Geographic disparities in performance of pediatric polysomnography to diagnose obstructive sleep apnea in a universal access health care system.

BACKGROUND: Diagnostic polysomnography (PSG) is recommended prior to adenotonsillectomy (AT) for children with obstructive sleep apnea (OSA) and certain high-risk characteristics, but resource limitations often prevent this practice. OBJECTIVE: We performed a population-based assessment of children across Ontario, Canada to describe and quantify disparities in PSG. METHODS AND MATERIALS: This retrospective cohort study was performed using provincial health administrative data held at ICES. We identified children 0-10 years old who underwent PSG and AT between 2009 and 2018, and those with a PSG within 18 months prior to and/or 12 months following AT. We calculated the odds of PSG prior to/following AT after adjustment for demographics, medical comorbidities, geographic and socioeconomic characteristics. Our main predictor was driving time/distance to the nearest pediatric sleep centre ascertained using spatial analysis and geographic information systems. RESULTS: We identified 27,837 children <10 years old who underwent AT for OSA in Ontario. Only 12.8% had a PSG within 18 months prior and 5.7% had a PSG within 12 months following AT. Shorter driving time/distance, older age, male sex and certain comorbidities were associated with increased odds of PSG. CONCLUSION: Only a small proportion of children in our cohort underwent PSG prior to or following AT surgery despite universal access to healthcare. This study suggests a need to increase overall PSG access, particularly for those living distant from existing pediatric sleep centres. Future studies could determine if increased PSG testing in 'underserviced areas' would reduce overall surgery rates and/or improve health outcomes.

A quieting ocean: unintended consequence of a fluctuating economy.

Simultaneous long-term monitoring of underwater sound and ship traffic provided an opportunity to study how low-frequency noise correlated with ocean-based commercial shipping trends. Between 2007 and 2010 changes in regional shipping off southern California occurred as a consequence of economic and regulatory events. Underwater average noise levels measured before and during these events showed a net reduction of 12 dB. Statistical models revealed that a reduction of 1 ship transit per day resulted in 1 dB decrease in average noise. This synthesis of maritime traffic statistics with ocean noise monitoring provides an important step in understanding the magnitude and potential effects of chronic noise in marine habitats.

Scale and pattern of broadnose sevengill shark Notorynchus cepedianus movement in estuarine embayments.

The detailed movements of 32 acoustically tagged broadnose sevengill shark Notorynchus cepedianus were documented in and around north-east Pacific Ocean estuarine embayments from 2005 to 2007. Arrangements of passive acoustic receivers allowed analysis of movement at several spatial scales, with sex and size examined as possible factors influencing the pattern and timing of these movements. Notorynchus cepedianus exhibited a distinctly seasonal pattern of estuary use over three consecutive years, entering Willapa Bay in the spring, residing therein for extended periods of time during the summer and dispersing into nearshore coastal habitats and over the continental shelf during the autumn. Notorynchus cepedianus within Willapa Bay showed spatio-temporal patterns of segregation by size and sex, with males and small females using peripheral southern estuary channels early in the season before joining large females, who remained concentrated in central estuary channels for the entire season. Individuals displayed a high degree of fidelity not only to Willapa Bay (63% were documented returning over three consecutive seasons), but also to specific areas within the estuary, showing consistent patterns of site use from year to year. Cross-estuary movement was common during the summer, with most fish also moving into an adjacent estuarine embayment for some extent of time. Most winter and autumn coastal detections of N. cepedianus were made over the continental shelf near Oregon and Washington, U.S.A., but there were also examples of individuals moving into nearshore coastal habitats further south into California, suggesting the feasibility of broad-scale coastal movements to known birthing and nursery grounds for the species. These findings contribute to a better understanding of N. cepedianus movement ecology, which can be used to improve the holistic management of this highly mobile apex predator in regional ecosystems.

John F. Enders and measles virus vaccine--a reminiscence.

