Bridging the Age Gap: a prognostic model that predicts survival and aids in primary treatment decisions for older women with oestrogen receptor-positive early breast cancer.

BACKGROUND: A prognostic model was developed and validated using cancer registry data. This underpins an online decision support tool, informing primary treatment choice for women aged 70 years or older with hormone receptor-positive early breast cancer. METHODS: Data from women diagnosed between 2002 and 2010 in the English Northern and Yorkshire and West Midlands regions were used to develop the model. Primary treatment options of surgery with adjuvant endocrine therapy or primary endocrine therapy were compared. Models predicting the hazard of breast cancer-specific mortality and hazard of other-cause mortality were combined to derive survival probabilities. The model was validated externally using data from the Eastern Cancer Registration and Information Centre. RESULTS: The model was developed using data from 23 842 women, and validated externally on a data set from 14 526 patients. The overall model calibration was good. At 2 and 5 years, predicted mortality from breast cancer and other causes differed from the observed rate by less than 1 per cent. At 5 years, there were slight overpredictions in breast cancer mortality (2629 predicted versus 2556 observed deaths; P = 0·142) and mortality from all causes (6399 versus 6320 respectively; P = 0·583). The discrepancy varied between subgroups. Model discrimination was 0·75 or above for all mortality measures. CONCLUSION: A prognostic model for older women with oestrogen receptor-positive early breast cancer was developed and validated in the present study. This forms a basis for an online decision support tool (https://agegap.shef.ac.uk/).

ANTECEDENTES: Se ha desarrollado y validado un modelo pronóstico utilizando datos del registro de cáncer. Ello ha permitido ofrecer una herramienta online para facilitar la toma de decisiones respecto a la elección del tratamiento inicial en mujeres mayores de 70 años con cáncer de mama precoz y receptores de hormonas positivos. MÉTODOS: Se incluyeron un total de 23.842 mujeres, diagnosticadas entre 2002 y 2010 en las regiones del Norte, Yorkshire y West Midlands inglesas que cumplieron con los criterios de inclusión. Se compararon dos opciones de tratamiento: cirugía primaria asociada a tratamiento endocrino adyuvante o tratamiento primario endocrino. Para estimar la probabilidad de supervivencia se combinaron modelos predictivos para el riesgo de mortalidad específica por cáncer de mama y para el riesgo de mortalidad por otras causas. Se realizó una validación externa con datos del Eastern Cancer Registration and Information Center (n = 14.526). RESULTADOS: La calibración global del modelo fue buena. A los 2 y 5 años, la mortalidad anticipada por cáncer de mama y por otras causas difería de la observada en menos del 1%. A los 5 años, hubo una ligera sobrevaloración de la predicción de mortalidad por cáncer de mama (prevista versus real: 2.629 versus 2.556, P = 0,78) y de la mortalidad por todas las causas (6.399 versus 6.320, P = 0,14). Esta discrepancia varió entre subgrupos. La capacidad discriminativa del modelo fue del 0,75 o superior para todas las medidas de mortalidad. CONCLUSIÓN: En este estudio, se desarrolló y validó un modelo pronóstico para mujeres mayores con cáncer de mama precoz positivo para receptores de estrógenos. Esta herramienta que facilita la toma de decisiones está disponible online (https://agegap.shef.ac.uk/).

Adjuvant Chemotherapy for Breast Cancer in Older Women: An Analysis of Retrospective English Cancer Registration Data.

