The management of brain metastases

Brain metastases occur in 20-50% of NSCLC and 50-80% of SCLC. In this review, we will look at evidence-based medicine data and give some perspectives on the management of BM. We will address the problems of multiple BM, single BM and prophylactic cranial irradiation. Recursive Partitioning Analysis (RPA) is a powerful prognostic tool to facilitate treatment decisions. Dealing with multiple BM, the use of corticosteroids was established more than 40 years ago by a unique randomized trial (RCT). Palliative effect is high (_80%) as well as side-effects. Whole brain radiotherapy (WBRT) was evaluated in many RCTs with a high (60-90%) response rate; several RT regimes are equivalent, but very high dose per fraction should be avoided. In multiple BM from SCLC, the effect of WBRT is comparable to that in NSCLC but chemotherapy (CXT) although advocated is probably less effective than RT. Single BM from NSCLC occurs in 30% of all BM cases; several prognostic classifications including RPA are very useful. Several options are available in single BM: WBRT, surgery (SX), radiosurgery (RS) or any combination of these. All were studied in RCTs and will be reviewed: the addition of WBRT to SX or RS gives a better neurological tumour control, has little or no impact on survival, and may be more toxic. However omitting WBRT after SX alone gives a higher risk of cerebro-spinal fluid dissemination. Prophylactic cranial irradiation (PCI) has a major role in SCLC. In limited disease, meta-analyses have shown a positive impact of PCI in the decrease of brain relapse and in survival improvement, especially for patients in complete remission. Surprisingly, this has been recently confirmed also in extensive disease. Experience with PCI for NSCLC is still limited, but RCT suggest a reduction of BM with no impact on survival. Toxicity of PCI is a matter of debate, as neurological or neuro-cognitive impairment is already present prior to PCI in almost half of patients. However RT toxicity is probably related to total dose and dose per fraction. Perspectives : Future research should concentrate on : 1) combined modalities in multiple BM. 2) Exploration of treatments in oligo-metastases. 3) Further exploration of PCI in NSCLC. 4) Exploration of new, toxicity-sparing radiotherapy techniques (IMRT, Tomotherapy etc).

Adhésion thérapeutique aux traitements oncologiques oraux et prise en charge interdisciplinaire [Therapeutic adherence to oral cancer therapy and interdisciplinary management].

Medication adherence is a well-known risk factor in internal medicine. However in oncology this dimension is emerging due to the increasing number of oral formulations. First results in the oral oncology literature suggest that patients' ability to cope with medical prescription decreases with time. This might preclude patients from reaching clinical outcomes. Factors impacting on medication adherence to oral oncology treatments have not been yet extensively described neither strategies to address them and support patient's needs. Oncologists and pharmacists in our University outpatient settings performed a pilot study which aimed at measuring and facilitating adherence to oral oncology treatments and at understanding determinants of patient's adherence. The ultimate purpose of such a patient-centered and interdisciplinary collaboration would be to promote patient self-management and complement the standard medical follow-up.

ESCMID* guideline for the diagnosis and management of Candida diseases 2012: developing European guidelines in clinical microbiology and infectious diseases.

The process to develop a guideline in a European setting remains a challenge. The ESCMID Fungal Infection Study Group (EFISG) successfully achieved this endeavour. After two face-to-face meetings, numerous telephone conferences, and email correspondence, an ESCMID task force (basically composed of members of the Society's Fungal Infection Study Group, EFISG) finalized the ESCMID diagnostic and management/therapeutic guideline for Candida diseases. By appreciating various patient populations at risk for Candida diseases, four subgroups were predefined, mainly ICU patients, paediatric, HIV/AIDS and patients with malignancies including haematopoietic stem cell transplantation. Besides treatment recommendations, the ESCMID guidelines provide guidance for diagnostic procedures. For the guidelines, questions were formulated to phrase the intention of a given recommendation, for example, outcome. The recommendation was the clinical intervention, which was graded by a score of A-D for the 'Strength of a recommendation'. The 'level of evidence' received a score of I-III. The author panel was approved by ESCMID, European Organisation for Research and Treatment of Cancer, European Group for Blood and Marrow Transplantation, European Society of Intensive Care Medicine and the European Confederation of Medical Mycology. The guidelines followed the framework of GRADE and Appraisal of Guidelines, Research, and Evaluation. The drafted guideline was presented at ECCMID 2011 and points of discussion occurring during that meeting were incorporated into the manuscripts. These ESCMID guidelines for the diagnosis and management of Candida diseases provide guidance for clinicians in their daily decision-making process.

