Outcomes of single versus double hormone receptor-positive breast cancer. A GEICAM/9906 sub-study.

BACKGROUND: Retrospective data suggest better outcomes for patients with double hormonal receptor (oestrogen [ER] and progesterone receptor [PgR])-positive (dHR+) early breast cancer, compared with single hormonal receptor-positive, sHR+, (ER+/PgR- or ER-/PgR+) disease. Here, we evaluate the classification according to intrinsic subtypes and clinical outcomes of sHR+ versus dHR+ in HER2-negative breast cancer patients enrolled in GEICAM/9906 study (NCT00129922). METHODS: Archival tumours were retrieved retrospectively for the analysis of ER, PgR and HER2 status and classified into intrinsic subtypes using the PAM50 gene expression assay. Disease-free survival (DFS) and overall survival (OS) were explored using a Cox proportional hazard analysis. RESULTS: Data on intrinsic subtypes were available in 571 (50%) patients with ER+ and/or PR+, and HER2-negative primary tumours. The incidence of luminal A and luminal B subtypes were 52%/36% in dHR+ tumours (ER+/PgR+), and 15%/58% in ER+/PgR-tumours. ER-/PgR+ tumours were mainly luminal A (52%). Compared with ER+/PgR+ patients, DFS was similar in ER-/PgR+ (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.57-2.34, p = 0.70) but worse in ER+/PgR- patients (HR 1.60, 95% CI 1.12-2.28, p < 0.01). Similar results were observed for OS (HR 1.50, p = 0.30 and HR 1.86, p < 0.01, respectively). CONCLUSIONS: The ER+/PgR- group is characterised by higher proliferation and worse outcomes. In spite of the ER-/PgR+ subgroup resembles ER+/PgR+ disease in terms of molecular subtypes and outcomes, the small number of patients in this subgroup prevents from drawing any conclusions. TRIAL REGISTRATION: EudraCT: 2005-003108-12 (retrospectively registered 28/06/2005). CLINICALTRIALS. GOV IDENTIFIER: NCT00129922 (retrospectively registered 10/08/2005).

The '6W' multidimensional model of care trajectories for patients with chronic ambulatory care sensitive conditions and hospital readmissions.

OBJECTIVES: To synthesize concepts and approaches related to the analysis of patterns or processes of care and patient's outcomes into a comprehensive model of care trajectories, focusing on hospital readmissions for patients with chronic ambulatory care sensitive conditions (ACSCs). STUDY DESIGN: Narrative literature review. METHODS: Published studies between January 2000 and November 2017, using the concepts of 'continuity', 'pathway', 'episode', and 'trajectory', and focused on readmissions and chronic ACSCs, were collected in electronic databases. Qualitative content analysis was performed with emphasis on key constituents to build a comprehensive model. RESULTS: Specific common constituents are shared by the concepts reviewed: they focus on the patient, aim to measure and improve outcomes, follow specific periods of time and consider other factors related to care providers, care units, care settings, and treatments. Using these common denominators, the comprehensive '6W' multidimensional model of care trajectories was created. Considering patients' attributes and their chronic ACSCs illness course ('who' and 'why' dimensions), this model reflects their patterns of health care use across care providers ('which'), care units ('where'), and treatments ('what'), at specific periods of time ('when'). CONCLUSIONS: The '6W' model of care trajectories could provide valuable information on 'missed opportunities' to reduce readmission rates and improve quality of both ambulatory and inpatient care.

Hyperglycaemia and Survival in Solid Tumours: A Systematic Review and Meta-analysis.

