Abstract Objective To examine the effectiveness of an intervention that combined continuing medical education with process improvement methods to implement “office systems” to improve the delivery of ...preventive care to children. Design Randomised trial in primary care practices. Setting Private paediatric and family practices in two areas of North Carolina. Participants Random sample of 44 practices allocated to intervention and control groups. Intervention Practice based continuing medical education in which project staff coached practice staff in reviewing performance and identifying, testing, and implementing new care processes (such as chart screening) to improve delivery of preventive care. Main outcome measure Change over time in the proportion of children aged 24-30 months who received age appropriate care for four preventive services (immunisations, and screening for tuberculosis, anaemia, and lead). Results The proportion of children per practice with age appropriate delivery of all four preventive services changed, after a one year period of implementation, from 7% to 34% in intervention practices and from 9% to 10% in control practices. After adjustment for baseline differences in the groups, the change in the prevalence of all four services between the beginning and the end of the study was 4.6-fold greater (95% confidence interval 1.6 to 13.2) in intervention practices. Thirty months after baseline, the proportion of children who were up to date with preventive services was higher in intervention than in control practices; results for screening for tuberculosis (54% v 32%), lead (68% v 30%), and anaemia (79% v 71%) were statistically significant (P < 0.05). Conclusion Continuing education combined with process improvement methods is effective in increasing rates of delivery of preventive care to children.
Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental ...approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the NIH launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines but also highlight the need to innovate the science of therapeutic discovery.
The Molecular Libraries Project began in 2005 to develop small-molecule tools to promote biological and biomedical discoveries. This Perspective highlights the last decade’s advances and looks at opportunities ahead for informed innovation in small-molecule drug discovery.
Because ivermectin (22,23-Dihydroavermectin B sub(1)) has been proposed as an oral treatment against sea lice infections of farmed salmonids, we investigated the toxicity and pathological effects of ...various doses of ivermectin administered orally every second day to steelhead trout Oncorhynchus mykiss, coho salmon Oncorhynchus kisutch, chinook salmon Oncorhynchus tshawytscha and Atlantic salmon Salmo salar under laboratory conditions. These species differed in their ability to tolerate ivermectin, with coho salmon the most tolerant followed by chinook, then Atlantic salmon. Unequivocal results for steelhead trout were not obtained due to a secondary disease outbreak (vibriosis). Histological examination of the major organ systems revealed no pathological changes that could be associated with ivermectin toxicity in any of the salmon species tested.
Family genetic variability of the rooting characteristics of white spruce (Picea glauca (Moench) Voss) cuttings harvested from 3-year-old stock plants was evaluated for 75 half-sib families. Growth, ...root system architecture, and gas exchange of the cuttings during the rooting phase (B+0) and the two subsequent growing seasons (B+1 and B+2) were evaluated. The root initiation phase (B+0) and the root development phases (B+1 and B+2) were found to be under strong genetic control. The weak correlations found between B+0 and the B+1 and B+2 phases may indicate that gene expression during B+0 is not related to root growth and development during B+1 and B+2. Strong positive correlations were observed between plant root and aboveground characteristics at the end of the B+1 and B+2 phases. This suggests that an indirect and efficient selection for white spruce families producing cuttings with heavier root dry masses could be based on the measures of aboveground morphological characteristics. Finally, the strong genetic control of morphological characteristics found in this study indicates that the selection of superior genotypes at a clonal level is possible for intensive forest management.
A 42-year-old woman was found to have intravenous leiomyomatosis of the uterus with extension into the inferior vena cava and right atrium. Intravenous leiomyomatosis is a rare neoplastic disease ...characterized by invasion of venous channels by a benign smooth muscle tumor arising either from the wall of a vessel or from a uterine myoma. Intracardiac extension is often initially misdiagnosed as a right atrial myxoma and may cause death by mechanical obstruction. The diagnosis of intravenous leiomyomatosis should be considered in young women with cardiac symptoms associated with a right atrial mass who also have a pelvic mass or who have previously undergone hysterectomy because of leiomyoma uteri.
Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. The relationship between calcium plus vitamin D (calcium/D) ...supplementation and coronary artery calcium (CAC) has not been previously assessed in a randomized trial setting. We compared CAC scores after trial completion between women randomized to calcium/vitamin D supplementation and women randomized to placebo.
