Surgical Margins in Breast Conservation

Significant progress has been made in the diagnosis and treatment of breast cancer during the past 30 years. The increased availability of screening mammography has resulted in a higher percentage of woman being diagnosed with early stage disease allowing the option of breast conservation therapy to be more widely available. Long-term follow-up studies clearly demonstrate equivalent survival with breast conservation surgery (lumpectomy) and radiotherapy versus total mastectomy [1–3]. The importance of obtaining clear lumpectomy surgical margins has been well established in minimizing the risk of local recurrence [4]. Unfortunately there is a lack of uniform guidelines in terms of what constitutes an adequately clear lumpectomy margin. Substantial debate about bigger margins being better continues [5]. This has led to wide variations in lumpectomy margin reexcision rates from 15 to 47% [6]. These additional surgical procedures cause significant patient distress, utilize health care resources, and can adversely affect cosmesis. From the patient perspective, they may wonder why we did not get it right the first time. They want their cancer gone while maintaining a normal appearance.This special issue highlights the areas of controversy and demonstrates current best practices and emerging novel approaches towards optimal breast conservation approach. The goal is to improve our ability to provide breast-conserving approaches for breast cancer while avoiding multiple surgical procedures, minimizing recurrence risk while obtaining excellent cosmesis. We have chosen 6 of 16 submissions to be published in this special issue. Each paper was evaluated by at least two expert reviewers and revised according to review comments

Transcatheter interatrial shunt device for the treatment of heart failure with preserved ejection fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure]): A phase 2, randomized, sham-controlled trial

Background -In non-randomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), less symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and mid-range or preserved ejection fraction (EF ≥ 40%). We conducted the first randomized, sham-controlled trial to evaluate the IASD in HF with EF ≥ 40%. Methods -REDUCE LAP-HF I was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association (NYHA) class III or ambulatory class IV HF, EF ≥ 40%, exercise PCWP ≥ 25 mmHg, and PCWP-right atrial pressure gradient ≥ 5 mmHg. Participants were randomized (1:1) to the IASD vs. a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness endpoint was exercise PCWP at 1 month. The primary safety endpoint was major adverse cardiac, cerebrovascular, and renal events (MACCRE) at 1 month. PCWP during exercise was compared between treatment groups using a mixed effects repeated measures model analysis of covariance that included data from all available stages of exercise. Results -A total of 94 patients were enrolled, of which n=44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared to sham-control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mmHg in the treatment group vs. 0.5±5.0 mmHg in the control group (P=0.14). There were no peri-procedural or 1-month MACCRE in the IASD group and 1 event (worsening renal function) in the control group (P=1.0). Conclusions -In patients with HF and EF ≥ 40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation. Clinical Trial Registration -URL: http://clinicaltrials.gov. Unique identifier: NCT02600234

Hypertension in Canada: Past, Present, and Future

Canada has an extremely successful hypertension detection and treatment program. The aim of this review was to highlight the historic and current infrastructure and initiatives that have led to this success, and the outlook moving forward into the future. We discuss the evolution of hypertension awareness and control in Canada; contributions made by organizations such as the Canadian Hypertension Society, Blood Pressure Canada, and the Canadian Hypertension Education Program; the amalgamation of these organizations into Hypertension Canada; and the impact that Hypertension Canada has had on hypertension care in Canada. The important contribution that public policy and advocacy can have on prevention and control of blood pressure in Canada is described. We also highlight the importance of population-based strategies, health care access and organization, and accurate blood pressure measurement (including ambulatory, home, and automated office modalities) in optimizing hypertension prevention and management. We end by discussing how Hypertension Canada will move forward in the near and longer term to address the unmet residual risk attributable to hypertension and associated cardiovascular risk factors. Hypertension Canada will continue to strive to enhance hypertension prevention and control rates, thereby improving the quality of life and cardiovascular outcomes of Canadians, while at the same time creating a hypertension care model that can be emulated across the world

Implantable cardioverter defibrillators for the treatment of arrhythmias and cardiac resynchronisation therapy for the treatment of heart failure: systematic review and economic evaluation