AIMS: Adjuvant chemotherapy is recommended as a treatment for women with high recurrence risk early breast cancer. Older women are less likely to receive chemotherapy than younger women. This study investigated the impact of chemotherapy on breast cancer-specific survival in women aged 70 + years using English registry data. MATERIALS AND METHODS: Cancer registration data were obtained from two English regions from 2002 to 2012 (n = 29 728). The impact of patient-level characteristics on the probability of receiving adjuvant chemotherapy was explored using logistic regression. Survival modelling was undertaken to show the effect of chemotherapy and age/health status on breast cancer-specific survival. Missing data were handled using multiple imputation. RESULTS: In total, 11 735 surgically treated early breast cancer patients were identified. Use of adjuvant chemotherapy has increased over time. Younger age at diagnosis, increased nodal involvement, tumour size and grade, oestrogen receptor-negative or human epidermal growth factor receptor 2-positive disease were all associated with increased probability of receiving chemotherapy. Chemotherapy was associated with a significant reduction in the hazard of breast cancer-specific mortality in women with high risk cancer, after adjusting for patient-level characteristics (hazard ratio 0.74, 95% confidence interval 0.67-0.81). DISCUSSION: Chemotherapy is associated with an improved breast cancer-specific survival in older women with early breast cancer at high risk of recurrence . Lower rates of chemotherapy use in older women may, therefore, contribute to inferior cancer outcomes. Decisions on potential benefits for individual patients should be made on the basis of life expectancy, treatment tolerance and patient preference.

Omission of surgery in older women with early breast cancer has an adverse impact on breast cancer-specific survival.

BACKGROUND: Primary endocrine therapy is used as an alternative to surgery in up to 40 per cent of women with early breast cancer aged over 70 years in the UK. This study investigated the impact of surgery versus primary endocrine therapy on breast cancer-specific survival (BCSS) in older women. METHODS: Cancer registration data for 2002-2010 were obtained from two English regions. A retrospective analysis was performed for women with oestrogen receptor (ER)-positive disease, using statistical modelling to show the effect of treatment (surgery or primary endocrine therapy) and age and health status on BCSS. Missing data were handled using multiple imputation. RESULTS: Cancer registration data on 23 961 women were retrieved. After data preprocessing, 18 730 of 23 849 women (78·5 per cent) were identified as having ER-positive disease; of these, 10 087 (53·9 per cent) had surgery and 8643 (46·1 per cent) had primary endocrine therapy. BCSS was worse in the primary endocrine therapy group than in the surgical group (5-year BCSS rate 69·4 and 89·9 per cent respectively). This was true for all strata considered, although the difference was less in the cohort with the greatest degree of co-morbidity. For older, frailer patients the hazard of breast cancer death had less relative impact on overall survival. CONCLUSION: BCSS in older women with ER-positive disease is worse if surgery is omitted. This treatment choice may contribute to inferior cancer outcomes. Selection for surgery on the basis of predicted life expectancy may permit choice of women for whom surgery confers little benefit.

Looking beyond the forest: Using harvest plots, gap analysis, and expert consultations to assess effectiveness, engage stakeholders, and inform policy.

We describe a combination of methods for assessing the effectiveness of complex interventions, especially where substantial heterogeneity with regard to the population, intervention, comparison, outcomes, and study design of interest is expected. We applied these methods in a recent systematic review of the effectiveness of reinforced home-based palliative care (rHBPC) interventions, which included home-based care with an additional and explicit component of lay caregiver support. We first summarized the identified evidence, deemed inappropriate for statistical pooling, graphically by creating harvest plots. Although very useful as a tool for summary and presentation of overall effectiveness, such graphical summary approaches may obscure relevant differences between studies. Thus, we then used a gap analysis and conducted expert consultations to look beyond the aggregate level at how the identified evidence of effectiveness may be explained. The goal of these supplemental methods was to step outside of the conventional systematic review and explore this heterogeneity from a broader perspective, based on the experience of palliative care researchers and practitioners. The gap analysis and expert consultations provided valuable input into possible underlying explanations in the evidence, which could be helpful in the further adaptation and testing of existing rHBPC interventions or the development and evaluation of new ones. We feel that such a combination of methods could prove accessible, understandable, and useful in informing decisions and could thus help increase the relevance of systematic reviews to the decision-making process.

Ten-year follow-up study of three alternative bearing surfaces used in total hip arthroplasty in young patients: a prospective randomised controlled trial.

