Measuring quality care in localized renal cell cancer: use of appropriate preoperative investigations in a population-based cohort.

INTRODUCTION: Obtaining appropriate preoperative risk-specific staging investigations for localized renal cell carcinoma (rcc) is a recognized quality indicator. The goal of the present work was to determine the use and appropriateness of preoperative investigations in patients undergoing curative surgery for rcc. METHODS: This population-based retrospective study of patients having surgery for localized rcc recorded the use of preoperative imaging and laboratory investigations within 6 months of surgery. "Appropriate" stage-specific investigations were determined using recognized published guidelines. RESULTS: The study cohort consisted of 544 patients with 72.8% being stage i, 18.4% being stage ii, and 8.8% being stage iii by clinical TNM (2002) criteria. In 61.6%, chest imaging was obtained by chest radiography or computed tomography (ct) within 3 months preoperatively; in 75.6%, such imaging was obtained within 6 months. Abdominal ct imaging was obtained in 97.1% of patients before surgery, with 77.5% of patients receiving such imaging within 3 months of surgery. Complete blood count, electrolytes, and creatinine were measured in 99.1% of patients, but those tests plus other recommended blood tests including calcium, alkaline phosphatase, and liver function were measured in only 17.7%. CONCLUSIONS: In this study, most patients received appropriate abdominal imaging, but chest imaging was underutilized in the overall cohort. Despite being recommended, blood tests such as liver function, alkaline phosphatase, and calcium were completed in fewer than 2 of 10 patients. This analysis provides the groundwork for quality improvement initiatives directed to the use of preoperative investigations in localized rcc.

Women's views about breast cancer prevention at mammography screening units and well women's clinics.

Background: Women attending mammography screening units (msus) and well women's clinics (wwcs) represent a motivated cohort likely to engage in interventions aimed at primary breast cancer (bca) prevention. Methods: We used a feasibility questionnaire distributed to women (40-49 or 50-74 years of age) attending msus and wwcs in Halifax, Nova Scotia, to examine■ women's views about bca primary prevention and sources of health care information,■ prevalence of lifestyle-related bca risk factors, and■ predictors of prior mammography encounters within provincial screening guidelines.Variables examined included personal profiling, comorbidities, prior mammography uptake, lifestyle behaviours, socioeconomic status, health information sources, and willingness to discuss or implement lifestyle modifications, or endocrine therapy, or both. A logistic regression analysis examined associations with prior mammography encounters. Results: Of the 244 responses obtained during 1.5 months from women aged 40-49 years (n = 75) and 50-74 years (n = 169), 56% and 75% respectively sought or would prefer to receive health information from within, as opposed to outside, health care. Lifestyle-related bca risk factors were prevalent, and most women were willing to discuss or implement lifestyle modifications (93%) or endocrine therapy (67%). Of the two age groups, 49% and 93% respectively had previously undergone mammography within guidelines. Increasing age and marital status (single, separated, or divorced vs. married or partnered) were independent predictors of prior mammography encounters within guidelines for women 40-49 years of age; no independent predictors were observed in the older age group. Conclusions: Women attending msus and wwcs seem to largely adhere to mammography guidelines and appear motivated to engage in bca primary prevention strategies, including lifestyle modifications and endocrine therapy. Women's views as observed in this study provide a rationale for the potential incorporation of bca risk assessment within the "mammogram point of care" to engage motivated women in bca primary prevention strategies.

Suicidal thoughts and attempts in First Nations communities: links to parental Indian residential school attendance across development.

