Quality of life after prostate cancer treatments in patients comparable at baseline.

BACKGROUND: Previous studies on the effects of different prostate cancer treatments on quality of life, were confounded because patients were not comparable. This study examined treatment effects in more comparable groups. METHODS: From 2008-2011, 240 patients with localised prostate cancer were selected to be eligible for both radical prostatectomy (RP) and external beam radiotherapy (EBRT). Brachytherapy (BT) was a third option for some. Health-related quality of life was measured by expanded prostate cancer index composite (EPIC) up to 12 months after treatment. RESULTS: In the sexual domain, RP led to worse summary scores (P<0.001) and more often to a clinically relevant deterioration from baseline than BT and EBRT (79%, 33%, 34%, respectively). In the urinary domain, RP also led to worse summary scores (P=0.014), and more deterioration from baseline (41%, 12%, 19%, respectively). Only on the irritative/obstructive urinary scale, more BT patients (40%) showed a relevant deterioration than RP (17%) and EBRT patients (11%). In the bowel domain, the treatment effects did not differ. CONCLUSION: This study provides a more unbiased comparison of treatment effects, as men were more comparable at baseline. Our results suggest that, for quality of life, radiotherapy is as least as good an option as RP for treating localised prostate cancer.

Implementation of clinical guidelines via a computer charting system: effect on the care of febrile children less than three years of age.

OBJECTIVE: The authors have shown that clinical guidelines embedded in an electronic medical record improved the quality, while lowering the cost, of care for health care workers who incurred occupational exposures to body fluid. They seek to determine whether this system has similar effects on the emergency department care of young children with febrile illness. DESIGN: Off-on-off, interrupted time series with intent-to-treat analysis. SETTING: University hospital emergency department. SUBJECTS: 830 febrile children less than 3 years of age and the physicians who treated them. INTERVENTIONS: Implementation of an electronic medical record that provides real-time advice regarding the content of the history and physical examination and recommendations regarding laboratory testing, treatment, diagnosis, and disposition. MEASUREMENTS: Documentation of essential items in the medical record and after-care instructions; compliance with guidelines regarding testing, treatment, and diagnosis; charges. RESULTS: The computer was used in 64 percent of eligible cases. Mean percentage documentation of 21 essential history and physical examination items increased from 80 percent during the baseline period to 92 percent in the intervention phase (13 percent increase; 95 percent CI, 10-15 percent). Mean percentage documentation of ten items in the after-care instructions increased from 48 percent at baseline to 81 percent during the intervention phase (33 percent increase; 95 percent confidence interval, 28-38 percent). All documentation decreased to baseline when the computer system was removed. There were no demonstrable improvements in appropriateness of care, nor was there evidence that appropriateness worsened. Mean charges were not changed by the intervention. CONCLUSION: The intervention markedly improved documentation, had little effect on the appropriateness of the process of care, and had no effect on charges. Results for the febrile child module differ from those for the module for occupational blood and body fluid exposure (a more focused and straightforward medical condition), underscoring the need for implementation methods to be tailored to specific clinical complaints.

Neuropeptide y attenuates stress-induced bone loss through suppression of noradrenaline circuits.

Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress-induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress-induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6-week restraint, or cold-stress protocol, Npy-null mice exhibit three-fold greater bone loss compared to wild-type mice, owing to suppression of osteoblast activity. This stress-protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin-releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy-null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy-null mice blocks the increase in circulating noradrenaline and the stress-induced bone loss. Thus, NPY protects against excessive stress-induced bone loss, through Y2 receptor-mediated modulation of central and peripheral noradrenergic neurons.

A bacteriophage system for screening and study of biologically active polycyclic aromatic hydrocarbons and related compounds.

The usefulness of bacterial viruses for detecting substances that are potentially carcinogenic is reexamined as a model system for screening biologically active polycyclic aromatic hydrocarbons. A modification of the original assay procedure allows one to distinguish between aromatics that can modify the biological activity of infectious nucleic acids directly and those polycyclic aromatic hydrocarbons that require metabolic activation by Escherichia coli enzymes. The effect of chemical modification of several different polycyclic aromatic hydrocarbons, with respect to their biological activity in the phage assay system, is described. Among the 31 different compounds examined, (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide was the most potent inhibitor of infectious phage nucleic acid. The (+) and (-) isomers of the above racemic mixture did not differ significantly in their capacity to inhibit phage replication.

Mechanism of phage phiX174 DNA inactivation by benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide.

A previous report from this laboratory has shown that certain derivatives of polycyclic aromatic hydrocarbons bind to phiX174 DNA and render it noninfectious. The present work describes the relationship between the extent of phiX174 DNA binding by (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide and the effect on infectivity. The results suggest that one molecule of bound diolepoxide is sufficient to inhibit the replication of a single molecule of phiX174 DNA. DNA synthesis studies, in vitro, indicate that when phiX DNA bound by benzo[a]pyrene groups serves as template the rate of DNA polymerization is reduced and less product is formed. In addition, the propagation of synthetic DNA strands is blocked so that incomplete complementary chains are assembled. The relationship of these findings to the mutagenic and carcinogenic process associated with the action of benzo[a]pyrene-diolepoxide is discussed.

Selective enhancement of pentamidine uptake in the lung by aerosolization and delivery in liposomes.

We examined the tissue distribution of pentamidine, both as free drug and encapsulated in liposomes, after intravenous (iv) and aerosol administration in healthy rodents. After iv injection, drug levels in the lung were increased as much as 34-fold by administration in liposomes. Concurrently, peak liver uptake was increased 4-fold and renal deposition reduced 3-fold. Liposome-mediated lung delivery was highly dependent on liposome size. Decreasing liposome mean diameter from 2.5 to 0.4 micron reduced lung uptake of pentamidine 90-fold while affecting extrapulmonary organ deposition to a much lesser degree. Aerosol delivery of pentamidine produced high, sustained lung levels, with no evidence of drug clearance from the lung between 1 and 48 h after administration. Extrapulmonary drug levels produced by aerosol delivery were negligible throughout this period. There were no significant differences in the organ distribution of aerosolized free versus liposome-encapsulated drug, apparently because of sequestration of pentamidine within the lung. Comparison of drug levels in material recovered by bronchoalveolar lavage suggests that aerosol delivery of pentamidine produces substantially higher deposition in the alveolar space than does iv drug injection. Light and electron microscopic (EM) examination of lung, kidney, and liver after iv or aerosol administration of liposomes revealed no tissue abnormalities, although isolated platelet clumps were noted in pulmonary capillaries by EM examination.