subjects rated both pain intensity and unpleasantness higher when sedated with propofol. The average pain intensity was 28/100 for placebo, 35/100 for mild, and 40/100 for moderate sedation. Pain unpleasantness was 23/100 for placebo, 29/100 for mild, and 33/100 for moderate sedation. This effect was unexpected and may be explained by a difference of subjective pain experience by a patient and the perceived level of analgesia by a health care provider in sedated patients. This finding calls further attention to the need for adequate analgesia in patients sedated with propofol.

Adult↗

PubMed2005

Total shoulder arthroplasty as an outpatient procedure using ambulatory perineural local anesthetic infusion: a pilot feasibility study.

We investigated the feasibility of converting total shoulder arthroplasty (TSA) into an outpatient procedure using ambulatory interscalene perineural ropivacaine infusion. Of the patients of the first phase (n = 8) who were required to remain hospitalized for at least 1 postoperative night, 5 met discharge criteria in the recovery room. Of the subsequent patients of the second phase (n = 6), all met discharge criteria in the recovery room after surgery, and 5 were discharged directly home. For all patients, postoperative pain was well controlled, oral opioid requirements and sleep disturbances were minimal, range-of-motion consistently reached or exceeded the surgeon's expectations, and patient satisfaction was high. These results suggest that TSA may be performed on an outpatient basis using perineural local anesthetic infusion. Additional research is required to define the appropriate subset of patients and assess the incidence of complications associated with this practice before its mainstream use.

Adult↗

PubMed2004

Increasing orgasm and decreasing dyspareunia by a manual physical therapy technique.

CONTEXT: Female sexual pain and dysfunction. OBJECTIVE: To evaluate the effectiveness of a new site-specific, manual soft-tissue therapy in increasing orgasm and reducing dyspareunia (painful intercourse) in women with histories indicating abdominopelvic adhesion formation. DESIGN AND INTERVENTION: A total of 29 new patients presenting with infertility or abdominopelvic pain-related problems, and also indicating sexual pain or dysfunction, received a series of treatments (mean, 19.5 hours) designed to address biomechanical dysfunction and restricted mobility due to adhesions affecting the reproductive organs and adjacent structures. OUTCOME MEASURES: Primary outcome measures were post-test vs pretest scores on: (1) the Female Sexual Function Index (FSFI) full scale, orgasm domain, and pain domain; and (2) 3 supplemental 10-point rating scales of sexual pain levels. Secondary outcome measures were post-test vs pretest scores in the other 4 FSFI domains (desire, arousal, lubrication, and satisfaction). The Wilcoxon signed-rank test was used for all statistical analyses. RESULTS: For the 23 patients available for follow-up, the paired FSFI post-test vs pretest scores were significant (P < or = .003) on all measures. Of the 17 patients who completed the 3 sexual pain scales, the paired post-test vs pretest scores were significant (P < or = .002). CONCLUSIONS: Many cases of inhibited orgasm, dyspareunia, and other aspects of sexual dysfunction seem to be treatable by a distinctive, noninvasive manual therapy with no risks and few, if any, adverse effects. The therapy should be considered a new adjunct to existing gynecologic and medical treatments.

Adult↗

PubMed2004

Treating female infertility and improving IVF pregnancy rates with a manual physical therapy technique.

