Differences in Time to Disease Progression Do Not Predict for Cancer-specific Survival in Patients Receiving Immediate or Deferred Androgen-deprivation Therapy for Prostate Cancer: Final Results of EORTC Randomized Trial 30891 with 12 Years of Follow-up

BACKGROUND Trials assessing the benefit of immediate androgen-deprivation therapy (ADT) for treating prostate cancer (PCa) have often done so based on differences in detectable prostate-specific antigen (PSA) relapse or metastatic disease rates at a specific time after randomization. OBJECTIVE Based on the long-term results of European Organization for Research and Treatment of Cancer (EORTC) trial 30891, we questioned if differences in time to progression predict for survival differences. DESIGN, SETTING, AND PARTICIPANTS EORTC trial 30891 compared immediate ADT (n=492) with orchiectomy or luteinizing hormone-releasing hormone analog with deferred ADT (n=493) initiated upon symptomatic disease progression or life-threatening complications in randomly assigned T0-4 N0-2 M0 PCa patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Time to first objective progression (documented metastases, ureteric obstruction, not PSA rise) and time to objective castration-resistant progressive disease were compared as well as PCa mortality and overall survival. RESULTS AND LIMITATIONS After a median of 12.8 yr, 769 of the 985 patients had died (78%), 269 of PCa (27%). For patients receiving deferred ADT, the overall treatment time was 31% of that for patients on immediate ADT. Deferred ADT was significantly worse than immediate ADT for time to first objective disease progression (p<0.0001; 10-yr progression rates 42% vs 30%). However, time to objective castration-resistant disease after deferred ADT did not differ significantly (p=0.42) from that after immediate ADT. In addition, PCa mortality did not differ significantly, except in patients with aggressive PCa resulting in death within 3-5 yr after diagnosis. Deferred ADT was inferior to immediate ADT in terms of overall survival (hazard ratio: 1.21; 95% confidence interval, 1.05-1.39; p [noninferiority]=0.72, p [difference] = 0.0085). CONCLUSIONS This study shows that if hormonal manipulation is used at different times during the disease course, differences in time to first disease progression cannot predict differences in disease-specific survival. A deferred ADT policy may substantially reduce the time on treatment, but it is not suitable for patients with rapidly progressing disease.

Arbeitslosigkeit und Bildungschancen von Kindern im Transformationsprozess. Eine empirische Studie über die Auswirkungen sozio-ökonomischer Deprivation auf intergenerationale Bildungsvererbung

Wie wirkt sich Arbeitslosigkeit ostdeutscher Eltern auf Bildungschancen von Kindern im gesellschaftlichen Umbruch aus? Es wird ein theoretisches Modell entwickelt, das relevante Mechanismen der Bildungsentscheidung sowohl auf der Ebene des Familienhaushaltes, insbesondere der Eltern-Kind-Beziehungen, als auch auf der individuellen Ebene des Kindes berücksichtigt. Neben Einkommensverlusten sind auf der Haushaltsebene Kapazitäten für die Anpassung und Verarbeitung von Arbeitslosigkeit, die Beeinträchtigung des Familienklimas, Störung der Kommunikation zwischen Eltern und Kindern wichtige Faktoren, die die Bildungsentscheidungen beim Übergang auf das Gymnasium modifizieren. Darüber hinaus beeinträchtigt auch die Abnahme des sozialen und kulturellen Kapitals des Elternhauses infolge von Arbeitslosigkeit die persönliche Entwicklung des Kindes und dessen Schulleistungen. Mit Längsschnittdaten über 327 Familien und 569 Kinder in Dresden wurde festgestellt, dass häufige wie langanhaltende Arbeitslosigkeit der Eltern die Bildungschancen betroffener Kinder verschlechtert. Insgesamt sind soziales und kulturelles Kapital des Elternhauses weitaus bedeutsamer für Bildungschancen als sozio-ökonomische Verluste im Transformationsprozess.

Harte Zeiten für Familien. Theoretische Überlegungen und empirische Analysen zu Auswirkungen von Arbeitslosigkeit und sozio-ökonomischer Deprivation auf die Qualität familialer Beziehungen Dresdner Familien

Ziel des vorliegenden Beitrages ist es, die Auswirkungen der Arbeitslosigkeit von Eltern und sozio-ökonomischer Deprivation auf das Familienklima zu beschreiben. Dabei stehen die Mechanismen, welche zwischen dem Ereignis Arbeitslosigkeit, dessen Bewältigung, deren Konsequenzen und der Beeinträchtigung des Familienklimas wirken, im Mittelpunkt unseres Interesses. Für die empirischen Analysen verwenden wir Daten einer postalischen Befragung von Dresdner Haushalten, welche im November 1997 durchgeführt wurde. Neben mehrfacher Arbeitslosigkeit und sozio-ökonomischer Deprivation sind vor allem bildungs- und klassenspezifische Bewältigungsressourcen und Beziehungsstrukturen für eine Beeinträchtigung des Familienklimas verantwortlich. Aber auch Aspekte der elterlichen Partnerschaft sowie vor allem die psycho-soziale Verarbeitung der Veränderungen im Familienkontext sind wichtige Mechanismen, welche den Einfluß von Arbeitslosigkeit auf die Qualität der familialen Beziehungen moderieren.