Tax differentials and agglomeration economies in intraregional firm location

This paper analyses empirically how differences in local taxes affect the intraregional location of new manufacturing plants. These effects are examined within the random profit maximization framework while accounting for the presence of different types of agglomeration economies (localization/ urbanization/ Jacobs’ economies) at the municipal level. We look at the location decision of more than 10,000 establishments locating between 1996 and 2003 across more than 400 municipalities in Catalonia, a Spanish region. It is necessary to restrict the choice set to the local labor market and, above all, to control for agglomeration economies so as to identify the effects of taxes on the location of new establishments.

An empirical analysis of wealth taxation: equity Vs.tax compliance

Capital taxation is currently under debate, basically due to problems of administrative control and proper assessment of the levied assets. We analyze both problems focusing on a capital tax, the annual wealth tax (WT), which is only applied in five OECD countries, being Spain one of them. We concentrate our analysis on top 1% adult population, which permits us to describe the evolution of wealth concentration in Spain along 1983-2001. On average top 1% holds about 18% of total wealth, which rises to 19% when tax incompliance and under-assessment is corrected for housing, the main asset. The evolution suggests wealth concentration has risen. Regarding WT, we analyze whether it helps to reduce wealth inequality or, on the contrary, it reinforces vertical inequity (due to especial concessions) and horizontal inequity (due to the de iure and to de facto different treatment of assets). We analyze in detail housing and equity shares. By means of a time series analysis, we relate the reported values with reasonable price indicators and proxies of the propensity to save. We infer net tax compliance is extremely low, which includes both what we commonly understand by (gross) tax compliance and the degree of under-assessment due to fiscal legislation (for housing). That is especially true for housing, whose level of net tax compliance is well below 50%. Hence, we corroborate the difficulties in taxing capital, and so cast doubts on the current role of the WT in Spain in reducing wealth inequality.

Changes in the demand for private medical insurance following a shift in tax incentives

The 1998 Spanish reform of the Personal Income Tax eliminated the 15% deduction for private medical expenditures including payments on private health insurance (PHI) policies. To avoid an undesirable increase in the demand for publicly funded health care, tax incentives to buy PHI were not completely removed but basically shifted from individual to group employer-paid policies. In a unique fiscal experiment, at the same time that the tax relief for individually purchased policies was abolished, the government provided for tax allowances on policies taken out through employment. Using a bivariate probit model on data from National Health Surveys, we estimate the impact of said reform on the demand for PHI and the changes occurred within it. Our findings suggest that the total probability of buying PHI was not significantly affected. Indeed, the fall in the demand for individual policies (by 10% between 1997 and 2001) was offset by an increase in the demand for group employer-paid ones, so that the overall size of the market remained virtually unchanged. We also briefly discuss the welfare effects on the state budget, the industry and society at large.

Device-specific weighted T-score for two quantitative ultrasounds: operational propositions for the management of osteoporosis for 65 years and older women in Switzerland.

