Precision-cut lung slices as an ex vivo model to study Pneumocystis murina survival and antimicrobial susceptibility.

IMPORTANCE: Our study reveals the potential of precision-cut lung slices as an ex vivo platform to study the growth/survival of Pneumocystis spp. that can facilitate the development of new anti-fungal drugs.

Genetic Mouse Models of Pneumocystis Pneumonia.

Pneumocystis jirovecii causes pneumonia in immunocompromised patients. A major challenge in drug susceptibility testing and in understanding host/pathogen interactions is that Pneumocystis spp. are not viable in vitro. Continuous culture of the organism is not currently available, and therefore, developing new drug targets is very limited. Due to this limitation, mouse models of Pneumocystis pneumonia have proven to be an invaluable resource to researchers. In this chapter, we provide an overview of selected methods used in mouse models of infection including, in vivo Pneumocystis murina propagation, routes of transmission, genetic mouse models available, a P. murina life form-specific model, a mouse model of PCP immune reconstitution inflammatory syndrome (IRIS), and the experimental parameters associated with these models.

Dissecting Driver Behaviors Under Cognitive, Emotional, Sensorimotor, and Mixed Stressors.

In a simulation experiment we studied the effects of cognitive, emotional, sensorimotor, and mixed stressors on driver arousal and performance with respect to (wrt) baseline. In a sample of n = 59 drivers, balanced in terms of age and gender, we found that all stressors incurred significant increases in mean sympathetic arousal accompanied by significant increases in mean absolute steering. The latter, translated to significantly larger range of lane departures only in the case of sensorimotor and mixed stressors, indicating more dangerous driving wrt baseline. In the case of cognitive or emotional stressors, often a smaller range of lane departures was observed, indicating safer driving wrt baseline. This paradox suggests an effective coping mechanism at work, which compensates erroneous reactions precipitated by cognitive or emotional conflict. This mechanisms' grip slips, however, when the feedback loop is intermittently severed by sensorimotor distractions. Interestingly, mixed stressors did not affect crash rates in startling events, suggesting that the coping mechanism's compensation time scale is above the range of neurophysiological latency.

Concentration of anti-Müllerian hormone in dairy heifers is positively associated with productive herd life.

Reliable biomarkers predictive of productive herd life (time in herd after birth of first calf) have heretofore not been discovered in dairy cattle. However, circulating concentrations of anti-Müllerian hormone (AMH) are positively associated with number of follicles or antral follicle count (AFC), ovarian function, and fertility, and approximately 25% of cows have a relatively low AFC and low AMH concentrations. The present study tested the hypothesis that heifers with the lowest AMH concentrations have suboptimal fertility and are removed from a herd for poor reproductive performance at a greater rate, and therefore have a shorter productive herd life compared with age-matched herdmates with higher AMH. To test this hypothesis, 11- to 15-mo-old Holstein heifers (n=281) were subjected to a single measurement of AMH. All heifers not removed from the herd had the opportunity to complete 2 lactations and start their third lactation after calving. During this time, performance and health parameters for each individual were recorded daily by herd managers. Results showed that the quartile of heifers with the lowest AMH concentration also had, on average, a shorter productive herd life (by 196 d), a reduced survival rate after birth of the first calf, the lowest level of milk production (first lactation), the lowest total percentage of cows pregnant (across all lactations), the highest culling rates (first and second lactations and overall), and the highest culling rate for poor reproduction (first lactation) compared with age-matched herdmates with higher AMH. We concluded that a single determination of AMH concentration in young adult dairy heifers may be a simple diagnostic method to predict herd longevity, and AMH may be a useful phenotypic marker to improve longevity of dairy cows.

Pharmacovigilance using clinical notes.