AIMS: Diabetes is associated with adverse cancer outcomes. However, the effect of hyperglycaemia in non-diabetic cancer patients is unclear. MATERIALS AND METHODS: A systematic search of electronic databases identified publications exploring the effect of hyperglycaemia on overall survival, disease-free survival (DFS) or progression-free survival (PFS). Data from studies reporting a hazard ratio and 95% confidence interval and/or a P-value were pooled in a meta-analysis using generic inverse-variance and random effects modelling. Subgroup analyses were conducted based on method of hyperglycaemia measurement (HbA1c, other) and stage (early, advanced, mixed). Meta-regression was performed to evaluate the influence of clinical characteristics including baseline diabetes status on the hazard ratio for overall survival. RESULTS: Twelve studies comprising a total of 9872 patients were included. All studies reported hazard ratios for overall survival. Three studies reported DFS; two reported PFS outcomes. Definitions of hyperglycaemia and cut-offs varied between studies. Hyperglycaemia was associated with worse overall survival (hazard ratio 2.05, 95% confidence interval 1.67-2.51; P < 0.001) and DFS (hazard ratio 1.98, 95% confidence interval 1.20-3.27; P = 0.007), but did not affect PFS (hazard ratio 1.08, 95% confidence interval 0.72-1.62; P = 0.71). The association with worse overall survival was maintained in subgroups based on method of hyperglycaemia measurement (subgroup difference P = 0.46) and stage (P = 0.14). Meta-regression showed a significantly greater magnitude of association between hyperglycaemia and decreased overall survival in studies with higher proportions of women and diabetic patients. CONCLUSIONS: Hyperglycaemia is associated with adverse overall survival and DFS in patients with cancer. The therapeutic role of glycaemic control in cancer patients warrants further investigation.

First Simultaneous Extraction of Spin-Dependent Parton Distributions and Fragmentation Functions from a Global QCD Analysis.

We perform the first global QCD analysis of polarized inclusive and semi-inclusive deep-inelastic scattering and single-inclusive e^{+}e^{-} annihilation data, simultaneously fitting the parton distribution and fragmentation functions using the iterative Monte Carlo method. Without imposing SU(3) symmetry relations, we find the strange polarization to be very small, consistent with zero for both inclusive and semi-inclusive data, which provides a resolution to the strange quark polarization puzzle. The combined analysis also allows the direct extraction from data of the isovector and octet axial charges, and is consistent with a small SU(2) flavor asymmetry in the polarized sea.

Evolution in the eligibility criteria of randomized controlled trials for systemic cancer therapies.

BACKGROUND: Eligibility criteria in randomized controlled trials (RCTs) reduce inter-patient heterogeneity, but may reduce generalizability of results. Here, we explore temporal changes in eligibility criteria of practice-changing RCTs for systemic cancer therapies and in the proportion of patients excluded from these trials after application of eligibility criteria. METHODS: An electronic search identified practice-changing RCTs published in six major journals between July 2010 and December 2012. Trial protocols were identified through journal websites and communication with authors or study sponsors. Eligibility criteria were extracted from protocols. The number of patients excluded after application of eligibility criteria was extracted from the CONSORT diagrams and text of publications. Changes in eligibility criteria over time were assessed by logistic regression and meta-regression was carried out to evaluate the impact of year of protocol on the proportion of patients who were excluded after screening. RESULTS: Eighty-six protocols written between 1987 and 2012 were included. Over time, there has been an increasing frequency of exclusion of patients with prior cerebrovascular events (OR 1.34, p=0.003), coagulation/bleeding disorders (OR 1.34, p=0.006), prior gastrointestinal bleeding (OR 1.33, p=0.01), cardiac co-morbidities (OR 1.24, p=0.004) and exclusion based on concurrent medication (OR 1.19, p=0.01). There has been a decrease in upper age limit usage (OR 0.83, p=0.01) and leukopenia (OR 0.83, p=0.009). The proportion of patients excluded from trials has increased from 9% prior to 2000 to 18% after 2010 (p-value for trend <0.001). CONCLUSIONS: RCTs have become less representative of cancer patients treated in routine practice with increased use of organ-specific and co-morbidity-based exclusion criteria.

A systematic review and quality appraisal of international guidelines for early breast cancer systemic therapy: Are recommendations sensitive to different global resources?

The breast cancer incidence in low and middle income countries (LMCs) is increasing globally, and patient outcomes are generally worse in these nations compared to high income countries (HICs). This is partly due to resource constraints associated with implementing recommended breast cancer therapies. Clinical practice guideline (CPG) adherence can improve breast cancer outcomes, however, many CPGs are created in HICs, and include costly recommendations that may not be feasible in LMCs. In addition, the quality of CPGs can be variable. The aim of this study was to perform a systematic review of CPGs on early breast cancer systemic therapy with potential international impact, to evaluate their content, quality, and resource sensitivity. A MEDLINE and gray literature search was completed for English language CPGs published between 2005 and 2010, and then updated to July 2014. Extracted guidelines were evaluated using the AGREE 2 instrument. Guidelines were specifically analyzed for resource sensitivity. Most of the extracted CPGs had similar recommendations with regards to systemic therapy. However, only one, the Breast Health Global Initiative, made recommendations with consideration of different global resources. Overall, the CPGs were of variable quality, and most scored poorly in the quality domain evaluating implementation barriers such as resources. Published CPGs for early breast cancer are created in HICs, have similar recommendations, and are generally resource-insensitive. Given the visibility and influence of these CPGs on LMCs, efforts to create higher quality, resource-sensitive guidelines with less redundancy are needed.

