Optimal designs for health risk assessments using fractional polynomial models.

Fractional polynomials (FP) have been shown to be more flexible than polynomial models for fitting data from an univariate regression model with a continuous outcome but design issues for FP models have lagged. We focus on FPs with a single variable and construct D-optimal designs for estimating model parameters and I-optimal designs for prediction over a user-specified region of the design space. Some analytic results are given, along with a discussion on model uncertainty. In addition, we provide an applet to facilitate users find tailor made optimal designs for their problems. As applications, we construct optimal designs for three studies that used FPs to model risk assessments of (a) testosterone levels from magnesium accumulation in certain areas of the brains in songbirds, (b) rats subject to exposure of different chemicals, and (c) hormetic effects due to small toxic exposure. In each case, we elaborate the benefits of having an optimal design in terms of cost and quality of the statistical inference.

Wish to die and hasten death in palliative care: a cross-sectional study factor analysis.

OBJECTIVES: The wish to die (WTD) is a complex experience sometimes accompanied by intention to hasten death. The aim of this study is to identify the predictive factors for WTD and hastening death intention (HDI) in Spanish patients with advanced illness. METHODS: This is a subanalysis of a larger cross-sectional study conducted on patients experiencing advanced illness (N=201). Sociodemographic data and data related to symptom burden (Edmonton Symptom Assessment System-Revised), depressive and anxious symptoms (Hospital Anxiety and Depression Scale), demoralisation (Spanish version of the Demoralisation Scale), perceived loss of dignity (Patient Dignity Inventory) and WTD (Assessing Frequency and Extent of Desire to Die) were collected. The analysis used univariate and multivariate logistic regression. RESULTS: The prevalence of WTD in the sample was 18%, with 8 out of 36 patients reporting HDI. The independent factors predictive of WTD were (1) knowledge of approximate prognosis (OR=4.78; 95% CI 1.20 to 10.8; p=0.001); (2) symptom burden (OR=1.05; 95% CI 1.00 to 1.09; p=0.038); and (3) the Demoralisation Scale subsection 'lack of meaning and purpose in life' (OR=1.61; 95% CI 1.30 to 1.99; p=0.000). An independent predictive factor for HDI was the Demoralisation Scale subsection 'patients' distress and coping abilities' (OR=1.47; 95% CI 1.04 to 2.08; p=0.028), while having religious beliefs was a protective factor (OR=0.13; 95% CI0.17 to 0.97; p=0.047). CONCLUSIONS: Demoralisation was found to be the only common triggering factor for WTD and HDI, although experiences share certain features. Identification of the predictive factors for WTD and HDI may contribute to their prevention and management.

Does Delirium Phenomenology in Persons with Advanced Cancer Follow a Specific Pattern?

Objective: Recognizing delirium phenomenology (DP) aids the early diagnosis of this syndrome and improves quality of life in patients with advanced cancer. The aim of this study was to identify the neurobehavioral and cognitive patterns of delirium-related symptoms in persons with advanced cancer. Methods: We conducted an observational comparative prospective study on delirium in patients with advanced cancer in different palliative care settings, assessing the presentation/evolution of DP with the Memorial delirium assessment scale (MDAS). Results: Two hundred twenty-seven patients were enrolled on hospital/hospice admission. Of these, 57 were admitted with delirium, 170 without delirium, and 31 developed delirium during hospitalization. Of the 88 patients admitted with delirium or who developed it during hospitalization, only 32 underwent two consecutive MDAS evaluations (at diagnosis and after one week). Delirium resolved in 22 patients (first average MDAS score 10.08 vs. second 3.6 [p < 0.001]). Disorientation, short-term memory, and memory span were altered in all patients with unresolved delirium. The same features were altered in 18 (80%), 17 (80%), and 16 (70%) of the patients with resolved delirium, respectively, and in 58 (35%), 114 (67%), and 38 (23%) of no-delirium patients, respectively. Conclusion: Cognitive-related symptoms appear to be the most prevalent and earliest signs of DP in patients with advanced cancer.