With increasing adoption of electronic health records (EHRs), there is an opportunity to use the free-text portion of EHRs for pharmacovigilance. We present novel methods that annotate the unstructured clinical notes and transform them into a deidentified patient-feature matrix encoded using medical terminologies. We demonstrate the use of the resulting high-throughput data for detecting drug-adverse event associations and adverse events associated with drug-drug interactions. We show that these methods flag adverse events early (in most cases before an official alert), allow filtering of spurious signals by adjusting for potential confounding, and compile prevalence information. We argue that analyzing large volumes of free-text clinical notes enables drug safety surveillance using a yet untapped data source. Such data mining can be used for hypothesis generation and for rapid analysis of suspected adverse event risk.

The design of neonatal incubators: a systems-oriented, human-centered approach.

OBJECTIVE: This report describes a multidisciplinary design project conducted in an academic setting reflecting a systems-oriented, human-centered philosophy in the design of neonatal incubator technologies. STUDY DESIGN: Graduate students in Architectural Design and Human Factors Engineering courses collaborated in a design effort that focused on supporting the needs of three user groups of incubator technologies: infant patients, family members and medical personnel. Design teams followed established human-centered design methods that included interacting with representatives from the user groups, analyzing sets of critical tasks and conducting usability studies with existing technologies. RESULT: An iterative design and evaluation process produced four conceptual designs of incubators and supporting equipment that better address specific needs of the user groups. CONCLUSION: This report introduces the human-centered design approach, highlights some of the analysis findings and design solutions, and offers a set of design recommendations for future incubation technologies.

Who cares for medicaid-enrolled children with chronic conditions?

OBJECTIVE: To estimate generalist, pediatric subspecialist, and any subspecialist use by Medicaid-enrolled children with chronic conditions and to determine the correlates of use. METHODS: We analyzed Medicaid claims data collected from 1989 to 1992 from 4 states for 57 328 children and adolescents with 11 chronic conditions. We calculated annual rates of generalist, subspecialist, and pediatric subspecialist use. We used logistic regression to determine the association of demographics, urban residence, and case-mix (Adjusted Clinical Groups) with the use of relevant pediatric and any subspecialist care. RESULTS: Most children with chronic conditions had visits to generalists (range per condition: 78%-90% for children with Supplemental Security Income [SSI] and 85%-94% for children without SSI) during the year studied. Fewer children visited any relevant subspecialists (24%-59% for children with SSI and 13%-56% for children without SSI) or relevant pediatric subspecialists (10%-53% for children with SSI and 3%-37% for children without SSI). In general, children who were more likely to use pediatric subspecialists were younger, lived in urban areas, were white (only significant for non-SSI children), and had higher Adjusted Clinical Groups scores. Use of any subspecialists followed a similar pattern except that urban residence is statistically significant only for children with SSI and the youngest age group does not differ from the oldest age group for children without SSI. CONCLUSIONS: Children who had chronic conditions and were enrolled in Medicaid received a majority of their care from generalist physicians. For most conditions, a majority of children did not receive any relevant subspecialty care during the year and many of these children did not receive care form providers with pediatric-specific training.

Switching to gatekeeping: changes in expenditures and utilization for children.

BACKGROUND: Gatekeeping has been a central strategy in the cost-containment initiatives of managed care organizations. Little empirical research describes the impact of switching into a gatekeeping plan on health care expenditures and utilization for children. OBJECTIVE: To determine the likelihood of a parent with a chronically ill child enrolling in a health plan with gatekeeping, as well as the effects of gatekeeping on health care expenditures and utilization for children, especially those with chronic conditions. DESIGN: We followed a cohort of 1839 children who either voluntarily switched to a gatekeeping plan or remained in an indemnity plan from 1991 through 1994. Study participants were children of employees of a large hospital. The gatekeeping plan was virtually identical to the previous indemnity plan except for lower monthly employee contribution and the requirement for a primary care physician to preapprove subspecialty referrals. We determined the likelihood of a household containing a child with a chronic condition enrolling in the gatekeeping plan, as well as mean annual total, subspecialty, and primary care expenditures and utilization for all children and children with chronic conditions. RESULTS: Households switching to gatekeeping were less likely to have children with chronic illness (8% vs 15%). Total and subspecialty expenditures for all children decreased more in the gatekeeping group (53% and 59%, respectively) than in the indemnity group (11% and 6%, respectively). For children with chronic conditions, mean visits to subspecialists decreased 57% in the gatekeeping group but increased 31% in the indemnity group. Mean visits to primary care physicians decreased 23% in the gatekeeping group compared with 13% in indemnity group. CONCLUSION: Parents of children with a chronic condition were much less likely than other parents to switch to a gatekeeping plan. Switching to gatekeeping was associated with reduced visits to specialists but did not increase the involvement of primary care physicians in the management of children with chronic conditions. The implications of these findings for the health of children are unknown.