AIMS: We present the ten-year data of a cohort of patients, aged between 18 and 65 years (mean age 52.7 years; 19 to 64), who underwent total hip arthroplasty. Patients were randomised to be treated with a cobalt-chrome (CoCr) femoral head with an ultra-high molecular weight polyethylene (UHMWPE), highly cross-linked polyethylene (XLPE) or ceramic-on-ceramic (CoC) bearing surface. PATIENTS AND METHODS: A total of 102 hips (91 patients) were randomised into the three groups. At ten years, 97 hips were available for radiological and functional follow-up. Two hips (two patients) had been revised (one with deep infection and one for periprosthetic fracture) and three were lost to follow-up. Radiological analysis was performed using a validated digital assessment programme to give linear, directional and volumetric wear of the two polyethylene groups. RESULTS: There was a significantly reduced rate of steady-state linear wear with XLPE (0.07 mm/yr) compared with UHMWPE (0.37 mm/yr) (p = 0.001). Volumetric wear was also significantly reduced in the XLPE group (29.29 mm3/yr) compared with the UHMWPE group (100.75mm3/yr) (p = 0.0001). There were six patients with UHMWPE who had non-progressive osteolysis and none in the XLPE group. All three bearing groups had significant improvements in 12-item short form health survey scores, Western Ontario and McMaster Universities Osteoarthritis Index score and Harris Hip Score. However, the improvement in HSS was significantly less in the UHMWPE group (p = 0.0188) than in the other two groups. At ten years, the rates of volumetric and linear wear in the XLPE group remain low and predominantly below the estimated threshold for osteolysis (1 mm/yr). The rate of linear wear in the XLPE group was three times less than in the UHMWPE group at five-year follow-up and five times less at ten years. The rate of volumetric wear was also three times less in the XLPE group at ten years. CONCLUSION: While CoC also performs well, XLPE at ten years remains a safe and excellent bearing option in young patients, with low rates of wear and no evidence of osteolysis. Cite this article: Bone Joint J 2017;99-B:1590-5.

N-linked glycan truncation causes enhanced clearance of plasma-derived von Willebrand factor.

Essentials von Willebrands factor (VWF) glycosylation plays a key role in modulating in vivo clearance. VWF glycoforms were used to examine the role of specific glycan moieties in regulating clearance. Reduction in sialylation resulted in enhanced VWF clearance through asialoglycoprotein receptor. Progressive VWF N-linked glycan trimming resulted in increased macrophage-mediated clearance. Click to hear Dr Denis discuss clearance of von Willebrand factor in a free presentation from the ISTH Academy SUMMARY: Background Enhanced von Willebrand factor (VWF) clearance is important in the etiology of both type 1 and type 2 von Willebrand disease (VWD). In addition, previous studies have demonstrated that VWF glycans play a key role in regulating in vivo clearance. However, the molecular mechanisms underlying VWF clearance remain poorly understood. Objective To define the molecular mechanisms through which VWF N-linked glycan structures influence in vivo clearance. Methods By use of a series of exoglycosidases, different plasma-derived VWF (pd-VWF) glycoforms were generated. In vivo clearance of these glycoforms was then assessed in VWF-/- mice in the presence or absence of inhibitors of asialoglycoprotein receptor (ASGPR), or following clodronate-induced macrophage depletion. Results Reduced amounts of N-linked and O-linked sialylation resulted in enhanced pd-VWF clearance modulated via ASGPR. In addition to this role of terminal sialylation, we further observed that progressive N-linked glycan trimming also resulted in markedly enhanced VWF clearance. Furthermore, these additional N-linked glycan effects on clearance were ASGPR-independent, and instead involved enhanced macrophage clearance that was mediated, at least in part, through LDL receptor-related protein 1. Conclusion The carbohydrate determinants expressed on VWF regulate susceptibility to proteolysis by ADAMTS-13. In addition, our findings now further demonstrate that non-sialic acid carbohydrate determinants expressed on VWF also play an unexpectedly important role in modulating in vivo clearance through both hepatic ASGPR-dependent and macrophage-dependent pathways. In addition, these data further support the hypothesis that variation in VWF glycosylation may be important in the pathophysiology underlying type 1C VWD.

