Predicting asthma control and exacerbations: chronic asthma as a complex dynamic model

PURPOSE OF REVIEW: Predicting asthma episodes is notoriously difficult but has potentially significant consequences for the individual, as well as for healthcare services. The purpose of this review is to describe recent insights into the prediction of acute asthma episodes in relation to classical clinical, functional or inflammatory variables, as well as present a new concept for evaluating asthma as a dynamically regulated homeokinetic system. RECENT FINDINGS: Risk prediction for asthma episodes or relapse has been attempted using clinical scoring systems, considerations of environmental factors and lung function, as well as inflammatory and immunological markers in induced sputum or exhaled air, and these are summarized here. We have recently proposed that newer mathematical methods derived from statistical physics may be used to understand the complexity of asthma as a homeokinetic, dynamic system consisting of a network comprising multiple components, and also to assess the risk for future asthma episodes based on fluctuation analysis of long time series of lung function. SUMMARY: Apart from the classical analysis of risk factor and functional parameters, this new approach may be used to assess asthma control and treatment effects in the individual as well as in future research trials.

Social control and smoking: Examining the moderating effects of different dimensions of relationship quality

A common form of social regulation of an individual’s health behavior is social control. The contextual model of social control assumes that higher relationship quality goes along with more beneficial effects of social control on health behavior. This study examined potential differential moderating effects of different dimensions of relationship quality on the associations between positive and negative social control and smoking behavior and hiding smoking. The sample consisted of 144 smokers (n = 72 women; mean age = 31.78, SD = 10.04) with a nonsmoking partner. Positive and negative social control, dimensions of relationship quality consensus, cohesion and satisfaction, numbers of cigarettes smoked (NCS), hiding smoking (HS), and control variables were assessed at baseline. Four weeks later NCS and HS were assessed again. Only for smokers with high consensus, but not cohesion and satisfaction, a negative association between positive control and NCS emerged. Moreover, smokers with high consensus tended to report more HS when being positively and negatively socially controlled. This also emerged for cohesion and positive control. Satisfaction with the relationship did not display any interaction effects. This study’s results emphasize the importance of differentiating not only between positive and negative social control but also between different dimensions of relationship quality in order to gain a comprehensive understanding of the dynamics in romantic dyads with regard to social regulation of behavioral change.

Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication. We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin's lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were hazard ratios for OS and tumor control as well as relative risks for complete response (CR). Meta-analyses were performed using RevMan5. Five randomized controlled trials involving 1,245 patients were included. The hazard ratio (HR) was 0.41 (95% confidence interval (CI) 0.25 to 0.66) for tumor control and 0.40 (95% CI 0.27 to 0.59) for OS for patients receiving CMT compared to chemotherapy alone. CR rates were similar between treatment groups. In sensitivity analyses another 6 trials were included that did not fulfill the inclusion criteria of our protocol but were considered relevant to the topic. These trials underlined the results of the main analysis. In conclusion, adding radiotherapy to chemotherapy improves tumor control and OS in patients with early stage Hodgkin's lymphoma.

Preliminary Experience in Treatment of Papillary and Macular Retinoblastoma: Evaluation of Local Control and Local Complications After Treatment with Linear Accelerator-Based Stereotactic Radiotherapy with Micromultileaf Collimator as Second-Line or Salvage Treatment after chemotherapy

To determine the local control and complication rates for children with papillary and/or macular retinoblastoma progressing after chemotherapy and undergoing stereotactic radiotherapy (SRT) with a micromultileaf collimator.

