A novel automated platform for quantifying the extent of skeletal tumour involvement in prostate cancer patients using the Bone Scan Index

Background

Nocturia, a common complaint in aging men and women, is frequently cited as the cause of nocturnal awakenings leading to sleep loss, daytime fatigue, and reduced quality of life (QOL).

Objective

Investigate the association of nocturia with QOL and depressive symptoms among men and women.

Design, setting, and participants

A population-based epidemiologic survey of urologic symptoms among persons aged 30-79 yr. A multistage stratified cluster sample design was used to randomly sample 5503 residents of Boston, MA, USA.

Measurements

Nocturia was defined as a self-report of two or more voiding episodes nightly or having to get up to urinate more than once nightly “fairly often,” “usually,” or “almost always.” QOL was assessed using the physical and mental health component scores of the 12-Item Short-Form Survey (SF-12). Depression was assessed using the Center for Epidemiological Studies Depression Scale. Multiple linear and logistic regression methods were used to model the nocturia and QOL association and to control for confounders.

Results and limitations

Nocturia was associated with decreased SF-12 scores for both the physical and mental health components after multivariate adjustment. Nocturia was also associated with increased odds of depressive symptoms (men: adjusted odds ratio [OR]: 2.79; 95% confidence interval [CI], 1.81-4.31; women: adjusted OR: 1.80; 95% CI, 1.29-2.51). Among women who reported sleep interference due to urologic symptoms, nocturia was associated with a threefold increase in odds of depression. In this cross-sectional analysis, the temporal sequence of causality of the nocturia and depression association could not be assessed.

Conclusions

Nocturia is associated with decreased QOL and with an increased prevalence of depressive symptoms in both men and women.     

Effects of a mandatory basic life support training programme on the no-flow fraction during in-hospital cardiac resuscitation: An observational study

Aim of the study

Many hospitals have basic life support (BLS) training programmes, but the effects on the quality of chest compressions are unclear. This study aimed to evaluate the no-flow fraction (NFF) during BLS provided by standard care nursing teams over a five-year observation period during which annual participation in the BLS training was mandatory.

Methods

All healthcare professionals working at Dresden University Hospital were instructed in BLS and automated external defibrillator (AED) use according to the current European Resuscitation Council guidelines on an annual basis. After each cardiac arrest occurring on a standard care ward, AED data were analyzed. The time without chest compressions during the period without spontaneous circulation (i.e., the no-flow fraction) was calculated using thoracic impedance data.

Results

For each year of the study period (2008–2012), a total of 1454, 1466, 1487, 1432, and 1388 health care professionals, respectively, participated in the training. The median no-flow fraction decreased significantly from 0.55 [0.42; 0.57] (median [25‰; 75‰]) in 2008 to 0.3 [0.28; 0.35] in 2012. Following revision of the BLS curriculum after publication of the 2010 guidelines, cardiac arrest was associated with a higher proportion of patients achieving ROSC (72% vs. 48%, P = 0.025) but not a higher survival rate to hospital discharge (35% vs. 19%, P = 0.073).

Conclusion

The NFF during in-hospital cardiac resuscitation decreased after establishment of a mandatory annual BLS training for healthcare professionals. Following publication of the 2010 guidelines, more patients achieved ROSC after in-hospital cardiac arrest.     

Alternative Strategies for Proof-of-Principle Studies of Antibacterial Agents

The proof that a new antibacterial agent is not only active in vitro but also effective in vivo under clinically relevant conditions is currently provided (i) by using appropriate nonclinical models of infection and pharmacokinetic-pharmacodynamic (PK-PD) analysis providing evidence of the likelihood of clinical efficacy and (ii) by examining the study drug in exploratory clinical trials, as well as dose and schedule finding during phase II of clinical development. This approach is both time-consuming and costly. Furthermore, PK-PD targets for any novel antibacterial agent cannot be derived from studies with experimental animals. Therefore, alternative strategies have to be identified to prove the principle that a novel antibacterial agent is active under clinically relevant conditions. This review summarizes evidence that the quantitative analysis of shifts in the viable counts of pathogens in infected patients or the evaluation of the PD effect of an investigational agent on indicator organisms of the human resident microflora or colonizers of healthy volunteers, if paralleled with PK monitoring of serum and the target site, provides an alternative to a classical proof-of-principle study in the course of a phase II study program.     

Enzalutamide After Docetaxel and Abiraterone Therapy in Metastatic Castration-Resistant Prostate Cancer

Introduction

Enzalutamide is a novel antiandrogen which is approved for the treatment of metastatic, castration-resistant prostate cancer (mCRPC) after taxane-based chemotherapy. The efficacy of enzalutamide after the sequence docetaxel and abiraterone is not proven.

Methods

Thirty-five mCRPC patients in the German compassionate use program, who received enzalutamide after progression with taxane-based chemotherapy and abiraterone were prospectively evaluated. The endpoints of the study were overall survival, radiologic progression-free survival and safety.

Results

The median treatment duration on enzalutamide was 2.8 months. The median overall survival was 7.5 months [95% confidence interval (CI) 4.7–10.3] while median progression-free survival assessed by imaging was 3.1 months (95% CI 1.4–4.8). The most common toxicities of all grades were anemia and weight loss.

Conclusion

Although the results are limited by a small patient number, the consecutive use of enzalutamide and abiraterone after taxane-based chemotherapy shows a modest clinical activity. Thus, sequence therapy alternating between chemotherapy and antihormonal drugs might be a more promising approach in mCRPC treatment.     

Customizing laboratory mice by modifying gut microbiota and host immunity in an early “window of opportunity”

We recently investigated how post-natal microbial gut colonization is important for the development of the immune system, especially in the systemic compartments. This addendum presents additional data which in accordance with our previous findings show that early life microbial colonization is critical for a fine-tuned immune homeostasis to develop also in the intestinal environment. A generalized reduction in the expression of immune signaling related genes in the small intestine may explain previously shown increased systemic adaptive immune reactivity, if the regulatory cross-talk between intra- and extra-intestinal immune cells is immature following a neonatal germ-free period. These findings are furthermore discussed in the context of recently published results on how lack of microbial exposure in the neonatal life modifies disease expression in rodents used as models mimicking human inflammatory diseases. In particular, with a focus on how these interesting findings could be used to optimize the use of rodent models.     

Real-time 3D imaging of Haines jumps in porous media flow

Newly developed high-speed, synchrotron-based X-ray computed microtomography enabled us to directly image pore-scale displacement events in porous rock in real time. Common approaches to modeling macroscopic fluid behavior are phenomenological, have many shortcomings, and lack consistent links to elementary pore-scale displacement processes, such as Haines jumps and snap-off. Unlike the common singular pore jump paradigm based on observations of restricted artificial capillaries, we found that Haines jumps typically cascade through 10–20 geometrically defined pores per event, accounting for 64% of the energy dissipation. Real-time imaging provided a more detailed fundamental understanding of the elementary processes in porous media, such as hysteresis, snap-off, and nonwetting phase entrapment, and it opens the way for a rigorous process for upscaling based on thermodynamic models.