Cross-sectional survey of the wish to die among palliative patients in Spain: one phenomenon, different experiences.

OBJECTIVE: Cultural backgrounds and values have a decisive impact on the phenomenon of the wish to die (WTD), and examination of this in Mediterranean countries is in its early stages. The objectives of this study were to establish the prevalence of WTD and to characterise this phenomenon in our cultural context. METHODS: A cross-sectional study with consecutive advanced inpatients was conducted. Data about WTD (Assessing Frequency & Extent of Desire to Die (AFFED) interview) and anxiety and depression (Edmonton Symptom Assessment System-revised (ESAS-r)) were collected through two face-to-face clinical encounters. Data were analysed with descriptive statistics, χ2 and analysis of variance. RESULTS: 201 patients participated and 165 (82%) completed both interviews. Prevalence of WTD was 18% (36/201) in the first interview and 16% (26/165) in the second interview (p=0.25). After the first interview, no changes in depression (p=0.60) or anxiety (p=0.90) were detected. The AFFED shows different experiences within WTD: 11% of patients reported a sporadic experience, while 7% described a persistent experience. Thinking about hastening death (HD) appeared in 8 (22%) out of 36 patients with WTD: 5 (14%) out of 36 patients considered this hypothetically but would never take action, while 3 (8%) out of 36 patients had a more structured idea about HD. In this study, no relation was detected between HD and frequency of the appearance of WTD (p=0.12). CONCLUSIONS: One in five patients had WTD. Our findings suggest the existence of different experiences within the same phenomenon, defined according to frequency of appearance and intention to hasten death. A linguistically grounded model is proposed, differentiating the experiences of the 'wish' or 'desire' to die, with or without HD ideation.

Unravelling gender-specific factors that link obesity to albuminuria.

BACKGROUND: Obesity is a major public health problem, which continues to be diagnosed and classified by BMI, excluding the most elemental concepts of the precision medicine approach. Obesity does not equally affect males and females, even with the same BMI. Microalbuminuria is a risk marker of cardiovascular disease closely related to obesity. The aim of this study was to evaluate the gender-dependent differences in the development of early obesity-related disease, focusing on pathologic microalbuminuria (PMA). MATERIAL AND METHODS: We developed a single-centre cross-sectional study including 1068 consecutive adults from May 2016 to January 2018, divided into two groups: one including the first 787 patients attended, evaluated as a description population; the second group included 281 subjects analysed as an external validation population. Collected data included medical history, anthropometric measures, abdominal bioimpedance and routine laboratory tests. RESULTS: First, we confirmed the lack of accuracy of classic obesity measures in predicting microalbuminuria. Second, we tested the utility of a tailored evaluation to predict PMA, with an area under the ROC curve of 0.78 for females and 0.82 for males. We also confirmed the different physiology of visceral adiposity for males when compared to females, in which small variations of fat mass entail major changes in the clinical repercussion. Third, we performed an external validation of our results, achieving a 77% accuracy rate. CONCLUSIONS: Our findings support that there is an individual threshold of fat amount necessary to develop obesity-dependent PMA and that gender plays a major role in the interplay between PMA and adiposity.

Trends analysis of specialized palliative care services in 51 countries of the WHO European region in the last 14 years.

BACKGROUND: Service provision is a key domain to assess national-level palliative care development. Three editions of the European Association for Palliative Care (EAPC) Atlas of Palliative Care monitored the changes in service provision across Europe since 2005. AIM: To study European trends of specialized service provision at home care teams, hospital support teams, and inpatient palliative care services between 2005 and 2019. DESIGN: Secondary analysis was conducted drawing from databases on the number of specialized services in 2005, 2012, and 2019. Ratios of services per 100,000 inhabitants and increase rates on number of services for three periods were calculated. Analysis of variance (ANOVA) analyses were conducted to determine significant changes and chi-square to identify countries accounting for the variance. Income-level and sub-regional ANOVA analysis were undertaken. SETTING: 51 countries. RESULTS: Forty-two countries (82%) increased the number of specialized services between 2005 and 2019 with changes for home care teams (104% increase-rate), inpatient services (82%), and hospital support teams (48%). High-income countries showed significant increase in all types of services (p < 0.001), while low-to-middle-income countries showed significant increase only for inpatient services. Central-Eastern European countries showed significant improvement in home care teams and inpatient services, while Western countries showed significant improvement in hospital support and home care teams. Home care was the most prominent service in Western Europe. CONCLUSION: Specialized service provision increased throughout Europe, yet ratios per 100,000 inhabitants fell below the EAPC recommendations. Western Europe ratios' achieved half of the suggested services, while Central-Eastern countries achieved only a fourth. High-income countries and Western European countries account for the major increase. Central-Eastern Europe and low-to-middle-income countries reported little increase on specialized service provision.

