Minimally invasive surgery for suspected early-stage ovarian cancer; a cost-effectiveness study.

OBJECTIVE: While there are a number of benefits to minimally invasive surgery (MIS) for women with ovarian cysts, there is an increased risk of ovarian capsule rupture during the procedure, which could potentially seed the abdominal cavity with malignant cells. We developed a decision model to compare the risks, benefits, effectiveness and cost of MIS versus laparotomy in women with ovarian masses. DESIGN: Cost-effectiveness study POPULATION: Hypothetical cohort of 10 000 women with ovarian masses who were undergoing surgical management. METHODS: The initial decision point in the model was performance of surgery via laparotomy or a MIS approach. Model probabilities, costs and utility values were derived from published literature and administrative data sources. Extensive sensitivity analyses were conducted to assess the robustness of the findings. MAIN OUTCOME MEASURES: The primary outcome was the cost-effectiveness of MIS versus laparotomy for women with a pelvic mass measured by incremental cost-effectiveness ratios (ICERs). RESULTS: MIS was the least costly strategy at $7,732 per women on average, compared with $17,899 for laparotomy. In our hypothetical cohort of 10 000 women, there were 64 cases of ovarian rupture in the MIS group and 53 in the laparotomy group, while there were 26 cancer-related deaths in the MIS group and 25 in the laparotomy group. MIS was more effective than laparotomy (188 462 QALYs for MIS versus 187 631 quality adjusted life years [QALYs] for laparotomy). Thus, MIS was a dominant strategy, being both less costly and more effective than laparotomy. These results were robust in a variety of sensitivity analyses. CONCLUSION: MIS constitutes a cost-effective management strategy for women with suspicious ovarian masses. TWEETABLE ABSTRACT: MIS is a cost-effective management strategy for women with suspicious ovarian masses.

Helminth parasites and zoonotic risk associated with urban coyotes (Canis latrans) in Alberta, Canada.

Coyotes (Canis latrans) are resilient, adaptable, cosmopolitan omnivores that are increasingly prevalent in urban environments, where they interact with both humans and domestic dogs. Coyotes potentially transmit zoonotic parasites, including the tapeworm Echinococcus multilocularis, which appears to be increasing in prevalence in western North America. In this study, we analysed the carcasses of 23 urban coyotes in Edmonton, Alberta, Canada. Focusing primarily on the helminth community, we recovered three tapeworm species (E. multilocularis, Taenia pisiformis, T. serialis), four nematodes (Toxascaris leonina, Uncinaria stenocephala, Capillaria sp., Physaloptera sp.), and two trematodes (Alaria arisaemoides and A. americana). Compared to previous studies of urban coyotes conducted in North America, we report one of the highest levels of E. multilocularis infection in North America: 65.2% infection prevalence. These results amplify concerns expressed by others about the increasing prevalence of this zoonotic parasite and the role coyotes may play in parasite transmission. More research is needed to better understand how various ecological factors, urbanization and wildlife management practices influence the transmission of potentially zoonotic parasites such as E. multilocularis.

Ambidextrous ungulates have more flexible behaviour, bolder personalities and migrate less.

Studies of wildlife have shown consistent individual variation in behavioural plasticity, which affects the rate of adaptation to changing environments. More flexible individuals may thus be more prone to habituation and conflict behaviour, but these applications of personality to wildlife management are little explored. Behavioural lateralization reflects cerebral specialization that may predict diverse expressions of behavioural plasticity. We recorded front-limb biases (i.e. handedness) in wild elk (Cervus canadensis), a species with facultative migration and high rates of habituation inside protected areas. Less lateralized elk responded more strongly to the application of aversive conditioning (predator-resembling chases by humans) by increasing their average flight response distances, but these same animals were also quicker to reduce their flight responses (i.e. habituate) when human approaches were benign. Greater laterality was correlated with, but not completely predicted by, bolder personalities, which we quantified via five correlated behavioural metrics. Lastly, lateralized elk were three times more likely to migrate, whereas less lateralized animals were similarly likely to remain near humans year-round. Lateralized behaviours can provide insight into behavioural flexibility enabling certain individuals to more quickly adapt to human-disturbed landscapes, and offer an especially productive arena for collaborative work by behaviourists, conservation biologists and wildlife managers.