Following their initial isolation in cell culture of the virus in 1954, a succession of investigators under the mentorship of John E Enders conducted the research, development, and initial clinical studies responsible for the licensure in 1963 of a successful live attenuated measles virus vaccine. Propagation of the virus successively in human kidney cells, human amnion cells, embryonated hens' eggs, and finally chick embryo cell cultures had selected virus that when inoculated into susceptible monkeys proved immunogenic without viremia or overt disease, in contrast to the early kidney cell-passaged material, which in similar monkeys produced viremia with illness mimicking human measles. Careful clinical studies in children by the Enders group and then by collaborating investigators in many sites established its safety, immunogenicity, and efficacy. This Edmonston strain measles virus became the progenitor of vaccines prepared, studied, and utilized throughout the United States and many other countries. With appreciation of measles morbidity and mortality, most marked among infants and children in the resource-limited lands, the vaccine was incorporated into the World Health Organization's (WHO) Expanded Programme of Immunization (EPI) in 1974 along with BCG, OPV, and DTP. Successful efforts to further reduce measles' burden were launched in 2001 and are continuing as the Measles Initiative (Partnership) under the leadership of the American Red Cross, International Red Cross, and Red Crescent societies, Centers for Disease Control (CDC), United Nations Children's Fund (UNICEF), WHO, and the United Nations Foundation.

Nebulizer choice for inhaled colistin treatment in cystic fibrosis.

STUDY OBJECTIVES: To develop practical ways of nebulizing colistin by determining the rate of drug output, total drug output, and particle-size distribution of two commercially available jet nebulizers, the disposable Hudson 1730 Updraft II (Hudson Respiratory Care; Temecula, CA) and the reusable Pari LC Star breath-enhanced nebulizer (Pari Respiratory Equipment; Midlothian, VA). METHODS: The nebulizers contained colistin, 75 mg, in 4 mL of isotonic solution. Particle-size distribution was measured by helium-neon laser diffraction, allowing calculation of the respirable fraction (RF), the mass of aerosol comprised of droplets < 5 microm. RESULTS: The mean (95% confidence interval [CI]) total rate of output of the Updraft II was 2.6 mg/min (2.0, 3.1; n = 4) with 1.3 mg/min (1.0, 1.5) mg/min within the RF. The rate of output of the LC Star increased in a quadratic relationship to the inspiratory flow, delivering 1.8 mg/min (0.7, 2.0; n = 4) with 1.4 mg/min (1.3, 1.6) within the RF, and 6.2 mg/min (5.6, 6.8) with 5.3 mg/min (4.8, 5.7) within the RF, at 0 L/min and 20 L/min inspiratory flows, respectively. Efficiency, as the rate of expected pulmonary deposition divided by rate of total output, was then calculated. The LC Star estimated 56% (51, 61) efficiency, with pulmonary delivery of 29% (26, 32) of the charge of the nebulizer, compared to the Updraft II at 22% (22, 23) efficiency and expected pulmonary deposition of 10% (10, 10) of the dose. CONCLUSIONS: Colistin can be successfully nebulized with both nebulizers tested. This study provides an estimate of in vivo efficiency and expected pulmonary deposition that may be used in future trials.

Phytoestrogens alter adrenocortical function: genistein and daidzein suppress glucocorticoid and stimulate androgen production by cultured adrenal cortical cells.

