The influence of resuscitation preferences on obstetrical management of periviable deliveries.

OBJECTIVE: To determine the relative influence of patients' resuscitation preferences on periviable delivery management. STUDY DESIGN: Surveyed 295 obstetrician-gynecologists about managing periviable preterm premature rupture of membranes. Across 10 vignettes, we systematically varied gestational age, occupation, method of conception and resuscitation preference. Physicians rated their likelihood (0 to 10) of proceeding with induction, steroids and cesarean. Data were analyzed via conjoint analysis. RESULT: Two hundred and five physician responses were included. Median ratings for management decisions were: induction 1.89; steroids 5.00; cesarean for labor 3.89; and cesarean for distress 4.11. Gestational age had the greatest influence on physician ratings across all decisions (importance values ranging from 72.6 to 86.6), followed by patient's resuscitation preference (range=9.3 to 21.4). CONCLUSION: Gestational age is weighted more heavily than patients' resuscitation preferences in obstetricians' decision making for periviable delivery management. Misalignment of antenatal management with parental resuscitation preferences may adversely affect periviable outcomes. Interventions are needed to facilitate more patient-centered decision making in periviable care.

Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group.

OBJECTIVE: This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). METHODS: Primary endpoints were maximum tolerated dose of sorafenib with weekly topotecan (phase I) and response rate (phase II). Secondary endpoints were progression free survival (PFS), overall survival (OS), toxicity, and rate of clinical benefit. Eligibility included recurrent platinum-resistant OC or PPC, <3 prior regimens, normal end-organ function. 3+3 dose escalation was used for phase I, sorafenib being tested at 400mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m(2) to 3.5mg/m(2) IV weekly. The phase II regimen was sorafenib 400mg daily and topotecan 3.5mg/m(2) weekly on days 1, 8, 15 of a 28 days cycle. RESULTS: 16 patients were enrolled in phase I and 14 patients in phase II. Median age was 52.5 years (range 35-79), 27 patients had OC, and 3 PPC. Median number of cycles administered was 2.5 (0-15). There were 5 partial responses (PR) (16.7%), and 14 patients (46.7%) with stable disease (SD). Four PRs were recorded during phase I and 1 during phase II. One of those PRs occurred in a patient with platinum-sensitive disease. Grade 3/4 toxicities included leukopenia/neutropenia (23%), thrombocytopenia (17%), anemia (10%), fatigue, nausea, vomiting (7% each). One case of grade 3 hand-foot syndrome was recorded. CONCLUSIONS: The combination of sorafenib and topotecan causes significant toxicity, precluding administration of full doses and resulting in modest clinical efficacy in platinum resistant OC or PPC.

Behavior problems in children at time of first recognized seizure and changes over the following 3 years.

OBJECTIVES: The purposes of this 36-month study of children with first recognized seizures were: (1) to describe baseline differences in behavior problems between children with and without prior unrecognized seizures; (2) to identify differences over time in behavior problems between children with seizures and their healthy siblings; (3) to identify the proportions of children with seizures and healthy siblings who were consistently at risk for behavior problems for 36 months; and (4) to identify risk factors for behavior problems 36 months following the first recognized seizure. Risk factors explored included demographic (child age and gender, caregiver education), neuropsychological (IQ, processing speed), seizure (epileptic syndrome, use of antiepileptic drug, seizure recurrence), and family (family mastery, satisfaction with family relationships, parent response) variables. METHODS: Participants were 300 children aged 6 through 14 years with a first recognized seizure and 196 healthy siblings. Data were collected from medical records, structured interviews, self-report questionnaires, and neuropsychological testing. Behavior problems were measured using the Child Behavior Checklist and the Teacher's Report Form. Data analyses included descriptive statistics and linear mixed models. RESULTS: Children with prior unrecognized seizures were at higher risk for behavior problems at baseline. As a group, children with seizures showed a steady reduction in behavior problems over time. Children with seizures were found to have significantly more behavior problems than their siblings over time, and significantly more children with seizures (11.3%) than siblings (4.6%) had consistent behavior problems over time. Key risk factors for child behavior problems based on both caregivers and teachers were: less caregiver education, slower initial processing speed, slowing of processing speed over the first 36 months, and a number of family variables including lower levels of family mastery or child satisfaction with family relationships, lower parent support of the child's autonomy, and lower parent confidence in their ability to discipline their child. CONCLUSIONS: Children with new-onset seizures who are otherwise developing normally have higher rates of behavior problems than their healthy siblings; however, behavior problems are not consistently in the at-risk range in most children during the first 3 years after seizure onset. When children show behavior problems, family variables that might be targeted include family mastery, parent support of child autonomy, and parents' confidence in their ability to handle their children's behavior.