A report card on quality improvement for children's health care.

OBJECTIVE: Improving the quality of health care is a national priority. Nonetheless, no systematic effort has assessed the status of quality improvement (QI) initiatives for children or reviewed past research in child health care QI. This assessment is necessary to establish priorities for QI programs and research. METHODS: To assess the status of QI initiatives and research, we reviewed the literature and interviewed experts experienced in QI for child health services. We defined QI as activities intended to close the gap between desired processes and outcomes of care and what is actually delivered. We classified reports published between 1985 and 1997 by publication characteristics, study design, clinical problem addressed, site of intervention, the QI method(s) used, and explicit association with a continuous quality improvement program. RESULTS: We reviewed 68 reports meeting our definition of QI. More than half (48) were published after 1994. The reviewed reports included controlled evaluations in 36% of all identified interventions, and 3% of the reports were associated with continuous quality improvement. QI methods demonstrating some effectiveness included reminder systems for office-based preventive services and inpatient pathways for complex care. Reportedly successful QI initiatives more commonly described improvement in administrative measures such as rate of hospitalization or length of stay rather than functional status or quality of life. Interviews found that barriers to QI for children were similar to those for adults, but were compounded by difficulties in measuring child health outcomes, limited resources among public organizations and small provider groups, and relative lack of competition for pediatric tertiary care providers. Research and dissemination of QI for children were seen as less well developed than for adults. CONCLUSIONS: Attempts to improve the quality of child health services have been increasing, and the evidence we reviewed suggests that it is possible to improve the quality of care for children. Nonetheless, numerous gaps remain in the understanding of QI for children, and widespread improvement in the quality of health services for children faces significant barriers.

Insurance and quality of care for children with acute asthma.

BACKGROUND: Increasing attention has been paid to the role of insurance in determining quality and outcomes of care. Pressures to reduce health costs and to improve quality have prompted attempts by managed care organizations to decrease the use of the emergency department (ED) for acute asthma, but performance comparisons between insurance types remain rare. METHODS: We used prospective data from the Multicenter Airway Research Collaboration on 965 children with acute asthma presenting to 36 EDs. We compared measures of quality of pre-ED care, acute severity, and short-term outcomes (length of stay, percent relapse, and percent with ongoing symptoms) across 4 different insurance categories: managed care, indemnity, Medicaid, and uninsured. We used multivariate regression to control for differences in education, estimated income, race/ethnicity, and chronic asthma severity and acute asthma characteristics. RESULTS: Children with managed care and indemnity had similar demographic and asthma characteristics, but these children differed significantly from Medicaid and uninsured patients. Managed care and indemnity insured children had similar ratings on all 7 quality measures, with Medicaid and uninsured children ranking significantly lower on most measures, including (1) percent with primary care provider (PCP) (P <.001), (2) percent using ED as usual site of asthma care (P <.001), (3) percent using ED for prescriptions (P <.001), (4) percent with a ratio of >1 of ED visits to acute office visits within the past year (P =.003), and (5) percent visiting their PCP within the week prior to ED visit (P <.001). Children with managed care were more acutely ill than were indemnity, Medicaid, or uninsured children on presentation to the ED (pulmonary index of 4.6, 4.0, 4.2, and 3.9, respectively, P =.007). There were no significant differences in length of hospital stay, relapse, and ongoing exacerbation. CONCLUSIONS: Our results indicate similar quality of care, greater severity of acute asthma, and no worse outcomes for children with managed care compared to children with indemnity insurance. We found uninsured children to have consistently poorer quality of care than insured patients.

