Prognostic and predictive value of low estrogen receptor expression in breast cancer.

PURPOSE: Anti-hormonal therapy (tamoxifen) is recommended for estrogen receptor (er)-positive breast cancer (bca); however, its effect on low-receptor cancers is unclear. We retrospectively evaluated the effect of adjuvant tamoxifen in patients with weakly er-positive bca. METHODS: We identified 2221 bca patients who had been er-tested by ligand-based assay (lba) during 1976-1995 and who had been treated and followed until 2008. Cox proportional hazards models adjusted for age, body mass index, tumour size, nodal status, surgery, and chemotherapy were used to assess the effect of er level on bca survival in patients who received tamoxifen. RESULTS: Overall, 17% (383) of patients were within 0-3 fmol/mg cytosol protein, and 12% (266) were within 4-9 fmol/mg cytosol protein. Patients with er levels of 0-3, 4-9, 10-19, 20-49, and 50 fmol/mg or more cytosol protein had 20-year bca survival rates of 56%, 56%, 63%, 71%, and 60% respectively. Of the 2221 patients studied, 661 (29.8%) received anti-hormonal therapy. Within the latter group, er levels of 0-3, 4-9, 10-19, 20-49, and 50 fmol/mg or more cytosol protein were associated with a hazard ratio for lower bca mortality: respectively, 1.00 (reference), 0.59 (p = 0.09), 0.19 (p < 0.0001), 0.26 (p < 0.0001), and 0.31 (p < 0.0001)-the risk reduction being significant only for er levels of 10 fmol/mg or more cytosol protein. CONCLUSIONS: Tamoxifen use in bca patients with a weakly positive er status (4-9 fmol/mg cytosol protein), compared with those having higher er levels (≥10 fmol/mg cytosol protein), is not associated with a significantly lower bca-specific mortality. Our results do not support treatment with anti-hormonal therapy for bca patients with a weakly positive er status as identified by lba.

No effect of scalp cooling on survival among women with breast cancer.

Scalp cooling can prevent chemotherapy-induced alopecia in some cancer patients. It is not used in all countries. No data are available regarding its impact, if any, on survival. The aim of this study was to compare overall survival according to whether or not scalp cooling was used during neoadjuvant or adjuvant chemotherapy for non-metastatic breast cancer. We conducted a retrospective cohort study of 1,370 women with non-metastatic invasive breast carcinoma who received chemotherapy in the neoadjuvant or adjuvant setting. A total of 553 women who used scalp cooling came from a tertiary breast cancer clinic in Quebec City (diagnosed between 1998 and 2002) and 817 were treated in other hospitals in the province of Quebec (between 1998 and 2003) where scalp cooling was not routinely available. Overall survival of women who used scalp cooling and those who did not was compared using Cox proportional hazards models. Median follow-up for the scalp-cooled and the non-scalp-cooled groups was 6.3 years and 8.0 years, respectively. Overall mortality was no different (adjusted hazard ratio 0.89, 95 % confidence interval: 0.68-1.17, p = 0.40) among scalp-cooled women, compared to those not getting scalp cooling. Among women getting neoadjuvant or adjuvant chemotherapy for non-metastatic breast cancer, scalp cooling used to prevent chemotherapy-induced alopecia had no negative effect on survival. To our knowledge, this is the first study to compare survival of women who used scalp cooling to that of women who did not.

Effort--reward imbalance and medically certified absence for mental health problems: a prospective study of white-collar workers.

OBJECTIVE: Little is known about the effects of psychosocial work factors on objectively assessed mental health problems leading to medically certified absence. Only one study has evaluated the prospective effects of effort-reward imbalance (ERI) at work with regards to this outcome. The present study aimed to evaluate the effects of ERI on the incidence of medically certified absence for mental health problems. METHODS: The study included 2086 white-collar workers (63.3% women) employed in public organisations in Quebec city. Participants were followed over a 9-year period. Medical absences from work were collected from employers' files and psychosocial factors were measured using the ERI questionnaire. Cox regression models were used to estimate the incidence of certified sickness absence due to mental health problems that lasted 5 workdays or more, while controlling for confounders. RESULTS: Workers exposed to ERI had a higher risk of a first spell of medically certified absence for mental health problems (HR=1.38, 95% CI 1.08 to 1.76) compared with unexposed workers. Low reward was significantly associated with a high risk among men (HR=2.80, 95% CI 1.34 to 5.89) but not in women. (HR=1.24, 95% CI 0.90 to 1.73). Effort at work had no effect on certified absence. All these effects were adjusted for potential confounders. CONCLUSIONS: ERI and low reward at work were prospectively associated with medically certified absence for mental health problems. These effects seem to differ by gender. Primary prevention that is aimed at reducing these stressors should be considered to help reduce the incidence of such severe mental health problems.