Optimal experimental design for cytogenetic dose-response calibration curves.

Purpose: To introduce optimal experimental design techniques in the cytogenetic biological dosimetry practice. This includes the development of a new optimality criterion for the calibration of radiation doses.Materials and methods: The most typical optimal design criterion and the one developed in this research are introduced and applied in an example from the literature. In another example from the literature, a simulation study has been performed to compare the standard error of the dose estimation using different experimental designs. An RStudio project and a GitHub project have been developed to reproduce these results.Results: In the paper, it is observed that the application of optimal experimental design techniques can reduce the standard error of biodosimetric dose estimations.Conclusions: Optimal experimental design techniques jointly with practitioners' requirements may be applied. This practice would not involve an additional laboratory work.

Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study.

BACKGROUND: Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by 18F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. METHODS: This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (> 70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2 days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. 18F-FDG-PET/CT focusing on several territories' vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68. RESULTS: The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r = 0.42 P = .02) and with 18F-FDG uptake (r = 0.38 P = .05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by 18F-FDG-PET. After a median follow-up of 1077 days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR = 1.15 P = .006). When the model was associated with the variables of interest, the risk predicted by 18F-FDG-PET was not significant. CONCLUSIONS: Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory.

Mapping Levels of Palliative Care Development in 198 Countries: The Situation in 2017.

CONTEXT: Palliative care is gaining ground globally and is endorsed in high-level policy commitments, but service provision, supporting policies, education, and funding are incommensurate with rapidly growing needs. OBJECTIVES: The objective of this study was to describe current levels of global palliative care development and report on changes since 2006. METHODS: An online survey of experts in 198 countries generated 2017 data on 10 indicators of palliative care provision, fitted to six categories of development. Factor analysis and discriminant analysis showed the validity of the categorization. Spearman correlation analyses assessed the relationship with World Bank Income Level (WBIL), Human Development Index (HDI), and Universal Health Coverage (UHC). RESULTS: Numbers (percentages) of countries in each development category were as follows: 1) no known palliative care activity, 47 (24%); 2) capacity-building, 13 (7%); 3a) isolated provision, 65 (33%); 3b) generalized provision, 22 (11%); 4a) preliminary integration into mainstream provision, 21 (11%); 4b) advanced integration, 30 (15%). Development levels were significantly associated with WBIL (rS = 0.4785), UHC (rS = 0.5558), and HDI (rS = 0.5426) with P < 0.001. Net improvement between 2006 and 2017 saw 32 fewer countries in Categories 1/2, 16 more countries in 3a/3b, and 17 more countries in 4a/4b. CONCLUSION: Palliative care at the highest level of provision is available for only 14% of the global population and is concentrated in European countries. An 87% global increase in serious health-related suffering amenable to palliative care interventions is predicted by 2060. With an increasing need, palliative care is not reaching the levels required by at least half of the global population.

Delirium Rates in Advanced Cancer Patients Admitted to Different Palliative Care Settings: Does It Make the Difference?

