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.

Variability of lung function predicts loss of asthma control following withdrawal of inhaled corticosteroid treatment

BACKGROUND One aspect of a multidimensional approach to understanding asthma as a complex dynamic disease is to study how lung function varies with time. Variability measures of lung function have been shown to predict response to beta(2)-agonist treatment. An investigation was conducted to determine whether mean, coefficient of variation (CV) or autocorrelation, a measure of short-term memory, of peak expiratory flow (PEF) could predict loss of asthma control following withdrawal of regular inhaled corticosteroid (ICS) treatment, using data from a previous study. METHODS 87 adult patients with mild to moderate asthma who had been taking ICS at a constant dose for at least 6 months were monitored for 2-4 weeks. ICS was then withdrawn and monitoring continued until loss of control occurred as per predefined criteria. Twice-daily PEF was recorded during monitoring. Associations between loss of control and mean, CV and autocorrelation of morning PEF within 2 weeks pre- and post-ICS withdrawal were assessed using Cox regression analysis. Predictive utility was assessed using receiver operator characteristics. RESULTS 53 out of 87 patients had sufficient PEF data over the required analysis period. The mean (389 vs 370 l/min, p<0.0001) and CV (4.5% vs 5.6%, p=0.007) but not autocorrelation of PEF changed significantly from prewithdrawal to postwithdrawal in subjects who subsequently lost control, and were unaltered in those who did not. These changes were related to time to loss of control. CV was the most consistent predictor, with similar sensitivity and sensitivity to exhaled nitric oxide. CONCLUSION A simple, easy to obtain variability measure of daily lung function such as the CV may predict loss of asthma control within the first 2 weeks of ICS withdrawal.

Responses to Central Oxotremorine and Scopolamine Support the Cholinergic Control of Male Mating Behavior in Hamsters

The responses of hamsters to intracranial injections of the cholinergic agonist oxotremorine (OXO) implicate cholinergic mechanisms in the medial preoptic area (MPOA) in the control of male mating behavior. To extend these observations, we ran three studies of responses to cholinergic drugs delivered singly or in combination to the vicinity of the MPOA. The first tested responses to OXO, confirming its ability to reduce the postejaculatory interval. The second complemented the first by examining responses to MPOA microinjections of the cholinergic antagonist scopolamine (SCO). These caused several changes revolving around intromission. These included increases in intromission frequency and ejaculation latency. They also included a change in the patterning of intromissions, marked by continuous strings without the usual separation by dismounts. The final study resembled the others in examining the effects of MPOA injections of OXO and SCO but focused on the ability of each drug to antagonize responses to the other. Most of the responses to OXO and SCO individually replicated earlier findings, though the measures examined here also permitted the description of effects on some noncopulatory sexual behaviors, specifically the male's inspection of the female. However, the most interesting results may be those suggesting asymmetry in the responses to the addition of the second drug: Whereas responses to OXO tended to be antagonized by SCO, OXO was less effective at counteracting responses to SCO. Though the explanation of this asymmetry is not completely clear, it is consistent with previous suggestions of differences in the affinities of these drugs for subtypes of muscarinic receptors. Therefore, it suggests that the cholinergic synapses and circuits controlling distinct elements of male behavior could differ in their dependence on these receptors. Copyright 2013 Elsevier Inc. All rights reserved.

Feasibility of Wii Fit Training to Improve Clinical Measures of Balance in Older Adults