Academic problems in children with seizures: relationships with neuropsychological functioning and family variables during the 3 years after onset.

OBJECTIVES: Children with long-standing epilepsy have a significantly increased risk of academic underachievement compared with healthy controls. We prospectively followed children from seizure onset to assess the relationship between change in neuropsychological functioning and change in academic achievement and to explore the risk and protective moderating effects of demographic, seizure, and family variables. METHODS: As part of a larger study, neuropsychological and academic data were collected at both baseline and 36 months for 219 children 6-14 years of age with seizures. Prior factor analysis of results from a battery of well-standardized neuropsychological tests yielded four factors: language, processing speed, attention/executive/construction, and verbal memory/learning. Academic achievement was measured with the Woodcock-Johnson Revised Achievement Test Battery. Correlation coefficients and linear mixed models were used for analysis. RESULTS: The reading and math scores of children with seizures and siblings did not differ at baseline, but children with seizures had lower scores than siblings at 36 months. Writing scores were significantly lower for affected children than siblings at both times. Among children with seizures, there were positive correlations between neuropsychological functioning and academic achievement at baseline and 36 months. Changes in language and in verbal memory/learning were positively correlated with change in reading achievement (r = 0.25 and r = 0.17, respectively). Age at onset moderated the association between change in neuropsychological functioning and change in reading and writing achievement (P ≤ 0.006), with stronger relationships among younger children (ß = 0.25-0.44). The association between change in language and change in writing achievement was moderated by caregiver anxiety (P = 0.04; stronger for more anxious parents, ß = 0.40), and the association between change in processing speed and change in math achievement was moderated by etiology (P = 0.02; stronger for symptomatic/cryptogenic vs idiopathic, ß = 0.29). Gender and other family variables did not have significant moderating effects. CONCLUSIONS: Changes in neuropsychological function were associated with changes in academic achievement following onset of seizures, with risk factors being younger age at onset, lower caregiver education, high parental anxiety, and symptomatic/cryptogenic etiology. Academic performance should be closely monitored in children with early-onset seizures.

Neuropsychological status at seizure onset in children: risk factors for early cognitive deficits.

OBJECTIVE: This large, prospective, community-based study characterized neuropsychological functioning and academic achievement at the time of the first recognized seizure and identified risk factors for cognitive deficits. METHODS: We compared 282 children (ages 6-14 years, IQ > or =70) with a first recognized seizure to 147 healthy siblings on a battery of well-standardized and widely used neuropsychological and academic achievement tests and examined relationships with demographic and clinical variables. RESULTS: In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychological deficits at or near onset. Risk factors associated with neuropsychological deficits included multiple seizures (i.e., second unprovoked seizure; odds ratio [OR] = 1.96), use of antiepileptic drugs (OR = 2.27), symptomatic/cryptogenic etiology (OR = 2.15), and epileptiform activity on the initial EEG (OR = 1.90); a child with all 4 risks is 3.00 times more likely than healthy siblings to experience neuropsychological deficits by the first clinic visit. Absence epilepsy carried increased odds for neuropsychological impairment (OR = 2.00). CONCLUSIONS: A subgroup of intellectually normal children with seizures showed neuropsychological deficits at onset. Academic achievement was unaffected, suggesting that there is a window early in the disorder for intervention to ameliorate the impact on school performance. Therefore, the risk factors identified here (especially if multiple risks are present) warrant swift referral for neuropsychological evaluation early in the course of the condition.