In an ancillary substudy of women randomized to calcium carbonate (1,000 mg of elemental calcium daily) plus vitamin D3 (400 IU daily) or placebo, nested within the Women's Health Initiative trial of estrogen among women who underwent hysterectomy, we measured CAC with cardiac CT in 754 women aged 50 to 59 years at randomization. Imaging for CAC was performed at 28 of 40 centers after a mean of 7 years of treatment, and scans were read centrally. CAC scores were measured by a central reading center with masking to randomization assignments.
Posttrial CAC measurements were similar in women randomized to calcium/D supplementation and those receiving placebo. The mean CAC score was 91.6 for women receiving calcium/D and 100.5 for women receiving placebo (rank test P value = 0.74). After adjustment for coronary risk factors, multivariate odds ratios for increasing CAC score cutpoints (CAC >0, > or =10, and > or =100) for calcium/D versus placebo were 0.92 (95% CI, 0.64-1.34), 1.29 (0.88-1.87), and 0.90 (0.56-1.44), respectively. Corresponding odds ratios among women with a 50% or higher adherence to study pills and for higher levels of CAC (>300) were similar.
Treatment with moderate doses of calcium plus vitamin D3 did not seem to alter coronary artery calcified plaque burden among postmenopausal women. Whether higher or lower doses would affect this outcome remains uncertain.
To search for circulating clonal T-cell populations in patients with systemic sclerosis (SSc), and to determine whether T-cell clonality in the blood predicts therapeutic response to photopheresis.
...Analysis of clonal T-cell receptor gamma gene rearrangements before photopheresis treatment and blinded clinical evaluation of cutaneous response to photopheresis in a case series.
University hospital setting.
Thirteen consecutive patients with SSc.
Photopheresis in 11 patients.
Clonality of T cells in the blood before photopheresis and clinical response to photopheresis.
Screening of blood samples from 13 SSc patients for clonal T-cell receptor gamma gene rearrangements revealed a monoclonal T cell population in 6 (46%) of 13 SSc patients. Clinical response to photopheresis in 11 patients was evaluated in a blinded manner using skin severity scores. Clonality of T cells appeared to be associated with a higher chance of response to photopheresis therapy, as 4 (67%) of 6 patients in the clone-positive group vs 1 (20%) of 5 in the clone-negative group experienced a clinically significant response to treatment.
A high proportion of patients with SSc have detectable expanded clonal T-cell populations in the peripheral blood, and such patients appear more likely to respond to photopheresis.
Abstract
BACKGROUND
Despite readily available treatments, control of blood pressure (BP) with population aging remains suboptimal. Further, there are gaps in the understanding of the management of ...high BP in the aged. We explored antihypertensive treatment and control among elderly hypertensive participants free from overt cardiovascular disease (CVD), and identified factors related to both “untreated” and “treated but uncontrolled” high BP.
METHODS
We analyzed baseline data from 19,114 individuals aged ≥65 years enrolled from Australia and United States (US) in the ASPirin in Reducing Events in the Elderly study. Hypertension was defined as an average systolic/diastolic BP ≥140/90 mm Hg and/or the use of any BP lowering medication. “Controlled hypertension” was defined if participants were receiving antihypertensive medication and BP <140 and 90 mm Hg. Descriptive analyses were used to summarize hypertension control rates; logistic regression was used to investigate relationships with treatment and BP control.
RESULTS
Overall, 74% (14,213/19,114) of participants were hypertensive; and of these 29% (4,151/14,213) were untreated. Among those treated participants, 53% (5,330/10,062) had BP ≥140/90 mm Hg. Participants who were untreated were more likely to be men, have higher educational status, and be in good physical health, and less likely to have significant comorbidities. The factors related to “treated but uncontrolled” BP included older age, male, Black race (vs. White), using antihypertensive monotherapy (vs. multiple) and residing in Australia (vs. US).
CONCLUSIONS
High levels of “untreated” and “treated but uncontrolled” BP occur in healthy elderly people without CVD, suggesting there are opportunities for better BP control in the primary prevention of CVD in this population.
CLINICAL TRIALS REGISTRATION
NCT01038583.
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