Pharmacokinetics and tolerability of oral sildenafil in adults with cystic fibrosis lung disease.

RATIONALE: Airway inflammation is central to cystic fibrosis (CF) pathophysiology. Pre-clinical models have shown that phosphodiesterase inhibitors (PDEi) like sildenafil have anti-inflammatory activity. PDEi have not been studied in CF subjects. OBJECTIVES: We evaluated the pharmacokinetics, tolerability, and safety of sildenafil in subjects with CF. Sputum biomarkers were used to explore efficacy. METHODS: An open-label pilot study of oral sildenafil administration was conducted in adults with mild to moderate CF lung disease. Subjects received oral sildenafil 20 or 40 mg p.o. t.i.d. for 6 weeks. MEASUREMENTS AND MAIN RESULTS: Twenty subjects completed the study. Estimated elimination rate constants were statistically different in subjects with CF compared to previously published non-CF subjects. Side effects were generally mild. There were no drug-related serious adverse events. Sputum neutrophil elastase activity decreased. CONCLUSIONS: Subjects with CF may eliminate sildenafil at a faster rate than non-CF subjects. Sildenafil administration was safe in subjects with CF and decreased sputum elastase activity. Sildenafil warrants further study as an anti-inflammatory in CF.

Trace elements in Pacific Dunlin (Calidris alpina pacifica): patterns of accumulation and concentrations in kidneys and feathers.

Trace element concentrations were measured in Pacific Dunlin (Calidris alpina pacifica) to identify factors that influence accumulation and to assess toxicity risks. We report concentrations of cadmium, copper, and zinc in kidneys as well as copper, lead, mercury, selenium and zinc in feathers. Relationships between element concentrations and Dunlin age, sex, bill length, habitat preference, trophic level, and sample group were investigated with regression analyses. Stable isotope ratios of carbon and nitrogen in Dunlin muscle tissue were used to determine habitat preference and trophic level, respectively. Cadmium concentrations in kidneys were significantly related to habitat preference: [Cd] in estuarine foragers >[Cd] in terrestrial foragers. Cadmium accumulation was age-dependent as concentrations increased significantly within 10 months of hatch dates but not afterward. Concentrations of cadmium and zinc in kidneys as well as lead and mercury in feathers were below those known to cause deleterious effects in birds. In contrast, selenium concentrations in feathers (range: 2.1-14.0 µg/g) were often at levels associated with toxicity risks (>5 µg/g). Toxicity thresholds are not available for copper in kidneys or copper and zinc in feathers; however, measured concentrations of these elements were within documented ranges for sandpipers. Future studies should assess potential impacts of selenium on embryonic development in Dunlin and other sandpipers. Risk assessments would yield more conclusive results for all elements if impacts under ecologically relevant stresses (e.g. development in the wild, migration, predation) were better understood.

Concentration and partitioning of metals in intertidal biofilms: implications for metal bioavailability to shorebirds.

We compared zinc, copper and cadmium concentrations and the operationally defined geochemical partitioning of the three metals in sediments enriched with biofilm versus sediments without obvious biofilm present (reference) sampled from five locations within the Fraser River Delta, British Columbia, Canada. Two-way ANOVA's with site and biofilm (enriched or reference) as the two factors were applied to determine if metal concentrations or the partitioning of the metal was dependent on the two factors. Sediment enriched in biofilm contained greater amounts of aqua regia extracted zinc and copper and tended to have greater amounts of reducible cadmium as compared to reference sediments. By contrast, reference sediments had greater concentrations of easily reducible copper suggesting differences in speciation between the two sediment types. Greater concentrations of reducible cadmium within biofilm may provide a route of contaminant exposure to shorebirds whose diet is dependent on biofilm.