More Money, Fewer Problems? Cross-Level Effects of Economic Deprivation on Political Representation

While equal political representation of all citizens is a fundamental democratic goal, it is hampered empirically in a multitude of ways. This study examines how the societal level of economic inequality affects the representation of relatively poor citizens by parties and governments. Using CSES survey data for citizens’ policy preferences and expert placements of political parties, empirical evidence is found that in economically more unequal societies, the party system represents the preferences of relatively poor citizens worse than in more equal societies. This moderating effect of economic equality is also found for policy congruence between citizens and governments, albeit slightly less clear-cut.

Combining Enzalutamide with Abiraterone, Prednisone, and Androgen Deprivation Therapy in the STAMPEDE Trial.

There are compelling reasons to study the addition of both enzalutamide and abiraterone, in combination, to standard-of-care for hormone-naïve prostate cancer. Through a protocol amendment, this will be assessed in the STAMPEDE trial, with overall survival as primary outcome measure.

Multimodal treatment for high-risk prostate cancer with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel and long-term androgen deprivation therapy: results of a prospective phase II trial.

BACKGROUND The optimal management of high-risk prostate cancer remains uncertain. In this study we assessed the safety and efficacy of a novel multimodal treatment paradigm for high-risk prostate cancer. METHODS This was a prospective phase II trial including 35 patients with newly diagnosed high-risk localized or locally advanced prostate cancer treated with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel-based chemotherapy and long-term androgen deprivation therapy. Primary endpoint was acute and late toxicity evaluated with the Common Terminology Criteria for Adverse Events version 3.0. Secondary endpoint was biochemical and clinical recurrence-free survival explored with the Kaplan-Meier method. RESULTS Acute gastro-intestinal and genito-urinary toxicity was grade 2 in 23% and 20% of patients, and grade 3 in 9% and 3% of patients, respectively. Acute blood/bone marrow toxicity was grade 2 in 20% of patients. No acute grade ≥ 4 toxicity was observed. Late gastro-intestinal and genito-urinary toxicity was grade 2 in 9% of patients each. No late grade ≥ 3 toxicity was observed. Median follow-up was 63 months (interquartile range 31-79). Actuarial 5-year biochemical and clinical recurrence-free survival rate was 55% (95% confidence interval, 35-75%) and 70% (95% confidence interval, 52-88%), respectively. CONCLUSIONS In our phase II trial testing a novel multimodal treatment paradigm for high-risk prostate cancer, toxicity was acceptably low and mid-term oncological outcome was good. This treatment paradigm, thus, may warrant further evaluation in phase III randomized trials.

A novel multidimensional geriatric screening tool in the ED: evaluation of feasibility and clinical relevance

PURPOSES Geriatric problems frequently go undetected in older patients in emergency departments (EDs), thus increasing their risk of adverse outcomes. We evaluated a novel emergency geriatric screening (EGS) tool designed to detect geriatric problems. BASIC PROCEDURES The EGS tool consisted of short validated instruments used to screen 4 domains (cognition, falls, mobility, and activities of daily living). Emergency geriatric screening was introduced for ED patients 75 years or older throughout a 4-month period. We analyzed the prevalence of abnormal EGS and whether EGS increased the number of EGS-related diagnoses in the ED during the screening, as compared with a preceding control period. MAIN FINDINGS Emergency geriatric screening was performed on 338 (42.5%) of 795 patients presenting during screening. Emergency geriatric screening was unfeasible in 175 patients (22.0%) because of life-threatening conditions and was not performed in 282 (35.5%) for logistical reasons. Emergency geriatric screening took less than 5 minutes to perform in most (85.8%) cases. Among screened patients, 285 (84.3%) had at least 1 abnormal EGS finding. In 270 of these patients, at least 1 abnormal EGS finding did not result in a diagnosis in the ED and was reported for further workup to subsequent care. During screening, 142 patients (42.0%) had at least 1 diagnosis listed within the 4 EGS domains, significantly more than the 29.3% in the control period (odds ratio 1.75; 95% confidence interval, 1.34-2.29; P<.001). Emergency geriatric screening predicted nursing home admission after the in-hospital stay (odds ratio for ≥3 vs <3 abnormal domains 12.13; 95% confidence interval, 2.79-52.72; P=.001). PRINCIPAL CONCLUSIONS The novel EGS is feasible, identifies previously undetected geriatric problems, and predicts determinants of subsequent care.

