Clinical commentary: Medical ethics and the ramifications of equipoise in clinical research. Is a confirmatory trial using a non-bevacizumab containing arm feasible in patients with recurrent cervical cancer?
The California Institute for Regenerative Medicine (CIRM) was created by a California ballot initiative to make stem cell research a constitutional right, in response to Bush administration restrictions on stem cell research. The initiative created a taxpayer-funded, multibillion-dollar institution, intended to advance public health by developing cures and treatments for diabetes, cancer, paralysis, and other conditions. The initiative has been highly controversial among stakeholders and watchdog groups concerned with organizational transparency, accountability, and the ethics of stem cell research. We interviewed major stakeholders-both supporters and opponents-and analyzed documents and meeting notes. We found that the CIRM has overcome start-up challenges, been selectively influenced by criticism, and adhered to its core mission.
Strong barriers prevent the financing of clinical information systems (CIS) in health care delivery system organizations in market segments serving disadvantaged patients. These segments include community health centers, public hospitals, unaffiliated rural hospitals, and some Medicaid-oriented solo and small-group medical practices. Policy interventions such as loans, grants, pay-for-performance and other reimbursement changes, and support services assistance will help lower these barriers. Without intervention, progress will be slow and worsen health care disparities between the advantaged and disadvantaged populations.
Improving asthma-related health outcomes among low-income, multiethnic, school-aged children: results of a demonstration project that combined continuous quality improvement and community health worker strategies.
The purpose of this work was to improve asthma-related health outcomes in an ethnically and geographically disparate population of economically disadvantaged school-aged children by using a team-based approach using continuous quality improvement and community health workers.
PATIENTS AND METHODS
A demonstration project was conducted with 7 community clinics treating approximately 3000 children with asthma 5 to 18 years of age. The overall clinic population with asthma was assessed for care-process changes through random cross-sectional chart reviews at baseline and 24 months (N = 560). A subset of patients with either moderate or severe persistent asthma or poorly controlled asthma (N = 405) was followed longitudinally for specific asthma-related clinical outcomes, satisfaction with care, and confidence managing asthma by family interview at baseline and at 12 or 24 months. Patient-centered and care-process outcomes included patient/parent assessment of quality of care and confidence in self-management, asthma action plan review, and documentation of guideline-based indicators of quality of care. Direct clinical outcomes included daytime and nighttime symptoms, use of rescue medications, acute care and emergency department visits, hospitalizations, and missed school days. Each clinic site's degree of adherence to the intervention model was evaluated and ranked to examine the correlation between model adherence and outcomes.
Cross-sectional data showed clinic-wide improvements in the documentation of asthma severity, review of action plans, health services use, and asthma symptoms. At follow-up in the longitudinal sample, fewer patients reported acute visits, emergency department visits, hospitalizations, frequent daytime and nighttime symptoms, and missed school days compared with baseline. More patients reported excellent or very good quality of care and confidence in asthma self-management. Linear regression analysis of the clinical sites' model adherence ranks against site-level combined scores estimating overall outcomes, clinical outcomes, and improvements in clinical care processes showed significant linear correlations with R2 > or = 0.60.
The demonstration produced major improvements in asthma-related care processes and clinical outcomes. Closer adherence to the demonstration model was directly associated with better outcomes.
Pitfalls in predicting resting energy requirements in critically ill children: a comparison of predictive methods to indirect calorimetry.
Critical illness in children is thought to have profound effects on nutritional status. It is essential to avoid complications associated with inadequate nutrition support and delivery of excess energy.
To compare the results of several commonly used methods for predicting energy requirements in a group of critically ill children indirect calorimetry was used to measure energy expenditure in these children.
Resting energy expenditures estimated by different prediction methods for energy were compared with measurements of actual resting energy expenditure obtained by indirect calorimetry in 52 children admitted to a pediatric intensive care unit. Agreement between each predictive method and indirect calorimetry was evaluated by Bland-Altman limits of agreement and by whether the methods met the predetermined criterion for accuracy of within 10% of the measured value.
None of the equations predicted individual values accurately. Each of the predictive equations gave a wide and variable scatter of predicted values around the median. The recommended dietary allowance for energy was the least accurate and differed significantly even from the other predictive methods, overestimating energy expenditure in 50 of 52 patients. None of the remaining methods stood out as being more precise.
Predictive methods commonly used to estimate energy expenditure in critically ill children are very imprecise and may lead to overprovision or underprovision of nutrition support. Resting energy expenditure should be measured by indirect calorimetry whenever possible.