The EP1 subtype of prostaglandin E2 receptor: role in keratinocyte differentiation and expression in non-melanoma skin cancer.

We have previously demonstrated that the EP1 subtype of PGE2 receptor is expressed in the differentiated compartment of normal human epidermis and is coupled to intracellular calcium mobilization. We therefore hypothesized that the EP1 receptor is coupled to keratinocyte differentiation. In in vitro studies, radioligand binding, RT-PCR, immunoblot and receptor agonist-induced second messenger studies demonstrate that the EP1 receptor is up-regulated by high cell density in human keratinocytes and this up-regulation precedes corneocyte formation. Moreover, two different EP1 receptor antagonists, SC51322 and AH6809, both inhibited corneocyte formation. SC51322 also inhibited the induction of differentiation-specific proteins, cytokeratin K10 and epidermal transglutaminase. We next examined the immunolocalization of the EP1 receptor in non-melanoma skin cancer in humans. Well-differentiated SCCs exhibited significantly greater membrane staining, while spindle cell carcinomas and BCCs had significantly decreased membrane staining compared with normal epidermis. This data supports a role for the EP1 receptor in regulating keratinocyte differentiation.

Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure.

PURPOSE: Because the bioavailability of oral furosemide is erratic and often incomplete, we tested the hypothesis that patients with heart failure who were treated with torsemide, a predictably absorbed diuretic, would have more favorable clinical outcomes than would those treated with furosemide. PATIENTS AND METHODS: We conducted an open-label trial of 234 patients with chronic heart failure (mean [+/- SD] age, 64 +/- 11 years) from an urban public health care system. Patients received oral torsemide (n = 113) or furosemide (n = 121) for 1 year. The primary endpoint was readmission to the hospital for heart failure. Secondary endpoints included readmission for all cardiovascular causes and for all causes, numbers of hospital days, and health-related quality of life. RESULTS: Compared with furosemide-treated patients, torsemide-treated patients were less likely to need readmission for heart failure (39 [32%] vs. 19 [17%], P <0.01) or for all cardiovascular causes (71 [59%] vs. 50 [44%], P = 0.03). There was no difference in the rate of admissions for all causes (92 [76%] vs. 80 [71%], P = 0.36). Patients treated with torsemide had significantly fewer hospital days for heart failure (106 vs. 296 days, P = 0.02). Improvements in dyspnea and fatigue scores from baseline were greater among patients treated with torsemide, but the differences were statistically significant only for fatigue scores at months 2, 8, and 12. CONCLUSIONS: Compared with furosemide-treated patients, torsemide-treated patients were less likely to be readmitted for heart failure and for all cardiovascular causes, and were less fatigued. If our results are confirmed by blinded trials, torsemide may be the preferred loop diuretic for patients with chronic heart failure.

Acceptance of hepatitis B vaccination among adult patients with sexually transmitted diseases.

BACKGROUND: Sexually transmitted disease (STD) clinic patients are at risk for hepatitis B virus infection, but have been relatively neglected in terms of hepatitis B virus (HBV) immunization. Acceptance of HBV vaccine among patients attending an STD clinic was examined. GOAL: To evaluate potential predictors of HBV vaccine acceptance. STUDY DESIGN: In this study, 99 patients attending an STD clinic completed a brief questionnaire that addressed knowledge of STD and vaccines as well as sexual behavior. After the questionnaire, each patient was offered HBV vaccine, then interviewed to assess reasons for acceptance or refusal. RESULTS: Among the patients in this study, 23% accepted the vaccine and 11% reported prior vaccination. Acceptors were younger, had less education, and used condoms less frequently than those who refused vaccination. The reasons given for acceptance or rejection typically involved health beliefs related to infection or vaccination. CONCLUSION: The findings indicate an unacceptably low rate of HBV vaccine acceptance in a group at high risk for infection. However, some of the reasons for refusal may be modifiable through brief, targeted interventions.

Reliability and validity of the compliance belief scales among patients with heart failure.

