TROPHY registry - status report.

INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.

Gene mutations with characteristic deletions in cord blood T lymphocytes associated with passive maternal exposure to tobacco smoke.

We have investigated the molecular effects of passive maternal cigarette exposure in a newborn population and consider the possible implications of the observed genetic changes in the development of neoplastic diseases in children. We present a distribution analysis of somatic mutational events in a reporter gene, HPRT, in cord blood T lymphocytes from newborns after transplacental exposure to cigarette smoke. Analysis of 30 HPRT mutant isolates from 12 newborn infants born to mothers with no evidence of environmental exposure to cigarette smoke and 37 HPRT mutant isolates from 12 infants born to mothers exposed to passive cigarette smoke showed a significant difference in the HPRT mutational spectrum in those exposed in utero to cigarette smoke. The most notable change was an increase in 'illegitimate' genomic deletions mediated by V(D)J recombinase, a recombination event associated with hematopoietic malignancies in early childhood. Recent epidemiological studies of maternal and paternal cigarette smoke exposure and childhood cancers may need to be re-interpreted, given these results.

Screening for breast cancer: time, travel, and out-of-pocket expenses.

BACKGROUND: We estimated the personal costs to women found to have a breast problem (either breast cancer or benign breast disease) in terms of time spent, miles traveled, and cash payments made for detection, diagnosis, initial treatment, and follow-up. METHODS: We analyzed data from personal interviews with 465 women from four communities in Florida. These women were randomly selected from those with a recent breast biopsy (within 6-8 months) that indicated either breast cancer (208 women) or benign breast disease (257 women). One community was the site of a multifaceted intervention to promote breast screening, and the other three communities were comparison sites for evaluation of that intervention. All P values are two-sided. RESULTS: In comparison with time spent and travel distance for women with benign breast disease (13 hours away from home and 56 miles traveled), time spent and travel distance were statistically significantly higher (P<.001) for treatment and follow-up of women with breast cancer (89 hours and 369 miles). Personal financial costs for treatment of women with breast cancer were also statistically significantly higher (breast cancer = $604; benign breast disease = $76; P < .001) but were statistically significantly lower for detection and diagnosis (breast cancer = $170; benign breast disease = $310; P < .001). Among women with breast cancer, time spent for treatment was statistically significantly lower (P = .013) when their breast cancer was detected by screening (68.9 hours) than when it was detected because of symptoms (84.2 hours). Personal cash payments for detection, diagnosis, and treatment were statistically significantly lower among women whose breast problems were detected by screening than among women whose breast problems were detected because of symptoms (screening detected = $453; symptom detected = $749; P = .045). CONCLUSION: There are substantial personal costs for women who are found to have a breast problem, whether the costs are associated with problems identified through screening or because of symptoms.

Gestational age and gender-specific in utero V(D)J recombinase-mediated deletions.

Recent studies have brought to the forefront the importance of somatic mutations during human fetal development and malignant transformation in children, specifically leukemia. Therefore, a better understanding of the frequency and mutational spectrum of spontaneous in utero mutations is essential for understanding the genetic mechanisms associated with pediatric malignancies. Previously we reported that the frequency of somatic mutations during the late stages of fetal development was dependent on both gestational age and gender. Here we present the hypoxanthine-guanine phosphoribosyltransferase (HPRT) reporter gene mutational spectra analysis for 60 T-cell mutant isolates from the umbilical cord blood of preterm newborns to gain insight into background mutational events during the late stages of fetal development. Logistic regression analyses showed a significant increase in HPRT deletions mediated by V(D)J recombinase in preterm newborns compared with full-term newborns (P = 0.009). A comparative analysis of deletion mutations also revealed that V(D)J recombinase-mediated HPRT deletions increased with decreasing gestational age (P = 0.012) and were significantly higher in females than males of the same developmental status (P = 0.031). Developmental and gender-specific differences in HPRT deletions mediated by V(D)J recombinase provide insight into the gender-specific differences seen in infant leukemia.

Ambient particulate matter causes activation of the c-jun kinase/stress-activated protein kinase cascade and DNA synthesis in lung epithelial cells.

