Biomedical subjects

James F Troendle

Publications and source records attributed to James F Troendle.

17 recordsLinked to original sources

PubMed2006

Likelihood approaches to the non-parametric two-sample problem for right-censored data.

The classical two-sample problem with random right-censoring is considered. We show that non- parametric likelihood techniques can be used to obtain tests for either the identity hypothesis or the non-parametric Behrens-Fisher hypothesis (NBFH). In the case of the identity hypothesis, a special imputed permutation distribution is used to estimate the distribution under the null hypothesis. In the case of the NBFH, simulation from the constrained non-parametric maximum likelihood estimate is used. Simulation shows that the tests using either approximation have excellent control of the type I error rate, even with quite small sample sizes. Further, for Lehmann-type alternatives the likelihood-based methods have similar power to the logrank test, while for the non-Lehmann-type alternatives tried here the likelihood-based methods have superior power.

Computer Simulation↗

PubMed2006

Testosterone deficiency in young women with 46,XX spontaneous premature ovarian failure.

OBJECTIVE: To determine whether women with 46,XX spontaneous premature ovarian failure have lower serum free-T levels than do control women. DESIGN: Cross-sectional. SETTING: National Institutes of Health Clinical Research Center. PATIENT(S): Women with 46,XX spontaneous premature ovarian failure (n = 130). INTERVENTION(S): Evaluation while off any estrogen therapy and then again after receiving a standardized hormone regimen. Regularly menstruating control women (n = 65) were sampled during the midfollicular phase. MAIN OUTCOME MEASURE(S): Serum total T by RIA after extraction and column chromatography, free T by equilibrium dialysis, and sex hormone-binding globulin by immunoradiometric assay. RESULT(S): While off estrogen therapy patients had a median serum free-T concentration that was statistically significantly lower than controls (2.2 vs. 3.3 pg/mL). This dropped significantly lower to 1.9 pg/mL while the patients were on physiologic transdermal E(2) therapy. This is despite the fact that sex hormone-binding globulin levels did not change. While on E(2) therapy, 13% of women (95% confidence interval, 7.9%-20.3%) had serum free-T levels below the lower limit of normal (<1.1 pg/mL). CONCLUSION(S): As a group, young women with 46,XX spontaneous premature ovarian failure have reduced circulating free-T levels, both during an interval off of estrogen therapy and while on physiologic transdermal E(2) therapy.

Chromosomes, Human, X↗

PubMed2006

Comparison of labor progression between induced and noninduced multiparous women.

OBJECTIVE: The incidence of labor induction is rising rapidly in the United States. Among multiparas, labor is often followed with traditional labor curves derived from noninduced pregnancies. We sought to determine how labor progression of multiparous women who presented in spontaneous labor differed from those who were electively induced with and from those induced without preinduction cervical ripening. METHODS: We analyzed data on all low-risk multiparous women with an elective induction or spontaneous onset of labor between 37(+0) and 40(+6) weeks of gestation from January 2002 to March 2004 at a single institution. The median duration of labor by each centimeter of cervical dilatation and the risk of cesarean delivery were computed for 61 women with preinduction cervical ripening and oxytocin induction, 735 women with oxytocin induction, and 1,885 women with a spontaneous onset of labor. An intracervical Foley catheter was used to ripen the cervix. RESULTS: Those women who experienced electively induced labor without cervical ripening had a shorter active phase of labor than did those admitted in spontaneous labor (99 minutes in induced labor versus 161 minutes in spontaneous labor, P < .001). However, the cesarean delivery rate was elevated in the induction group (3.9% versus 2.3%, P < .05). Women who underwent preinduction cervical ripening also had a shorter active phase than those admitted in spontaneous labor (109 minutes versus 161 minutes, P = .01). CONCLUSION: The pattern of labor progression differs for women with an electively induced labor without cervical ripening compared with those who present with spontaneous onset of labor.

Adult↗

PubMed2006

Hypothesis: Neonatal respiratory distress may be related to asymptomatic colonization with group B streptococci.