Homogeneity in structure and function are broadly assumed to be characteristics of the acinar pancreatic digestive enzyme-secreting tissue. In recent years, physiological studies have shown that the pancreas stores the digestive enzymes in heterogeneously composed pools and releases them from these pools in a cyclic and secretagoguec fashion. The cellular basis for pancreatic heterogeneity is unknown; classical light and electron microscopic preparations appear homogeneous. We applied a panel of biotinylated lectins to pancreatic tissue sections; acinar cell glycoconjugates were localized in situ with peroxidase and fluorescent techniques and lectin-gold complexes. The lectin-binding properties of both fasting rabbit and rat pancreas revealed extensive and specific heterogeneity of the acinar cell population. Light and electron microscopy demonstrated highly heterogeneous labeling of the zymogen granule contents of specific acinar cells with the lectins Ulex europaeus agglutinin (UEA) and Erythrina cristagalli (ECA), which also showed preferential labeling of peri-insular acini. Other lectins also demonstrated heterogeneous binding to specific cellular regions. The striking acinar cell heterogeneity confirms earlier predictions, and may eventually prove to be the cellular basis for the secretion of different enzyme mixtures from heterogeneous sources within the pancreas.
The gastrointestinal and nutritional complications of cystic fibrosis are diverse. As longevity improves in patients with cystic fibrosis, management of these complications is becoming increasingly important . This article provides overviews of the molecular aspects of the pathogenesis of cystic fibrosis, the current status of gene therapy, and a review of the gastrointestinal manifestations and nutritional care.
The role and mechanism of nonparallel pancreatic secretion of digestive enzymes, in which enzyme proportions change in rapidly regulated fashion, remain controversial. Secretion was collected from male 2.2-kg New Zealand rabbits in 5-min intervals for 3 h under basal conditions or constant stimulation with cholecystokinin (CCK; 0.1 microgram per kg per h i.v.) or methacholine chloride (MCh; 40 micrograms per kg per h i.v.). Both CCK and MCh produced an 8-fold stimulation of protein output. Enzymes were separated by SDS/PAGE and quantitated by densitometry of Coomassie blue-stained gels. Under both basal conditions and constant MCh infusion, rapid neurosecretory-like 12-min cyclic changes occurred in the proportions of amylase, lipase I, chymotrypsinogen, and trypsinogen. During constant infusion their percentages changed as much as 10-fold, and their ratios cycled by as much as 30-fold. The mean percentage for the entire infusion period for lipase I declined > 25% with CCK or MCh, for amylase it rose approximately 30%, and for chymotrypsinogen and trypsinogen it doubled (for all, P
Maternal knowledge, attitude and practices regarding childhood acute respiratory infections in Kumasi, Ghana.
Acute respiratory infections (ARI) are a major cause of paediatric mortality and morbidity, particularly when associated with delays in treatment. A study of mothers' knowledge, attitudes and practices regarding ARI in their children aged less than 5 years was conducted in an urban Ghanaian population. One hundred and forty-three women traders were interviewed in open air markers in Kumasi, Ghana. Based on Western standards, there was a poor maternal understanding of the aetiology of ARI. A variety of herbal and home care therapies, including some which have potentially harmful effects, were routinely employed for the prophylaxis and treatment of ARI. For example, castor oil and enemas (25.9%) were reported as agents to prevent ARI, and antibiotics were prescribed by the parents in 39.9% for treating coughs. While the mothers exhibited an understanding of symptoms which differentiate between mild and severe ARI, a substantial number indicated that they would delay accessing a health care facility in the presence of the following symptoms which signify severe respiratory distress: dyspnoea (11.2%); tachypnoea (18.9%); chest retraction (21.7%); cough, fever and anorexia (30.0%); and cough, fever and lethargy (57.3%). These findings support the need for an ARI health education programme in Ghana.
Studies evaluating adverse effects of oral theophylline on learning and behavior have been performed on children with asthma receiving long-term theophylline therapy. To further differentiate the effects of asthma itself from the drugs used, we evaluated 20 asthmatic children (6 to 12 years of age) who had not received oral bronchodilators for at least 6 months. A double blind, placebo-controlled, parallel format was used with a 4-week theophylline or placebo period preceded by a 2-week baseline. Theophylline serum levels were maintained between 10 to 20 micrograms/mL. During baseline and treatment periods, the child's home and school behavior/performance were monitored independently by their parents and teachers using standardized report forms. A battery of psychologic tests was administered at the end of baseline and treatment periods. Seven children receiving theophylline were noted to have a change in school behavior and/or performance during their 4 weeks on drug compared to baseline, whereas none of the children receiving placebo were noted to be different (P = .004). Thus, the short-term administration of theophylline to asymptomatic asthmatic children not receiving oral bronchodilators can adversely affect school performance and behavior. Because this population represents the majority of asthmatic children, one needs to use theophylline cautiously in this age group, monitor school performance closely, or seek other treatment modalities.