Blood mRNA biomarkers for detection of treatment response in acute pulmonary exacerbations of cystic fibrosis.

BACKGROUND: Acute pulmonary exacerbations accelerate pulmonary decline in cystic fibrosis (CF). There is a critical need for better predictors of treatment response. OBJECTIVE: To test whether expression of a panel of leucocyte genes directly measured from whole blood predicts reductions in sputum bacterial density. METHODS: A previously validated 10-gene peripheral blood mononuclear cell (PBMC) signature was prospectively tested in PBMC and whole blood leucocyte RNA isolated from adult subjects with CF at the beginning and end of treatment for an acute pulmonary exacerbation. Gene expression was simultaneously quantified from PBMCs and whole blood RNA using real-time PCR amplification. Test characteristics including sensitivity, specificity, positive and negative predictive values were calculated and receiver operating characteristic curves determined the best cut-off to diagnose a microbiological response. The findings were then validated in a smaller independent sample. RESULTS: Whole blood transcript measurements are more accurate than forced expiratory volume in 1 s (FEV(1)) or C reactive protein (CRP) alone in identifying reduction of airway infection. When added to FEV(1), the whole blood gene panel improved diagnostic accuracy from 64% to 82%. The specificity of the test to detect reduced infection was 88% and the positive predictive value for the presence of persistent infection was 86%. The area under the curve for detecting treatment response was 0.81. Six genes were the most significant predictors for identifying reduction in airway bacterial load beyond FEV(1) or CRP alone. The high specificity of the test was replicated in the validation cohort. CONCLUSIONS: The addition of blood leucocyte gene expression to FEV(1) and CRP enhances specificity in predicting reduced pulmonary infection and may bolster the assessment of CF treatment outcomes.

Effects of road networks on bird populations.

One potential contributor to the worldwide decline of bird populations is the increasing prevalence of roads, which have several negative effects on birds and other vertebrates. We synthesized the results of studies and reviews that explore the effects of roads on birds with an emphasis on paved roads. The well-known direct effects of roads on birds include habitat loss and fragmentation, vehicle-caused mortality, pollution, and poisoning. Nevertheless, indirect effects may exert a greater influence on bird populations. These effects include noise, artificial light, barriers to movement, and edges associated with roads. Moreover, indirect and direct effects may act synergistically to cause decreases in population density and species richness. Of the many effects of roads, it appears that road mortality and traffic noise may have the most substantial effects on birds relative to other effects and taxonomic groups. Potential measures for mitigating the detrimental effects of roads include noise-reduction strategies and changes to roadway lighting and vegetation and traffic flow. Road networks and traffic volumes are projected to increase in many countries around the world. Increasing habitat loss and fragmentation and predicted species distribution shifts due to climate change are likely to compound the overall effects of roads on birds.

Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men.

Aging is associated with reduced GH, IGF-I, and sex steroid axis activity and with increased abdominal fat. We employed a randomized, double-masked, placebo-controlled, noncross-over design to study the effects of 6 months of administration of GH alone (20 microg/kg BW), sex hormone alone (hormone replacement therapy in women, testosterone enanthate in men), or GH + sex hormone on total abdominal area, abdominal sc fat, and visceral fat in 110 healthy women (n = 46) and men (n = 64), 65-88 yr old (mean, 72 yr). GH administration increased IGF-I levels in women (P = 0.05) and men (P = 0.0001), with the increment in IGF-I levels being higher in men (P = 0.05). Sex steroid administration increased levels of estrogen and testosterone in women and men, respectively (P = 0.05). In women, neither GH, hormone replacement therapy, nor GH + hormone replacement therapy altered total abdominal area, sc fat, or visceral fat significantly. In contrast, in men, administration of GH and GH + testosterone enanthate decreased total abdominal area by 3.9% and 3.8%, respectively, within group and vs. placebo (P = 0.05). Within-group comparisons revealed that sc fat decreased by 10% (P = 0.01) after GH, and by 14% (P = 0.0005) after GH + testosterone enanthate. Compared with placebo, sc fat decreased by 14% (P = 0.05) after GH, by 7% (P = 0.05) after testosterone enanthate, and by 16% (P = 0.0005) after GH + testosterone enanthate. Compared with placebo, visceral fat did not decrease significantly after administration of GH, testosterone enanthate, or GH + testosterone enanthate. These data suggest that in healthy older individuals, GH and/or sex hormone administration elicits a sexually dimorphic response on sc abdominal fat. The generally proportionate reductions we observed in sc and visceral fat, after 6 months of GH administration in healthy aged men, contrast with the disproportionate reduction of visceral fat reported after a similar period of GH treatment of nonelderly GH deficient men and women. Whether longer term administration of GH or testosterone enanthate, alone or in combination, will reduce abdominal fat distribution-related cardiovascular risk in healthy older men remains to be elucidated.