Clinical data integration model. Core interoperability ontology for research using primary care data.

INTRODUCTION: This article is part of the Focus Theme of METHODS of Information in Medicine on "Managing Interoperability and Complexity in Health Systems". BACKGROUND: Primary care data is the single richest source of routine health care data. However its use, both in research and clinical work, often requires data from multiple clinical sites, clinical trials databases and registries. Data integration and interoperability are therefore of utmost importance. OBJECTIVES: TRANSFoRm's general approach relies on a unified interoperability framework, described in a previous paper. We developed a core ontology for an interoperability framework based on data mediation. This article presents how such an ontology, the Clinical Data Integration Model (CDIM), can be designed to support, in conjunction with appropriate terminologies, biomedical data federation within TRANSFoRm, an EU FP7 project that aims to develop the digital infrastructure for a learning healthcare system in European Primary Care. METHODS: TRANSFoRm utilizes a unified structural / terminological interoperability framework, based on the local-as-view mediation paradigm. Such an approach mandates the global information model to describe the domain of interest independently of the data sources to be explored. Following a requirement analysis process, no ontology focusing on primary care research was identified and, thus we designed a realist ontology based on Basic Formal Ontology to support our framework in collaboration with various terminologies used in primary care. RESULTS: The resulting ontology has 549 classes and 82 object properties and is used to support data integration for TRANSFoRm's use cases. Concepts identified by researchers were successfully expressed in queries using CDIM and pertinent terminologies. As an example, we illustrate how, in TRANSFoRm, the Query Formulation Workbench can capture eligibility criteria in a computable representation, which is based on CDIM. CONCLUSION: A unified mediation approach to semantic interoperability provides a flexible and extensible framework for all types of interaction between health record systems and research systems. CDIM, as core ontology of such an approach, enables simplicity and consistency of design across the heterogeneous software landscape and can support the specific needs of EHR-driven phenotyping research using primary care data.

The Wnt pathway regulator DKK1 is preferentially expressed in hormone-resistant breast tumours and in some common cancer types.

In addition to new tumour antigens, new prognostic and diagnostic markers are needed for common cancers. In this study, we report the expression of Dickkopf-1 (DKK1) in multiple common cancers. This constitutes a comprehensive analysis of the DKK1 expression profile. Dickkopf-1 expression was evaluated by classical and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbant assay for protein determination, in cancer lines and clinical specimens of several cancer origins. For breast cancer, expression was correlated with clinicopathological parameters. Dickkopf-1 expression was confirmed in several cancer cell lines derived from breast and other common cancers. Dickkopf-1 protein secretion was documented in breast, prostate and lung cancer lines, but was negligible in melanoma. Analysis of DKK1 expression in human cancer specimens revealed DKK1 expression in breast (21 out of 73), lung (11 out of 23) and kidney cancers (six out of 20). Interestingly, DKK1 was preferentially expressed in oestrogen and progesterone receptor-negative tumours (ER(-)/PR(-); P=0.005) and in tumours from women with a family history of breast cancer (P=0.024). Importantly, DKK1 protein production was confirmed in multiple breast cancer specimens that were positive by RT-PCR. This work establishes DKK1 as a potential prognostic and diagnostic marker for cohorts of breast cancer patients with poor prognosis. Dickkopf-1 may also become a relevant candidate target for immunotherapy of different cancers.

Activin and inhibin receptor gene expression in the ewe pituitary throughout the oestrous cycle.