Leaving gatekeeping behind--effects of opening access to specialists for adults in a health maintenance organization.

BACKGROUND: Gatekeeping refers to the prior approval of referrals to specialists by a primary care physician. Although many health plans view gatekeeping as an essential tool for controlling costs and coordinating care, many patients and physicians object to it. METHODS: On April 1, 1998, Harvard Vanguard Medical Associates, a large, multispecialty, capitated group practice previously known as Harvard Community Health Plan, eliminated a gatekeeping system that had been in place for over 25 years. We determined the effects of opening access to specialists on visits to primary care physicians and specialists by adults. In randomly selected cohorts of 10,000 members each, we analyzed visits during 6-month periods for the 3 years before and 18 months after gatekeeping was eliminated. RESULTS: Adults visited a primary care physician an average of 1.21 times and 1.19 times per six-month period before and after the elimination of gatekeeping, respectively (P=0.05); the average number of visits to a specialist was 0.78 per six-month period both before and after its elimination (P=0.35). There was little change in the percentage of visits to specialists included in the analysis as a proportion of all visits (39.1 percent before the elimination of gatekeeping and 39.5 percent afterward). The percentage of first visits to specialists as a proportion of all visits to specialists included in the analysis increased from 24.7 to 28.2 percent (P<0.001). There were small increases in the numbers of visits to orthopedists and physical or occupational therapists. The proportion of visits to specialists for low back pain that were new consultations increased from 26.6 to 32.9 percent (P=0.01). CONCLUSIONS: In a capitated, multispecialty group practice, we found little evidence of substantial changes in the use of specialty services by adults in the first 18 months after the elimination of gatekeeping.

Rates of U.S. physicians counseling adolescents about smoking.

BACKGROUND: The health care system provides an important opportunity for addressing tobacco use among youths, but there is little information about how frequently physicians discuss smoking with their adolescent patients. We analyzed data from the National Ambulatory Medical Care Surveys to assess the prevalence and the predictors of physicians' identification of smoking status and counseling about smoking at office visits by adolescents. METHODS: From 1991 through 1996, 5087 physicians recorded data on 16 648 visits by adolescents aged 11-21 years. We determined the proportion of office visits at which physicians identified an adolescent's smoking status and counseled about smoking and then identified predictors of these outcomes with logistic regression. Statistical tests were two-sided. RESULTS: In 1991, physicians identified an adolescent's smoking status at 72.4% of visits but provided smoking counseling at only 1.6% of all adolescent visits and 16.9% of visits by adolescents identified as smokers. These proportions did not increase from 1991 through 1996. Compared with specialists, primary care physicians were more likely to identify smoking status (odds ratio [OR] = 1.70; 95% confidence interval [CI] = 1.53-1.89) and to counsel about smoking (OR = 3.43; 95% CI = 2.18-5.38). Patients with diagnoses of conditions potentially complicated by smoking were more likely to have their smoking status identified and to be counseled about smoking. Younger and nonwhite adolescents were less likely to be counseled about smoking than older and white teens. CONCLUSIONS: We found that physicians frequently identified adolescents' smoking status but rarely counseled them about smoking. Physicians' practices did not improve in the first half of the 1990s, despite a clear consensus about the importance of this activity and the publication of physician guidelines targeting this population. Physicians treating adolescents are missing opportunities to discourage tobacco use among teens.

Holistic pediatrics: a research agenda.

