Evaluation of Petrifilm™ aerobic count plates as an equivalent alternative to drop plating on R2A agar plates in a biofilm disinfectant efficacy test.

This paper compares Petrifilm™ aerobic count (AC) plates to drop plating on R2A agar plates as an alternative method for biofilm bacteria enumeration after application of a disinfectant. A Pseudomonas aeruginosa biofilm was grown in a Centers for Disease Control and Prevention biofilm reactor (ASTM E2562) and treated with 123 ppm sodium hypochlorite (as free chlorine) according to the Single Tube Method (ASTM E2871). Aliquots from the same dilution tubes were plated on Petrifilm™ AC plates and drop plated on R2A agar plates. The Petrifilm™ AC and R2A plates were incubated for 48 and 24 h, respectively, at 36 ± 1 °C. After nine experimental runs performed by two technicians, the mean difference in biofilm log densities [log biofilm density (LD) = log10(CFU/cm(2))] between the two methods for control coupons, treated coupons, and log reduction (LR) was 0.052 (p = 0.451), -0.102 (p = 0.303), and 0.152 (p = 0.313). Equivalence testing was used to assess equivalence of the two plating methods. The 90 % confidence intervals for the difference in control and treated mean LDs between methods were (-0.065, 0.170) and (-0.270, 0.064), both of which fall within a (-0.5, +0.5) equivalence criterion. The 90 % confidence interval for the mean LR difference (-0.113, 0.420) also falls within this equivalence criterion. Thus, Petrifilm™ AC plates were shown to be statistically equivalent to drop plating on R2A agar for the determination of control LDs, treated LDs, and LR values in an anti-biofilm efficacy test. These are the first published results that establish equivalency to a traditional plate counting technique for biofilms and for a disinfectant assay.

Indicators of successful implementation of programs to promote healthy weight among women.

Obesity rates have steadily increased over the past two decades. To address the epidemic in women, the Health Resources and Services Administration's Maternal and Child Health Bureau, Division of Healthy Start and Perinatal Services (HRSA/MCHB/DHSPS) awarded 14 demonstration grants to community health centers, health departments, universities and community-based organizations in 12 states to develop innovative approaches aimed at reducing the prevalence of overweight and obesity, specifically in women of childbearing age. Grantees implemented modified or existing evidence-based programs (EBP) or promising practices tailored to the geographic locations, cultures and traditional values of the communities. A review of the 15 programs implemented from 2004 to 2007 was conducted using the methodology outlined in the Transparent Reporting of Evaluations with Nonrandomized Designs Statement to identify indicators of successful program implementation. The six indicators identified were: (1) supportive organizational culture with adequate resources and appropriate staff; (2) attention to the needs of the service population; (3) a referral system that links participants to appropriate services; (4) flexible schedules; (5) support for child care and transportation; and (6) formal and informal support systems to keep participants engaged and motivated. Two of the programs that reported improved participant outcomes are available for replication: La Vida Sana, La Vida Feliz in Illinois was designated as a promising practice by the Association of Maternal and Child Health Programs and Sisters in Action in Michigan was rated as a moderate evidence-based program by the Agency for Healthcare Research and Quality.

The use of C(av) rather than AUC in safety assessment.

Toxicokinetic data have traditionally been presented as maximum observed plasma concentrations (C(max)) and area under the concentration time curve (AUC) values. These values have been used to compare exposures across studies and species to provide valuable interpretation of drug safety data. Increasingly, questions are asked of toxicology studies to more accurately describe the concentration effect relationships in terms of compound affinity for target and off-target receptors. C(max) values can immediately be referenced to known pharmacological activities, particularly when the extent of plasma protein binding is taken into account. This provides a measure of the more pharmacologically relevant free drug exposure. AUC values on the other hand contain the component of time, which means that direct comparison to pharmacological activity values are not immediately possible. Conversion of AUC to average plasma concentration (C(av)) provides a simple and convenient means to allow such a comparison without losing any information imparted by AUC values. In this paper, the benefit and advantage of applying C(av) values is illustrated using examples taken from the literature.

Species differences in the multiple-dose pharmacokinetics of the non-nucleoside reverse transcriptase inhibitor (NNRTI) UK-453,061 in animals and man: implications for safety considerations.