The Indian residential school (IRS) system in Canada ran for over a century until the last school closed in 1996. Conditions in the IRSs resulted in generations of Indigenous children being exposed to chronic childhood adversity. The current investigation used data from the 2008-2010 First Nations Regional Health Survey to explore whether parental IRS attendance was associated with suicidal thoughts and attempts in childhood, adolescence and in adulthood among a representative sample of First Nations peoples living on-reserve across Canada. Analyses of the adult sample in Study 1 (unweighted n=7716; weighted n=186,830) revealed that having a parent who attended IRS was linked with increased risk for suicidal thoughts and attempts in adolescence and adulthood. Although females were negatively affected by having a parent who attended IRS, the link with suicidal ideation in adulthood was greater for males. Analyses of the youth sample in Study 2 (unweighted n=2883; weighted n=30,190) confirmed that parental IRS attendance was associated with an increased risk for suicidal ideation and attempts. In contrast to the adult sample, parental IRS attendance had a significantly greater relation with suicidal ideation among female youth. A significant interaction also emerged between parental IRS attendance and age in the youth sample, with the influence of parental attendance being particularly strong among youth ages 12-14, compared with those 15-17 years. These results underscore the need for culturally relevant early interventions for the large proportions of Indigenous children and youth intergenerationally affected by IRSs and other collective traumas.

Evaluation of a pharmacist-led antimicrobial stewardship service in a pediatric emergency department.

Background To improve antimicrobial use, incorporation of a pharmacist in antimicrobial stewardship initiatives in the emergency department has been recommended. Recognizing the potential value, a pharmacist-led antimicrobial stewardship (AMS) service which included review and follow up of microbiology results for patients discharged from the pediatric emergency department (PED) with suspected infections was implemented at our local institution. Objective The objective of this study was to evaluate the impact of pharmacists delivering this service compared to usual care. Setting Pediatric emergency department at the IWK Health Centre in Halifax, Canada. Method This study was completed as a retrospective chart review of pediatric patients discharged from the PED 6 months before and after implementation of the pharmacist-led AMS service. Data was extracted from electronic medical records. Data were reported descriptively and compared using a two-sided chi-square test and ordinal logistic regression. Main outcome measures The primary outcome measure was rate of return visits to the PED within 96 h of initial presentation. Results This study included 1070 patient encounters pre-implementation and 1040 patient encounters post-implementation. The rate of return visits to the PED within 96 h was 12.0% (129/1070) pre-implementation vs. 10.0% (100/1049) post-implementation (p = 0.07). The rate of return visits or hospitalization at 30 days was 22.1% (237/1070) pre-implementation compared to 19.9% (207/1040) in the post-implementation phase (p = 0.21). Inappropriate antimicrobial therapy was identified more often in the pre-implementation phase (7.0%, 68/975) vs. the post-implementation phase (5.0%, 46/952), p = 0.047. Time to notification within the first day after discharge occurred more frequently in the post-implementation phase (53.3%, 80/150) as compared to the pre-implementation phase (40.3%, 52/129, p = 0.0298). Conclusion Although this pharmacist-led AMS service did not significantly affect the rate of return visits or hospitalization, it may have led to more judicious use of antimicrobial agents and faster time to notification.

RAD sequencing reveals genomewide divergence between independent invasions of the European green crab (Carcinus maenas) in the Northwest Atlantic.

Genomic studies of invasive species can reveal both invasive pathways and functional differences underpinning patterns of colonization success. The European green crab (Carcinus maenas) was initially introduced to eastern North America nearly 200 years ago where it expanded northwards to eastern Nova Scotia. A subsequent invasion to Nova Scotia from a northern European source allowed further range expansion, providing a unique opportunity to study the invasion genomics of a species with multiple invasions. Here, we use restriction-site-associated DNA sequencing-derived SNPs to explore fine-scale genomewide differentiation between these two invasions. We identified 9137 loci from green crab sampled from 11 locations along eastern North America and compared spatial variation to mitochondrial COI sequence variation used previously to characterize these invasions. Overall spatial divergence among invasions was high (pairwise FST ~0.001 to 0.15) and spread across many loci, with a mean FST ~0.052 and 52% of loci examined characterized by FST values >0.05. The majority of the most divergent loci (i.e., outliers, ~1.2%) displayed latitudinal clines in allele frequency highlighting extensive genomic divergence among the invasions. Discriminant analysis of principal components (both neutral and outlier loci) clearly resolved the two invasions spatially and was highly correlated with mitochondrial divergence. Our results reveal extensive cryptic intraspecific genomic diversity associated with differing patterns of colonization success and demonstrates clear utility for genomic approaches to delineating the distribution and colonization success of aquatic invasive species.