Numerous epidemiological studies have demonstrated a positive association between ambient air pollution and adverse health effects including respiratory morbidity, asthma, and lung cancer. It has been suggested in some experimental studies that airborne particulate matter (PM) can produce inflammatory effects, but nothing is known about the possible proliferative and carcinogenic effects of these particles on cells of the lung. We show here that exposure of pulmonary epithelial cells, a cell type affected in acute lung injury, asthma, and lung carcinomas, to nontoxic concentrations of PM in vitro results in increases in c-jun kinase activity, levels of phosphorylated cJun immunoreactive protein, and transcriptional activation of activator protein-1-dependent gene expression. These changes are accompanied by elevations in numbers of cells incorporating 5'-bromodeoxyuridine, a marker of unscheduled DNA synthesis and/or cell proliferation. Data here are the first to demonstrate that interaction of ambient PM with target cells of the lung initiates a cell signaling cascade related causally to aberrant cell proliferation and carcinogenesis.

Inhibition of protein kinase C prevents asbestos-induced c-fos and c-jun proto-oncogene expression in mesothelial cells.

Asbestos and the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), increase c-fos and c-jun mRNA levels and AP-1 DNA binding activity in rat pleural mesothelial (RPM) cells, a target cell of asbestos-induced mesotheliomas (N. H. Heintz et al., Proc. Natl. Acad. Sci. USA, 90: 3299-3303, 1993). Because protein kinase C (PKC) is the intracellular receptor of phorbol ester tumor promoters and asbestos is a putative tumor promoter in the respiratory tract, we hypothesized that PKC might play a critical role in asbestos-induced cell signaling pathways associated with regulation of proto-oncogenes. Using a panel of PKC antibodies, we identified PKC alpha as the major PKC isozyme in RPM cells. We then pretreated cells with phorbol ester dibutyrate to down-modulate PKC or with calphostin C, a specific PKC inhibitor, to determine if depletion of PKC alpha could block asbestos-induced c-fos/c-jun expression. Quantitation of Northern blots showed that fiber-associated c-fos/c-jun mRNA levels were significantly lower either after PKC alpha down-modulation or pretreatment with calphostin C. In addition, to determine whether tyrosine kinases also were involved in proto-oncogene activation by asbestos, tyrphostin AG82 or herbimycin A was added to RPM cells before exposure to asbestos. These inhibitors decreased crocidolite-induced c-fos but not c-jun levels, suggesting that tyrosine kinases have different regulatory roles in asbestos-induced c-fos versus c-jun signaling pathways. The ability to block induction of asbestos-induced proto-oncogene expression using pharmacological intervention may be important in prevention and treatment of asbestos-induced proliferative diseases including lung cancers, mesothelioma, and pulmonary fibrosis.

Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells.

Only two DNA repair enzymes, DNA polymerase beta and O6-methylguanine-DNA methyltransferase, have been shown to be inducible in mammalian cells by genotoxic agents. We show here that crocidolite asbestos induces the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothelioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 microg/cm2 significantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleural mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle. Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus but also in mitochondria. Our data are the first to demonstrate the inducibility of AP-endonuclease by a human class I carcinogen associated with oxidant stress in normal cells of the lung.

Smoking cessation counseling during periodic health examinations.

Periodic health examinations are an excellent opportunity to counsel smokers to quit. The impact of a specialized smoking cessation counselor on the smoking behavior of patients having periodic health examinations was studied in a general internal medicine practice. One hundred fifty-five smokers having periodic health examinations were randomly assigned to a control group who received usual physician advice or an intervention group who received usual physician advice and two counseling sessions with a smoking cessation counselor. The two groups were similar in all demographic variables, smoking-related baseline variables, and baseline levels of motivation and intention to quit smoking. The smoking status of 97% of the subjects was assessed 6 months later. In the intervention group, 46% made quit attempts and 19% quit, compared with 34% and 12%, respectively, in the control group. Intervention-group smokers made more quit attempts (mean +/- SD, 5.0 +/- 2.5 vs 1.8 +/- 0.2) and had a greater reduction in daily cigarette use (8.4 +/- 1.5 vs 3.5 +/- 1.3). Of the 74% of smokers with higher levels of motivation to quit smoking, more intervention-group smokers attempted to quit (70.8% vs 45.5%) and succeeded in quitting at the 6-month follow-up (27.1% vs 10.9%). Periodic health examinations are an excellent opportunity to counsel smokers to quit, especially those smokers with higher levels of motivation to quit smoking.

Metallothionein in human lung carcinoma.