Clitics, affixes, and wordhood in Garifuna (Arawak): A multidimensional continuum of morphosyntactic boundness

Recent research on wordhood and morphosyntactic boundness suggests that the domains word and clitic do not lend themselves to cross-linguistic categorization but must be defined language specifically. In most languages, it is necessary to define word on two separate levels, the phonological word (p-word) and the grammatical word (g-word), and to describe mismatches between the two. This paper defines those domains for Garifuna, an Arawak language spoken in Honduras, Central America. Garifuna has auxiliary and classifier constructions which make up two p-words, and only one g-word. P-words made up of more than one g-word involve second position enclitics, word scope clitics, and proclitic connectives and prepositions. Garifuna clitics are typically unstressed, able to attach to hosts of any word class and able to string together into clusters. Enclitics are used to express tense-aspect, modality, and adverbial meanings, among others. In other languages, clitic clusters tend to display a fixed order; Garifuna clitic order seems quite free, although certain orders are preferred. Also, contrary to cross-linguistic tendencies, proclitic connectives can act as hosts for enclitic clusters, contradicting the commonly used definition of clitics as phonologically weak elements that need to attach to a host to form a p-word; such clitic-only p-words are problematic for traditional definitions of clitics.

Pulse-shaping assisted multidimensional coherent electronic spectroscopy

Understanding nuclear and electronic dynamics of molecular systems has advanced considerably by probing their nonlinear responses with a suitable sequence of pulses. Moreover, the ability to control crucial parameters of the excitation pulses, such as duration, sequence, frequency, polarization, slowly varying envelope, or carrier phase, has led to a variety of advanced time-resolved spectroscopic methodologies. Recently, two-dimensional electronic spectroscopy with ultrashort pulses has become a more and more popular tool since it allows to obtain information on energy and coherence transfer phenomena, line broadening mechanisms, or the presence of quantum coherences in molecular complexes. Here, we present a high fidelity two-dimensional electronic spectroscopy setup designed for molecular systems in solution. It incorporates the versatility of pulse-shaping methods to achieve full control on the amplitude and phase of the individual exciting and probing pulses. Selective and precise amplitude- and phase-modulation is shown and applied to investigate electronic dynamics in several reference molecular systems.

Synergistic action of image-guided radiotherapy and androgen deprivation therapy.

The combined use of androgen deprivation therapy (ADT) and image-guided radiotherapy (IGRT) can improve overall survival in aggressive, localized prostate cancer. However, owing to the adverse effects of prolonged ADT, it is imperative to identify the patients who would benefit from this combined-modality therapy relative to the use of IGRT alone. Opportunities exist for more personalized approaches in treating aggressive, locally advanced prostate cancer. Biomarkers--such as disseminated tumour cells, circulating tumour cells, genomic signatures and molecular imaging techniques--could identify the patients who are at greatest risk for systemic metastases and who would benefit from the addition of systemic ADT. By contrast, when biomarkers of systemic disease are not present, treatment could proceed using local IGRT alone. The choice of drug, treatment duration and timing of ADT relative to IGRT could be predicated on these personalized approaches to prostate cancer medicine. These novel treatment intensification and reduction strategies could result in improved prostate-cancer-specific survival and overall survival, without incurring the added expense of metabolic syndrome and other adverse effects of ADT in all patients.

The spectrum of the non-rapid eye movement sleep electroencephalogram following total sleep deprivation is trait-like

The sleep electroencephalogram (EEG) spectrum is unique to an individual and stable across multiple baseline recordings. The aim of this study was to examine whether the sleep EEG spectrum exhibits the same stable characteristics after acute total sleep deprivation. Polysomnography (PSG) was recorded in 20 healthy adults across consecutive sleep periods. Three nights of baseline sleep [12 h time in bed (TIB)] following 12 h of wakefulness were interleaved with three nights of recovery sleep (12 h TIB) following 36 h of sustained wakefulness. Spectral analysis of the non-rapid eye movement (NREM) sleep EEG (C3LM derivation) was used to calculate power in 0.25 Hz frequency bins between 0.75 and 16.0 Hz. Intraclass correlation coefficients (ICCs) were calculated to assess stable individual differences for baseline and recovery night spectra separately and combined. ICCs were high across all frequencies for baseline and recovery and for baseline and recovery combined. These results show that the spectrum of the NREM sleep EEG is substantially different among individuals, highly stable within individuals and robust to an experimental challenge (i.e. sleep deprivation) known to have considerable impact on the NREM sleep EEG. These findings indicate that the NREM sleep EEG represents a trait.

Differences Between Monetary and Multidimensional Poverty in the Lao PDR: Implications for Targeting of Poverty Reduction Policies and Interventions

This study compares monetary and multidimensional poverty measures for the Lao People’s Democratic Republic. Using household data of 2007/2008, we compare the empirical outcomes of the country’s current official monetary poverty measure with those of a multidimensional poverty measure. We analyze which population subgroups are identified as poor by both measures and thus belong to the category of the poorest of the poor; and we look at which subgroups are identified as poor by only one of the measures and belong either to the category of the income-poor (identified as poor only by the monetary measure) or to that of the overlooked poor (identified as poor only by the multidimensional poverty measure). Furthermore, we examined drivers of these differences using a multinomial regression model and found that monetary poverty does not capture the multiple deprivations of ethnic minorities, who are only identified as poor when using a multidimensional poverty measure. We conclude that complementing the monetary poverty measure with a multidimensional poverty index would enable more effective targeting of poverty reduction efforts.