Specialist integrated haematological malignancy diagnostic services: an Activity Based Cost (ABC) analysis of a networked laboratory service model.

AIMS: Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDS) were introduced as a standard of care within the UK National Health Service to reduce diagnostic error and improve clinical outcomes. Two broad models of service delivery have become established: 'co-located' services operating from a single-site and 'networked' services, with geographically separated laboratories linked by common management and information systems. Detailed systematic cost analysis has never been published on any established SIHMDS model. METHODS: We used Activity Based Costing (ABC) to construct a cost model for our regional 'networked' SIHMDS covering a two-million population based on activity in 2011. RESULTS: Overall estimated annual running costs were £1 056 260 per annum (£733 400 excluding consultant costs), with individual running costs for diagnosis, staging, disease monitoring and end of treatment assessment components of £723 138, £55 302, £184 152 and £94 134 per annum, respectively. The cost distribution by department was 28.5% for haematology, 29.5% for histopathology and 42% for genetics laboratories. Costs of the diagnostic pathways varied considerably; pathways for myelodysplastic syndromes and lymphoma were the most expensive and the pathways for essential thrombocythaemia and polycythaemia vera being the least. CONCLUSIONS: ABC analysis enables estimation of running costs of a SIHMDS model comprised of 'networked' laboratories. Similar cost analyses for other SIHMDS models covering varying populations are warranted to optimise quality and cost-effectiveness in delivery of modern haemato-oncology diagnostic services in the UK as well as internationally.

Self-report pain and symptom measures for primary dysmenorrhoea: a critical review.

Primary dysmenorrhoea (PD) is highly prevalent among women of reproductive age and it can have significant short- and long-term consequences for both women and society as a whole. Validated symptom measures are fundamental for researchers to understand women's symptom experience of PD and to test symptom interventions. The objective of this paper was to critically review the content and psychometric properties of self-report tools to measure symptoms of PD. Databases including PubMed, PsychoINFO, Cumulative Index of Nursing and Allied Health Literature, and Health and Psychosocial Instruments were searched for self-report symptom measures that had been used among women with either PD or perimenstrual symptoms. A total of 15 measures met inclusion criteria and were included in the final analysis. The measures were categorized into generic pain measures, dysmenorrhoea-specific measures, and tools designed to measure perimenstrual symptoms. These measures had varying degrees of comprehensiveness of symptoms being measured, relevance to PD, multidimensionality and psychometric soundness. No single measure was found to be optimal for use, but some dysmenorrhoea-specific measures could be recommended if revised and further tested. Key issues in symptom measurement for PD are discussed. Future research needs to strengthen dysmenorrhoea-specific symptom measures by including a comprehensive list of symptoms based on the pathogenesis of PD, exploring relevant symptom dimensions beyond symptom severity (e.g., frequency, duration, symptom distress), and testing psychometric properties of the adapted tools using sound methodology and diverse samples.

Verifying the geographic origin of mahogany (Swietenia macrophylla King) with DNA-fingerprints.

Illegal logging is one of the main causes of ongoing worldwide deforestation and needs to be eradicated. The trade in illegal timber and wood products creates market disadvantages for products from sustainable forestry. Although various measures have been established to counter illegal logging and the subsequent trade, there is a lack of practical mechanisms for identifying the origin of timber and wood products. In this study, six nuclear microsatellites were used to generate DNA fingerprints for a genetic reference database characterising the populations of origin of a large set of mahogany (Swietenia macrophylla King, Meliaceae) samples. For the database, leaves and/or cambium from 1971 mahogany trees sampled in 31 stands from Mexico to Bolivia were genotyped. A total of 145 different alleles were found, showing strong genetic differentiation (δ(Gregorious)=0.52, F(ST)=0.18, G(ST(Hedrick))=0.65) and clear correlation between genetic and spatial distances among stands (r=0.82, P<0.05). We used the genetic reference database and Bayesian assignment testing to determine the geographic origins of two sets of mahogany wood samples, based on their multilocus genotypes. In both cases the wood samples were assigned to the correct country of origin. We discuss the overall applicability of this methodology to tropical timber trading.