BACKGROUND: Phospholipids from the group B streptococcal (GBS) cell wall cause pulmonary hypertension in experimental animals. When exposed to penicillin, Streptococcus mutans releases phospholipids immediately. We hypothesize that newborns colonized with GBS receive bacterial phospholipids leading to pulmonary hypertension and respiratory distress, especially in the situation of newborns of penicillin-treated mothers. We examined clinical and epidemiologic data on these relations. METHODS: We used data from a prospective multicenter GBS study conducted from 1995 to 1999 in which 1674 of 17,690 newborns cultured at 4 sites were colonized with GBS. Our analyses included 1610 colonized newborns > or =32 weeks gestation without early-onset disease. Clinical features were compared between 1003 lightly colonized (GBS positive at < or =2 sites) and 607 heavily colonized (positive at 3 or 4 sites) newborns. The rates of respiratory distress were compared between colonized newborns of penicillin-treated mothers and those of untreated mothers. RESULTS: Of the 1610 colonized newborns, 8.8% had signs of respiratory distress within 48 hours after birth (cases). Oxygen supplementation was used in 60% of the cases, mechanical ventilation was required in 5% and persistent pulmonary hypertension was diagnosed in 2%. Compared with light colonization, heavy colonization increased the rate of respiratory distress 1.73-fold (95% CI, 1.26-2.38), a discharge diagnosis of respiratory disorder 2.02-fold (95% CI, 1.16-3.52), a blood/cerebrospinal fluid obtained for culture 1.54-fold (95% CI, 1.24-1.93) and antibiotic administration after birth 1.87-fold (95% CI, 1.34-2.61). Penicillin use during labor was associated with a 2.62-fold (95% CI, 1.79-3.83) increase in respiratory distress in the colonized newborn. CONCLUSIONS: Our findings support the association of neonatal respiratory distress with asymptomatic GBS colonization and with penicillin use during labor. These data require confirmation.

Female↗

PubMed2006

The impact of parity on course of labor in a contemporary population.

BACKGROUND: Few studies have examined in depth the labor progression of multiparas to determine if there is any additional impact of being parous beyond the first birth. The objective of this study was to determine the effect of parity on labor progression in contemporary obstetric practice. METHODS: Our sample consisted of all low-risk women who delivered a term, live-born infant from January 2002 to March 2004 at a single institution in Delaware, United States (n = 5,589). The median duration of labor by each centimeter of cervical dilation was computed for parity = 0 (n = 2,645); parity = 1 (n = 1,839); parity = 2 (n = 750); and parity = 3 + (n = 355). RESULTS: Multiparas had a significantly faster labor progression from 4 to 10 cm (293, 300, and 313 min, respectively, for parity = 1, parity = 2, and parity = 3 +), compared with nulliparas (383 min for parity = 0), as well as a shorter second stage of labor. However, no significant differences were found in duration of the active phase or the second stage of labor among multiparas. CONCLUSIONS: Additional childbearing appears to have no effect of on the progression of labor among multiparous subgroups. The difference in duration of the active phase between nulliparas and multiparas is substantially smaller in a contemporary population.

Adult↗

PubMed2006

Methodological challenges in studying labour progression in contemporary practice.

In the 1950s, Emanuel Friedman described the first comprehensive method of evaluating labour in clinical practice. In this landmark work, Friedman described the relationship between the duration of labour and cervical dilation as a sigmoid curve and outlined a tool for following labour progression and for identifying abnormal labour. His definitions of labour protraction and arrest continue to be applied in contemporary obstetric practice, although there have been considerable changes since in the clinical management of labour and delivery. This paper provides an overview of Friedman's work, addresses various methodological challenges in studying labour progression, and describes the utility of more advanced statistical methods for studying labour progression, such as survival analysis, compared with other approaches. Additional research that utilises and refines such methods will provide greater insight into labour progression and may assist in updating the diagnostic criteria for labour protraction and arrest disorders in contemporary obstetric practice. Moreover, such detailed information could have important clinical implications towards reducing the rate of primary caesarean delivery in the United States.