Experiences and treatment patterns of hypogonadal men in a U.S. health system.

OBJECTIVE: To examine self-reported experiences with hypogonadism (HG) and patterns of testosterone replacement therapy (TRT) in men seeking care in a U.S. healthcare system. METHODS: Men ≥ 18 years old with HG were identified from the 2008-2010 Reliant electronic medical records database. Surveys, including validated instruments for measuring symptoms of HG, were collected and evaluated for demographic and behavioural data. RESULTS: Surveys were mailed to 133 men with HG in 2012. Of the 107 surveys returned, 95 were included in the final analysis. Most respondents were Caucasian (90.5%). Men reported developing symptoms of HG, as well as being diagnosed, at a median age of 50 years. The most common symptoms reported as reasons for seeking treatment were erectile dysfunction (66.3%), fatigue (59.0%) and decreased sex drive (57.9%). These continued to be the most bothersome symptoms at the time of the survey regardless of whether the patient received treatment, although men who were currently taking TRT reported less severe symptoms. Approximately 88% of men reported taking TRT at some point, with 61.9% on therapy at the time of the survey. CONCLUSIONS: This study examined men's experiences with HG, including symptoms, quality of life, and treatments. Some symptoms continued despite treatment, and therapy was discontinued at a high rate, which men generally attributed to cost and perceptions of efficacy. In light of this lack of adherence, patients may benefit from appropriate expectation setting regarding reasonable timelines for symptom improvement, the strengths and challenges of various TRT formulations, the importance of adherence and the benefits and risks of TRT.

Currents connecting communities: nearshore community similarity and ocean circulation.

Understanding the mechanisms that create spatial heterogeneity in species distributions is fundamental to ecology. For nearshore marine systems, most species have a pelagic larval stage where dispersal is strongly influenced by patterns of ocean circulation. Concomitantly, nearshore habitats and the local environment are also influenced by ocean circulation. Because of the shared dependence on the seascape, distinguishing the relative importance of the local environment from regional patterns of dispersal for community structure remains a challenge. Here, we quantify the "oceanographic distance" and "oceanographic asymmetry" between nearshore sites using ocean circulation modeling results. These novel metrics quantify spatial separation based on realistic patterns of ocean circulation, and we explore their explanatory power for intertidal and subtidal community similarity in the Southern California Bight. We find that these metrics show significant correspondence with patterns of community similarity and that their combined explanatory power exceeds that of the thermal structure of the domain. Our approach identifies the unique influence of ocean circulation on community structure and provides evidence for oceanographically mediated dispersal limitation in nearshore marine communities.

The changing face of hepatitis in boys with haemophilia associated with increased prevalence of obesity.

Hepatitis in children with haemophilia was historically most often associated with transfusion-transmitted infections. However, with the use of recombinant clotting factor concentrates, acquisition of such infections has now become rare. We studied the profile of hepatitis in North-American children with haemophilia in the modern era of safe blood products and excess childhood obesity. A total of 173 boys (<18 years) registered in the Pediatric Comprehensive Care Haemophilia Program were included in this retrospective study. Hospital records were reviewed for baseline data, serial height and weight measurements and serial alanine aminotransferase (ALT) levels. A body mass index (BMI) ranking was available for 170 boys, of whom 25 (14.7%, 95% CI 9.7-20.9%) were obese. The rate of obesity was higher in severe haemophilic boys. Compared with the general childhood population, the rate of obesity trended towards being higher in young haemophilic boys (2-5 years), but was similar in other age groups. A persistently high ALT (≥80 U L(-1) ) was documented in 5 boys and was associated with obesity. Three boys had clinical and imaging studies compatible with non-alcoholic fatty liver disease (NAFLD). Overweight and obesity are common among haemophilic boys, especially those who are younger and with severe disease. In this large group of haemophilic boys, chronic viral hepatitis was rare and NAFLD was a more common cause of liver disease. Overweight and obese haemophilic boys should be evaluated for NAFLD and interventional programmes should be designed to reduce the potential complications associated with obesity.