Prescribing high-dose lipid-lowering therapy early to avoid subsequent cardiovascular events: is this a cost-effective strategy?

BACKGROUND: While evidence shows high-dose statins reduce cardiovascular events compared with moderate doses in individuals with acute coronary syndrome (ACS), many primary care trusts (PCT) advocate the use of generic simvastatin 40 mg/day for these patients. METHODS AND RESULTS: Data from 28 RCTs were synthesized using a mixed treatment comparison model. A Markov model was used to evaluate the cost-effectiveness of treatments taking into account adherence and the likely reduction in cost for atorvastatin when the patent expires. There is a clear dose-response: rosuvastatin 40 mg/day produces the greatest reduction in low-density lipoprotein cholesterol (56%) followed by atorvastatin 80 mg/day (52%), and simvastatin 40 mg/day (37%). Using a threshold of £20,000 per QALY, if adherence levels in general practice are similar to those observed in RCTs, all three higher dose statins would be considered cost-effective compared to simvastatin 40 mg/day. Using the net benefits of the treatments, rosuvastatin 40 mg/day is estimated to be the most cost-effective alternative. If the cost of atorvastatin reduces in line with that observed for simvastatin, atorvastatin 80 mg/day is estimated to be the most cost-effective alternative. CONCLUSION: Our analyses show that current PCT policies intended to minimize primary care drug acquisition costs result in suboptimal care.

Magnetic resonance for assessment of axillary lymph node status in early breast cancer: a systematic review and meta-analysis.

INTRODUCTION: Current methods of identifying axillary node metastases in breast cancer patients are highly accurate, but are associated with several adverse events. This review evaluates the diagnostic accuracy of magnetic resonance imaging (MRI) techniques for identification of axillary metastases in early stage newly diagnosed breast cancer patients. METHODS: Comprehensive searches were conducted in April 2009. Study quality was assessed. Sensitivity and specificity were meta-analysed using a bivariate random effects approach, utilising pathological diagnosis via node biopsy as the comparative gold standard. RESULTS: Based on the highest sensitivity and specificity reported in each of the nine studies evaluating MRI (n = 307 patients), mean sensitivity was 90% (95% CI: 78-96%; range 65-100%) and mean specificity 90% (95% CI: 75-96%; range 54-100%). Across five studies evaluating ultrasmall super-paramagnetic iron oxide (USPIO)-enhanced MRI (n = 93), mean sensitivity was 98% (95% CI: 61-100%) and mean specificity 96% (95% CI: 72-100%). Across three studies of gadolinium-enhanced MRI (n = 187), mean sensitivity was 88% (95% CI: 78-94%) and mean specificity 73% (95% CI: 63-81%). In the single study of in-vivo proton MR spectroscopy (n = 27), sensitivity was 65% (95% CI: 38-86%) and specificity 100% (95% CI: 69-100%). CONCLUSIONS: USPIO-enhanced MRI showed a trend towards higher sensitivity and specificity and may make a useful addition to the current diagnostic pathway. Additional larger studies with standardised methods and standardised criteria for classifying a node as positive are needed. Current estimates of sensitivity and specificity do not support replacement of SLNB with any current MRI technology in this patient group.

Positron emission tomography (PET) and magnetic resonance imaging (MRI) for the assessment of axillary lymph node metastases in early breast cancer: systematic review and economic evaluation.