In mammals, activin and inhibin are important regulators of FSH secretion. Previous studies have demonstrated that primary ovine pituitary cells express different activin receptor subtypes: activin receptor-like (ALK)2, ALK4, activin type II receptor A (ActRIIA), ActRIIB and Smad proteins in vitro. Here, we have carried out physiological studies to investigate the pattern of mRNA expression of the activin receptor subunits in the ewe pituitary throughout the oestrous cycle. The oestrous cycles of ewes were synchronized with progestagen sponges. The animals were killed 36 h (before the preovulatory surge, n=4), 48 h (during the preovulatory surge, n=4), 72 h (during the second surge of FSH, n=6) and 192 h (during the luteal phase, n=4) after sponge removal. Using Northern blots, we have shown that the levels of ALK2, ALK4 and ActRIIB mRNA were significantly higher before the preovulatory surge and during the secondary surge of FSH as compared with both during the preovulatory surge and the luteal phase, whereas the level of the ActRIIA mRNA was similar throughout the oestrous cycle. Using Western blots we have also demonstrated that the level of phospho-Smad2 did not vary during the reproductive cycle. Inhibin binding protein (InhBP/p120) and the transforming growth factor-beta type III receptor, betaglycan, have been identified as putative inhibin co-receptors. In this study, we cloned a fragment of both InhBP/p120 and betaglycan cDNAs in the ewe and showed by Northern blot that pituitary betaglycan and InhBP/p120 mRNA levels did not fluctuate across the oestrous cycle nor did they correlate with serum FSH levels.

Canadian survey of clinical status at dialysis initiation 1998-1999: a multicenter prospective survey.

AIMS: The current growth in end-stage kidney disease populations has led to increased efforts to understand the impact of status at dialysis initiation on long-term outcomes. Our main objective was to improve the understanding of current Canadian nephrology practice between October 1998 and December 1999. METHODS: Fifteen nephrology centers in 7 provinces participated in a prospective data collection survey. The main outcome of interest was the clinical status at dialysis initiation determined by: residual kidney function, preparedness for chronic dialysis as measured by presence or absence of permanent peritoneal or hemodialysis access, hemoglobin and serum albumin. Uremic symptoms at dialysis initiation were also recorded, however, in some cases these symptom data were obtained retrospectively. RESULTS: Data on 251 patients during 1-month periods were collected. Patients commenced dialysis at mean calculated creatinine clearance levels of approximately 10 ml/min, with an average of 3 symptoms. 35% of patients starting dialysis had been known to nephrologists for less than 3 months. These patients are more likely to commence without permanent access and with lower hemoglobin and albumin levels. Even of those known to nephrologists, only 66% had permanent access in place. CONCLUSIONS: Patients commencing dialysis in Canada appear to be doing so in relative concordance with published guidelines with respect to timing of initiation. Despite an increased awareness of kidney disease, a substantial number of patients continues to commence dialysis without previous care by a nephrologist. Of those who are seen by nephrologists, clinical and laboratory parameters are suboptimal according to current guidelines. This survey serves as an important baseline for future comparisons after the implementation of educational strategies for referring physicians and nephrologists.

Recruitment and development of the follicle; the roles of the transforming growth factor-beta superfamily.

Peripheral endocrine hormones and local paracrine and autocrine factors contribute, in a coordinated fashion, to the processes of recruitment, development or atresia, selection and ovulation of follicles. Among the local ovarian factors, there is growing evidence from genetic and experimental data that many members of the transforming growth factor (TGFbeta) superfamily have a biological role to play in folliculogenesis. These members include activin, inhibin, TGFbeta, BMP, GDF9 and perhaps MIS. In this review, we discuss the potential roles of the TGFbeta superfamily members, in particular activin, during folliculogenesis. Since the actions of these factors are determined by ligand availability, receptor expression and modulation of their signal transduction pathways, we also collate information on the expression of their signalling components in the follicle. We conclude that the TGFbeta superfamily signalling pathways, in particular activin's pathway, reside in the ovary. Furthermore, follistatin and beta-glycan-components of the accessory binding protein system that modifies activin action-are also present in follicles. In the post-natal rat ovary, the changes in receptor/Smad expression coincide with granulosa cell proliferation and antrum formation. We hypothesise that these pathway components are expressed in a temporal and cell-specific manner to meet the changing demands of cells during follicular development. The analysis of the components of the signal transduction pathways of the TGFbeta family members in populations of defined follicles and the identification of activated pathways in individually stimulated follicles should help clarify the roles of the TGFbeta members in folliculogenesis.

Cardiovascular disease in patients with chronic kidney disease: getting to the heart of the matter.