Posttraumatic stress symptoms and salivary cortisol levels.

OBJECTIVE: This study assessed the relationship between posttraumatic stress symptoms and salivary cortisol levels after a severe ice storm. METHOD: Posttraumatic stress symptoms (Impact of Event Scale scores) and salivary cortisol levels were determined in 115 victims of an ice storm and in 27 healthy comparison subjects 1 month and approximately 1 year after the ice storm. RESULTS: One month after the storm, Impact of Event Scale scores for the victims (mean=20.31, SD=15.23) exceeded those of the comparison subjects (mean=5.30, SD=9.78) but were reduced approximately 1 year later (mean=14.01, SD=13.68). A quadratic relation was found to exist between Impact of Event Scale scores and cortisol levels. CONCLUSIONS: One month after the storm, cortisol levels were found to be elevated among the victims but were diminished among those with the highest Impact of Event Scale scores. This relationship was found not to exist approximately 1 year later.

Effect of carbenoxolone sodium on steroid-induced sodium transport in the toad bladder: further studies.

The licorice derivative, carbenoxolone sodium, is a potent inhibitor of the enzyme 11 beta-hydroxysteroid dehydrogenase. When this enzyme is suppressed or is absent, endogenous glucocorticoids induce mineralocorticoid-like sodium retention by the kidney. Carbenoxolone sodium administered in vivo to an adrenalectomized rat has also recently been shown to enhance the mineralocorticoid response to submaximal concentrations of aldosterone, deoxycorticosterone (DOC) and 11-dehydrocorticosterone (compound A). In the present studies conducted on the urinary bladder isolated from the Dominican toad, Bufo marinus, a concentration of carbenoxolone sodium shown previously to increase glucocorticoid-induced sodium transport (2.5 x 10(-5) M) did not appear to alter the response to submaximal concentrations of aldosterone 10(-8) M, DOC 10(-7) M, or compound A 10(-5) M. These findings are consistent with the view that in the whole animal carbenoxolone sodium may modify additional steroid metabolic pathways and/or physiological processes in several organs to produce the enhanced renal response to mineralocorticoids and compound A.

Responding to sexual discrimination: the effects of societal versus self-blame.

Although self-blame has been considered to be a useful coping tool for victims, its benefits within the context of group discrimination are equivocal. The present research hypothesized that women encouraged to engage in self-blame for sex discrimination would be more likely to endorse accepting the situation or to endorse the use of individual, normative actions. In contrast, women encouraged to engage in societal blame for sex discrimination would be more likely to participate in nonnormative actions aimed at enhancing the status of women as a group. Female students in Canada were subjected to a situation of discrimination and were encouraged to blame either themselves or society. They were then given the opportunity to respond to the discrimination by endorsing various actions. A profile analysis of the endorsed actions indicated that the women encouraged to blame themselves were most likely to endorse accepting the situation, whereas the women encouraged to blame society endorsed nonnormative individual confrontation.

Genotypic and phenotypic variation in diatom silicification under paleo-oceanographic conditions.

Diatoms have co-evolved with the silicon cycle and are largely responsible for reducing surface concentrations of silicate in the ocean to their present levels. We quantify silicification in marine diatoms at a range of high silicate concentrations representative of environments found over their geological history. The species examined include Stephanopyxis turris, an ancient centric species found throughout the Cenozoic, Thalassiosira pseudonana and Thalassiosira weissflogii, two younger centric species, and two pennate ecotypes of Staurosirella pinnata isolated from different nutrient regimes. Frustule thickness and micromorphological structure are strongly affected by silicate concentration. All species become increasingly silicified with silicate concentrations at concentrations vastly in excess of surface ocean concentrations today. In contrast, the half-saturation constant for silicate uptake for most modern diatoms is below 2 µM. Based on the results, we hypothesize that silicate uptake is multiphasic in diatoms and that multiple silicate transport systems may have evolved in response to decreases in surface silicate concentration over geological time. The oldest species examined is more heavily silicified than the more modern species, presumably reflecting the conditions under which it originated. Yet diversification in silicification can be rapid, as illustrated by greater silicification in onshore versus the offshore ecotype of the same modern species. This work suggests that silicification of fossil frustules may eventually provide a paleoproxy for surface silicate concentrations over the Cenozoic, although development of species-specific calibrations will be necessary and the effects of a range of environmental conditions must be investigated.