Background and purpose: Numerous interventions have been proposed to improve balance in older adults with varying degrees of success. A novel approach may be to use an off-the-shelf video game system utilizing real-time force feedback to train older adults. The purpose of this study is to investigate the feasibility of using Nintendo's Wii Fit for training to improve clinical measures of balance in older adults and to retain the improvements after a period of time. Methods: Twelve healthy older adults (aged >70 years) were randomly divided into two groups. The experimental group completed training using Nintendo's Wii Fit game three times a week for 3 weeks while the control group continued with normal activities. Four clinical measures of balance were assessed before training, 1 week after training, and 1 month after training: Berg Balance Scale (BBS), Fullerton Advanced Balance (FAB) scale, Functional Reach (FR), and Timed Up and Go (TUG). Friedman two-way analysis of variance by ranks was conducted on the control and experimental group to determine if training using the Wii Balance Board with Wii Fit had an influence on clinical measures of balance. Results: Nine older adults completed the study (experimental group n = 4, control group n = 5). The experimental group significantly increased their BBS after training while the control group did not. There was no significant change for either group with FAB, FR, and TUG. Conclusion: Balance training with Nintendo's Wii Fit may be a novel way for older adults to improve balance as measured by the BBS.

Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control

Since 1987, when bovine spongiform encephalopathy (BSE) emerged as a novel disease in cattle, enormous efforts were undertaken to monitor and control the disease in ruminants worldwide. The driving force was its high economic impact, which resulted from trade restrictions and the loss of consumer confidence in beef products, the latter because BSE turned out to be a fatal zoonosis, causing variant Creutzfeldt-Jakob disease in human beings. The ban on meat and bone meal in livestock feed and the removal of specified risk materials from the food chain were the main measures to successfully prevent infection in cattle and to protect human beings from BSE exposure. However, although BSE is now under control, previously unknown, so-called atypical transmissible spongiform encephalopathies (TSEs) in cattle and small ruminants have been identified by enhanced disease surveillance. This report briefly reviews and summarizes the current level of knowledge on the spectrum of TSEs in cattle and small ruminants and addresses the question of the extent to which such atypical TSEs have an effect on disease surveillance and control strategies.

Prevention and control of surgical site infections: review of the Basel Cohort Study

INTRODUCTION: Surgical site infections (SSI) are the most common hospital-acquired infections among surgical patients, with significant impact on patient morbidity and health care costs. The Basel SSI Cohort Study was performed to evaluate risk factors and validate current preventive measures for SSI. The objective of the present article was to review the main results of this study and its implications for clinical practice and future research. SUMMARY OF METHODS OF THE BASEL SSI COHORT STUDY: The prospective observational cohort study included 6,283 consecutive general surgery procedures closely monitored for evidence of SSI up to 1 year after surgery. The dataset was analysed for the influence of various potential SSI risk factors, including timing of surgical antimicrobial prophylaxis (SAP), glove perforation, anaemia, transfusion and tutorial assistance, using multiple logistic regression analyses. In addition, post hoc analyses were performed to assess the economic burden of SSI, the efficiency of the clinical SSI surveillance system, and the spectrum of SSI-causing pathogens. REVIEW OF MAIN RESULTS OF THE BASEL SSI COHORT STUDY: The overall SSI rate was 4.7% (293/6,283). While SAP was administered in most patients between 44 and 0 minutes before surgical incision, the lowest risk of SSI was recorded when the antibiotics were administered between 74 and 30 minutes before surgery. Glove perforation in the absence of SAP increased the risk of SSI (OR 2.0; CI 1.4-2.8; p <0.001). No significant association was found for anaemia, transfusion and tutorial assistance with the risk of SSI. The mean additional hospital cost in the event of SSI was CHF 19,638 (95% CI, 8,492-30,784). The surgical staff documented only 49% of in-hospital SSI; the infection control team registered the remaining 51%. Staphylococcus aureus was the most common SSI-causing pathogen (29% of all SSI with documented microbiology). No case of an antimicrobial-resistant pathogen was identified in this series. CONCLUSIONS: The Basel SSI Cohort Study suggested that SAP should be administered between 74 and 30 minutes before surgery. Due to the observational nature of these data, corroboration is planned in a randomized controlled trial, which is supported by the Swiss National Science Foundation. Routine change of gloves or double gloving is recommended in the absence of SAP. Anaemia, transfusion and tutorial assistance do not increase the risk of SSI. The substantial economic burden of in-hospital SSI has been confirmed. SSI surveillance by the surgical staff detected only half of all in-hospital SSI, which prompted the introduction of an electronic SSI surveillance system at the University Hospital of Basel and the Cantonal Hospital of Aarau. Due to the absence of multiresistant SSI-causing pathogens, the continuous use of single-shot single-drug SAP with cefuroxime (plus metronidazole in colorectal surgery) has been validated.