The high prevalence of cardiovascular disease (CVD) in patients with kidney disease is well described. This Canadian, multicenter, observational cohort study reports the prevalence and risk factors of CVD associated with kidney disease, in a cohort of patients with established chronic kidney disease (CKD), who are followed-up by nephrologists. This analysis sought to answer 2 questions: (1) in patients with established CKD, are the prevalence and progression of CVD accounted for by conventional or uremia-related risk factors, and (2) to what extent can progression to renal replacement therapy (RRT) be explained by CVD versus traditional risk factors for kidney disease? This study population consists of 313 patients (predominantly men) who had a mean age of 56 years and a mean creatinine clearance of 36 mL/min. Thirty percent were diabetic. The overall prevalence of CVD was 46%, and was independent of severity of kidney dysfunction (P = 0.700). The median follow-up time was 23 months, for a total of 462 patient years. We note the overall incidence of CVD events (new CVD or worsening of CVD) was 47/244 (20%). The best predictors of new CVD events among those without preexisting CVD were diabetes (odds ratio [OR] = 5.35, P = 0.018) and age (OR = 1.26, P = 0.08). In those with preexisting CVD, low diastolic pressure (DP) (OR =.72, P = 0.004) and high triglycerides (OR = 1.48, P = 0.019) at baseline were independent predictors of progression of CVD. We could not determine an independent impact of kidney function on CVD in the overall cohort. Furthermore, we determined that the presence of CVD itself confers an increased risk for progression to RRT (relative risk [RR] = 1.58, P = 0.047), adjusted for kidney function. This is the first in-depth analysis of CVD in a cohort of patients with established chronic kidney disease who are not on dialysis. The question regarding the impact of the altered biology of uremia in contributing to CVD progression remains unanswered, and clearly needs further study. However, the findings do raise the issue of whether aggressive treatment of CVD and risk factors might, in fact, reduce progression to RRT. Further large-scale, observational studies as well as interventional studies are needed to more clearly understand the complex biology of cardiovascular and kidney disease progression.

Production and actions of inhibin and activin during folliculogenesis in the rat.

Evidence to enhance the premise that inhibin and activin are local regulators of ovarian folliculogenesis is presented in this review. Granulosa cells (GC) have been identified as the source of inhibin/activin in the ovary on the basis of mRNA and protein localisation and the measurement of the inhibin forms in GC conditioned media. Expression of the subunit mRNAs changed with follicular development, being maximal in the ovaries of 8-day-old rats, where secondary follicles predominate. The expression of beta subunit mRNAs by GC isolated from diethylstilboestrol (DES)-treated immature rats, was reduced in the absence of any change in alpha subunit mRNA expression. Dimeric inhibin-A, -B and free alpha subunit were produced by ovarian cell cultures prepared from 4- to 12-day-old rats. Inhibin-A production by these cultures was responsive to FSH and TGF-beta, with preantral follicles of day 8 ovaries exerting effects so profound that the inhibin A/alpha subunit ratio increased, most likely due to a stimulation of beta(A) subunit production. In contrast, inhibin-B was not stimulated by TGF-beta until day 8 and FSH until day 12. Fractionation of GC conditioned media revealed a prominence of free alpha subunit and inhibin-A, but little inhibin-B, suggesting that inhibin-B production declines with follicular development. Activin receptor types I and II, Smads 1-8 and betaglycan (beta-glycan) mRNAs were present in the rat ovary and showed distinct patterns of expression between postnatal days 4 and 12. Oocytes and GC localised activin receptor, Smad and beta-glycan proteins, with beta-glycan also present in theca cells (TC). These data indicate that activin/TGF-beta signalling machinery and factors which influence these pathways, are present in the postnatal rat ovary. Our hypothesis that inhibin and activin play important and changing autocrine/paracrine roles in the growth and differentiation of follicles, including the oocyte, has been supported by these studies.

Roles of activin and its signal transduction mechanisms in reproductive tissues.