Variations of the Atlantic meridional overturning circulation in control and transient simulations of the last millennium

The variability of the Atlantic meridional overturing circulation (AMOC) strength is investigated in control experiments and in transient simulations of up to the last millennium using the low-resolution Community Climate System Model version 3. In the transient simulations the AMOC exhibits enhanced low-frequency variability that is mainly caused by infrequent transitions between two semi-stable circulation states which amount to a 10 percent change of the maximum overturning. One transition is also found in a control experiment, but the time-varying external forcing significantly increases the probability of the occurrence of such events though not having a direct, linear impact on the AMOC. The transition from a high to a low AMOC state starts with a reduction of the convection in the Labrador and Irminger Seas and goes along with a changed barotropic circulation of both gyres in the North Atlantic and a gradual strengthening of the convection in the Greenland-Iceland-Norwegian (GIN) Seas. In contrast, the transition from a weak to a strong overturning is induced by decreased mixing in the GIN Seas. As a consequence of the transition, regional sea surface temperature (SST) anomalies are found in the midlatitude North Atlantic and in the convection regions with an amplitude of up to 3 K. The atmospheric response to the SST forcing associated with the transition indicates a significant impact on the Scandinavian surface air temperature (SAT) in the order of 1 K. Thus, the changes of the ocean circulation make a major contribution to the Scandinavian SAT variability in the last millennium.

Disruption of the histidine triad nucleotide-binding hint2 gene in mice affects glycemic control and mitochondrial function

The histidine triad nucleotide-binding (Hint2) protein is a mitochondrial adenosine phosphoramidase expressed in liver and pancreas. Its physiological function is unknown. To elucidate the role of Hint2 in liver physiology, the Hint2 gene was deleted. Hint2(-/-) and Hint2(+/+) mice were generated in a mixed C57Bl6/J x 129Sv background. At 20 weeks, the phenotypic changes in Hint2(-/-) relative to Hint2(+/+) mice were an accumulation of hepatic triglycerides, decreased tolerance to glucose, a defective counter-regulatory response to insulin-provoked hypoglycaemia, an increase in plasma interprandial insulin but a decrease in glucose stimulated insulin secretion and defective thermoregulation upon fasting. Leptin mRNA in adipose tissue and plasma leptin were elevated. In mitochondria from Hint2(-/-) hepatocytes, state 3 respiration was decreased, a finding confirmed in HepG2 cells where HINT2 mRNA was silenced. The linked complex II to III electron transfer was decreased in Hint2(-/-) mitochondria, which was accompanied by a lower content of coenzyme Q. HIF-2α expression and the generation of reactive oxygen species were increased. Electron microscopy of mitochondria in Hint2(-/-) mice aged 12 months revealed clustered, fused organelles. The hepatic activities of 3-hydroxyacyl-CoA dehydrogenase short chain and glutamate dehydrogenase (GDH) were decreased by 68% and 60%, respectively, without a change in protein expression. GDH activity was similarly decreased in HINT2-silenced HepG2 cells. When measured in the presence of purified sirtuin 3, latent GDH activity was recovered (126% in Hint2(-/-) vs. 83% in Hint2(+/+) ). This suggests a greater extent of acetylation in Hint2(-/-) than in Hint2(+/+) . Conlusions: Hint2 positively regulates mitochondrial lipid metabolism and respiration, and glucose homeostasis. The absence of Hint2 provokes mitochondrial deformities and a change in the pattern of acetylation of selected proteins. (HEPATOLOGY 2012.).

Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 microg ethinyl estradiol and 3 mg drospirenone

BACKGROUND: The objective of this study was to compare cycle control, cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive (COC) containing 30 microg of ethinyl estradiol and 3 mg of drospirenone. METHODS: A randomized, multicentre, open-label trial in which 983 women were treated (intent-to-treat population) with NuvaRing or the COC for 13 cycles. RESULTS: Breakthrough bleeding or spotting during cycles 2-13 was in general less frequent with NuvaRing than that with the COC (4.7-10.4%) and showed a statistically significant odds ratio of 0.61 (95% confidence interval: 0.46, 0.80) with longitudinal analysis. Intended bleeding was significantly better for all cycles with NuvaRing (55.2-68.5%) than that with the COC (35.6-56.6%) (P < 0.01). Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences. CONCLUSION: NuvaRing was associated with better cycle control than the COC, and there was no clinically relevant difference between the two groups in bodyweight.