BACKGROUND: Breast cancer is the most common type of cancer in women. Evaluation of axillary lymph node metastases is important for breast cancer staging and treatment planning. OBJECTIVES: To evaluate the diagnostic accuracy, cost-effectiveness and effect on patient outcomes of positron emission tomography (PET), with or without computed tomography (CT), and magnetic resonance imaging (MRI) in the evaluation of axillary lymph node metastases in patients with newly diagnosed early-stage breast cancer. DATA SOURCES: A systematic review of literature and an economic evaluation were carried out. Key databases (including MEDLINE, EMBASE and nine others) plus research registers and conference proceedings were searched for relevant studies up to April 2009. A decision-analytical model was developed to determine cost-effectiveness in the UK. REVIEW METHODS: One reviewer assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers and screened them against inclusion criteria. Data from included studies were extracted by one reviewer using a standardised data extraction form and checked by a second reviewer. Discrepancies were resolved by discussion. Quality of included studies was assessed using the quality assessment of diagnostic accuracy studies (QUADAS) checklist, applied by one reviewer and checked by a second. RESULTS: Forty-five citations relating to 35 studies were included in the clinical effectiveness review: 26 studies of PET and nine studies of MRI. Two studies were included in the cost-effectiveness review: one of PET and one of MRI. Of the seven studies evaluating PET/CT (n = 862), the mean sensitivity was 56% [95% confidence interval (CI) 44% to 67%] and mean specificity 96% (95% CI 90% to 99%). Of the 19 studies evaluating PET only (n = 1729), the mean sensitivity was 66% (95% CI 50% to 79%) and mean specificity 93% (95% CI 89% to 96%). PET performed less well for small metastases; the mean sensitivity was 11% (95% CI 5% to 22%) for micrometastases (≤ 2 mm; five studies; n = 63), and 57% (95% CI 47% to 66%) for macrometastases (> 2 mm; four studies; n = 111). The smallest metastatic nodes detected by PET measured 3 mm, while PET failed to detect some nodes measuring > 15 mm. Studies in which all patients were clinically node negative showed a trend towards lower sensitivity of PET compared with studies with a mixed population. Across five studies evaluating ultrasmall super-paramagnetic iron oxide (USPIO)-enhanced MRI (n = 93), the mean sensitivity was 98% (95% CI 61% to 100%) and mean specificity 96% (95% CI 72% to 100%). Across three studies of gadolinium-enhanced MRI (n = 187), the mean sensitivity was 88% (95% CI 78% to 94%) and mean specificity 73% (95% CI 63% to 81%). In the single study of in vivo proton magnetic resonance spectroscopy (n = 27), the sensitivity was 65% (95% CI 38% to 86%) and specificity 100% (95% CI 69% to 100%). USPIO-enhanced MRI showed a trend towards higher sensitivity and specificity than gadolinium-enhanced MRI. Results of the decision modelling suggest that the MRI replacement strategy is the most cost-effective strategy and dominates the baseline 4-node sampling (4-NS) and sentinel lymph node biopsy (SLNB) strategies in most sensitivity analyses undertaken. The PET replacement strategy is not as robust as the MRI replacement strategy, as its cost-effectiveness is significantly affected by the utility decrement for lymphoedema and the probability of relapse for false-negative (FN) patients. LIMITATIONS: No included studies directly compared PET and MRI. CONCLUSIONS: Studies demonstrated that PET and MRI have lower sensitivity and specificity than SLNB and 4-NS but are associated with fewer adverse events. Included studies indicated a significantly higher mean sensitivity for MRI than for PET, with USPIO-enhanced MRI providing the highest sensitivity. However, sensitivity and specificity of PET and MRI varied widely between studies, and MRI studies were relatively small and varied in their methods; therefore, results should be interpreted with caution. Decision modelling based on these results suggests that the most cost-effective strategy may be MRI rather than SLNB or 4-NS. This strategy reduces costs and increases quality-adjusted life-years (QALYs) because there are fewer adverse events for the majority of patients. However, this strategy leads to more FN cases at higher risk of cancer recurrence and more false- positive (FP) cases who would undergo unnecessary axillary lymph node dissection. Adding MRI prior to SLNB or 4-NS has little effect on QALYs, though this analysis is limited by lack of available data. Future research should include large, well-conducted studies of MRI, particularly using USPIO; data on the long-term impacts of lymphoedema on cost and patient utility; studies of the comparative effectiveness and cost-effectiveness of SLNB and 4-NS; and more robust UK cost data for 4-NS and SLNB as well as the cost of MRI and PET techniques. FUNDING: This study was funded by the Health Technology Assessment programme of the National Institute of Health Research.