Stress and stress counselling.

This is a report by the 1989 National Association of Clinical Tutors Wyeth Travelling Fellow to the United States of America. The stresses of postgraduate training and attempts to modify these are described, including stress counselling. The significance of stress and the relevance of the findings for postgraduate training in the United Kingdom are considered.

Uganda: stolen children, stolen lives.

PIP: This news article discusses conditions in Uganda due to the 12-year war that jeopardize the health and well-being of children. Since 1995 the rebel Sudan-backed Lord's Resistance Army (LRA) has secured new recruits to add to their diminishing numbers by abducting children. As many as 8000 children, ages 11 years and older, have been appropriated in the war effort. The children are abducted, trained as soldiers, and forced to commit brutal crimes and murders. Abducted girls are held as sex slaves and forced to marry. Those children who manage to escape need special psychological and medical interventions during their integration back into normal life. World Vision Uganda and Gulu Support the Children Organization (GUSCO) have set up psychosocial counseling programs to help these children overcome their traumatic experiences. The programs offer the children vocational training, trauma counseling, and reintegration into their families. Children return to their families within 3-6 weeks. The large number of children in need has resulted in difficult follow-up and lack of long-term support. The GUSCO reception center houses about 100 children, 15% of whom are girls. The philosophy of recovery is based on the view that 1) the children are survivors with individual resources and not sick victims; and 2) most of the children will experience a healing process when given protection and understanding. GUSCO uses a community participatory approach that includes children in decision-making and relies on local traditions. The psychosocial supportive environment helps children re-establish self-esteem, trust with other people, and a civilian identity. GUSCO works with families, local groups, teachers, and authorities. Reintegration follow-up occurs after 3 weeks, 3 months, 6 months, and 1 year. The international community should put pressure on Sudan to end its support of the LRA.^ieng

Effects of judicial instructions and case characteristics in a mock jury trial of battered women who kill.

This study examined the effects of judicial instructions on the outcome of a mock jury trial that involved a woman who pleaded self-defense after killing her abusive spouse. Jurors were instructed to adopt either an objective or a subjective standard of reasonableness when reaching a verdict. Within objective/subjective instruction conditions, half of the juries viewed a case in which the woman killed her abuser while he was attacking her (confrontational) and the remaining half viewed a case in which she killed him while he was asleep (no confrontation). Juries in the subjective conditions returned significantly more not guilty verdicts than jurors in the objective conditions. At the individual juror level, participants hearing subjective instructions were significantly more likely to rate the defendant as not guilty than jurors given objective instructions when the abuse was nonconfrontational.

Forum. The use of atracurium besylate for laparoscopy.

An anaesthetic technique is described for laparoscopy using an intravenous induction, atracurium 0.2 mg/kg for muscle relaxation and intermittent positive pressure ventilation of the lungs with nitrous oxide and oxygen. It was found to be a suitable and simple technique. Recovery of spontaneous ventilation was achieved without the use of reversal agents in all 40 patients. A 15% incidence of cutaneous histaminoid reactions was noted. This is no higher than reported in other studies of atracurium, and further clinical trials are awaited.

11-Dehydrocorticosterone, a glucocorticoid metabolite, inhibits aldosterone action in toad bladder.