Increasing numbers of American families seek complementary and alternative medical care (CAM) for their children; at the same time health care organization and financing are undergoing radical changes. The combination of these factors provides a powerful incentive for research on the effectiveness and safety of CAM therapies and their role in treating children. This article describes a rationale, spectrum, priorities, and methodologies for a research agenda in holistic pediatrics. The top priorities are clinical research projects addressing the safety and effectiveness of alternative therapies used for vulnerable children suffering from serious illnesses. Additionally, major research questions involve the impact of the various definitions such as "alternative," "complementary," "folk," "integrative," and "holistic" medicine on perceptions of health care, professional education, and funding of products and services. Research efforts in alternative therapies need to address explicitly the tremendous heterogeneity between and among the practices, beliefs, and providers of professional and lay services. Qualitative ethnographic research is needed to understand the consequences of diverse explanatory models and meanings of health and illness for patient-provider communication, adherence with professional recommendations, and satisfaction with care. Health services researchers need to address questions related to the epidemiology of CAM practices, health manpower issues, practice characteristics and the process and content of health care and how discoveries about CAM care may enhance the quality of mainstream health services. A rationale is provided for prioritizing certain conditions and therapies within these efforts.

Changes in the daily practice of primary care for children.

BACKGROUND: The environment in which medicine is practiced has changed in the past 2 decades, but little information has been available on how the day-to-day practice of primary care for children has changed during this period. OBJECTIVE: To identify aspects of primary care practices for children that are undergoing substantial changes. DESIGN: Analysis of National Ambulatory Medical Care Surveys from 1979 to 1981, 1985, and 1989 to 1994. PARTICIPANTS: Primary care practitioners recorded data on 58,488 child visits. MAIN OUT COME MEASURES: Characteristics and insurance status of children, physician activities during visits, and disposition after visit. RESULTS: Child visits to primary care physicians increased by 22% between 1979 and 1994. The mean age of children visiting primary care physicians decreased from 6.7 years in 1979 to 5.7 years in 1994 (P for trend, < .001). The ethnic diversity of child visits increased primarily as a result of an increasing proportion of visits by Hispanic (6.0% in 1979 to 12.6% in 1994, P for trend, < .001) and Asian patients (1.6% in 1979 to 4.1% in 1994, P for trend, < .001). Medicaid and managed care increased dramatically as sources of payment. Changes in physician activities included an increase in some preventive services, changes in the most commonly encountered medications, and an increased mean duration of patient visits (11.8 minutes in 1979 to 14.2 minutes in 1994, P for trend, < .001). CONCLUSIONS: These data may assist in the development of educational and research initiatives for physicians caring for children. The declining proportion of adolescent visits may present physicians with challenges in the care of adolescents. Physician prescribing practices showed changes without evidence of a benefit to child health. The increased ethnic diversity and provision of preventive services were associated with an increased mean duration of primary care visits. The increased duration of child visits may conflict with the managed care emphasis on physician productivity.

When the patient dies: a survey of medical housestaff about care after death.

Our objectives were to determine medical housestaff exposure to the tasks of care after a death in the hospital and to characterize their practices, training, and attitudes toward this care. The study design was a review of hospital records and survey of housestaff at two academic medical centers. Forty-seven of 239 medical housestaff were surveyed. In one of the two hospitals studied, the number of death certificates completed by interns during 1 year was determined, and an estimate of exposure to hospital deaths and three other common discharge diagnoses during the same period was calculated. Housestaff were surveyed about the tasks of care after a death, including the determination of death, preparation of the body, notification of family, documentation, review of death with staff, and follow-up with family. Interns at one hospital completed a death certificate an average of 7 (range 1 to 13) times a year and were involved annually with approximately 30 inpatient deaths on ward teams. Exposure to a hospital death was comparable in frequency to that for pneumonia (48 cases/yr), congestive heart failure (32 cases/yr), or AIDS (24 cases/hr). Housestaff reported little or no formal training for the tasks of care after a death. Considerable variation among housestaff was noted in such routine tasks as how death was determined, discussions with the family, and providing bereavement care. Only 12% of respondents regularly reviewed personal reactions to a death with the medical team. In response to open-ended questioning, housestaff described significant distress and uncertainty regarding their roles in completing the tasks of care after a patient death. Medical housestaff are regularly exposed to hospital deaths, yet report minimal training, wide variations in practice, and significant distress with the performance of tasks after a death. We encourage greater attention to teaching about this important area of medical practice.