Cortisol and GH secretory dynamics, and their interrelationships, in healthy aged women and men.

We studied 130 healthy aged women (n = 57) and men (n = 73), age 65-88 yr, with age-related reductions in insulin-like growth factor I and gonadal steroid levels to assess the interrelationships between cortisol and growth hormone (GH) secretion and whether these relationships differ by sex. Blood was sampled every 20 min from 8:00 PM to 8:00 AM; cortisol was measured by RIA and GH by immunoradiometric assay, followed by deconvolution analyses of hormone secretory parameters and assessment of approximate entropy (ApEn) and cross-ApEn. Cortisol mass/burst, cortisol production rate, and mean and integrated serum cortisol concentrations (P < 0.0005), and overnight basal GH secretion (P < 0.05), were elevated in women vs. men. Integrated cortisol concentrations were directly related to most measures of GH secretion in women (P < 0.01) and with mean and integrated GH concentrations in men (P < 0.05). Integrated GH concentrations were directly related to mean and integrated cortisol levels in women (P < 0.005) and men (P < 0.05), with no sex differences. There were no sex differences in cortisol or GH ApEn values; however, the cross-ApEn score was greater in women (P < 0.05), indicating reduced GH-cortisol pattern synchrony in aged women vs. men. There were no significant relationships of integrated cortisol secretion with GH ApEn, or vice versa, in either sex. Thus postmenopausal women appear to maintain elevated cortisol production in patterns that are relatively uncoupled from those of GH, whereas mean hormone outputs remain correlated.

Interrelationships of spontaneous growth hormone axis activity, body fat, and serum lipids in healthy elderly women and men.

Aging is associated with decreased growth hormone (GH) secretion and plasma insulin-like growth factor-I (IGF-I) levels, increased total and abdominal fat, total and low-density lipoprotein (LDL) cholesterol, and triglycerides, and reduced high-density lipoprotein (HDL) cholesterol. Similar changes in lipids and body composition occur in nonelderly GH-deficient adults and are reversed with GH administration. To examine whether GH/IGF-I axis function in the elderly is related to the lipid profile independently of body fat, we evaluated GH secretion, serum IGF-I and IGF binding protein-3 (IGFBP-3) levels, adiposity via the body mass index (BMI), waist to hip ratio (WHR), dual-energy x-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI), and circulating lipids in 101 healthy subjects older than 65 years. Integrated nocturnal GH secretion (log IAUPGH) was inversely related (P < .005) to DEXA total and abdominal fat and MRI visceral fat in both genders. Log IAUPGH was inversely related to visceral fat in women (P < .005) and men (P < .0001), but was not significantly related to total fat in either gender. In women, log IAUPGH was related inversely to total and LDL cholesterol and positively to HDL cholesterol (P < .008). In men, log IAUPGH was inversely related to total cholesterol and triglycerides (P < .005). In women, HDL cholesterol was inversely related to the WHR (P < .005). In men, triglycerides were positively related (P < .001) to the WHR and DEXA abdominal and MRI visceral fat. Multivariate regression revealed log IAUPGH, but not DEXA total body fat, to be an independent determinant of total (P < .001 for women and P = .01 for men) and LDL (P < .007 and P = .05) cholesterol in both sexes and of HDL cholesterol (P < .005) and triglycerides (P < .03) in women. Log IAUPGH, but not DEXA abdominal fat, was related to total (P < .005 and P < .03) and LDL (P < .03 and P = .05) cholesterol in both genders and to HDL in women (P < .05). Log IAUPGH, but not MRI visceral fat, was related to total cholesterol (P < .03 and P = .05) in women and men. Age, IGF-I, and IGFBP-3 were not significantly related to any body fat or lipid measures, except for a positive correlation of IGF-I with triglycerides in men. Thus, endogenous nocturnal GH secretion predicts total, LDL, and HDL cholesterol levels independently of total or abdominal fat, suggesting that it is an independent cardiometabolic risk factor in healthy elderly people.