The World Health Organization (WHO) criteria for the diagnosis of osteoporosis are mainly applicable for dual X-ray absorptiometry (DXA) measurements at the spine and hip levels. There is a growing demand for cheaper devices, free of ionizing radiation such as promising quantitative ultrasound (QUS). In common with many other countries, QUS measurements are increasingly used in Switzerland without adequate clinical guidelines. The T-score approach developed for DXA cannot be applied to QUS, although well-conducted prospective studies have shown that ultrasound could be a valuable predictor of fracture risk. As a consequence, an expert committee named the Swiss Quality Assurance Project (SQAP, for which the main mission is the establishment of quality assurance procedures for DXA and QUS in Switzerland) was mandated by the Swiss Association Against Osteoporosis (ASCO) in 2000 to propose operational clinical recommendations for the use of QUS in the management of osteoporosis for two QUS devices sold in Switzerland. Device-specific weighted "T-score" based on the risk of osteoporotic hip fractures as well as on the prediction of DXA osteoporosis at the hip, according to the WHO definition of osteoporosis, were calculated for the Achilles (Lunar, General Electric, Madison, Wis.) and Sahara (Hologic, Waltham, Mass.) ultrasound devices. Several studies (totaling a few thousand subjects) were used to calculate age-adjusted odd ratios (OR) and area under the receiver operating curve (AUC) for the prediction of osteoporotic fracture (taking into account a weighting score depending on the design of the study involved in the calculation). The ORs were 2.4 (1.9-3.2) and AUC 0.72 (0.66-0.77), respectively, for the Achilles, and 2.3 (1.7-3.1) and 0.75 (0.68-0.82), respectively, for the Sahara device. To translate risk estimates into thresholds for clinical application, 90% sensitivity was used to define low fracture and low osteoporosis risk, and a specificity of 80% was used to define subjects as being at high risk of fracture or having osteoporosis at the hip. From the combination of the fracture model with the hip DXA osteoporotic model, we found a T-score threshold of -1.2 and -2.5 for the stiffness (Achilles) determining, respectively, the low- and high-risk subjects. Similarly, we found a T-score at -1.0 and -2.2 for the QUI index (Sahara). Then a screening strategy combining QUS, DXA, and clinical factors for the identification of women needing treatment was proposed. The application of this approach will help to minimize the inappropriate use of QUS from which the whole field currently suffers.

Sistemes integrats de gestió (Integrated Management Systems - IMS): Anàlisi empíric a les empreses de Catalunya

Projecte de recerca elaborat a partir d’una estada al Auditing and Integration of Management Systems Research Laboratory de la Universitat d’Alberta, Canadà, des de maig fins a setembre del 2007. Aquest centre porta a terme recerca de caire teòrica i bàsica aplicada a l’assegurament de la qualitat, i més concretament a l’estandardització i integració de sistemes de gestió. En primer lloc, s’han analitzat les dades obtingudes en l’estudi empíric descriptiu realitzat a Catalunya durant l’any 2005, focalitzat en els estàndards de gestió més utilitzats per les empreses catalanes, en que s’hi incloïen les normes ISO 9001, ISO 14001, OSHAS 18001 així com els nous estàndards de suport de la sèrie ISO 10000. En segon terme, i a partir d’aquest anàlisis previ, s’ha iniciat el disseny d’una metodologia flexible per a la integració dels sistemes de gestió basats en estàndards internacionals.

Role of surgery in the management of brain arteriovenous malformations: prospective cohort study.

BACKGROUND AND PURPOSE: Management of brain arteriovenous malformation (bAVM) is controversial. We have analyzed the largest surgical bAVM cohort for outcome. METHODS: Both operated and nonoperated cases were included for analysis. A total of 779 patients with bAVMs were consecutively enrolled between 1989 and 2014. Initial management recommendations were recorded before commencement of treatment. Surgical outcome was prospectively recorded and outcomes assigned at the last follow-up visit using modified Rankin Scale. First, a sensitivity analyses was performed to select a subset of the entire cohort for which the results of surgery could be generalized. Second, from this subset, variables were analyzed for risk of deficit or near miss (intraoperative hemorrhage requiring blood transfusion of ≥2.5 L, hemorrhage in resection bed requiring reoperation, and hemorrhage associated with either digital subtraction angiography or embolization). RESULTS: A total of 7.7% of patients with Spetzler-Ponce classes A and B bAVM had an adverse outcome from surgery leading to a modified Rankin Scale >1. Sensitivity analyses that demonstrated outcome results were not subject to selection bias for Spetzler-Ponce classes A and B bAVMs. Risk factors for adverse outcomes from surgery for these bAVMs include size, presence of deep venous drainage, and eloquent location. Preoperative embolization did not affect the risk of perioperative hemorrhage. CONCLUSIONS: Most of the ruptured and unruptured low and middle-grade bAVMs (Spetzler-Ponce A and B) can be surgically treated with a low risk of permanent morbidity and a high likelihood of preventing future hemorrhage. Our results do not apply to Spetzler-Ponce C bAVMs.