Positron emission tomography (PET) for assessment of axillary lymph node status in early breast cancer: A systematic review and meta-analysis.

PURPOSE: Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) are used to assess axillary nodal status in breast cancer, but are invasive procedures associated with morbidity, including lymphoedema. This systematic review evaluates the diagnostic accuracy of positron emission tomography (PET), with or without computed tomography (CT), for assessment of axillary nodes in early breast cancer. METHODS: Eleven databases including MEDLINE, EMBASE and the Cochrane Library, plus research registers and conference proceedings, were searched in April 2009. Study quality was assessed using the QUality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. Sensitivity and specificity were meta-analysed using a bivariate random effects approach. RESULTS: Across 26 studies evaluating PET or PET/CT (n = 2591 patients), mean sensitivity was 63% (95% CI: 52-74%; range 20-100%) and mean specificity 94% (95% CI: 91-96%; range 75-100%). Across 7 studies of PET/CT (n = 862), mean sensitivity was 56% (95% CI: 44-67%) and mean specificity 96% (90-99%). Across 19 studies of PET-only (n = 1729), mean sensitivity was 66% (50-79%) and mean specificity 93% (89-96%). Mean sensitivity was 11% (5-22%) for micrometastases (≤2 mm; five studies; n = 63), and 57% (47-66%) for macrometastases (>2 mm; four studies; n = 111). CONCLUSIONS: PET had lower sensitivity and specificity than SLNB. Therefore, replacing SLNB with PET would avoid the adverse effects of SLNB, but lead to more false negative patients at risk of recurrence and more false positive patients undergoing unnecessary ALND. The present evidence does not support the routine use of PET or PET-CT for the assessment of the clinically negative axilla.

A rare case of frontal linear scleroderma (en coup de sabre) with intra-oral and dental involvement.

En coup de sabre is a linear scleroderma that presents on the frontal or frontoparietal scalp. This case describes a 36-year-old female who presented with a history of en coup de sabre with subsequent oral and dental involvement which to the authors' knowledge has never been reported previously. The clinical presentation, pathology and laboratory findings together with a brief discussion of the management of this case are discussed.

A program with a dedicated coordinator improved chart documentation of osteoporosis after fragility fracture.

UNLABELLED: Post-fracture osteoporosis care is becoming recognized as essential by the orthopaedic community, but programs and systems are needed to ensure that this care is routinely provided. Chart documentation related to OP, which is valuable for continuity of care, increased significantly following establishment of an osteoporosis program with a dedicated coordinator. INTRODUCTION: Post-fracture osteoporosis (OP) care has been repeatedly reported to be inadequate. Through a coordinator-based program, we addressed OP care for more than 95% of fragility fracture patients (1), but we do not know if documentation by orthopaedic surgeons improved. The literature suggests that chart documentation, though underestimating true care, is an indicator of the salient aspects of a condition. Thus chart documentation could be used to reflect an emerging recognition of OP as an important issue to be addressed in the orthopaedic management of the fragility fracture. The purpose of this study was to evaluate if there was an increased documentation of OP by orthopaedic surgeons before and after introduction of a coordinator-based program where the coordinator was known to address OP in 95% of cases. METHODS: Chart audits were conducted to quantify OP documentation for patients treated after program initiation compared with age-, sex-, and fracture type-matched controls who presented prior to program implementation. Documentation rates were compared using chi(2) tests. Multivariable logistic regression analyses were performed to identify patient characteristics associated with OP-related documentation. RESULTS: After program implementation, chart documentation of OP diagnosis (unadjusted OR 2.2, 95% CI 1.1-4.4), of referral for OP follow-up (unadjusted OR 3.1, 95% CI 1.5-6.1), and of initiation of OP management (unadjusted OR 8.2, 95% CI 4.0-16.5) by orthopaedic surgeons was more likely. Being in the post-implementation group was stronger than any patient factors in predicting OP charting. CONCLUSIONS: Physicians working in a clinic with a coordinator-based OP program were more likely to document OP-related care in patients' medical charts. We believe this in turn reflected increased attention to OP by physicians in the orthopaedic management of fragility fractures.