Cesarean Section↗

PubMed2005

Multiple comparisons between two groups on multiple Bernoulli outcomes while accounting for covariates.

The problem of adjusting for multiplicity when one has multiple outcome variables can be handled quite nicely by step-down permutation tests. More difficult is the problem when one wants an analysis of each outcome variable to be adjusted for some covariates and the outcome variables are Bernoulli. Special permutations can be used where the outcome vectors are permuted within each strata of the data defined by the levels of the (made discrete) covariates. This method is described and shown to control the familywise error rate at any prespecified level. The method is compared through simulation to a vector bootstrap approach, also using a step-down testing procedure. It is seen that the method using permutations within strata is superior to the vector bootstrap in terms of error control and power. The method is illustrated on a data set of 55 minor malformations of babies of diabetic and non-diabetic mothers.

Analysis of Variance↗

PubMed2005

Sequential testing for efficacy in clinical trials with non-transient effects.

This paper describes a new type of sequential testing for clinical trials. The sequential nature of the data is not from additional patients, but rather from longer follow-up times. At each analysis, the null hypothesis that all treatments are equivalent in effect on the outcome after that amount of time is tested. The trial might still have staggered entry or not, but the key feature is that a different statistical hypothesis is tested at each analysis. It is assumed that any effect of treatment is non-transient, allowing a conclusion to be drawn in favour of one treatment or the other based on a difference at a single follow-up time. It is shown that a general method based on the Bonferroni inequality can be used to obtain critical cutpoints for sequential testing, that controls the chance of a type I error for the clinical decision. This method is applicable regardless of the test used at each analysis. In the case of a two-armed trial with a Gaussian outcome variable, it is shown how simulation can be used to obtain critical cutpoints that maintain the chance of a type I error for the clinical decision. The methods are compared by Monte-Carlo simulation, and it is seen that in most practical cases the Bonferroni method is not very conservative. The Bonferroni procedure is illustrated on the results of a real clinical trial of Pirfenidone on pulmonary fibrosis in Hermansky-Pudlak Syndrome.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2005

Controlled trial of pamidronate in children with types III and IV osteogenesis imperfecta confirms vertebral gains but not short-term functional improvement.

UNLABELLED: Bisphosphonates have been widely administered to children with OI based on observational trials. A randomized controlled trial of q3m intravenous pamidronate in children with types III and IV OI yielded positive vertebral changes in DXA and geometry after 1 year of treatment, but no further significant improvement during extended treatment. The treated group did not experience significantly decreased pain or long bone fractures or have increased motor function or muscle strength. INTRODUCTION: Bisphosphonates, antiresorptive drugs for osteoporosis, are widely administered to children with osteogenesis imperfecta (OI). Uncontrolled pamidronate trials in OI reported increased BMD, vertebral coronal area, and mobility, and decreased pain. We conducted a randomized controlled trial of pamidronate in children with types III and IV OI. MATERIALS AND METHODS: This randomized trial included 18 children (4-13 years of age) with types III and IV OI. The first study year was controlled; 9 children received pamidronate (10 mg/m2/day IV for 3 days every 3 months). Four children in each group also received recombinant growth hormone (rGH) injections (0.06 mg/kg/day for 6 days/week). Seven children in the treatment group received pamidronate for an additional 6-21 months. All patients had L1-L4 DXA, spine QCT, spine radiographs, and musculoskeletal and functional testing. RESULTS: In the controlled phase, treated patients experienced a significant increase in L1-L4 DXA z score (p < 0.001) and increased L1-L4 mid-vertebral height (p = 0.014) and total vertebral area (p = 0.003) compared with controls. During extended treatment, DXA z scores and vertebral heights and areas did not increase significantly beyond the 12-month values. Fracture rate decreased significantly in the upper extremities (p = 0.04) but not the lower extremities (p = 0.09) during the first year of treatment. Gross motor function, muscle strength, and pain did not change significantly during the controlled or extended treatment phases. CONCLUSIONS: A controlled trial confirmed the spine benefits of short-term pamidronate treatment in children with types III and IV OI. Pamidronate increased L1-L4 vertebral DXA and decreased vertebral compressions and upper extremity fractures. Vertebral measures did not improve during the extended treatment phase. The treatment group did not experience decreased lower extremity long bone fractures, significant improvement in growth, ambulation, muscle strength, or pain. There was substantial variability in individual response to treatment.