Multinational Firms’ Heterogeneity in Tax Responsiveness: the Role of Transfer Pricing

In this paper we show that the ability of multinational firms to manipulate transfer prices affects the tax sensitivity of foreign direct investment (FDI). We offer a model of international capital allocation where firms are heterogeneous in their ability to manipulate transfer prices. Perhaps paradoxically, we show that the ability to shift profits can make parent companies' investment more sensitive to host-country tax rates, as long as investors expect fisscal authorities to use price and profit detection methods. We then offer a comprehensive empirical study to test our predictions in the case of Japanese FDI. We exploit the finding that the unobservable ability to manipulate transfer prices is correlated with whole ownership of a±liates and R&D expenditure. Based on country, parent firm and sector characteristics, we estimate an investment equation on a sample of 3614 Japanese affiliates in 49 emerging countries. We obtain a greater semi-elasticity of investment to the statutory tax rate in a±liates that are wholly-owned and that have R&D intensive parents. We interpret these results as indirect evidence that abusive transfer pricing is one of the determinants of FDI activity.

Tax Structure, Growth and Welfare in the UK

This paper studies the quantitative implications of changes in the composition of taxes for long-run growth and expected lifetime utility in the UK economy over 1970-2005. Our setup is a dynamic stochastic general equilibrium model incorporating a detailed scal policy struc- ture, and where the engine of endogenous growth is human capital accumulation. The government s spending instruments include pub- lic consumption, investment and education spending. On the revenue side, labour, capital and consumption taxes are employed. Our results suggest that if the goal of tax policy is to promote long-run growth by altering relative tax rates, then it should reduce labour taxes while simultaneously increasing capital or consumption taxes to make up for the loss in labour tax revenue. In contrast, a welfare promoting policy would be to cut capital taxes, while concurrently increasing labour or consumption taxes to make up for the loss in capital tax revenue.

Do political incentives matter for tax policies? Ideology, opportunism and the tax structure

This paper investigates the importance of political ideology and opportunism in the choice of the tax structure. In particular, we examine the effects of cabinet ideology and elections on the distribution of the tax burden across factors of production and consumption for 21 OECD countries over the period 1970-2000 by employing four alternative cabinet ideology measures and by using the methodology of effective tax rates. There is evidence of both opportunistic and partisan effects on tax policies. More precisely, we find that left-wing governments rely more on capital relative to labor income taxation and that they tend to increase consumption taxes. Moreover, we find that income tax rates (but not consumption taxes) tend to be reduced in preelectoral periods and that capital effective tax rates (defined broadly to include taxes on selfemployed income) are reduced by more than effective labor tax rates.

Are two tax rates better than one?

Abstract: Should two–band income taxes be progressive given a general income distribution? We provide a negative answer under utilitarian and max-min welfare functions. While this result clarifies some ambiguities in the literature, it does not rule out progressive taxes in general. If we maximize total or weighted utility of the poor, as often intended by the society, progressive taxes can be justified, especially when the ‘rich’ are very rich. Under these objectives we obtain new necessary conditions for progressive taxes, which only depend on aggregate features of income distributions. The validity of these conditions is examined using plausible income distributions.