Phytoestrogens influence a variety of biological processes. As 17beta-estradiol alters adrenocortical cell function, we examined whether the dietary phytoestrogens, genistein and daidzein, have related effects. In cultured human fetal and postnatal adrenal cortical cells, genistein and daidzein (both 0.4-40 micromol/L) decreased ACTH-stimulated cortisol production to basal levels (ED50, 1-4 micromol/L). In the adult adrenocortical cell line, H295, genistein, daidzein, and 17beta-estradiol (10 micromol/L) decreased cAMP-stimulated cortisol synthesis in a similar fashion. Neither genistein nor daidzein altered basal or ACTH-stimulated dehydroepiandosterone sulfate (DHEA-S) production in fetal adrenocortical cells, whereas in postnatal adrenocortical cells, DHEA and DHEA-S were markedly increased (ED50, 1-4 micromol/L). In H295 cells, basal and cAMP-stimulated DHEA production were similarly increased by the phytoestrogens and 17beta-estradiol. Genistein and daidzein did not affect the expression of steroid-metabolizing enzymes. However, genistein and daidzein specifically inhibited the activity of 21-hydroxylase (P450c21); the activities of other steroidogenic enzymes were not affected. Thus, phytoestrogens may decrease cortisol synthesis by suppressing the activity of P450c21 and, as a consequence, increase DHEA/DHEA-S synthesis by shunting metabolites away from the glucocorticoid synthetic pathway. Therefore, consumption of foods containing phytoestrogens may alter adrenocortical function by decreasing cortisol and increasing androgen production.

Safety and immunogenicity of HIV recombinant envelope vaccines in HIV-infected infants and children. National Institutes of Health-sponsored Pediatric AIDS Clinical Trials Group (ACTG-218).

Study objectives were to evaluate the safety and immunogenicity of three HIV recombinant glycoproteins in HIV-infected infants and children between 1 month and 18 years of age with asymptomatic (P-1) infection. Using Chiron rgp 120 (SF-2) 15 or 50 microg; MicroGeneSys rgp 160 (IIIB) 40 or 320 microg; Genentech rgp120 (MN) 75 or 300 microg; or adjuvant control (Alum or MF-59), children were randomized to a double-blind, placebo-controlled, dose-escalating study of vaccine administered intramuscularly at entry and 1, 2, 3, 4, and 6 months later. No adverse events were attributed to study vaccines. Between 30% and 56% of volunteers exhibited a lymphoproliferative response as defined in terms of stimulation index (SI) to vaccine antigens; 65% of vaccinees but none of placebo recipients exhibited moderate or strong responses after enzyme immunoassay to HIV specific antigens. CD4 cell counts and quantitative HIV culture did not differ significantly among vaccine and control groups, nor were differences found among groups in HIV disease progression. The rgp160 and gp120 subunit vaccines were safe and immunogenic in this population.

Asymmetric bipedal locomotion--an adaptive response to incomplete spinal injury in the chick.

The purpose of this study was to compare the asymmetric gait induced by unilateral spinal cord injury in chicks with asymmetric gaits of other bipeds and quadrupeds. After lateral hemisection of the left thoracic spinal cord, kinetic (ground reaction forces) and kinematic (distance and timing) data were recorded as chicks moved overground unrestrained. Ground reaction forces were analyzed to obtain the mechanical energy changes throughout the stride. Kinematic measurements were obtained over a range of speeds to determine the velocity-dependent characteristics of the gait. Hemisected chicks adopted an asymmetric hopping gait in which the animals hopped from the right leg (contralateral to the lesion) onto the left (ipsilateral) leg but then fell forward onto the right leg. Mechanical energy fluctuations throughout a single stride (i.e., two steps) approximated the oscillations that occur during a single walking step of control animals. When examined over a range of velocities, asymmetries in limb timing remained constant, but distance measurements such as step length became more symmetric as speed increased. The results show that, after spinal hemisection, adaptations of the remaining neural circuitry permitted the production of a locomotor pattern that, in addition to providing effective support and propulsion, incorporated some of the energy-conserving mechanisms of the normal walk. Adjustment of this novel locomotor pattern for different velocities further demonstrates the flexibility of locomotor circuitry. Comparisons with other studies shows that this gait shares some temporal and energetic features with asymmetric gaits of several bipedal species, including humans. In particular, hemisected chicks and some hemiplegic humans adopt an asymmetric gait in which maximum energy recovery occurs during the stance of the affected limb; these similarities probably relate to common mechanical constraints imposed on bipedal forms of terrestrial locomotion.