Activins were identified initially as gonadal proteins having a stimulating effect on FSH production by the pituitary gland. Strong evidence has accumulated that activins are important regulating factors for many reproductive processes. Activin may have paracrine or autocrine roles rather than solely an endocrine action on FSH secretion. Activins together with their signalling molecules must be shown to be produced locally in a particular tissue to provide support for their paracrine or autocrine action in that tissue. The discovery of the activin receptors, the intracellular signalling mediators (Smads) and some transcription co-factors involved in activin responses has helped to unravel the activin-transforming growth factor beta signalling mechanism. However, few reports have clearly demonstrated the presence of all of the activin signalling molecules in reproductive tissues, despite the important roles of activin in these tissues. Several activin receptor types and Smad molecules have been identified, indicating either a redundancy in signalling molecules or different signalling pathways. At present, it is not clear which particular subset of these signalling molecules is important in reproductive processes. The aim of this review is to collate the information available on activin actions, as well as on the signalling molecules, to understand how activins may transduce their paracrine or autocrine signals in reproductive tissues.

Topological analysis and role of the transmembrane domain in polar targeting of PilS, a Pseudomonas aeruginosa sensor kinase.

In Pseudomonas aeruginosa, synthesis of pilin, the major protein subunit of the pili, is regulated by a two-component signal transduction system in which PilS is the sensor kinase. PilS is an inner membrane protein found at the poles of the bacterial cell. It is composed of three domains: an N-terminal hydrophobic domain; a central cytoplasmic linker region; and the C-terminal transmitter region conserved among other sensor kinases. The signal that activates PilS and, consequently, pilin transcription remains unknown. The membrane topology of the hydrophobic domain was determined using the lacZ and phoA gene fusion approach. In this report, we describe a topological model for PilS in which the hydrophobic domain forms six transmembrane helices, whereas the N- and C-termini are cytoplasmic. This topology is very stable, and the cytoplasmic C-terminus cannot cross the inner membrane. We also show that two of the six transmembrane segments are sufficient for membrane anchoring and polar localization of PilS.

Veno-venous continuous renal replacement therapy for burned patients with acute renal failure.

From 1995 to 1998, 12 burned patients with acute renal failure (ARF) were treated by veno-venous continuous renal replacement therapy (CRRT) at the Burn Unit of Hôtel-Dieu de Montréal. Their mean (+/-SD) age was 51+/-12 years, and the mean burned surface covered 48.6+/-15.8% of total body surface area. All patients were mechanically ventilated and presented evidence of sepsis. The mean delay before occurrence of ARF was 15+/-6 days and ARF was mainly related to sepsis and hypotension. Main reasons for CRRT initiation were azotemia and fluid overload. A total of 15 CRRT modalities were applied (12 continuous veno-venous hemodiafiltration, CVVHDF; two continuous veno-venous hemofiltration, CVVH; and one continuous veno-venous hemodialysis, CVVHD) over 14+/-13 days. For CRRT, nine patients received heparin and three were not anticoagulated. Mean values for dialysate and reinjection flow rates were 1134+/-250 ml/h and 635+/-327 ml/h, respectively. Admission weight was 78.8+/-12.7 kg with a mean weight gain before CRRT initiation of 10.0+/-5.8 kg and a mean weight loss during CRRT of 8.9+/-5.5 kg. Nine patients received enteral plus parenteral nutrition, and three, parenteral nutrition only; the total caloric intake was 31.5+/-7.0 kcal/kg/day and protein intake, 1.8+/-0.4 g/kg/day. The normalized protein catabolic rate (nPCR) was evaluated at 2.28+/-0.78 g/kg/day during CRRT. The mortality rate was 50%. The six survivors all recovered normal renal function with four of them requiring intermittent hemodialysis for short periods. In conclusion, veno-venous CRRT is particularly well suited for this selected population allowing smooth fluid removal and aggressive nutritional support.

Elevated levels of serum creatinine: recommendations for management and referral.