Cost-effectiveness of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers as first-line treatment in autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a rare kidney disorder impacting ∼1:2,500 individuals among the general US population. Hypertension is a significant predictor of ADPKD progression, and a risk factor for development of cardiovascular disease (CVD), the most common cause for mortality among ADPKD patients. Angiotensin-converting enzymes inhibitors (ACE-I) are widely used as first-line treatment in ADPKD for the management of hypertension. However, their cost-effectiveness relative to other hypertensive medications, such as angiotensin II receptor blockers (ARB), has never been assessed. OBJECTIVE: To determine if ARB are more cost-effective than ACE-Is as first-line treatment in ADPKD. METHODS: A Markov-state decision model was constructed for estimation of cost and outcome benefits in hypertensive ADPKD patients. Transition probabilities were extrapolated from a retrospective cohort study comparing chronic kidney disease (CKD) stage transitions in ADPKD patients. Annual pharmaceutical costs per average daily dose per CKD stage were extracted from a US healthcare claims database. Median total healthcare costs per CKD stage or transplant were extracted from the published literature. The time horizon was set to 30 years, with 1-year duration to cycle shift. A cost-effectiveness analysis was conducted to estimate the incremental cost-effectiveness ratio (ICER) of ACE-I vs ARB per additional year of prevented transplant and/or death. A one-way probabilistic sensitivity analysis was conducted, with 10% variation in probabilities and cost. RESULTS: Total annual healthcare costs accrued after 30 years among ADPKD patients taking ACE-Is was estimated to be $3,505,028.41, compared to ARB at $3,644,327.65. Life expectancy was increased by 1.39 years among patients taking ACE-I. Approximate 10-year survival in patients taking ACE-Is was 47% compared to ARB at 34%. CONCLUSIONS: ACE-I dominated ARB and displayed greater cost-effectiveness due to lower cost and increased capacity to prolong years of life without transplant or death among hypertensive ADPKD patients. This model strengthens the value of ACE-I over ARB as first-line treatment for hypertension management in ADPKD patients.

Persistent spatial structuring of coastal ocean acidification in the California Current System.

The near-term progression of ocean acidification (OA) is projected to bring about sharp changes in the chemistry of coastal upwelling ecosystems. The distribution of OA exposure across these early-impact systems, however, is highly uncertain and limits our understanding of whether and how spatial management actions can be deployed to ameliorate future impacts. Through a novel coastal OA observing network, we have uncovered a remarkably persistent spatial mosaic in the penetration of acidified waters into ecologically-important nearshore habitats across 1,000 km of the California Current Large Marine Ecosystem. In the most severe exposure hotspots, suboptimal conditions for calcifying organisms encompassed up to 56% of the summer season, and were accompanied by some of the lowest and most variable pH environments known for the surface ocean. Persistent refuge areas were also found, highlighting new opportunities for local adaptation to address the global challenge of OA in productive coastal systems.

Time trends in systemic adjuvant treatment for node-negative breast cancer.

PURPOSE: We conducted a population-based study in Quebec, Canada, to assess longitudinal changes in systemic adjuvant therapy for node-negative breast cancer. MATERIALS AND METHODS: A stratified random sample was selected among women with newly diagnosed node-negative breast cancer in 1988, 1991, and 1993. Information on the patient, her tumor, source of care, and treatment was abstracted from medical charts. Patients were classified as being at minimal, moderate, or high risk of recurrence on the basis of criteria proposed at the 4th International Conference on Adjuvant Therapy of Primary Breast Cancer (St. Gallen, Switzerland, 1992), and systemic adjuvant treatment received was dichotomized as being consistent or not consistent with consensus recommendations. RESULTS: Overall, 1,578 cases of invasive breast carcinoma were reviewed. The proportion of patients who were given hormonal or cytotoxic treatment increased from 51.7% to 73.1% from 1988 to 1993. Virtually all women at minimal risk were treated in 1991 and 1993 according to the consensus statement. The proportions of women so treated were 75.0% and 65.4% in the moderate- and high-risk categories, respectively, in 1991. In 1993, these proportions were 71.4% and 67.0%, respectively. Omission of chemotherapy, especially in high-risk women with estrogen receptor-negative tumors who were 50 to 69 years of age, was the most frequent inconsistency with guidelines. CONCLUSION: Systemic adjuvant therapy for node-negative breast cancer has gained acceptance. Better understanding of the decision-making process, of the perception of the risks and benefits involved, and of the impact of alternative strategies for the dissemination of consensus recommendations are needed to promote the use of chemotherapy in specific categories of women who are at high risk of recurrence.

Human papillomaviruses and vulvar vestibulitis.

