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Perry D.C.,University of Liverpool | Metcalfe D.,Center for Surgery and Public Health | Griffin X.L.,University of Oxford | Costa M.L.,University of Oxford
BMJ (Online)

Objectives: To determine whether the use of total hip arthroplasty (THA) among individuals with a displaced intracapsular fracture of the femoral neck is based on national guidelines or if there are systematic inequalities. Design: Observational cohort study using the National Hip Fracture Database (NHFD). Setting: All hospitals that treat adults with hip fractures in England, Wales, and Northern Ireland. Participants: Patients within the national database (all aged ≥60) who received operative treatment for a nonpathological displaced intracapsular hip fracture from 1 July 2011 to 31 April 2015. Main outcom e measures: Provision of THA to patients considered eligible under criteria published by the National Institute for Health and Care Excellence (NICE). Results: 114 119 patients with hip fracture were included, 11 683 (10.2%) of whom underwent THA. Of those who satisfied the NICE criteria, 32% (6780) received a THA. Of patients who underwent THA, 42% (4903) did not satisfy the NICE criteria. A recursive partitioning algorithm found that the NICE eligibility criteria did not optimally explain which patients underwent THA. A model with superior explanatory power drew distinctions that are not supported by NICE, which were an age cut off at 76 and a different ambulation cut off. Among patients who satisfied the NICE eligibility, the use of THA was less likely with higher age (odds ratio 0.88, 95% confidence interval 0.87 to 0.88), worsening abbreviated mental test scores (0.49 (0.41 to 0.58) for normal cognition v borderline cognitive impairment)), worsening American Society of Anesthesiologists score (0.74, 0.66 to 0.84), male sex (0.85, 0.77 to 0.93), worsening ambulatory status (0.32, 0.28 to 0.35 for walking with a stick v independent ambulation), and fifths of worsening socioeconomic area deprivation (0.76 (0.66 to 0.88) for least v most deprived fifth). Patients receiving treatment during the working week were more likely to receive THA than at the weekend (0.90, 0.83 to 0.98). Conclusions: There are wide disparities in the use of THA among individuals with hip fractures, and compliance with NICE guidance is poor. Patients with higher levels of socioeconomic deprivation and those who require surgery at the weekend were less likely to receive THA. Inconsistent compliance with NICE recommendations means that the optimal treatment for older adults with hip fractures can depend on where and when they present to hospital. © BMJ Publishing Group Ltd 2016. Source

Rose B.S.,Harvard University | Jiang W.,Center for Surgery and Public Health | Punglia R.S.,Dana-Farber Cancer Institute
Breast Cancer Research and Treatment

We investigated whether increasing size of lymph nodes (LN) metastases is associated with lower breast cancer-specific survival (BCSS) and overall survival (OS) independent of the number of positive LNs. Using Surveillance, Epidemiology, and End Results registry data, we identified 8791 women diagnosed between 1990 and 2003 with node-positive, non-metastatic invasive breast cancer treated with surgery and axillary LN dissection. Size of the largest involved LN metastasis was categorized as ≤2 mm, >2 mm to <2 cm, and ≥2 cm. BCSS and OS were estimated using the Kaplan–Meier method and compared using log-rank statistics. Adjusted hazard ratios (HR) were calculated using Cox proportional hazards models. Median follow-up was 109 months. Largest LN size was ≤2 mm, >2 mm to <2 cm, and ≥2 cm in 2219 (25.2 %), 5047 (57.4 %), and 1525 (17.3 %) women, respectively. The 10-year BCSS for women with LNs ≤2 mm, >2 mm to <2 cm, and ≥2 cm was 82.9, 75.5, 64.8 %, respectively (p < 0.001). On multivariable analysis, large (≥2 cm) LN size was significantly associated with worsened BCSS (HR: 1.169; p = 0.026) and OS (HR: 1.169; p = 0.006) in addition to age, race, grade, PR status, adjuvant radiation, T-stage, and number of positive LNs. Large (≥2 cm) LNs metastases were associated with lower BCSS and OS after controlling for other known prognostic factors including number of positive LNs. LN size could be useful to risk-stratify patients for adjuvant therapy if these results are validated in future prospective studies. © 2015, Springer Science+Business Media New York. Source

Owens C.D.,University of California at San Francisco | Kim J.M.,University of California at San Francisco | Hevelone N.D.,Center for Surgery and Public Health | Hevelone N.D.,Brigham and Womens Hospital | And 4 more authors.
Journal of Vascular Surgery