Managed health care: a concept not understood by rural Oklahomans.

OBJECTIVE: The purpose of the study was to find out what people in rural Oklahoma know and understand about managed care. METHODS: A fourteen-statement survey instrument was developed. A panel of managed care professionals were asked to participate to provide a "standard" to compare the responses of the general public. The survey was administered to the general public in five rural communities and to recipients of the Oklahoma AHEC Newsletter. RESULTS: Overall, the panel tended to agree and created an industry profile useful in comparison to the responses of the general public: (1) 55-65% of the respondents answered I Don't Know or Neither Agree nor Disagree to statements using the term "managed care" and only 15-20% of the public respondents answered I Don't Know to statements not including the term, "managed care." (2) 25-30% of the general public answered in accordance with the managed care panel. (3) Over 50% of the public respondents Agreed that changes are necessary in the health sector. CONCLUSIONS: The results of this survey suggest that rural Oklahomans are uninformed about the concept of managed care and need to become better informed.

Oklahoma's rural health providers and consumers prioritizing rural health issues.

The Clinton administration has been busy for many months devising a new health care plan to address national needs. Over the last three years, rural health providers and consumers in the State of Oklahoma have also been actively reviewing their state health issues and concerns and determining the priorities. The purpose of this paper is threefold: (1) to illustrate why it is vital to have a strong health care sector in rural Oklahoma; (2) to review the issues and concerns identified by rural Oklahomans; and, (3) to provide a philosophical basis for possible solutions to the barriers identified.

Prostacyclin production in acute, chronic, and long-term experimental portal hypertension.

BACKGROUND: Chronic portal hypertension (PHT) is characterized by a high portosystemic shunt (PSS) and increased splanchnic blood flow. It has been suggested that the splanchnic vasodilator, prostacyclin (PGI2), mediates this increased flow. We studied splanchnic PGI2 production both in normal rabbits and in three groups of rabbits after partial portal vein ligation (PVL-PHT): acute (within 30 minutes of ligation), chronic (3 weeks after ligation), and long-term (3 months after ligation) to determine whether increased splanchnic production is a mechanism for the elevated PGI2 in PHT. METHODS: Levels of 6-keto prostaglandin F1 alpha were determined by radioimmunoassay, and splanchnic hemodynamics were measured with Doppler flowmetry in four groups of rabbits: portal normotensive rabbits, and PVL-PHT rabbits 30 minutes, 3 weeks, or 3 months after partial PVL. Splanchnic PGI2 production (PGI2 PROD) was then calculated. RESULTS: Portal pressure and PSS in chronic and long-term groups were significantly elevated in all groups compared with normals (p < 0.001). Splanchnic blood flow initially fell from 84 +/- 4.8 to 37.4 +/- 7 ml/min/100 gm immediately and then rose to 144.7 +/- 9.6 ml/min/100 gm and 137 +/- 15 ml/min/100 gm at 3 weeks and 3 months after ligation, respectively. PGI2 production rose immediately after partial portal ligation from 62 +/- 10 to 164 +/- 4.1 ng/min/100 gm and remained elevated thereafter. CONCLUSIONS: The mechanism for elevated PGI2 in acute PHT is unclear, but in chronic and long-term PHT, it is probably due in part to increased splanchnic PGI2 production.