Energy-Economical Heuristically Based Control of Compass Gait Walking on Stochastically Varying Terrain

Investigation uses simulation to explore the inherent tradeoffs ofcontrolling high-speed and highly robust walking robots while minimizing energy consumption. Using a novel controller which optimizes robustness, energy economy, and speed of a simulated robot on rough terrain, the user can adjust their priorities between these three outcome measures and systematically generate a performance curveassessing the tradeoffs associated with these metrics.

The Impact of Parental Psychological Control on College Students’ Relational Aggression and Friendship Quality

The present study investigated the relationships between parental psychological control and college students’ relational aggression and friendship quality. Based on previous research, it was expected that parents’ use of psychological control would be associated with students’ increased use of relational aggression with peers and lower friendship quality. Students completed a series of survey measures assessing their mothers’ and fathers’ use of psychological control, behavioral control, and warmth/acceptance. Students also completed a series of survey measures assessing their friendship quality, social skills, relational aggression, self-esteem, and social desirability. The study’s findings revealed that parental psychological control was associated with and predicted students’ increased use of relational aggression with peers. Parental psychological control was also associated with students’ lower friendship quality. However, parents’ use of psychological control did not predict students’ friendship quality after accounting for the influence of students’ personal and peer relationship variables. This finding suggests that characteristics of peer relationships may play a larger role than parenting behaviors in shaping college students’ friendships. The study also found that students who displayed higher levels of relational aggression had lower quality friendships. Other findings revealed that the relationship between parental psychological control and students’ friendship quality can be partially explained by students’ use of relational aggression with peers. Students’ friendship quality can also help to explain the influence of parental psychological control on students’ relational aggression. In addition, the study found that combinations of parenting behaviors were more informative predictors of students’ relational aggression and friendship quality than psychological control alone. Finally, this study revealed the importance of assessing participants’ social desirability when measuring sensitive personal qualities such as relational aggression, friendship quality, and self-esteem. Overall, this study contributes to the field of research on parental psychological control by revealing its effects on college students’ relational aggression and friendship quality.

Induction of the Neurokinin 1 Receptor by TNFα in Endometriotic Tissue Provides the Potential for Neurogenic Control Over Endometriotic Lesion Growth

Context: Endometriosis is characterized by the growth of ectopic endometrial tissue. Nerve fibers are frequently associated with ectopic lesions, and neurogenic inflammation may play a role in endometriosis. Objective: The purpose of this study was to determine the presence of tachykinin receptors in endometriotic lesions and the role of TNFα on their expression. Design: This study was an assessment of matching eutopic and ectopic endometrial tissue and peritoneal fluid from patients with endometriosis and an in vitro analysis of primary endometrial cells. Setting: The setting was a university hospital. Patients: Participants were premenopausal women undergoing laparoscopy. Interventions: Endometriotic lesions were removed surgically. Main Outcome Measures: Tachykinin mRNA (TACR1/2) and protein (neurokinin 1 receptor [NK1R]) expression in both eutopic and ectopic endometrial tissue from patients with endometriosis and the correlation to peritoneal fluid TNFα were measured. Primary endometrial epithelial and stromal cells were assessed in vitro to determine the induction of TACR1/2 and NK1R expression after TNFα treatment. Cell viability of endometrial stromal cells after substance P exposure was also assessed. Results: Expression of both TACR1 and TACR2 mRNA was significantly higher in the ectopic than in the eutopic tissue. Both TACR1 mRNA and NK1R protein expression was significantly correlated with peritoneal fluid TNFα, and in vitro studies confirmed that TNFα treatment induced both TACR1 mRNA and NK1R protein expression in endometrial stromal cells. In endometrial stromal cells, substance P treatment enhanced cell viability, which was inhibited by a specific NK1R antagonist. Conclusions: NK1R expression is induced in ectopic endometrial tissue by peritoneal TNFα. Induction of NK1R expression may permit endometriotic lesion maintenance via exposure to substance P.