Patients with advanced peripheral artery disease (PAD) have a high prevalence of cardiovascular (CV) risk factors and shortened life expectancy. However, CV risk factors poorly predict midterm (<5 years) mortality in this population. This study tested the hypothesis that baseline biochemical parameters would add clinically meaningful predictive information in patients undergoing lower extremity bypass operations. This was a prospective cohort study of patients with clinically advanced PAD undergoing lower extremity bypass surgery. The Cox proportional hazard model was used to assess the main outcome of all-cause mortality. A clinical model was constructed with known CV risk factors, and the incremental value of the addition of clinical chemistry, lipid assessment, and a panel of 11 inflammatory parameters was investigated using the C statistic, the integrated discrimination improvement index, and Akaike information criterion. The study monitored 225 patients for a median of 893 days (interquartile range, 539-1315 days). In this study, 50 patients (22.22%) died during the follow-up period. By life-table analysis (expressed as percent surviving ± standard error), survival at 1, 2, 3, 4, and 5 years, respectively, was 90.5% ± 1.9%, 83.4% ± 2.5%, 77.5% ± 3.1%, 71.0% ± 3.8%, and 65.3% ± 6.5%. Compared with survivors, decedents were older, diabetic, had extant coronary artery disease, and were more likely to present with critical limb ischemia as their indication for bypass surgery (P < .05). After adjustment for the above, clinical chemistry and inflammatory parameters significant (hazard ratio [95% confidence interval]) for all-cause mortality were albumin (0.43 [0.26-0.71]; P = .001), estimated glomerular filtration rate (0.98 [0.97-0.99]; P = .023), high-sensitivity C-reactive protein (hsCRP; 3.21 [1.21-8.55]; P = .019), and soluble vascular cell adhesion molecule (1.74 [1.04-2.91]; P = .034). Of the inflammatory molecules investigated, hsCRP proved most robust and representative of the integrated inflammatory response. Albumin, eGFR, and hsCRP improved the C statistic and integrated discrimination improvement index beyond that of the clinical model and produced a final C statistic of 0.82. A risk prediction model including traditional risk factors and parameters of inflammation, renal function, and nutrition had excellent discriminatory ability in predicting all-cause mortality in patients with clinically advanced PAD undergoing bypass surgery. © 2012 Society for Vascular Surgery. Source

Zogg C.K.,Center for Surgery and Public Health
Journal of Oncology

Exemplified by cancer cells' preference for glycolysis, for example, the Warburg effect, altered metabolism in tumorigenesis has emerged as an important aspect of cancer in the past 10-20 years. Whether due to changes in regulatory tumor suppressors/oncogenes or by acting as metabolic oncogenes themselves, enzymes involved in the complex network of metabolic pathways are being studied to understand their role and assess their utility as therapeutic targets. Conversion of glycolytic intermediate 3-phosphoglycerate into phosphohydroxypyruvate by the enzyme phosphoglycerate dehydrogenase (PHGDH) - a rate-limiting step in the conversion of 3-phosphoglycerate to serine - represents one such mechanism. Forgotten since classic animal studies in the 1980s, the role of PHGDH as a potential therapeutic target and putative metabolic oncogene has recently reemerged following publication of two prominent papers near-simultaneously in 2011. Since that time, numerous studies and a host of metabolic explanations have been put forward in an attempt to understand the results observed. In this paper, I review the historic progression of our understanding of the role of PHGDH in cancer from the early work by Snell through its reemergence and rise to prominence, culminating in an assessment of subsequent work and what it means for the future of PHGDH. © 2014 Cheryl K. Zogg. Source

McClure R.S.,Brigham and Womens Hospital | Narayanasamy N.,Brigham and Womens Hospital | Wiegerinck E.,Brigham and Womens Hospital | Lipsitz S.,Center for Surgery and Public Health | And 5 more authors.
Annals of Thoracic Surgery

Background: This study reviews a single institution experience with the Carpentier-Edwards pericardial aortic valve bioprosthesis, concentrating on late outcomes. Methods: From December 1991 to June 2002, 1,000 patients underwent aortic valve replacement with the Carpentier-Edwards pericardial valve (mean follow-up 6.01 ± 3.56 years). The institutional database was reviewed. Follow-up data were acquired through telephone interviews and mail-in questionnaires. Time-to-event analyses were performed by the Kaplan-Meier method. Mean age was 74.1 years; 545 patients (54.5%) were male. Mean preoperative ejection fraction was 52.5%. Isolated aortic valve replacement occurred in 372 cases (37.2%). Combined aortic valve replacement with coronary artery bypass grafting occurred in 443 cases (44.3%). The remaining 185 patients (18.5%) underwent complex procedures with concomitant mitral, tricuspid, or arch repair. One hundred forty patients (14.0%) had prior aortic valve surgery. Follow-up was 99.4% complete. Results: Overall operative mortality was 7.2% (72 of 1,000). There were 503 late deaths (50.3%). Age-stratified survival at 15 years was 43.7% for patients less than 65 years of age; 18.2% for patients aged 65 to 75; and 9.4% for patients aged more than 75 years. There were 26 failed bioprostheses (2.6%) requiring reoperation. Structural valve deterioration was the cause in 13 of 26 cases (50%), endocarditis in 11 of 26 (42%), and perivalvular leak in 2 of 26 (7.6%). Age-stratified freedom from reoperation due to structural valve deterioration at 15 years was 34.7% for patients less than 65 years of age; 89.4% for patients aged 65 to 75; and 99.5% for patients aged more than 75 years. Conclusions: The Carpentier-Edwards pericardial bioprosthesis shows long-term durability with low rates of structural failure. © 2010 The Society of Thoracic Surgeons. Source

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