The requirements for safe testing of pharmaceuticals in humans places substantial emphasis on the translation of safety testing performed in animals to man. The comparison of systemic exposure in animals and man has taken on increasing importance in this assessment, with the underlying assumption that plasma concentrations will elicit the same response in different species. This assumption may be flawed for a number of different reasons, one of which is differences in drug disposition between species leading to high doses required in animal species to yield equivalent systemic exposure to humans and consequent higher exposure to organs such as the intestine and liver. Hepatic clearance can vary substantially, particularly between rodents and man, resulting in vast differences in the dose-exposure relationship. A specific example of a non-nucleoside reverse transcriptase inhibitor, which causes substantial auto-induction in rodents, is used to illustrate this situation and the impact this has on the interpretation of safety extrapolation from animals to man. In such circumstances, it is important to recognize the impact of species differences in drug clearance and disposition and consider broader input in the assessment of clinical safety.

Preclinical assessment of the distribution of maraviroc to potential human immunodeficiency virus (HIV) sanctuary sites in the central nervous system (CNS) and gut-associated lymphoid tissue (GALT).

1. Growing knowledge of the pathogenesis of human immunodeficiency virus (HIV)-1 infection has led to the identification of potential virus sanctuary sites within the central nervous system and gut-associated lymphoid tissue. 2. Maraviroc is a novel CCR5 antagonist for the treatment of HIV-1 infection. Disposition studies have been performed within the preclinical testing of maraviroc to determine its distribution to these anatomical sites. 3. Maraviroc, which is a substrate of the efflux transporter P-glycoprotein, shows limited distribution to the central nervous system as evidenced by cerebrospinal fluid concentrations that were 10% of the free plasma concentration following intravenous infusion to rats. Tissue distribution studies also indicated limited distribution of radioactivity into brain tissue of rats. 4. Radioactivity in gut-associated lymphoid tissue lymph nodes exceeded the concentrations in blood and concentrations in the contents of thoracic ducts of the lymphatic system were similar to blood levels following intravenous administration to rats.

Chronic conditions, socioeconomic risks, and behavioral problems in children and adolescents.

Children with a chronic health condition have long been considered at excess risk for psychosocial morbidity. Despite an increasing prevalence of chronic childhood conditions and heightened concerns for the quality of life of the chronically ill, population-based studies of behavior problems among children with chronic physical conditions are rare. Findings on the epidemiology of behavior problems in a nationally representative sample of 11,699 children and adolescents aged 4 to 17 years in the United States are reported. Data included a 32-item parent-reported behavior problem index, measures of chronic childhood conditions, measures of school placement and performance, and sociodemographic variables. Analyses confirmed that chronic physical conditions were a significant risk factor for behavior problems, independent of sociodemographic variables. Among children these differences were observed across all subscales; among adolescents the largest differences were found for the Depression/Anxiety and Peer Conflict/Social Withdrawal subscales. Rates of extreme behavior problem scores (those in the top 10th percentile) were 1.55 times higher among children with a chronic health condition compared with children without a chronic condition (95% confidence interval 1.29 to 1.86). These independent odds were lowered to 1.44 when covariates for confounding were introduced via a multivariate logistic regression. Other independent risks included the absence of either biologic parent (odds ratio 2.05), male gender (1.53), low vs high family income (1.30), low vs high maternal education (1.51), and young vs old maternal age at childbirth (2.57). Chronic health conditions were also a major risk factor for placement in special education classes and having to repeat grades. Despite evidence for effective interventions, health services for children with chronic conditions--particularly mental health services--remain fragmented, signaling the need for increased attention to behavioral problems and their treatment among all health professionals caring for children.

Maternal smoking and childhood asthma.

According to a substantial literature, passive smoking by children is associated with an increased incidence of lower respiratory illness and diminished pulmonary function. The relationship between passive smoking and childhood asthma, however, is not clear. Data from the Child Health Supplement to the 1981 National Health Interview Survey were analyzed with information about 4331 children aged 0 to 5 years to study the relationship between maternal smoking and (1) the prevalence of childhood asthma, (1) the likelihood of taking asthma medication, (3) the age of onset of children's asthma, and (4) the number of hospitalizations among children with and without asthma. An odds ratio for asthma of 2.1 was shown by multivariate logistic regressions among children whose mothers smoke 0.5 packs of cigarettes or more per day compared with children of nonsmokers (P = .001). In similar analyses maternal smoking of 0.5 packs per day was identified as an independent risk for children's use of asthma medications (odds ratio 4.6, P = .0006) and for asthma developing in the first year of life (odds ratio 2.6, P = .0006). Maternal smoking is also associated with increased numbers of hospitalizations by its association with an increased risk of asthma as well as by contributing to hospitalizations independently of a child having asthma. Among children with asthma, however, maternal smoking is not associated with increased numbers of hospitalizations. It was concluded that maternal smoking is associated with higher rates of asthma, an increased likelihood of using asthma medications, and an earlier onset of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Health insurance coverage and physician use among children with disabilities: findings from probability samples in five metropolitan areas.