Eleven pairs of surgically resected lung cancers and corresponding non-neoplastic lung tissue were evaluated for metallothionein (MT) and metal content (cadmium and copper) by the heme/109Cd binding assay and atomic absorption spectroscopy, respectively. Tissue samples, obtained from patients ranging in age from 51 to 79, included six adenocarcinomas, two small cell carcinomas, one mixed cell carcinoma, one squamous cell carcinoma, and one carcinoma of non-primary origin (i.e., melanoma). Paired t-tests showed that metallothionein and copper concentrations in lung tumor tissue were significantly elevated when compared to non-malignant lung tissue. Cu was the major metal associated with the 10 kDa MT fraction in lung tumors whereas Cd was the primary metal bound to MT from non-neoplastic lung tissue. Since Cu-thionein is also known to be elevated in fetal lung tissue, the possibility exists that MT might represent an oncodevelopmental product which is useful as a biomarker for the early detection of lung carcinoma.

Handwashing and glove use in a long-term-care facility.

OBJECTIVES: To determine glove use and handwashing practices, the factors associated with infection control practices, and the frequency of potential microbial transmission in a long-term-care facility (LTCF). DESIGN: Observational study of 230 staff-resident interactions in an LTCF. We recorded resident characteristics, type of activity, staff credentials, and movements of the staff member's hands, then used the LTCF's guidelines to judge appropriateness of glove use and handwashing. SETTING: 255-bed, university-based LTCF in Baltimore, Maryland. PARTICIPANTS: A systematic sample of staff-resident interactions. RESULTS: Gloves were worn in 139 (82%) of 170 interactions when indicated, but changed appropriately in only 1 (16%) of 132. Hands were washed when needed before an interaction in 27%, during an interaction in 0%, and after an interaction in 63%. Gloves were less likely to be used when caring for residents with gastrostomy tubes compared with other residents (relative risk, 0.85; 95% confidence interval, 0.73-0.98). Guidelines were followed more frequently during wound care than during other activities. Microbial transmission potentially could have occurred in 158 (82%) of 193 evaluable interactions. CONCLUSIONS: We documented marked deficiencies in glove and handwashing, demonstrated the possible impact of these deficiencies, and identified factors associated with inadequate handwashing and glove use. This information can be used in future educational and research efforts to improve infection control practices.

Smoking in pregnancy, exhaled carbon monoxide, and birth weight.

OBJECTIVE: To examine the relation of cigarette consumption and exhaled carbon monoxide levels during pregnancy and to assess the effect of these smoking measures on birth weight. METHODS: Cigarette consumption and exhaled carbon monoxide levels were recorded at the first prenatal visit and the 36-week visit from women who smoked early in pregnancy. Analysis of variance was used to compare birth weights for differing levels of cigarette consumption and exhaled carbon monoxide. Correlation and regression analyses were used to estimate the effects of the smoking measures at both prenatal visits on birth weight. RESULTS: Cigarette consumption and exhaled carbon monoxide levels at both visits were associated significantly with birth weight. After the first prenatal visit, a reduction in cigarette consumption of at least nine cigarettes per day or in exhaled carbon monoxide of 8 parts per million (ppm) was associated with gains in birth weight of 100 g or more. The proportion of low birth weight (LBW) infants increased significantly with increasing levels of cigarette consumption and with increasing concentrations of exhaled carbon monoxide. CONCLUSION: Substantial reductions in cigarette consumption or in exhaled carbon monoxide levels after the first prenatal visit are needed to achieve gains in birth weight. Not smoking, or having an exhaled carbon monoxide level less than 5 ppm minimizes the likelihood of having an LBW infant.

Predicting hospital charges for trauma care.

Diagnosis related groups (DRGs) have sharply decreased the amount of compensation hospitals can expect for providing trauma care. A total of 637 patients admitted for acute traumatic injuries between Oct 1, 1985, and July 30, 1986, had their DRG classifications, Injury Severity Scores, trauma scores, and ages compared with hospital charges in an attempt to identify factors that could be used to accurately predict hospital charges. The best prediction of charges was obtained when DRG assignment was combined with Injury Severity Scores and age. When the equation obtained by this approach was applied to a separate population of 301 patients, the average difference between the actual charge and that predicted was $38 and would have led to a 33-fold decrease in money lost by the hospital. Altering the DRG payment schedule as proposed would allow hospitals to be fairly compensated for the care of trauma patients.

The epidemiologic features of nosocomial infections in patients with trauma.