Background: Delirium in advanced cancer inpatient ranges between 13% and 85%. Reasons for this variability on the reported data could be related to the setting where they are admitted. Methods: This is an observational, comparative, prospective study on delirium diagnosis and delirium course of advanced cancer inpatients in two different palliative care settings. Hospice (C1) versus palliative care supportive team (C2). Differences between delirium precipitants, delirium treatment, and delirium survival were observed. Results: From 582 consecutive admissions, 494 from C1 and 88 from C2, finally 227 patients met inclusion criteria, were entered in the study. Total population delirium rate at admission, if we add both centers, was 57 patients (25%), 46 (26%) from C1 and 11 (22%) from C2; no statistically significant differences between delirium rate at admission between the two centers were found (χ2). When delirium course between delirious patients admitted in C1 and C2 was analyzed, a significantly higher rate of delirium reversibility was found in C2 [11/14 (78%)] versus [9/65 (14%)] in C1 (χ2p ≤ 0.001). Conclusion: The frequency of delirium at admission and during the hospitalization in advanced cancer patients does not seem to be related to the setting, what seems to be related is the delirium course.

Student's Inventory of Professionalism (SIP): A Tool to Assess Attitudes towards Professional Development Based on Palliative Care Undergraduate Education.

Introduction: Quality medical education, centered on a patient's needs, is crucial to develop the health professionals that our society requires. Research suggests a strong contribution of palliative care education to professionalism. The aim of this study was to design and validate a self-report inventory to measure student's professional development. Method: Sequential exploratory strategy mixed method. The inventory is built based on the themes that emerged from the analysis of four qualitative studies about nursing and medical students' perceptions related to palliative care teaching interventions (see Ballesteros et al. 2014, Centeno et al. 2014 and 2017, Rojí et al. 2017). The structure and psychometrics of the inventory obtained is tested in two different surveys with two different groups of medical students. Inventory reliability and construct validity are tested in the first survey group. To verify the inventory structure, a confirmatory factor analysis is performed in a second survey group. Results: The inventory has 33 items and seven dimensions: a holistic approach, caring for and understanding the patient, personal growth, teamwork, decision-making, patient evaluation, and being a health care professional. Cronbach's-alpha was 0.73-0.84 in all seven domains, ICC: 0.95. The confirmatory factor analysis comparative fit index (CFI) was 1 with a standardized root mean square Index 0.088 (SRMR) and obtained a 0.99 goodness-of-fit R-square coefficient. Conclusions: this new inventory is grounded on student's palliative care teaching experiences and seems to be valid to assess student's professional development.

Consensus Building on Health Indicators to Assess PC Global Development With an International Group of Experts.

CONTEXT: International consensus on indicators is necessary to standardize the global assessment of palliative care (PC) development. OBJECTIVES: To identify the best indicators to assess current national-level PC development. METHODS: Experts in PC development were invited to rate 45 indicators organized by domains of the World Health Organization Public Health Strategy in a two-round RAND/UCLA-modified Delphi process. In the first round, experts rated indicators by relevance, measurability, and feasibility (1-9). Ratings were used to calculate a global score (1-9). Indicators scoring >7 proceeded to the second round for fine-tuning of global scores. Median, confidence interval, Content Validity Index, and Disagreement Index were calculated. Indicators scoring a lower limit 95% confidence interval of ≥7 and a Content Validity Index of ≥0.30 were selected. RESULTS: 24 experts representing five continents and several organizations completed the study. 25 indicators showed a high content validity and level of agreement. Policy indicators (n = 8) included the existence of designated staff in the National Ministry of Health and the inclusion of PC services in the basic health package and in the primary care level list of services. Education indicators (n = 4) focused on processes of official specialization for physicians, inclusion of teaching at the undergraduate level, and PC professorship. Use of medicines indicators (n = 4) consisted of opioid consumption, availability, and prescription requirements. Services indicators (n = 6) included number and type of services for adults and children. Additional indicators for professional activity (n = 3) were identified. CONCLUSION: The first list including 25 of the best indicators to evaluate PC development at a national level has been identified.

Multicenter Study of the Psychometric Properties of the New Demoralization Scale (DS-II) in Spanish-Speaking Advanced Cancer Patients.