Background This assessment updates and expands on two previous technology assessments that evaluated implantable cardioverter defibrillators (ICDs) for arrhythmias and cardiac resynchronisation therapy (CRT) for heart failure (HF). Objectives To assess the clinical effectiveness and cost-effectiveness of ICDs in addition to optimal pharmacological therapy (OPT) for people at increased risk of sudden cardiac death (SCD) as a result of ventricular arrhythmias despite receiving OPT; to assess CRT with or without a defibrillator (CRT-D or CRT-P) in addition to OPT for people with HF as a result of left ventricular systolic dysfunction (LVSD) and cardiac dyssynchrony despite receiving OPT; and to assess CRT-D in addition to OPT for people with both conditions. Data sources Electronic resources including MEDLINE, EMBASE and The Cochrane Library were searched from inception to November 2012. Additional studies were sought from reference lists, clinical experts and manufacturers’ submissions to the National Institute for Health and Care Excellence. Review methods Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. Data were synthesised through narrative review and meta-analyses. For the three populations above, randomised controlled trials (RCTs) comparing (1) ICD with standard therapy, (2) CRT-P or CRT-D with each other or with OPT and (3) CRT-D with OPT, CRT-P or ICD were eligible. Outcomes included mortality, adverse events and quality of life. A previously developed Markov model was adapted to estimate the cost-effectiveness of OPT, ICDs, CRT-P and CRT-D in the three populations by simulating disease progression calculated at 4-weekly cycles over a lifetime horizon. Results A total of 4556 references were identified, of which 26 RCTs were included in the review: 13 compared ICD with medical therapy, four compared CRT-P/CRT-D with OPT and nine compared CRT-D with ICD. ICDs reduced all-cause mortality in people at increased risk of SCD, defined in trials as those with previous ventricular arrhythmias/cardiac arrest, myocardial infarction (MI) > 3 weeks previously, non-ischaemic cardiomyopathy (depending on data included) or ischaemic/non-ischaemic HF and left ventricular ejection fraction ≤ 35%. There was no benefit in people scheduled for coronary artery bypass graft. A reduction in SCD but not all-cause mortality was found in people with recent MI. Incremental cost-effectiveness ratios (ICERs) ranged from £14,231 per quality-adjusted life-year (QALY) to £29,756 per QALY for the scenarios modelled. CRT-P and CRT-D reduced mortality and HF hospitalisations, and improved other outcomes, in people with HF as a result of LVSD and cardiac dyssynchrony when compared with OPT. The rate of SCD was lower with CRT-D than with CRT-P but other outcomes were similar. CRT-P and CRT-D compared with OPT produced ICERs of £27,584 per QALY and £27,899 per QALY respectively. The ICER for CRT-D compared with CRT-P was £28,420 per QALY. In people with both conditions, CRT-D reduced the risk of all-cause mortality and HF hospitalisation, and improved other outcomes, compared with ICDs. Complications were more common with CRT-D. Initial management with OPT alone was most cost-effective (ICER £2824 per QALY compared with ICD) when health-related quality of life was kept constant over time. Costs and QALYs for CRT-D and CRT-P were similar. The ICER for CRT-D compared with ICD was £27,195 per QALY and that for CRT-D compared with OPT was £35,193 per QALY. Limitations Limitations of the model include the structural assumptions made about disease progression and treatment provision, the extrapolation of trial survival estimates over time and the assumptions made around parameter values when evidence was not available for specific patient groups. Conclusions In people at risk of SCD as a result of ventricular arrhythmias and in those with HF as a result of LVSD and cardiac dyssynchrony, the interventions modelled produced ICERs of < £30,000 per QALY gained. In people with both conditions, the ICER for CRT-D compared with ICD, but not CRT-D compared with OPT, was < £30,000 per QALY, and the costs and QALYs for CRT-D and CRT-P were similar. A RCT comparing CRT-D and CRT-P in people with HF as a result of LVSD and cardiac dyssynchrony is required, for both those with and those without an ICD indication. A RCT is also needed into the benefits of ICD in non-ischaemic cardiomyopathy in the absence of dyssynchrony. Study registration This study is registered as PROSPERO number CRD42012002062. Funding The National Institute for Health Research Health Technology Assessment programme