The effect of insurance coverage on physician use for children in the United States who have been identified as disabled by their schools under the provisions of the Education for All Handicapped Children Act (PL 94-142) is examined. The research is based on identically drawn stratified random samples of children from the elementary school special education populations of five large metropolitan school systems. It was found that health insurance coverage was a predictor of whether a disabled child had seen a doctor in the past year even after adjustment for site, family background characteristics, type and severity of childhood disability, and structural access factors (adjusted odds ratio, 1.76, P less than .05); Hispanic children with disabilities were more likely than white children to be without any health insurance (adjusted odds ratio, 3.63; P less than .001), but there was no similar statistically significant difference between blacks and whites; and wide variations persist in scope of insurance payment for care, such that parents of publicly insured children paid out of pocket for only 5% of all physician visits as compared to 30% of visits for the privately insured. Even for children with various low-prevalence disabilities, when privately insured, parents paid out of pocket for 23% of all physician visits. These data help clarify the extent of health insurance coverage among children with disabilities and indicate that insurance remains an important predictor of physician use even though it continues to pay for only certain elements of care.

Providing therapeutic services to children in special educational placements: an analysis of the related services provisions of Public Law 94-142 in five urban school districts.

Using the sample of 1726 special education students from the Collaborative Study of Children With Special Needs, the authors describe the related services being provided to the children and then analyze the relationship between service provision and class placement. Related services are provided in all settings, with a concentration in special schools and special classes. For even the most severely involved children the trade-off with academics is no more than 1 hour per day. It is argued that schools now are major sites of therapeutic service provision for children with special needs.

Technology's children: report of a statewide census of children dependent on medical supports.

In April 1987, a census of children dependent on medical technology was carried out in Massachusetts to determine the one-month point prevalence. All medical and educational providers in the state who were likely to interact with such children were contacted and asked to complete a two-sided data form on youngsters (aged 3 months to 18 years) with tracheostomies, supplementary oxygen, respirators, suctioning, gastric feeding, central venous lines, ostomies, ureteral diversion, urethral catheterization and dialysis. Nearly 1250 children were found meeting these criteria. Capture-recapture analysis set the lower bound for technology dependence at 0.08% of the state's children. An analysis of the organ systems involved showed that 57% of the children had neurologic involvement--13% multisystem, 7% gastrointestinal-metabolic, 4% renal-genitourinary, and 3% musculoskeletal. Less than 1% of the children were reported as having immunologic or "other" disorders. Review of putative etiologies indicated that 45% of the children had congenital anomalies, 33% chronic medical diseases, 9% perinatal conditions, 7% hereditary-genetic disorders, 5% injuries, 2% infections, and 3% "other." The substantial prevalence of technology dependency among children creates challenges at the social, economic, and policy-making levels. It will be important to carry out systematic reporting and monitoring activities throughout time and across sites. This census is an example of one such statewide effort.

Monitoring and evaluating managed care for children with chronic illnesses and disabilities.

OBJECTIVE: Children with chronic illnesses and disabilities are increasingly enrolling in managed care arrangements. Yet, the rapid expansion of managed care has unknown consequences for children with chronic conditions and disabilities. As managed care is likely to become the predominant mode of medical practice for children with chronic health problems, information gained from a thorough assessment of existing managed care models could be helpful in indicating adjustments and modifications that could result in improved outcomes for this population. the purpose of this article is to outline a new strategy for collecting needed information on the effects of managed care on children with chronic health problems. METHODS: We reviewed the literature on the effects of managed care on children with chronic conditions and disabilities. We identified key domains relevant to monitoring and evaluating managed care for this population. RESULTS: Two research approaches can provide helpful information for assessing the effects of managed care on children with chronic conditions. First, a monitoring strategy could be pursued in which enrollment trends in managed care, enrollee perceptions of access and satisfaction with care, and other general indicators of outcomes would be tracked over time using inexpensive and rapid turnaround data sources. Second, an evaluative strategy could be pursued using experimental or quasiexperimental designs, in which outcomes across a variety of domains for children with chronic conditions in managed care are compared with: (a) outcomes for the same children before enrollment in managed care; or (b) outcomes for similar children remaining in traditional fee-for-service settings. Evaluation and monitoring strategies should focus on outcomes in a number of domains including: (1) access to care; (2) utilization of services; (3) quality of care; (4) satisfaction with care; (5) expenditures for care; (6) health outcomes; and (7) family impact. CONCLUSION: Assessing outcomes that result from enrollment in managed care for children with chronic health problems presents a formidable challenge. The research strategy outlined in this article presents one approach to meeting that challenge. The monitoring and evaluation strategies described here would require commitment of additional resources on the part of government, private foundations, and/or health plans. Given the paucity of existing information and the stakes for children with chronic conditions and their families, investment of added resources in a comprehensive monitoring and evaluation strategy is essential.