Adolescent↗

PubMed2005

Labor progression and risk of cesarean delivery in electively induced nulliparas.

OBJECTIVE: To describe the pattern of labor progression and risk of cesarean delivery in women whose labor was electively induced. METHODS: We analyzed data on all low-risk, nulliparous women with an elective induction or spontaneous onset of labor between 37 + 0 and 40 + 6 weeks from January 2002 to March 2004 at a single institution. The median duration of labor by each centimeter of cervical dilation and the risk of cesarean delivery were computed for 143 women with preinduction cervical ripening and oxytocin induction, 286 women with oxytocin induction, and 1,771 women with a spontaneous onset of labor. An intracervical Foley catheter was used to ripen the cervix. RESULTS: Electively induced labor with cervical ripening had substantially slower latent and early active phases. After controlling for potential confounders, women who had an elective induction with cervical ripening had 3.5 times the risk of cesarean delivery during the first stage of labor (95% confidence interval 2.7-4.5), compared with those admitted in spontaneous labor. Elective induction without cervical ripening, on the other hand, was associated with a faster labor progression from 4 to 10 cm (266 compared with 358 minutes, P < .01) and did not increase the risk of cesarean delivery, compared with those in spontaneous labor. CONCLUSION: The pattern of labor progression differs substantially for women with an electively induced labor compared with those with spontaneous onset of labor. Furthermore, elective induction in nulliparous women with an unfavorable cervix has a high rate of labor arrest and a substantially increased risk of cesarean delivery. LEVEL OF EVIDENCE: II-2.

Adult↗

PubMed2005

Growth plate senescence is associated with loss of DNA methylation.

The overall body size of vertebrates is primarily determined by longitudinal bone growth at the growth plate. With age, the growth plate undergoes programmed senescence, causing longitudinal bone growth to slow and eventually cease. Indirect evidence suggests that growth plate senescence occurs because stem-like cells in the growth plate resting zone have a finite proliferative capacity that is gradually exhausted. Similar limits on replication have been observed when many types of animal cells are placed in cell culture, an effect known as the Hayflick phenomenon. However, we found that the number of population doublings of rabbit resting zone chondrocytes in culture did not depend on the age of the animal from which the cells were harvested, suggesting that the mechanisms limiting replicative capacity of growth plate chondrocytes in vivo are distinct from those in vitro. We also observed that the level of DNA methylation in resting zone chondrocytes decreased with age in vivo. This loss of methylation appeared to occur specifically with the slow proliferation of resting zone chondrocytes in vivo and was not observed with the rapid proliferation of proliferative zone chondrocytes in vivo (i.e. the level of DNA methylation did not change from the resting zone to the hypertrophic zone), with proliferation of chondrocytes in vitro, or with growth of the liver in vivo. Thus, the overall level of DNA methylation decreases during growth plate senescence. This finding is consistent with the hypothesis that the mechanism limiting replication of growth plate chondrocytes in vivo involves loss of DNA methylation and, thus, loss of DNA methylation might be a fundamental biological mechanism that limits longitudinal bone growth in mammals, thereby determining the overall adult size of the organism.

Aging↗

PubMed2004

The effect of early epidural versus early intravenous analgesia use on labor progression: a natural experiment.