CONTEXT: Infertility and pregnancy. OBJECTIVE: To assess the effectiveness of site-specific manual soft tissue therapy in (1) facilitating natural fertility and (2) improving in vitro fertilization (IVF) pregnancy rates in women with histories indicating abdominopelvic adhesion formation. DESIGN AND INTERVENTION: Pursuant to 2 promising pilot studies, 53 infertile, premenopausal patients received a 10- to 20-hour series of site-specific manual physical therapy treatments. Seventeen patients hoped to achieve a natural pregnancy; 36 planned to undergo IVF within 15 months. The primary criteria for inclusion in the studies were the inability to conceive following a minimum of 12 months of unprotected intercourse and suspected or confirmed pelvic adhesions due to abdominal and/or pelvic surgery, infectious or inflammatory disease (eg, endometriosis, PID), or trauma. Treatments were specifically designed to address biomechanical dysfunctions of the pelvis, sacrum, and coccyx and restricted soft tissue and visceral mobility due to adhesions or microadhesions affecting the reproductive organs and adjacent structures. MAIN OUTCOME MEASURES: (1) Natural fertility group: pregnancy within 1 year of therapy and subsequent full-term delivery; (2) Pre-IVF group: pregnancy (via transfer of fresh embryos from nondonor eggs) within 15 months of the last manual treatment date. RESULTS: Natural fertility group: Of the 14 patients available for follow-up (ages 25 to 44; mean, 33.5 years), 10 (71.4%) became pregnant within 1 year, and 9 (64.3%) reported full-term deliveries. Three of the 9 women who delivered reported a subsequent pregnancy, suggesting that the treatment protocol might have lasting effects. Two women have had a second live birth delivery; and the third is still pregnant. Pre-IVF group: Of the 25 patients available for follow-up (ages 28 to 44; mean, 36 years), clinical pregnancies were documented in 22 of 33 embryo transfers vs the US Centers for Disease Control and Prevention (CDC) 2001 age-adjusted expected number of 12.7 (P < .001). The estimated odds ratio for a successful pregnancy in a cycle (manual treatment: no treatment) is 3.20 (95% confidence interval = 1.55-8.4). CONCLUSIONS: The data trend across these studies suggests that this innovative site-specific protocol of manual soft-tissue therapy facilitates fertility in women with a wide array of adhesion-related infertility and biomechanical reproductive organ dysfunction. The therapy, designed to improve function by restoring visceral, osseous, and soft-tissue mobility, is a nonsurgical, noninvasive manual technique with no risks and few, if any, adverse side effects or complications. As such, it should be considered a new adjunct to existing medical infertility treatments.

Adult↗

PubMed2004

One-year protocol liver biopsy can stratify fibrosis progression in liver transplant recipients with recurrent hepatitis C infection.

Determinants of progression to cirrhosis in hepatitis C virus (HCV) infection have been well described in the immunocompetent population but remain poorly defined in liver transplant (LT) recipients. This cohort study determines the factors contributing to the development of fibrosis and its rate of progression in the allograft. Predictive factors analyzed include: demographics, host and donor factors, surgery-related variables (cold and warm ischemia time), rejection episodes, cytomegalovirus infection (CMV), and immunosuppression. Over 12 years, 842 adult LTs were performed at our institution; 358 for the indication of HCV. A total of 264 patients underwent protocol liver biopsies at month 4 and yearly after LT. Using the modified Knodell system of Ishak for staging fibrosis, the median fibrosis progression rate was .8 units/year (P < .001). Rapid fibrosis progression (> .8 units/year) was best identified by liver histology performed at 1 year. Donor age > 55 years was associated with rapid fibrosis progression and development of cirrhosis (P < .001). In contrast, donor age < 35 years was associated with slower progression of fibrosis (P = .003). Risk factors for graft loss due to recurrent HCV included recipient age > 35 years (P = .01), donor age > 55 years (P = .005), and use of female donor allografts (P = .03). In conclusion, fibrosis progression in HCV-infected LT recipients occurs at a rate of .8 units/year. Increased donor age has a major impact on disease progression, graft failure, and patient survival. A liver biopsy performed at 1 year posttransplant can help identify those patients more likely to develop progressive disease and may allow better targeting of antiviral therapy.

Adult↗

PubMed2004

Sample sizes based on exact unconditional tests for phase II clinical trials with historical controls.

Investigated in the setting of phase II clinical trials is the two-sample binomial problem of testing H0: pe = pc H1: pe > pc, where pe and pc are the unknown target population response rates for the experimental and control groups, respectively, using the usual Z-statistic with pooled variance estimator. The cornerstones that make this paper unique are as follows. First, the emphasis is on determining the sample size given that the control group information has already been collected (historical control). Second, exact unconditional inference, rather than an asymptotic method, is utilized. Sample size tables, contrasting the exact and asymptotic methods, are provided. Although asymptotic results were usually fairly close to the exact results, some important differences were observed.

Clinical Trials, Phase II as Topic↗