Sepsis is a major cause of morbidity and mortality in patients with trauma. To elucidate factors that might lead to infection, we studied the epidemiologic characteristics of nosocomial infections in our patient population with trauma. During a 3.5-year period, 2496 patients were entered into our hospital trauma registry and cross-matched with hospital infection control surveillance information. Two hundred twenty-nine patients with trauma and nosocomial infections were identified (9.2%), a figure that was nearly twice the nosocomial infection rate for the general hospital population. The majority of those infected were either orthopedic (51%), general surgical (25%), or neurosurgical (13%) patients. The most common sites of first infection were urinary tract (61%) or respiratory system (14%). Patients developing nosocomial infections were significantly older and had a higher Injury Severity Score than those who did not. Injury site was related to risk of infection with injuries of the spine, chest, and extremity showing the most significant relationship. The length of stay as well as hospital charges were significantly related to the occurrence of infectious complications. By determining the patient with trauma at risk for infection, treatment strategies can be designed to minimize septic complications.

Decreasing the incidence of surgical wound infections. Validation of a surveillance-notification program.

In an attempt to validate the observations of a previously published ten-year study of surgical wounds, we studied 8,474 wounds over an 18-month period using a protocol nearly identical to that of the previous study. Our study corroborated the following predictors of clean-wound infection: increasing duration of surgery, age less than 1 or greater than 50 years, increasing duration of preoperative hospitalization, use of drains, and shaving and emergency surgery. We failed to corroborate use of wound irrigation as a protective measure or time of preoperative shaving as a significant variable. Most importantly, we found a 42% reduction in the clean-wound infection rate during the study period (1.9% to 1.1%), adding support to the concept that a wound surveillance program with surgeon notification is both efficacious and cost-effective.

Helping women quit smoking: baseline observations for a community health education project.

INTRODUCTION: Our objectives were (1) to examine the relationship between women's intention of stopping smoking in the next month and a broad range of mediating variables and (2) to assess the implications of these relationships for intervention components of a comprehensive community-wide health education program to help women quit smoking. METHODS: In preparation for the community-wide program to help women quit smoking, baseline data were collected through a random digit dialing telephone survey of 6,324 adult women, 18-64 years of age. RESULTS: At baseline, smoking prevalence, defined as smoking an average of one or more cigarettes per day, was 25.8% and showed clear relationships with age and income, but most strikingly with education, indicating the need for programs for women of childbearing age with low incomes and fewer years of schooling. Among female smokers, knowledge of the health effects of smoking; motivations toward quitting; confidence in controlling weight, or handling stress, anger or boredom; number of strategies named to cope when upset of angry; number of community smoking cessation resources named; perceptions of support for quitting; and perceptions of norms concerning women smoking varied significantly with level of intention to quit smoking in the next month. CONCLUSIONS: These relationships provided support for the broad range of health behavior change strategies proposed for this community-based program to help women quit smoking.

Educational and psychosocial needs of patients with chronic disease. A survey of preferences of patients with rheumatoid arthritis.

There is increasing interest in better defining and meeting the nonmedical needs of patients with chronic diseases, such as rheumatoid arthritis (RA). We surveyed patients with RA about the importance of eight psychosocial and eight educational issues, and asked patients from what source they preferred to get help with these issues and which sources they would not use. We also looked at individual variables, including sex, age, disease duration, and disease severity, to see if they affected patients' choices. The issues rated most important by patients included communicating with the doctor, understanding medication, dealing with pain, and the effects of arthritis on energy level, the future, and work. Most patients preferred to seek help from their physicians, although up to 75% were willing to attend groups, and 68% were willing to see individual counselors for some issues.

Ankle ligament injury risk factors: a prospective study of college athletes.

Over two million individuals suffer ankle ligament trauma each year in the United States, more than half of these injuries are severe ligament sprains; however, very little is known about the factors that predispose individuals to these injuries. The purpose of this study was to determine the risk factors associated with ankle injury. We performed a prospective study of 118 Division I collegiate athletes who participated in soccer, lacrosse, or field hockey. Prior to the start of the athletic season, potential ankle injury risk factors were measured, subjects were monitored during the athletic season, and injuries documented. The number of ankle injuries per 1,000 person-days of exposure to sports was 1.6 for the men and 2.2 for the women. There were 13 injuries among the 68 women (19%) and seven injuries among the 50 men (13%), but these proportions were not significantly different. Women who played soccer had a higher incidence of ankle injury than those who played field hockey or lacrosse. Among men, there was no relationship between type of sport and incidence of injury. Factors associated with ankle ligament injury differ for men relative to women. Women with increased tibial varum and calcaneal eversion range of motion are at greater risk of suffering ankle ligament trauma, while men with increased talar tilt are at greater risk. Generalized joint laxity, strength, postural stability, and muscle reaction time were unrelated to injury.