OBJECTIVE: The purpose of this study was to compare the effect of early epidural with the use of early intravenous analgesia on labor progression. STUDY DESIGN: We systematically selected singleton, nulliparous term pregnancies with a spontaneous labor and analgesia placement <or=4 cm who were delivered at a hospital where the rate of epidural analgesia in labor increased from 1% (before) to 84% (after) in 1 year (a natural experiment). In the before period (n=223 pregnancies), 98% of women used intravenous analgesia, and 2% of women used epidural analgesia. In the after period (n=278 pregnancies), 92% of women used epidural analgesia, and 8% of women used intravenous analgesia. The median duration of labor by each centimeter of cervical dilation was computed and used as a measurement of labor progression. RESULTS: After adjustment had been made for confounders, women in the after period had a slower labor progression only from 4 to 5 cm, compared with those women in the before period. Interestingly, the process of labor admission and epidural analgesia placement, rather than analgesia use per se, appeared to explain most of the slowdown. No significant difference in the rest of the active phase was observed between the 2 groups. CONCLUSION: Our data support recent American College of Obstetricians and Gynecologists guidelines that the restraining use of epidural analgesia at <4 cm of cervical dilation is unnecessary.

Adult↗

PubMed2004

Maternal prepregnancy overweight and obesity and the pattern of labor progression in term nulliparous women.

OBJECTIVE: To examine the effect of maternal overweight and obesity on labor progression. METHODS: We analyzed data from 612 nulliparous women with a term pregnancy that participated in the Pregnancy, Infection, and Nutrition Study from 1995 to 2002. The median duration of labor by each centimeter of cervical dilation was computed for normal-weight (body mass index [BMI] 19.8-26.0 kg/m2), overweight (BMI 26.1-29.0 kg/m2), and obese (BMI > 29.0 kg/m2) women and used as a measurement of labor progression. RESULTS: After adjusting for maternal height, labor induction, membrane rupture, oxytocin use, epidural analgesia, net maternal weight gain, and fetal size, the median duration of labor from 4 to 10 cm was significantly longer for both overweight and obese women, compared with normal-weight women (7.5, 7.9, and 6.2 hours, respectively). For overweight women, the prolongation was concentrated around 4-6 cm, whereas for obese women, their labor was significantly slower before 7 cm. CONCLUSION: Labor progression in overweight and obese women was significantly slower than that of normal-weight women before 6 cm of cervical dilation. Given that nearly one half of women of childbearing age are either overweight or obese, it is critical to consider differences in labor progression by maternal prepregnancy BMI before additional interventions are performed.

Body Mass Index↗

PubMed2004

Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial.

GH is often used to treat children with idiopathic short stature despite the lack of definitive, long-term studies of efficacy. We performed a randomized, double-blind, placebo-controlled trial to determine the effect of GH on adult height in peripubertal children. Subjects (n = 68; 53 males and 15 females), 9-16 yr old, with marked, idiopathic short stature [height or predicted height < or = -2.5 sd score (SDS)] received either GH (0.074 mg/kg) or placebo sc three times per week until they were near adult height. At study termination, adult height measurements were available for 33 patients after mean treatment duration of 4.4 yr. Adult height was greater in the GH-treated group (-1.81 +/- 0.11 SDS, least squares mean +/- sem) than in the placebo-treated group (-2.32 +/- 0.17 SDS) by 0.51 SDS (3.7 cm; P < 0.02; 95% confidence interval, 0.10-0.92 SDS). A similar GH effect was demonstrated in terms of adult height SDS minus baseline height SDS and adult height SDS minus baseline predicted height SDS. Modified intent-to-treat analysis in 62 patients treated for at least 6 months indicated a similar GH effect on last observed height SDS (0.52 SDS; 3.8 cm; P < 0.001; 95% confidence interval, 0.22-0.82 SDS) and no important dropout bias. In conclusion, GH treatment increases adult height in peripubertal children with marked idiopathic short stature.

Adolescent↗

PubMed2002

Sample size determination for phase II studies of new vaccines.