Separation of Ownership from Control and Discretionary Managerial Behaviour in a Transition Economy

This study was the final stage of a four-year study of managerial behaviour and company performance in Bulgaria and examined the influence of changing ownership and control structures of companies on managerial behaviour and initiative. It provides a theoretical summary of the specific types of ownership, control, governance structures and managerial strategies in the Bulgarian transitional economy during 1992-1996. It combines two theoretical approaches, the property-rights approach to show concentrated property-rights structure and private and majority types of control as determinants of efficient enterprise risk bearing and constrained managerial discretion, and the agency theory approach to reveal the efficient role of direct non-market governance mechanisms over managers. Mr. Peev also used empirical information collected from the Central Statistical office in Bulgaria, three different enterprise investigations of corporatised state-owned enterprises between 1992 and 1994, and his own data base of privatised and private de novo industrial companies in 1996-1996. The project gives a detailed description of the main property-rights structures in Bulgaria at the present time and of the various control structures related to these. It found that there is a strong owner type of control in private and privatised firms, although, contrary to expectations, 100% state -owned enterprises tended to be characterised by a separation of ownership from control, leaving scope for managerial discretion. Mr. Peev predicts that after the forthcoming mass privatisation, many companies will acquire a dispersed ownership structure and there will be a greater separation of ownership from control and potential or inefficient managerial behaviour. The next aspect considered in detail was governance structures and the influence of the generally unstable macroeconomic environment in the country during the period in question. In examining managerial strategies, Mr. Peev divided the years since 1990 into 3 periods. Even in the first period (1990-1992) there were some signs of a more efficient role for managers and between 1992 and 1994 the picture of control structures and different managerial behaviour in state-owned companies became more diversified. Managerial strategies identified included managerial initiatives for privatisation, where managers took initiative in resolving problems of property rights and introducing restructuring measures and privatisation proposals, managerial initiatives for restructuring without privatisation, and passive adjustment and passive management, where managers seek outside services for marketing, finance management, etc. in order to adjust to the new environment. During 1995-1996 some similarities and differences between the managerial behaviour of privatised and state-owned firms emerged. Firstly, the former have undergone many changes in investment and technology, while managers of state-owned companies have changed little in this field, indicating that the private property-rights structure is more efficient for the long-term adaptation of enterprises. In the area of strategies relating to product quality, marketing, and pricing policy there was little difference between managers of private, privatised and state-owned firms. The most passive managerial behaviour was found in non-incorporated state-owned firms, although these have only an insignificant stake in the economy.

Control of muscle relaxation during anesthesia: a novel approach for clinical routine

During general anesthesia drugs are administered to provide hypnosis, ensure analgesia, and skeletal muscle relaxation. In this paper, the main components of a newly developed controller for skeletal muscle relaxation are described. Muscle relaxation is controlled by administration of neuromuscular blocking agents. The degree of relaxation is assessed by supramaximal train-of-four stimulation of the ulnar nerve and measuring the electromyogram response of the adductor pollicis muscle. For closed-loop control purposes, a physiologically based pharmacokinetic and pharmacodynamic model of the neuromuscular blocking agent mivacurium is derived. The model is used to design an observer-based state feedback controller. Contrary to similar automatic systems described in the literature this controller makes use of two different measures obtained in the train-of-four measurement to maintain the desired level of relaxation. The controller is validated in a clinical study comparing the performance of the controller to the performance of the anesthesiologist. As presented, the controller was able to maintain a preselected degree of muscle relaxation with excellent precision while minimizing drug administration. The controller performed at least equally well as the anesthesiologist.