Issues involved in the definition and classification of chronic health conditions.

The need for a widely applicable definition of chronic conditions for research, policy, and program development has led to an extensive review of the development of such definitions, the considerations involved in their use, and some recommendations for a new approach. This paper examines some of the methodologic and conceptual issues related to defining and classifying chronic conditions and describes some consequences resulting from decisions made about these issues. While most examples are taken from child health applications, the basic concepts apply to all age groups. The dominant method for identifying and classifying children as having a chronic condition has relied on the presence of an individual health condition of lengthy duration. This condition-specific or "categorical" approach has increasingly seemed neither pragmatically nor conceptually sound. Thus, the development of a "generic" approach, which focuses on elements that are shared by many conditions, children, and families, is recommended. Such a definition might reflect the child's functional status or ongoing use of medical services over a specified time period. In addition, it is suggested that conditions be classified based on the experience of individual children, thus emphasizing the tremendous variability in expression of seemingly similar conditions.

Balloon dilatation of the stenosed aortic valve: how does it work? Why does it fail?

The hemodynamic changes that may occur in patients undergoing aortic balloon valvuloplasty were examined in the circulatory model. Four conclusions were reached. (1) Significant transvalvular pressure gradients appear only if the orifice is severely narrowed. (2) The magnitude of this gradient is highly flow dependent. (3) At critical narrowings, minute alterations in orifice size may induce most significant changes in the transvalvular gradient. (4) In low flow states significant gradients appear only if the stenosis is extreme. In patients with aortic stenosis, especially those with failing hearts and low cardiac output, the pressure gradient may be effectively decreased by minimal dilatation of the aortic orifice. These patients, however, remain in jeopardy because recurrent narrowing may cause a gradient incompatible with life.

New generation tissue valves. Their in vitro function in the mitral position.

The in vitro function of six tissue valves from four manufacturers has been assessed. One porcine bioprosthesis (Carpentier-Edwards supra-annular) and five pericardial valves (Edwards, Hancock, Ionescu-Shiley, Ionescu-Shiley low-profile, and Mitral Medical Mitroflow) were tested. Valve function was measured in a pulse duplicator simulating conditions of sinus rhythm (60, 80, and 120 beats/min and stroke volume 70 ml) and supraventricular tachycardia (200 beats/min and stroke volume 30 ml). Under each of these test conditions, mean transvalvular pressure, regurgitation, and transvalvular energy loss were determined and used to compare valve function. The porcine valve showed the largest mean transvalvular pressure during forward flow. The total energy loss of this valve, however, was not the largest for the valves tested. The total transvalvular energy loss ranged between 3% and 12% for all valves and conditions. For all valves, energy loss and regurgitation were greatest during simulated tachycardia.

In vitro assessment of mitral valve prostheses.

The performance of five prosthetic mitral valves (Ionescu-Shiley, Hancock, Carpentier-Edwards, Starr-Edwards, and Björk-Shiley), all of the same nominal size (29 mm), has been assessed in a hydromechanical simulation of the left heart at three pulse rates. The mean and maximum transvalvular pressure differences, the observed and/or calculated area, and the energy loss for each valve were compared. It was found that each measure of performance rates the valves in the same order or merit, with the Ionescu-Shiley valve performing the best and the Hancock the worst among the valves tested.

Chronically ill children in schools: programmatic and policy directions for the future.

Children with arthritic diseases and other chronic illnesses will need some form of "special" consideration by the educational system at some point in their school careers. There is great variability among schools, school systems, and states in how the problems of educating chronically ill children are handled and how the state and federal special education laws and health codes are implemented. This paper reviews current practices and makes recommendations for improvements in school-based services to children with chronic illnesses.

How well does the questionnaire for identifying children with chronic conditions identify individual children who have chronic conditions?