CONTEXT: Demoralization is a state of existential distress in patients with advanced illness, typically with coping difficulties, feelings of loss of sense, and purpose in life and despair, among other things. The New Demoralization Scale (DS-II) is an evaluation tool for this syndrome, which has recently been reformulated on a shorter scale. OBJECTIVES: The objective of this study was to obtain a Spanish version of the DS-II and to assess its psychometric properties in advanced cancer patients in Spain and a number of Latin American countries. METHODS: Following a translation-back translation process, a validation study and a confirmatory analysis using structural equation models with their corresponding latent constructs were undertaken. Patients completed the DS-II in Spanish (DS-II (es)), the Hospital Anxiety and Depression Scale, and the Edmonton Symptom Assessment System-revised. Reliability was studied according to internal consistency; construct validity and concurrent validity with the Hospital Anxiety and Depression Scale and the Edmonton Symptom Assessment System-revised; discriminant validity using the Karnofsky Performance Status scale; and feasibility, with response ratio and required time. Cutoff points were established, and sensitivity and specificity were studied. RESULTS: The DS-II (es) was obtained. One hundred fifty patients completed the validation study. The confirmatory analysis showed coherence, and all items correlated positively with their subscales and with the overall scale. Cronbach's alpha for the DS-II (es) was 0.88, for the sense and purpose subscale 0.83, and for the coping ability 0.79. Demoralization correlated significantly with emotional distress (rho = 0.73, P < 0.001). The tool distinguished between patients with diverse functional levels (rho = -0.319, P = 0.001). Cutoff points at 10 and 20 out of 32 were established. The scale showed high sensitivity (81.97%) and specificity (80.90%). The prevalence of demoralization was 33% in our sample. CONCLUSION: The Spanish version of the new Kissane DS-II demoralization scale has shown to be valid, reliable, and feasible with adequate psychometric properties.

An Analysis of Palliative Care Development in Africa: A Ranking Based on Region-Specific Macroindicators.

CONTEXT: To date, there is no study comparing palliative care (PC) development among African countries. OBJECTIVES: To analyze comparatively PC development in African countries based on region-specific indicators. METHODS: Data were obtained from the African PC Association Atlas of PC in Africa, and a comparative analysis was conducted. Nineteen indicators were developed and defined through qualitative interviews with African PC experts and a two-round modified Delphi consensus process with international experts on global PC indicators. Indicators were grouped by the World Health Organization public health strategy for PC dimensions. These indicators were then sent as a survey to key informants in 52 of 54 African countries. Through an expert weighting process and ratings from the modified Delphi, weights were assigned to each indicator. RESULTS: Surveys were received from 89% (48 of 54) of African countries. The top three countries in overall PC development were, in order, Uganda, South Africa, and Kenya. Variability existed by dimension. The top three countries in specialized services were Uganda, South Africa, and Nigeria; in policies, it was Botswana followed by parity among Ethiopia, Rwanda, and Swaziland; in medicines, it was Swaziland, South Africa, then Malawi; and in education, it was equivalent between Uganda and Kenya, then Ghana and Zambia. CONCLUSION: Uganda, South Africa, and Kenya are the highest performing countries and were the only ones with composite scores greater than 0.5 (50%). However, not one country universally supersedes all others across all four PC dimensions. The breakdown of rankings by dimension highlights where even high-performing African countries can focus their efforts to further PC development.

Publications on Palliative Care Development Can Be Used as an Indicator of Palliative Care Development in Africa.

BACKGROUND: Palliative care (PC) research in Africa has been proposed as a fifth dimension of the World Health Organization PC Public Health Strategy. We conducted a scoping review of published articles (2005-2016) on palliative care development (PCD) in African countries. Forty-seven articles were found across 26 countries. OBJECTIVE: To study whether the number of published articles on PCD in countries in Africa can be used as an indicator of PCD. DESIGN: This is a secondary analysis of a completed scoping review. MEASUREMENTS: Spearman correlations were applied to the number of published articles ("published articles") and the number of published articles with a coauthor from a high-income country (HIC) ("HIC published articles") with level of PCD using Lynch et al's updated world map (PC World Map) as a proxy. A subanalysis was undertaken for Anglophone versus non-Anglophone countries. RESULTS: There were positive Spearman correlations (r) between the PC World Map's levels and published articles (r = 0.73; p < 0.001), and with HIC published articles (r = 0.68; p < 0.001). For Anglophone countries, the r was statistically significant (p < 0.001) at 0.69 and 0.70, versus 0.58 and 0.45 for non-Anglophone countries for published articles and HIC published articles, respectively. Kruskal-Wallis test showed a statistically significant difference between Anglophone and non-Anglophone countries for both published articles and HIC published articles (p < 0.01). CONCLUSION: Published articles and HIC published articles on PCD in Africa had strong positive r's with the PC World Map. These measures may be considered as two indicators of PCD for countries in Africa, particularly for Anglophone countries.