OBJECTIVE: To assess the relationship between human papillomavirus (HPV) infection and vulvar vestibulitis syndrome. METHODS: From November 1995 to December 1997, 135 women with vulvar vestibulitis were compared with 322 controls who had no evidence of vulvar vestibulitis. Human papillomavirus DNA was amplified by polymerase chain reaction and detected with liquid-capture molecular assay. RESULTS: Human papillomavirus DNA was found in 29.6% of cases and in 23.9% of controls (relative risk [RR] 1.4; 95% confidence interval [CI].8, 2.2). The prevalence of HPV tended to decrease with increasing duration of pain among cases. Thus, prevalences were 37. 5%, 29.6%, and 22.0% for pain durations of 3-6 months, 7-12 months, and 13-24 months, respectively (P =.14). Prevalence of HPV also tended to increase with pain intensity among cases, but that association was not statistically significant (P =.57). Prevalence percentages for women with low, moderate, or severe pain were 27.5%, 28.8%, and 34.4%, respectively. Prevalence of HPV was slightly higher in cases with the most severe pain (34.4%) than in controls (23.9%) (RR 1.8; 95% CI.8, 4.0). In cases with the most pain in the shortest time (3-6 months), prevalence of HPV was double that of controls (50% versus 23.9%) (RR 3.5; 95% CI 1.0, 12.7; P =.054). CONCLUSION: There was little support for the idea that HPV might be related to vulvar vestibulitis.

[Internal consistency, factorial validity and discriminant validity of the French version of the psychological demands and decision latitude scales of the Karasek "Job Content Questionnaire"]. / Cohérence interne, validité factorielle et validité discriminante de la traduction française des échelles de demande psychologique et de latitude décisionnelle du "Job Content Questionnaire" de Karasek.

BACKGROUND: The job demands-control model developed by Karasek has greatly influenced research on psychosocial factors at work and health. Validity of the English version of the psychological demands and decision latitude scales is documented. Psychometric qualities of the French version are investigated here in a representative sample of the general population, including blue-collars and white-collars. METHODS: The French translation of the psychological demand and decision latitude scales was administered by interview in a representative sample of the Quebec working population (N = 1,110). Internal consistency and factorial validity of the instrument were studied among white-collars and blue-collars separately. Discriminant validity was assessed for the whole population. RESULTS: Cronbach alpha coefficients, varying between 0.68 and 0.85, support the internal consistency of the scales. Demographic distribution of the scales and intercorrelations were consistent with the English version. Results of the factor analysis were consistent with the two dimensions expected from the theory. Mean scale scores and variations in the prevalence of high psychological demands combined with low decision latitude by age, sex, education, and job category support the discriminant validity of the instrument. CONCLUSIONS: Results support internal consistency, factorial validity, and discriminant validity of the French version of the psychological demands and decision latitude scales of the Karasek "Job Content Questionnaire" for white-collars and for blue-collars of the general population.

Diabetes complications and adverse health outcomes after coronary revascularization.

AIMS: To examine effects of diabetes complications on health outcomes following coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), comparing outcomes for patients with diabetes complications to those without diabetes complications. METHODS: Retrospective analysis of discharge data for 61,566 patients with diabetes age 45 or older who had CABG or PCI in 2007 in United States community hospitals, using data from the Nationwide Inpatient Sample. Analysis included propensity score-adjusted logistic regression. RESULTS: Of all patients, 21.2% of the weighted sample had diabetes complications. Older patients, Blacks and Hispanics, and those with greater illness severity were more likely to have diabetes complications. Unadjusted rates of in-hospital mortality, postoperative stroke, and renal failure were higher for patients with diabetes complications (rate ratios 2.2, 1.8, and 9.8, respectively; all p<0.0001). In adjusted results, having diabetes complications was associated with higher odds of in-hospital mortality (odds ratio, OR 1.62, 95% confidence interval, CI 1.37-1.91) and renal failure (OR 3.03, CI 1.71-5.39). Compared to CABG, PCI was associated with extra risk of postoperative renal failure for those with diabetes complications. CONCLUSION: Among patients with diabetes having revascularization, those with diabetes complications have higher risks of in-hospital death and renal failure irrespective of having CABG or PCI.

Repeated exposure to effort-reward imbalance, increased blood pressure, and hypertension incidence among white-collar workers: effort-reward imbalance and blood pressure.