Prior to the evaluation of protective efficacy, experimental vaccines conventionally undergo phase II randomized controlled clinical trials to evaluate safety and immunogenicity. Typically, an experimental vaccine is compared to another vaccine or to a placebo with respect to adverse events or immune responses, or both. Various strategies and methods are available for design and analysis of such studies. A key aspect of design is the determination of sample size. Often a sample size is chosen that gives a high probability ("power") of finding a statistically significant difference in an outcome of interest, if a difference of a specified size exists. This approach is appropriate when the primary goal of the study is to demonstrate that a difference exists between two groups or treatments. It may not, however, give adequate assurance that a confidence interval around the observed difference will be narrow enough to exclude the possibility of an unacceptably low immune response or unacceptably high adverse event frequency in recipients of the experimental vaccine. In this paper, we apply the "non-inferiority" trial design to phase II vaccine studies; that is, we design the trial to rule out a difference between the vaccine and control in immunogenicity or reactogenicity that is considered unacceptable. We also consider a setting in which the desire is to show that the difference between immune response rates for vaccine and control is greater than a specified value.

Cholera Vaccines↗

PubMed2002

Birthweight and gestational age effects on motor and social development.

The number of children at risk for delays in motor and social development (MSD) associated with preterm delivery and low birthweight is increasing, but such children are generally not seen as being in need of evaluation. The objective of these analyses was to determine whether there are independent effects of birthweight and gestational age on MSD and the magnitude of effects. Subjects were a representative sample of 4621 US-born singleton children, aged 2-47 months, examined in the third National Health and Nutrition Examination Survey (1988-94). MSD was assessed using an age-appropriate scale. Birthweight and gestational age were taken from birth certificates. Mexican-American and 'other' race/ethnicity (other than non-Hispanic white, non-Hispanic black or Mexican-American), low parental education level, older maternal age, higher birth order, low birthweight (LBW, <2500 g) and preterm delivery (<37 weeks) were all found to be associated with significant (P < 0.01) delays in MSD. Three per cent of the infants and children were preterm LBW and 2.2% term LBW (<2500 g, 37-44 weeks). Adjusting for socio-demographic factors, preterm LBW children had lower MSD scores (-1.5 +/- 0.3 points, P < 0.0001) through early childhood, as did term LBW children (0.8 +/- 0.4 points, P < 0.03). For females, LBW was the most important perinatal predictor of a lowered score (-0.9 +/- 0.3 points compared with normal birthweight, P < 0.04). For males, scores were additionally decreased by -0.1 +/- 0.03 points/week (P=0.001) of early delivery. LBW children had less muscle mass, but adjusting for muscularity did not diminish the effects of birth size on MSD. LBW status and preterm delivery are associated independently with small, but measurable, delays in MSD through early childhood and should be considered along with other known risk factors for development delays in determining the need for developmental evaluation.

Adult↗

PubMed2002

Reassessing the labor curve in nulliparous women.

OBJECTIVES: Our purpose was to examine the pattern of labor progression in nulliparous parturients in contemporary obstetric practice. STUDY DESIGN: We extracted detailed labor data from 1329 nulliparous parturients with a term, singleton, vertex fetus of normal birth weight after spontaneous onset of labor. Cesarean deliveries were excluded. We used a repeated-measures regression with a 10th-order polynomial function to discover the average labor curve under contemporary practice. With use of an interval-censored regression with a log normal distribution, we also computed the expected time interval of the cervix to reach the next centimeter, the expected rate of cervical dilation at each phase of labor, and the duration of labor for fetal descent at various stations. RESULTS: Our average labor curve differs markedly from the Friedman curve. The cervix dilated substantially slower in the active phase. It took approximately 5.5 hours from 4 cm to 10 cm, compared with 2.5 hours under the Friedman curve. We observed no deceleration phase. Before 7 cm, no perceivable change in cervical dilation for more than 2 hour was not uncommon. The 5th percentiles of rate of cervical dilation were all below 1 cm per hour. The 95th percentile of time interval for fetal descent from station +1/3 to +2/3 was 3 hours at the second stage. CONCLUSION: Our results suggest that the pattern of labor progression in contemporary practice differs significantly from the Friedman curve. The diagnostic criteria for protraction and arrest disorders of labor may be too stringent in nulliparous women.

Adult↗