Evaluation of surrogate markers and clinical outcomes in two-year follow-up of eighty-six human immunodeficiency virus-infected pediatric patients.

OBJECTIVES: To evaluate the prognostic value of surrogate markers (HIV RNA copy number, CD4 counts and CDC clinical and immunologic categories) in HIV-infected children through a 2-year period. METHODS: Eighty-six HIV-infected children followed by the Duke Pediatric HIV Clinic in the fall of 1994 were evaluated for plasma HIV RNA concentration (viral load), CD4 lymphocyte percentage, age, antiretroviral treatment status and CDC clinical and immunologic categories. Follow-up evaluations were performed for approximately 2 years, and the time to progression to a new CDC category C diagnosis or death was noted. RESULTS: Of 86 children 22 had progression to new Category C diagnosis or death. Seven children died, 17 had a new Category C diagnosis and 2 had both. Among children who progressed, the median CD4 percentage at entry was 3% (absolute count, 75 cells/mm3), whereas children who had no disease progression entered with a median of 29% (868 cells/mm3). The overall median viral load at study entry was 4.58 log10 copies/ml (38,019 copies/ml, with a range of 1.7 to 6.78 logs). Children who had no disease progression had a median log copy number of 4.43, whereas 5.18 was the median for children whose disease progressed. Log copy number declined over time in children < 3 years of age, whereas it remained fairly consistent for children 3 years or older. Progression rates were determined by entry plasma HIV RNA concentration quartiles [quartile boundaries < 4.18, 4.58, > 5.08 log RNA copy/ml (< 15,136, 38,019 and > 120,226 copies/ml, respectively)]. Progression rates by quartile were 0 of 21, 4 of 22, 5 of 21 and 13 of 22. Kaplan-Meier survival curves defined by CD4% less than or greater than 15 and log RNA less than or greater than 5.0 (100,000) revealed that patients with CD4% less than 15 and plasma HIV RNA concentration > 5 log10 copies/ml did least well: 11 of 12 (92%) had a progression event at a median of 179 days. Patients with a high CD4 percentage and high viral load, or a low CD4 percentage and low viral load did similarly; 5 of 14 (36%) and 4 of 12 (33%) had progression events, respectively. Patients with high CD4 percentage and low viral load did best: only 2 of 48 (4%) had a progression event. CONCLUSIONS: The two most significant prognostic indicators of disease progression were the initial CD4 percentage and the plasma HIV RNA concentration, and a combination of CD4 percentage and virus load best predicted which children had progression events. Progression was less common in children who had < 100,000 HIV RNA copies/ml initially (6 of 60 vs. 16 of 26; P < 0.001; relative risk 0.16). Therefore it seems reasonable that in a child for whom complete suppression is not possible, a threshold of 100,000 (5 log10 copies/ml) can be used to mandate a change in therapy.

Future vaccines and a global perspective.

Advances in medical biotechnology mean that vaccines to prevent more than 75 infectious diseases are being or have been developed. Vaccination is unfortunately not reliant purely on biotechnology but also on politics and resources. Countries with the greatest demand for vaccines have the least ability to pay for or produce them. Health-care Infrastructure and diagnostic facilities also hamper immunisation projects in developing countries. Charitable organisations are relied on heavily to support such projects but the challenge to ensure all infants are immunised against the most common infections of childhood is still enormous. Difficulties that present themselves now should not prevent us looking into future possibilities such as immunisation during pregnancy and targeting of children for immunisation against sexually transmitted diseases. Other avenues for research are in administration of vaccines. A move to mucosal immunisation rather than use of the syringe and needle would be positive both economically and from the point of view of risk of needle contamination. Plant science may also provide a new vehicle for vaccines by engineering plants such as the banana tree to be naturally bioencapsulated vaccines. Prospects for control and eradication of infectious disease in the next century are certainly good.