The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) metabolizes glucocorticoid hormones and diminishes their ability to induce sodium transport. In these studies, we determined the location of this enzyme in toad bladder and assessed the biological role for its 11-dehydro end product. Employing a polyclonal antibody directed toward 11 beta-OHSD and immunofluorescence techniques, we located the enzyme in the epithelial cell layer of the toad bladder. Although corticosterone (10(-7) M) can partially suppress aldosterone (10(-7) M)-stimulated short-circuit current (SCC), a clear excess of corticosterone (10(-6) M) did not inhibit the aldosterone-induced induced (10(-8) M) rise in SCC (n = 6). The 11-dehydro product of corticosterone, 11-dehydrocorticosterone (compound A) added to the serosal bath suppressed aldosterone (10(-8) M) peak SCC (360 min) in a dose-dependent fashion reaching 46 +/- 5% of control values at 10(-5) M (n = 6; P less than 0.001). Compound A (10(-5) M) in the mucosal bath also was capable of partially inhibiting the peak aldosterone rise in SCC to 63 +/- 7% of control values with aldosterone at 10(-8) M (n = 6; P less than 0.01) and to 64 +/- 10% of control values with aldosterone at 10(-7) M (n = 9; P less than 0.01). Compound A alone at 10(-5) M did not have any effect on SCC. Isolated toad bladders were not able to transform compound A (at 10(-8) and 10(-5) M) back to corticosterone. Thus the 11-dehydro end product of 11 beta-OHSD (compound A) may play a biologic role by regulating a component of mineralocorticoid-induced sodium transport.

Effect of carbenoxolone on glucocorticoid metabolism and Na transport in toad bladder.

In humans, diminished 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) enzyme activity has been associated with sodium retention and hypertension. These studies show that the toad bladder, another target tissue epithelium displaying steroid-induced sodium transport, possesses the enzyme 11 beta-OHSD. The toad urinary bladder rapidly transformed corticosterone (3 x 10(-8) M) (50% by 10 min and 90% by 180 min) with 11-dehydrocorticosterone being the major metabolite. The 11-dehydrocorticosterone produced reached an apparent plateau when the tissue incubations were repeated with higher concentrations of corticosterone (10(-7) and 10(-6) M). Carbenoxolone sodium (2.5 x 10(-5) M), a water soluble derivative of glycyrrhetinic acid, markedly inhibited the metabolism of corticosterone (3 x 10(-8) M) to 11-dehydrocorticosterone similar to previous observations in the mammalian kidney. Carbenoxolone sodium (2.5 x 10(-5) M) did not significantly affect short-circuit current (SCC) in toad bladders when added to either the serosal or mucosal bath. However, when carbenoxolone sodium was added to the mucosal bath and 60 min later corticosterone 10(-6) M was placed in the serosal bath, bladders generated a SCC 2.07 +/- 0.17 (mean +/- SE) times above base line at 360 min compared with 1.48 +/- 0.11 in bladders exposed to corticosterone alone (P less than 0.02). In parallel experiments, carbenoxolone sodium in the mucosal bath enhanced the rise in SCC induced by cortisol 10(-6) M; 1.66 +/- 0.16 times above base line at 360 min compared with 1.07 +/- 0.14 with cortisol alone (P less than 0.02). We conclude that the toad bladder contains 11 beta-OHSD and inhibition of this enzyme with carbenoxolone sodium is associated with amplification of glucocorticoid-induced transepithelial sodium transport in this tissue. However, since the quantity of 11-dehydro-product produced appears to be limited, other factors in addition to inhibition of 11 beta-OHSD may play a role in this amplification of sodium transport.

Changes in intracellular sodium during the hydroosmotic response to vasopressin.

During vasopressin (VP)-induced water movement, toad urinary bladder epithelial cells undergo unique morphological changes. The osmolality within these responding cells remains relatively stable despite the large transcellular transport of water. We hypothesized that the hydroosmotic response to VP may be associated with a net increase in sodium either as an aid in maintaining the intracellular osmolality or as part of a Na-Ca exchange process. Changes in intracellular sodium (Nai) were monitored over time in individual hemibladders using 23Na NMR. Hemibladders were mounted as bags on glass pipets and filled with deionized water. During NMR studies, the serosal bath consisted of aerated 2.4 mM HCO3 amphibian Ringer's (pH 8.1) made up with 15% D2O containing the shift reagent, dysprosium tripolyphosphate (1 mM). This reagent allowed for visualization of Nai by shifting the extracellular Na signal; it did not affect basal or VP stimulated water flow, short-circuit current, or high energy phosphate metabolism as seen by 31P NMR. Changes in Nai were determined by integrating the area under the unshifted Na peak at each measurement and expressing differences as a ratio relative to baseline. The initial Nai signal from unstimulated hemibladders remained stable in these tissues over at least 180 minutes. Within 30 minutes of VP (20 mU/ml) exposure, however, the Nai peak increased 2.47 times above pretreatment baseline (N = 16, P less than 0.001). The Nai signal returned toward baseline values with removal of VP from the serosal bath but only after approximately 90 minutes. When change in cell shape and water movement were prevented by having isotonic sorbitol in the mucosal bath, VP produced no change in the Nai signal (N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental changes in rat renal 11 beta-hydroxysteroid dehydrogenase.