The clinical and economic benefits of capecitabine and tegafur with uracil in metastatic colorectal cancer.

Two oral fluoropyrimidine therapies have been introduced for metastatic colorectal cancer. One is a 5-fluorouracil pro-drug, capecitabine; the other is a combination of tegafur and uracil administered together with leucovorin. The purpose of this study was to compare the clinical effectiveness and cost-effectiveness of these oral therapies against standard intravenous 5-fluorouracil regimens. A systematic literature review was conducted to assess the clinical effectiveness of the therapies and costs were calculated from the UK National Health Service perspective for drug acquisition, drug administration, and the treatment of adverse events. A cost-minimisation analysis was used; this assumes that the treatments are of equal efficacy, although direct randomised controlled trial (RCT) comparisons of the oral therapies with infusional 5-fluorouracil schedules were not available. The cost-minimisation analysis showed that treatment costs for a 12-week course of capecitabine (Pounds 2132) and tegafur with uracil (Pounds 3385) were lower than costs for the intravenous Mayo regimen (Pounds 3593) and infusional regimens on the de Gramont (Pounds 6255) and Modified de Gramont (Pounds 3485) schedules over the same treatment period. Oral therapies result in lower costs to the health service than intravenous therapies. Further research is needed to determine the relative clinical effectiveness of oral therapies vs infusional regimens.

Stereotaxic core needle biopsy of breast microcalcifications obtained using a standard mammography table with an add-on unit.

OBJECTIVE: To demonstrate the reliability of stereotaxic biopsy of indeterminate microcalcifications using a standard mammography table with an add-on unit. METHODS: In 121 cases of indeterminate microcalcifications, core biopsy was performed using a standard mammography table with an add-on stereotaxic unit. Microcalcifications were identified on radiography of core specimens. RESULTS: Microcalcifications and a definitive histologic diagnosis were obtained in 112 core biopsies (92.6%), with no significant complications. In 23 lesions frank malignancy was diagnosed, and all of these diagnoses were confirmed on surgery. Pathologic examination suggested carcinoma in 4 lesions, and open biopsy confirmed malignancy in 3 of these cases. Four lesions showed atypical ductal hyperplasia. Benign disease was diagnosed in 81 lesions, of which 78 remained stable on mammographic follow-up (mean 16 months later) and 3 were subjected to surgical biopsy (of which 1 was malignant and 2 were benign). Nine cases were technically unsatisfactory because microcalcifications were not sampled. CONCLUSION: Stereotaxic core biopsy performed with an add-on unit is a safe and reliable technique for biopsy of indeterminate microcalcifications. For successful biopsy, microcalcifications must be harvested. Pathologic results should be correlated with mammographic findings. The accuracy rate compares favourably with results reported using prone biopsy tables. In an era of cost containment, this alternative to prone biopsy tables could result in significant savings in terms of capital investment and use of hospital rooms. In this study, surgical biopsy could have been avoided in 64.5% of cases.

Tetracycline sclerotherapy for the treatment of recurrent pooling of plasma in the submandibular tissue space: case report.

We present an unusual case of recurrent swelling after removal of the submandibular and sublingual salivary glands which was found to be the result of a collection of plasma. This was successfully treated by an injection of tetracycline to induce sclerosis.