18F-fluorodeoxyglucose positron emission tomography in the diagnosis of malignancy in patients with paraneoplastic neurological syndrome: a systematic review and meta-analysis.

PURPOSE: The detection of occult cancer in patients suspected of having a paraneoplastic neurological syndrome (PNS) poses a diagnostic challenge. The aim of our study was to perform a systematic review and meta-analysis to assess the diagnostic performance of FDG PET for the detection of occult malignant disease responsible for PNS. METHODS: A systematic review of the literature (MEDLINE, EMBASE, Cochrane, and DARE) was undertaken to identify studies published in any language. The search strategy was structured after addressing clinical questions regarding the validity or usefulness of the test, following the PICO framework. Inclusion criteria were studies involving patients with PNS in whom FDG PET was performed to detect malignancy, and which reported sufficient primary data to allow calculation of diagnostic accuracy parameters. When possible, a meta-analysis was performed to calculate the joint sensitivity, specificity, and detection rate for malignancy (with 95% confidence intervals [CIs]), as well as a subgroup analysis based on patient characteristics (antibodies, syndrome). RESULTS: The comprehensive literature search revealed 700 references. Sixteen studies met the inclusion criteria and were ultimately selected. Most of the studies were retrospective (12/16). For the quality assessment, the QUADAS-2 tool was applied to assess the risk of bias. Across 16 studies (793 patients), the joint sensitivity, specificity, and detection rate for malignancy with FDG PET were 0.87 (95% CI: 0.80-0.93), 0.86 (95% CI: 0.83-0.89), and 14.9% (95% CI: 11.5-18.7), respectively. The area under the curve (AUC) of the summary ROC curve was 0.917. Homogeneity of results was observed for sensitivity but not for specificity. Some of the individual studies showed large 95% CIs as a result of small sample size. CONCLUSIONS: The results of our meta-analysis reveal high diagnostic performance of FDG PET in the detection of malignancy responsible for PNS, not affected by the presence of onconeural antibodies or clinical characteristics.

KL-optimal experimental design for discriminating between two growth models applied to a beef farm.

The body mass growth of organisms is usually represented in terms of what is known as ontogenetic growth models, which represent the relation of dependence between the mass of the body and time. The paper is concerned with a problem of finding an optimal experimental design for discriminating between two competing mass growth models applied to a beef farm. T-optimality was first introduced for discrimination between models but in this paper, KL-optimality based on the Kullback-Leibler distance is used to deal with correlated obsevations since, in this case, observations on a particular animal are not independent.

Basal ¹8F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer.

AIM: To explore the relationship between basal (18) F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). METHODS: This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent (18) F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. RESULTS: The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. CONCLUSION: PET imaging with (18) F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively.

Optimal experimental designs for accelerated failure time with Type I and random censoring.

Proportional Hazards models have been widely used to analyze survival data. In many cases survival data do not verify the assumption of proportional hazards. An alternative to the PH models with more relaxed conditions are Accelerated Failure Time models. These models are fairly commonly used in the field of manufacturing, but they are more and more frequent for modeling clinical trial data. They focus on the direct effect of the explanatory variables on the survival function allowing an easier interpretation of the effect of the corresponding covariates on the survival time. Optimal experimental designs are computed in this framework for Type I and random arrival. The results are applied to clinical models used to prevent tuberculosis in Ugandan adults infected with HIV.