BACKGROUND: The Questionnaire for Identifying Children With Chronic Conditions (QuICCC) is an instrument based on a conceptual noncategorical definition that uses parental responses to identify children with chronic conditions for epidemiological purposes. OBJECTIVES: To determine whether the QuICCC is sufficiently valid, sensitive, and specific to be used to identify individual children as having a chronic condition or disability; whether parents are accurate enough that their answers to QuICCC items can be accepted as valid; and what kinds of errors in classification occur when the QuICCC is used to identify children with chronic conditions. METHODS: The sample consisted of 424 children who were patients of 9 physicians in separate practice settings throughout New England. Each physician was briefly trained in the conceptual definition on which the QuICCC is based and then was asked to identify 25 children in his or her practice who met the definition and 25 children who did not meet the definition. The QuICCC was administered to the parents of these children by blinded interviewers via telephone. The QuICCC classification was compared with physician categorization. Discrepant cases were then followed up by asking physicians and parents to answer the original questions a second time. RESULTS: Complete data were available on 379 (89.4%) of 424 children. There was agreement on 89% (kappa = 0.78). The sensitivity was 94%; specificity, 83%; positive predictive value, 86%; and negative predictive value, 92%. Of the 42 discordant cases, 30 parent reports on the QuICCC qualified the child as having a chronic condition when the physician classified the child as being without such a condition. Fewer (n = 12) discrepancies occurred because physicians identified children with chronic conditions that the QuICCC failed to identify. When the questions were readministered at follow-up, physicians corrected errors in rating in 9 cases; mothers changed their answers in 5 instances. In 13 instances the issues were known to both parties and appeared to arise in the "gray zone" or boundary area, where there was disagreement over whether a particular child qualified using the theoretical definition. For 11 children identified as having a chronic condition only by the parent's responses to the QuICCC, physician report appeared to be inaccurate primarily due to the physician's lack of information. In 3 cases where the physician reported the child to have a chronic condition, but the parent did not, the physician appeared to be correct. Follow-up data were incomplete on 1 child. CONCLUSIONS: These data support the validity of parent-generated information for the evaluation of health status. Although these findings should be replicated, this study suggests that the QuICCC may be applicable also as a screening tool for individual child identification, provided that several sources of error are considered.

Assessing managed care for children with chronic conditions.

This paper reviews opportunities to monitor managed care for children and adolescents with chronic conditions and considers how well the Health Plan Employer Data and Information Set, version 3.0 (HEDIS 3.0), assesses care for these children. We propose four steps to strengthen the applicability of HEDIS to children with chronic conditions: (1) develop methods of identifying and monitoring groups of children with chronic conditions; (2) report HEDIS indicators for these children separately from those for other children; (3) develop and implement consumer and provider surveys that elicit information specific to these populations; and (4) develop specific structure, process, and outcomes indicators for children with chronic conditions.

Effects of streptozotocin-induced diabetes and insulin treatment on substance P of the rat arterial wall.

Substance P (SP) is present in perivascular nerves throughout the mammalian vasculature. Reports of diminished SP levels in nerve and gastrointestinal tissues of diabetic rats led us to examine SP-like immunoreactivity (SP-LI) in large arteries by RIA. Six weeks after inducing diabetes with streptozotocin (STZ), SP-LI was measured in the thoracic aorta, abdominal aorta, and the proximal superior mesenteric artery. In diabetics we measured a doubling (P<0.01) of SP-LI in all three artery wall preparations. This finding was verified in a second experiment which included a subset of diabetics treated daily with insulin for the sixth week of the holding period. Again, we measured a two-fold or greater increase of SP-LI (P<0.01-0.05) in arteries from the diabetics and found that insulin treatment significantly reduced SP-LI (P<0.05). In contrast to reports of diminished SP content in other tissues of diabetic rats, our findings demonstrate that the artery wall experiences at least a two-fold increase of SP-LI in the diabetic state. Furthermore, this elevation of SP-LI is reduced by insulin. We speculate that these changes of arterial wall SP-LI may contribute to altered regulation of the vascular system in the diabetic state.

A database obtained from in vitro function testing of mechanical heart valves.

The in vitro function of the CarboMedics, Medtronic Hall, Omniscience, Starr-Edwards, St. Jude and Sorin (formerly Shiley) Monostrut heart valves have been compared using a pulsatile flow model left heart and load system. A wide range of flows and heart rates were used. The above valves in all sizes and in both aortic and mitral positions were tested. Results for transvalvular pressure, regurgitation and effective orifice area are presented. The small size St. Jude valves showed the least transvalvular pressure and largest effective orifice area. For large valves, the least regurgitation was exhibited by the Starr-Edwards valve. The data provides a reference for the range of normal performance that can be expected of mechanical prosthetic heart valves.