OBJECTIVES: To determine whether men and women with repeated ERI exposure have increased BP means or higher hypertension incidence over a 3-year follow-up. To examine the potential modifying effect of age and overcommitment. METHODS: The study cohort was composed of 1,595 white-collar workers (629 men and 966 women) assessed at baseline and 3-year follow-up. Ambulatory BP measures were taken every 15 min during a working day. ERI at work was self-reported using validated scales. BP means at follow-up and cumulative incidence of hypertension were respectively modeled with analyses of covariance (ANCOVA) and log-binomial regression. RESULTS: Among men, no association was observed between repeated ERI exposure and BP. Among women, age had a modifying effect. Women <45 years old exposed to ERI at both times had significantly higher BP means at follow-up (122.2/78.9 mmHg) than those unexposed (120.4/77.4 mmHg). In women ≥45 years old, the cumulative incidence of hypertension was 2.78 (95% CI: 1.26-6.10) times higher among those exposed to ERI at both times. Men and women in the higher tertile of overcommitment had higher BP means (men: 128.9/82.2 mmHg, women: 121.9/78.0 mmHg) than those in the lower tertile (men: 127.2/81.3 mmHg, women: 120.6/77.0 mmHg). CONCLUSION: This prospective study showed that, among women, repeated ERI exposure led to a significant age-specific increase in BP means and a major age-specific increase in hypertension incidence. These results suggest that primary intervention aimed at reducing ERI may contribute to lower BP and prevent hypertension in women.

High expression of insulin-like growth factor binding protein-2 messenger RNA in epithelial ovarian cancers produces elevated preoperative serum levels.

The molecular etiology of epithelial ovarian cancer remains unclear. Using microarray expression analysis, we recently reported that expression of the insulin-like growth factor binding protein-2 (IGFBP-2) gene is elevated in advanced epithelial ovarian cancers. The aim of this study was to further delineate the role of IGFBP-2 in the pathoetiology of epithelial ovarian cancer and determine if elevated ovarian cancer IGFBP-2 gene expression is reflected in serum. Relative IGFBP-2 expression was measured using quantitative real-time polymerase chain reaction in 113 epithelial ovarian cancers and 6 normal ovarian surface epithelial samples. Preoperative serum IGFBP-2 levels were measured by radioimmunoassay in 84 women (42 ovarian cancers, 26 benign gynecological conditions, and 10 healthy female controls). Ovarian cancers demonstrated 38-fold higher mean IGFBP-2 expression than normal ovarian epithelium (P < 0.01). Serum IGFBP-2 levels were elevated in women with early- and advanced-stage ovarian cancer compared to controls and patients with benign gynecological conditions (P = 0.05 and P < 0.01, respectively). Epithelial ovarian cancers express high levels of IGFBP-2 relative to normal ovarian epithelium, and this is associated with elevated serum IGFBP-2 levels compared to both normal controls and patients with benign gynecological disease. Our findings provide further support that the insulin-like growth factor pathway plays a significant role in epithelial ovarian cancer pathogenesis. Further, IGFBP-2 may represent an additional serum biomarker with utility in detection and monitoring of epithelial ovarian cancer.

Hydrodynamics, shell shape, behavior and survivorship in the owl limpet Lottia gigantea.

On wave-swept rocky shores, limpets are subjected to water velocities in excess of 20 m s(-1), which may impose large hydrodynamic forces. Despite the extreme severity of this flow environment, predictions from conical models suggest that limpets' shells are typically far from the optimal shape that would minimize the risk of dislodgment, a deviation that is allowed by the high tenacity of the limpets' adhesive system. In this study, we test this conclusion using an actual limpet. The shell of Lottia gigantea differs substantially from the hydrodynamic optimum in that its apex is displaced anteriorly to form a plough, which is used to defend the limpet's territory. The hydrodynamic effects of this shape are similar to those observed in conical models: the animal experiences an increased lift when facing into the flow and a decreased lift when the flow is at its back. However, neither effect has a substantial impact on the risk of dislodgment. When the animal is stationary, its adhesion to the substratum is very strong, and its risk of being dislodged is small regardless of its orientation to the flow and despite its sub-optimal shape. In contrast, when the animal is crawling rapidly, its adhesion is substantially decreased, and it would probably be dislodged by rapid flow even if the shell were shaped optimally. The risk of dislodgment by waves is therefore functionally independent of shell shape. In essence, despite the extremely high water velocities to which this species is subjected, its shell has had the 'permission' of the flow environment to respond to other selective factors, in particular those associated with its aggressive, territorial behavior. The result is a shell that is both a potent territorial weapon and a functional (albeit less than optimal) hydrodynamic shape.