BACKGROUND: Lack of medication and dietary compliance leads to troublesome symptoms and hospitalization in patients with heart failure. Compliance behaviors are influenced by beliefs about the behavior. OBJECTIVE: The purpose of this study was to evaluate the reliability and validity of the Beliefs about Medication Compliance Scale (BMCS) and the Beliefs about Dietary Compliance Scale (BDCS) among patients with heart failure. THEORETICAL FRAMEWORK: This study's theoretical framework is the Health Belief Model. METHODS: A convenience sample of 234 patients with heart failure completed the BMCS and the BDCS. Patients completed the scales at baseline by face-to-face interviews and at 8 and 52 weeks after baseline by telephone interview. RESULTS: Construct validity of the scales was supported by confirmatory factor analysis. Both the BMCS and the BDCS had benefits and barriers scales with clear factor loadings. The internal consistency reliability estimates of the scales ranged from.63 to.88, with the BMCS having some estimates lower than.70. The test-retest reliability estimates ranged from.07 to.57. The intraclass correlation coefficient estimates were higher between the 8-week and 52-week scores for all scales. Possible reasons for the varying estimates are discussed. CONCLUSIONS: The BMCS and the BDCS have documented reliability and validity. Future work should be directed at evaluating the responsiveness of the scales to changing patient conditions and testing interventions to improve medication and dietary compliance through changing beliefs.

A high-resolution radiation hybrid map of the human genome draft sequence.

We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

Social support and health-related quality of life in chronic heart failure patients.

OBJECTIVES: Objectives of this study were to: (1) describe perceived social support during a baseline hospitalization and 12 months later among heart failure patients; (2) examine differences in social support as a function of gender and age (less than 65 and 65 years or older); and (3) examine social support as a predictor of health-related quality of life. BACKGROUND: Social support is a predictor of well-being and mortality, but little is known about support patterns among heart failure patients and how they influence quality of life. METHODS: The sample included 227 hospitalized patients with heart failure who completed the Social Support Survey and the Chronic Heart Failure Questionnaire at baseline; 147 patients completed these questionnaires again 12 months after baseline. RESULTS: Mean baseline and 12-month total support scores were 56 and 53, respectively, with a score of 76 indicating the most positive perceptions of support. The ANOVA indicated significant interactions of gender by age for total (F = 5.04; p = 0.03) and emotional/informational support (F = 4.87; p = 0.03) and for positive social interactions (F = 4.43; p = 0.04), with men under age 65 perceiving less support than men aged 65 and older and women in either age group. Baseline support did not predict 12-month health-related quality of life, but changes in social support significantly predicted changes in health-related quality of life (R2 = 0.14). CONCLUSIONS: Overall, perceptions of support were moderate to high, but there was wide variation in perceptions over time. Men under age 65 reported less support than other groups of patients. Importantly, changes in social support were significant predictors of changes in health-related quality of life.

The use of propensity scores in pharmacoepidemiologic research.

PURPOSE: To describe the application of propensity score analysis in pharmacoepidemiologic research using a study comparing the renal effects of two commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs). METHOD: Observational data were collected on the change in renal function, as measured by serum creatinine concentration, before and after use of two NSAIDs, Ibuprofen and Sulindac. To estimate the treatment effect of the different NSAIDs, we used the propensity score methodology to reduce the potential confounding effects caused by unbalanced covariates. After estimating the propensity scores (the probabilities of each patient being prescribed Sulindac) from a logistic regression model, we stratified the data based on sample quintiles of the propensity score distribution. The final estimate of the treatment effect was then obtained by averaging the treatment estimates from the stratified samples. RESULTS: Initially, 23 covariates differed significantly between the two treatment groups. Using the propensity score methodology, we were able to balance the distributions of 16 covariates. The imbalances in the remaining seven covariates were also greatly reduced. Although the use of either drug resulted in a decrease in renal function, overall differences between them were not statistically significant with respect to their effect on creatinine concentrations based on the propensity score analysis. CONCLUSION: Observational studies often produce treatment groups that are not directly comparable due to imbalances in covariate distributions between the treatment groups. Propensity score analysis provides a simple and effective way of controlling the effects of these covariates and obtaining a less biased estimate of the treatment effect. Copyright (c) 2000 John Wiley & Sons, Ltd.