Quantification of the expanded role of the nurse practitioner: a discriminant analysis approach.

Graduates of a family nurse practitioner program and a sample of nonpractitioner nurses were compared in terms of their professional roles and concomitant attitudes. The stepwide discriminant analysis technique used in the study permitted adjustments for variables that affect nursing roles and provided a method for quantifying differences between the two groups of nurses. Role differences were characterized by the nurse practitioners' more frequent performance of functions relatively new to the nursing profession, such as physical assessment and prescription of medications, as well as functions more traditional to nursing. Among the latter were several dimensions of patient education and counseling. Attitudes of the nurses toward their own role also differed between the two groups and may reflect a commitment to professional growth on the part of the nurse practitioners which is not as prominent among their nonpractitioner counterparts.

Factors associated with arm swelling after breast cancer surgery.

PURPOSE: As life expectancy improves for women with breast cancer, more women will be living with symptoms of lymphedema. This study reports the incidence of arm or hand swelling and associated risk factors in women with invasive breast cancer following surgery. METHODS: Data were obtained from baseline and follow-up interviews of women with invasive breast cancer (n = 145), and mammography and pathology records. The Kaplan-Meier method was used to estimate the probability of developing arm or hand swelling over time. Univariate and multivariate logistic regression analyses were conducted to identify risk factors for arm or hand swelling. RESULTS: Of women in this study, 38% self-reported arm or hand swelling. There was a significantly increased risk of arm swelling if women were under 50 years of age, had axillary node dissection, received chemotherapy, worked outside the home, and had a high household income. There was no association of body weight with swelling. A significantly decreased risk of arm swelling was found in women who were on treatment for high blood pressure. After adjustment for nodal dissection, only age had a significant independent effect. CONCLUSIONS: Our study highlights two important areas of future research that could reduce the incidence of lymphedema. There is a need to better understand the role that treatment for high blood pressure may play in protecting women from arm edema. Second, the potential effect of weight as a modifiable lymphedema risk factor needs to be studied in more detail in light of the conflicting results of different studies.

Biomarkers for assessing occupational exposures to 1,3-butadiene.

The overall objective of this study was to evaluate a continuum of biomarkers in blood and urine for their sensitivities as indicators of low level occupational exposures to 1,3 butadiene (BD). The study design was largely cross-sectional, with biological samples collected within a short timeframe. Personal 8-h BD exposure measures were made on several occasions over a 60-day period for each potentially exposed worker in order provide maximum accuracy for this independent variable and to accommodate the different expression intervals of the several biomarkers. Co-exposures to styrene, toluene and benzene were also measured. The study included 24 BD monomer production workers (mean BD exposure=0.642 mg/m(3)), 34 polymerization workers (mean BD exposure=1.794 mg/m(3)) and 25 controls (mean BD exposure=0.023 mg/m(3)). The several biomarkers were measured by a consortium of investigators at different locations in the US and Europe. These biomarkers included: (1) metabolic genotypes (CYP2E1, EH, GST M1, GST T1, ADH2, ADH3), determined in Prague and Burlington, VT; (2) urinary M1 and M2 metabolites (1,2-dihydroxy-4-[N-acetylcysteinyl]-butane and 1-hydroxy-2-[N-acetylcysteinyl]-3-butene, respectively), determined in Albuquerque, NM and Leiden; (3) hemoglobin adducts (N-[2-dihydroxy-3-butenyl]valine=HBVal and N-[2,3,4-trihydroxybutyl]valine=THBVal), determined in Amsterdam and Chapel Hill, NC, respectively; (4) HPRT mutations determined by autoradiographic assay in Galveston, TX, with slides re-read in Burlington, VT; (6) hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutations determined by cloning assay in Leiden with mutational spectra characterized in Burlington, VT; (7) sister chromatid exchanges and chromosome aberrations determined by standard methods and FISH analysis in Prague. Urinary M1 and M2 metabolites and HBVal and THBVal hemoglobin adducts were all significantly correlated with BD exposure levels, with adducts being the most highly associated. No significant relationships were observed between BD exposures and HPRT mutations or any of the cytogenetic endpoints, regardless of method of assay.