11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) transforms endogenous glucocorticoids to their respective "biologically inert" 11-dehydro derivatives. A decrease in enzyme activity allows glucocorticoids to induce mineralocorticoid-like renal sodium retention. Since positive sodium balance is required for optimum growth in the newborn, we hypothesized that renal 11 beta-OHSD activity would be low in the postnatal period, a time of active growth. To test this, incubations with corticosterone were carried out using minces or homogenates prepared from kidneys of newborn, 8-day-old, and mature Sprague-Dawley rats. 11 beta-OHSD activity in renal minces, assessed by the percent of corticosterone (10(-8) M) transformed to 11-dehydrocorticosterone (compound A), was significantly lower in the newborn kidney (newborn 45.7 +/- 3.8%, 8 day 70.2 +/- 3.8%, and adult 73.4 +/- 3.1%, P < 0.001 1 vs. 8 day). Parallel studies were conducted using an antibody directed against liver 11 beta-OHSD counter stained with immunofluorescent labeled IgG. Kidneys from mature rats were brightly stained at S2 and S3 segments of proximal tubules. In contrast, staining was barely detectable in kidneys from the newborn and 8-day-old rats. When enzyme kinetics were examined in kidney homogenates (average protein concentration 2.5 mg/ml) in the presence of 200 microM NADP+, the apparent Km for corticosterone in the adult was 4.42 x 10(-6) M with a corresponding Vmax of 1.33 x 10(-9) mol/min/mg protein, while the apparent Km for corticosterone in the newborn was calculated to be 12.8 x 10(-8) M with a Vmax of 2.08 x 10(-11) mol/min/mg protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity of 11 beta-hydroxysteroid dehydrogenase in toad bladder: effects of 11-dehydrocorticosterone.

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) transforms circulating glucocorticoids to their "biologically inert" 11-dehydro derivatives. Isoforms of 11 beta-OHSD with different cofactor requirements and biochemical properties [Michaelis constant (Km) and maximal velocity (Vmax)] exist in the kidney. Since epithelial cells derived from the toad bladder also contain this enzyme, we wished to further characterize its properties in prepared cell homogenates. 11 beta-OHSD from toad bladder demonstrated a clear preference for NAD+ over NADP+ as a cofactor similar to that observed in renal cortical collecting duct (CCD) cells. Furthermore, 11 beta-OHSD had a rapid onset of action. The apparent Km for corticosterone was 16.3 x 10(-8) M, a value comparable to that observed for enzyme from CCD, and a Vmax of 4.8 x 10(-12) mol.mg protein-1.min-1. The end product, 11-dehydrocorticosterone (compound A), influenced enzyme activity; it increased 11 beta-OHSD activity at corticosterone concentrations below the apparent Km for the enzyme and inhibited 11 beta-OHSD activity at corticosterone concentrations above the Km for the enzyme. The inhibitory effects of compound A appeared noncompetitive with an apparent equilibrium constant (Ki) of 2.8 x 10(-7) M. Consistent with its inhibitory action on 11 beta-OHSD, compound A (10(-6) M) enhanced the short-circuit current response to corticosterone (10(-7) M) in the intact toad bladder (experimental 2.03 +/- 0.33 vs. control 1.40 +/- 0.17 times above baseline; n = 7, P < 0.01). Thus 11 beta-OHSD in toad bladder resembles the isoform found in CCD, and compound A may be biologically important as a regulator of 11 beta-OHSD.