BACKGROUND: The potential benefits of earlier referral to a nephrologist of patients with elevated levels of serum creatinine include identifying and treating reversible causes of renal failure, slowing the rate of decline associated with progressive renal insufficiency, managing the coexisting conditions associated with chronic renal failure and facilitating efficient entry into dialysis programs for all patients who might benefit. METHODS: A subcommittee of the Canadian Society of Nephrology, which included representatives from family practice and internal medicine, conducted a MEDLINE search for the period 1966 to 1998 using the key words referral and consultation, dialysis, hemodialysis, peritoneal dialysis, renal replacement therapy and kidney diseases. Where published evidence was lacking, conclusions were reached by consensus. GUIDELINES: Earlier referral to nephrologists of patients with elevated creatinine levels is expected to lead to better health care outcomes and lower costs for both the patients and the health care system. All patients with newly discovered renal insufficiency (as evidenced by serum creatinine elevated to a level above the upper limit of the normal range of that laboratory, adjusted for age and height in children) must undergo investigations to determine the potential reversibility of disease, to evaluate the prognosis and to optimize planning of care. All patients with an established, progressive increase in serum creatinine level should be followed with a nephrologist. Adequate preparation for dialysis or transplantation (or both) requires at least 12 months of relatively frequent contact with a renal care team. Nephrologists should provide consultation in a timely manner for any patient with an elevated serum creatinine level. In addition, they should provide advice about what aspects of the condition require particularly urgent or emergency assessment. SPONSORS: This clinical practice guideline has been endorsed by the Canadian Society of Nephrology and the College of Family Physicians of Canada. Meeting, teleconference and travel expenses of the Referral Guideline Subcommittee were covered by The Momentum Program, a collaboration between Baxter Corp. and Janssen-Ortho Inc. However, the authors are solely responsible for the editorial content of this article.

Left ventricular mass index increase in early renal disease: impact of decline in hemoglobin.

Cardiovascular disease occurs in patients with progressive renal disease both before and after the initiation of dialysis. Left ventricular hypertrophy (LVH) is an independent predictor of morbidity and mortality in dialysis populations and is common in the renal insufficiency population. LVH is associated with numerous modifiable risk factors, but little is known about LV growth (LVG) in mild-to-moderate renal insufficiency. This prospective multicenter Canadian cohort study identifies factors associated with LVG, measured using two-dimensional-targeted M-mode echocardiography. Eight centers enrolled 446 patients, 318 of whom had protocol-mandated clinical, laboratory, and echocardiographic measurements recorded. We report 246 patients with assessable echocardiograms at both baseline and 12 months with an overall prevalence of LVH of 36%. LV mass index (LVMI) increased significantly (>20% of baseline or >20 g/m2) from baseline to 12 months in 25% of the population. Other than baseline LVMI, no differences in baseline variables were noted between patients with and without LVG. However, there were significant differences in decline of Hgb level (-0.854 v -0.108 g/dL; P = 0.0001) and change in systolic blood pressure (+6.50 v -1.09 mm Hg; P = 0.03) between the groups with and without LVG. Multivariate analysis showed the independent contribution of decrease in Hgb level (odds ratio [OR], 1.32 for each 0.5-g/dL decrease; P = 0.004), increase in systolic blood pressure (OR, 1.11 for each 5-mm Hg increase; P = 0.01), and lower baseline LVMI (OR, 0.85 for each 10-g/m2; P = 0.011) in predicting LVG. Thus, after adjusting for baseline LVMI, Hgb level and systolic blood pressure remain independently important predictors of LVG. We defined the important modifiable risk factors. There remains a critical need to establish optimal therapeutic strategies and targets to improve clinical outcomes.

Preliminary findings from a teleultrasound study in Alberta.

BACKGROUND AND OBJECTIVES: Ultrasound practice in Alberta requires direct supervision by an ultrasound-accredited specialist physician (sonologist). This requirement limits access to ultrasound examinations in many rural communities. A prospective study was performed to evaluate the adequacy of teleultrasound service in High Level, Alberta, with remote sonologist supervision from Edmonton, Alberta. METHODS: A total of 146 patients were evaluated in two groups. Group A (72 patients) was evaluated by both an on-site radiologist in High Level and a remote supervising radiologist in Edmonton. Group B (74 patients) was evaluated only by the remote supervising radiologist in Edmonton. The teleultrasound service included digital store-and-forward capabilities using a commercially available teleradiology system, with videoconferencing review for real-time scanning. RESULTS: The teleultrasound service was helpful to the referring physician. It made transfer unnecessary in 42% of patients, and the results of the ultrasound assessment influenced management in 59% of patients. The sonographer on site and the remote radiologists agreed on the quality of the images. The information required for diagnosis was available from the sonographer's study in the majority of cases, with second-look scanning by the on-site radiologist or videoconferencing by the remote radiologist providing a major new diagnosis in only 1% of patients. CONCLUSION: Teleultrasound service to High Level could be provided reliably with remote supervision, comparable to direct on-site supervision.