Semiparametric Estimation in General Repeated Measures Problems

This paper considers a wide class of semiparametric problems with a parametric part for some covariate effects and repeated evaluations of a nonparametric function. Special cases in our approach include marginal models for longitudinal/clustered data, conditional logistic regression for matched case-control studies, multivariate measurement error models, generalized linear mixed models with a semiparametric component, and many others. We propose profile-kernel and backfitting estimation methods for these problems, derive their asymptotic distributions, and show that in likelihood problems the methods are semiparametric efficient. While generally not true, with our methods profiling and backfitting are asymptotically equivalent. We also consider pseudolikelihood methods where some nuisance parameters are estimated from a different algorithm. The proposed methods are evaluated using simulation studies and applied to the Kenya hemoglobin data.

Increased parietal activity after training of interference control

Recent studies suggest that computerized cognitive training leads to improved performance in related but untrained tasks (i.e. transfer effects). However, most study designs prevent disentangling which of the task components are necessary for transfer. In the current study, we examined whether training on two variants of the adaptive dual n-back task would affect untrained task performance and the corresponding electrophysiological event-related potentials (ERPs). Forty three healthy young adults were trained for three weeks with a high or low interference training variant of the dual n-back task, or they were assigned to a passive control group. While n-back training with high interference led to partial improvements in the Attention Network Test (ANT), we did not find transfer to measures of working memory and fluid intelligence. ERP analysis in the n-back task and the ANT indicated overlapping processes in the P3 time range. Moreover, in the ANT, we detected increased parietal activity for the interference training group alone. In contrast, we did not find electrophysiological differences between the low interference training and the control group. These findings suggest that training on an interference control task leads to higher electrophysiological activity in the parietal cortex, which may be related to improvements in processing speed, attentional control, or both.

Public health risks of enterobacterial isolates producing extended-spectrum β-lactamases or AmpC β-lactamases in food and food-producing animals: an EU perspective of epidemiology, analytical methods, risk factors, and control options

The blaESBL and blaAmpC genes in Enterobacteriaceae are spread by plasmid-mediated integrons, insertion sequences, and transposons, some of which are homologous in bacteria from food animals, foods, and humans. These genes have been frequently identified in Escherichia coli and Salmonella from food animals, the most common being blaCTX-M-1, blaCTX-M-14, and blaCMY-2. Identification of risk factors for their occurrence in food animals is complex. In addition to generic antimicrobial use, cephalosporin usage is an important risk factor for selection and spread of these genes. Extensive international trade of animals is a further risk factor. There are no data on the effectiveness of individual control options in reducing public health risks. A highly effective option would be to stop or restrict cephalosporin usage in food animals. Decreasing total antimicrobial use is also of high priority. Implementation of measures to limit strain dissemination (increasing farm biosecurity, controls in animal trade, and other general postharvest controls) are also important.

Patterns of exposure to infectious diseases and social contacts in early life and risk of brain tumours in children and adolescents: an International Case-Control Study (CEFALO)

BACKGROUND Infectious diseases and social contacts in early life have been proposed to modulate brain tumour risk during late childhood and adolescence. METHODS CEFALO is an interview-based case-control study in Denmark, Norway, Sweden and Switzerland, including children and adolescents aged 7-19 years with primary intracranial brain tumours diagnosed between 2004 and 2008 and matched population controls. RESULTS The study included 352 cases (participation rate: 83%) and 646 controls (71%). There was no association with various measures of social contacts: daycare attendance, number of childhours at daycare, attending baby groups, birth order or living with other children. Cases of glioma and embryonal tumours had more frequent sick days with infections in the first 6 years of life compared with controls. In 7-19 year olds with 4+ monthly sick day, the respective odds ratios were 2.93 (95% confidence interval: 1.57-5.50) and 4.21 (95% confidence interval: 1.24-14.30). INTERPRETATION There was little support for the hypothesis that social contacts influence childhood and adolescent brain tumour risk. The association between reported sick days due to infections and risk of glioma and embryonal tumour may reflect involvement of immune functions, recall bias or inverse causality and deserve further attention.