Rural nurses as self-directed learners: overcoming obstacles to continuing education.

Evaluation of a fieldtest of a self-directed learning (SDL) program included assessing rural nurses' self-perceived competencies in this method and loci of control for motivation. A significant negative relationship occurred between high scores for learner skills and internal motivation ratings. Sixty-two percent rated themselves above the mean as self-directed learners regardless of perceived loci of control in the stressful rural practice environment. SDL can offer an alternative way to meet continuing education needs of rural nurses in their efforts to overcome the many obstacles to professional growth in rural practice.

Hemodynamic effects of intravenous digoxin in patients with severe heart failure initially treated with diuretics and vasodilators.

The purpose of this study was to assess the hemodynamic effects of intravenous digoxin in patients with New York Heart Association class IV heart failure, who had never previously been treated with digitalis drugs, and who were initially treated only with diuretics and systemic vasodilators to clinical end points of compensation. Eleven male patients, 5 with idiopathic and 6 with ischemic cardiomyopathy, had sinus rhythm and were hospitalized with congestive heart failure not precipitated by an acute ischemic event. All 11 patients were treated with intravenous furosemide and various vasodilators without invasive hemodynamic monitoring for a mean period of 4.3 +/- 2.1 days. This therapy resulted in subjective and objective improvement in all patients as reflected by a significant decrease in heart failure score from 9.5 +/- 2.2 to 2.7 +/- 2.3 (p less than 0.001). When compensation was achieved by clinical criteria, the patients were instrumented and hemodynamics obtained before and serially thereafter for 6 hours after the intravenous administration of digoxin given in two 0.5 mg doses 2 hours apart. In response to digoxin, cardiac index increased from 2.6 +/- 0.7 liters/min per m2 to a peak of 3.3 +/- 0.6 liters/min per m2 (p less than 0.005); left ventricular stroke work index (g X m/m2) increased from 27 +/- 16 to 43 +/- 23 (p less than 0.005) and the ejection fraction (eight patients) increased from 21 +/- 13% to 29 +/- 11% (p less than 0.04). Mean pulmonary capillary wedge pressure decreased from 24 +/- 7 to a minimum of 17 +/- 4 mm Hg (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Short- and long-term treatment of stable effort angina with nicardipine, a new calcium channel blocker: a double-blind, placebo-controlled, randomised, repeated cross-over study.

This study evaluated 1 year the efficacy of therapy with nicardipine in patients with chronic stable angina pectoris. Twenty-five male patients were entered. After a placebo run-in phase, the patients received nicardipine 30 mg, nicardipine 40 mg, and placebo, three times daily given in random, double-blind manner for 8 weeks. A double-blind, cross-over study comparing nicardipine with placebo was then undertaken. After 5 months of open treatment with nicardipine 90 or 120 mg day-1, patients received either placebo or nicardipine for 3 weeks, each followed by the alternative treatment for an additional 3 weeks and further open-label treatment with nicardipine for another 3-5 months. There were no significant changes in the PR, QRS or QT intervals, or in the QRS pattern during the short-term and long-term studies. There were no significant differences in mean heart rate after nicardipine compared with baseline. During treatment with nicardipine 120 mg day-1, patients reported significantly fewer anginal attacks compared with placebo, and nitroglycerin consumption also decreased. Nicardipine increased treadmill time, time to onset of angina, and time to one mm ST segment depression. These effects were maintained after 6 months of continued nicardipine therapy. Adverse effects were minor and well tolerated and included headache, dizziness, gastrointestinal upset, flushing paraesthesia and pedal oedema. Abrupt withdrawal of nicardipine at the end of the study resulted in a rapid return of the original symptoms but without further deterioration from the baseline measurements. Nicardipine was effective in the treatment of stable effort angina pectoris; this benefit was maintained for the entire year of treatment.