Measuring large-scale structure with quasars in narrow-band filter surveys

We show that a large-area imaging survey using narrow-band filters could detect quasars in sufficiently high number densities, and with more than sufficient accuracy in their photometric redshifts, to turn them into suitable tracers of large-scale structure. If a narrow-band optical survey can detect objects as faint as i=23, it could reach volumetric number densities as high as 10^{-4} h^3 Mpc^{-3} (comoving) at z~1.5 . Such a catalog would lead to precision measurements of the power spectrum up to z~3-4. We also show that it is possible to employ quasars to measure baryon acoustic oscillations at high redshifts, where the uncertainties from redshift distortions and nonlinearities are much smaller than at z<1. As a concrete example we study the future impact of J-PAS, which is a narrow-band imaging survey in the optical over 1/5 of the unobscured sky with 42 filters of ~100 A full-width at half-maximum. We show that J-PAS will be able to take advantage of the broad emission lines of quasars to deliver excellent photometric redshifts, \sigma_{z}~0.002(1+z), for millions of objects.Comment: Matches version published in MNRAS (2012

Observation of a 1750 MeV/c^2 Enhancement in the Diffractive Photoproduction of K^+K^-

Using the FOCUS spectrometer with photon beam energies between 20 and 160 \gev, we confirm the existence of a diffractively photoproduced enhancement in $K^+K^-$ at 1750 \mevcc with nearly 100 times the statistics of previous experiments. Assuming this enhancement to be a single resonance with a Breit-Wigner mass shape, we determine its mass to be $1753.5\pm 1.5\pm 2.3$ \mevcc and its width to be $122.2\pm 6.2\pm 8.0$ \mevcc. We find no corresponding enhancement at 1750 \mevcc in $K^*K$, and again neglecting any possible interference effects we place limits on the ratio $\Gamma (X(1750) \to K^*K)/\Gamma (X(1750) \to K^+K^-)$. Our results are consistent with previous photoproduction experiments, but, because of the much greater statistics, challenge the common interpretation of this enhancement as the $\phi (1680)$ seen in $e^+e^-$ annihilation experiments.Comment: 10 pages, 5 figure

Search for Rare and Forbidden 3-body Di-muon Decays of the Charmed Mesons D+ and Ds+

Using a high statistics sample of photo-produced charm particles from the FOCUS experiment at Fermilab, we report results of a search for eight rare and Standard-Model-forbidden decays: D+, Ds+ > h+/- muon-/+ muon+ (with h=pion or Kaon). Improvement over previous results by a factor of 1.7--14 is realized. Our branching ratio upper limit D+ > pion+ muon- muon+ of 8.8E-6 at the 90% C.L. is below the current MSSM R-Parity violating constraint.Comment: 17 pages, 7 figure file

Personality Traits and Personal Values:A Meta-Analysis

Personality traits and personal values are important psychological characteristics, serving as important predictors of many outcomes. Yet, they are frequently studied separately, leaving the field with a limited understanding of their relationships. We review existing perspectives regarding the nature of the relationships between traits and values and provide a conceptual underpinning for understanding the strength of these relationships. Using 60 studies, we present a meta-analysis of the relationships between the Five-Factor Model (FFM) of personality traits and the Schwartz values, and demonstrate consistent and theoretically meaningful relationships. However, these relationships were not generally large, demonstrating that traits and values are distinct constructs. We find support for our premise that more cognitively based traits are more strongly related to values and more emotionally based traits are less strongly related to values. Findings also suggest that controlling for personal scale-use tendencies in values is advisable

Conducting Molecular Epidemiological Research in the Age of HIPAA: A Multi-Institutional Case-Control Study of Breast Cancer in African-American and European-American Women

Breast cancer in African-American (AA) women occurs at an earlier age than in European-American (EA) women and is more likely to have aggressive features associated with poorer prognosis, such as high-grade and negative estrogen receptor (ER) status. The mechanisms underlying these differences are unknown. To address this, we conducted a case-control study to evaluate risk factors for high-grade ER- disease in both AA and EA women. With the onset of the Health Insurance Portability and Accountability Act of 1996, creative measures were needed to adapt case ascertainment and contact procedures to this new environment of patient privacy. In this paper, we report on our approach to establishing a multicenter study of breast cancer in New York and New Jersey, provide preliminary distributions of demographic and pathologic characteristics among case and control participants by race, and contrast participation rates by approaches to case ascertainment, with discussion of strengths and weaknesses