Benefit of immediate revascularization in women with critical limb ischemia in an intention-to-treat analysis

Evidence for the best treatment strategy in women with critical limb ischemia (CLI) is limited and controversial with studies contradicting each other. Therefore, we determined the benefit of immediate revascularization compared to medical therapy (MT) with optional delayed revascularization in men and women with CLI.

Smoking behaviour, former quit attempts and intention to quit in urban adolescents and young adults: A five-year longitudinal study

OBJECTIVES: To examine smoking behaviour, former quit attempts and intention to quit among Swiss adolescents and young adults over five year's time. STUDY DESIGN: five-year longitudinal study (2003, 2005 and 2008) based on a random urban community sample (N = 1345 complete cases). METHODS: Data were collected by computer-assisted telephone interviews with adolescents (16-17) and young adults (18-24). Main outcome measures included self-reported smoking behaviour, former quit attempts, smoking cessation methods and current intentions to quit smoking. RESULTS: Adolescents were more often non-smokers and less often daily smokers when compared to young adults at baseline (χ(2)(4) = 28.68, P < .001). Their smoking behaviour increased significantly from baseline to follow-up (T = 1445.50, r = .20, P < .001) in contrast to the stable smoking behaviour in young adults (χ(2)(2) = .12, n.s.). In longitudinal analyses young adults were also more stable in their smoking status at the later measurement points. In comparison adolescents changed their smoking status more often being non-smokers at baseline and smokers later on. Independently of the age group, the majority of smokers already had previously attempted to quit (65%) or intended to give up smoking at some point (72%). However only 17% were motivated to make the quit attempt within the next 6 months. Self-quitting was the preferred method, and 25% of the self-quitters had been successful. CONCLUSION: This study illustrates that different developments in smoking behaviour exist in adolescents and young adults. Our study reveals that a majority of smokers are willing to quit but often fail. Furthermore, the data indicates that for adolescents the focus should lie on primary prevention.

Perceived organizational support and intention to stay in host countries among self-initiated expatriates: the role of career satisfaction and networks

Previous literature in SIE (self-initiated expatriation) has been mostly focused on an individual perspective. Studies on SIEs in organizational context are scarce. The current paper sought to examine the effect of perceived organizational support (POS) on SIE employees’ intention to stay in the host country, mediated by career satisfaction. Furthermore, we examined the moderating roles of career-related social networks with host and home country nationals on the effectiveness of POS. Data from 112 SIE employees in Germany were collected and analyzed. Empirical results partially supported our proposed model: there were significant negative indirect effect between POS and intention to stay, when career network size with home country nationals was high. The direct effect between POS and intention to stay was positive. For HR practice, our paper gave insight to understand SIE employees’ needs for support and mobility preferences, which can help organizations to develop more targeted HR development measures and assignment strategies for them.

Explaining car drivers' intention to prevent road-traffic noise: An application of the Norm Activation Model

Strengthening car drivers’ intention to prevent road-traffic noise is a first step toward noise abatement through voluntary change of behavior. We analyzed predictors of this intention based on the norm activation model (i.e., personal norm, problem awareness, awareness of consequences, social norm, and value orientations). Moreover, we studied the effects of noise exposure, noise sensitivity, and noise annoyance on problem awareness. Data came from 1,002 car drivers who participated in a two-wave longitudinal survey over 4 months. Personal norm had a large prospective effect on intention, even when the previous level of intention was controlled for, and mediated the effect of all other variables on intention. Almost 60% of variance in personal norm was explained by problem awareness, social norm, and biospheric value orientation. The effects of noise sensitivity and noise exposure on problem awareness were small and mediated by noise annoyance. We propose four communication strategies for strengthening the intention to prevent road-traffic noise in car drivers.

Reporting of randomized controlled trials in Hodgkin lymphoma in biomedical journals

BACKGROUND: Randomized controlled trials (RCTs) are the best tool to evaluate the effectiveness of clinical interventions. The Consolidated Standards for Reporting Trials (CONSORT) statement was introduced in 1996 to improve reporting of RCTs. We aimed to determine the extent of ambiguity and reporting quality as assessed by adherence to the CONSORT statement in published reports of RCTs involving patients with Hodgkin lymphoma from 1966 through 2002. METHODS: We analyzed 242 published full-text reports of RCTs in patients with Hodgkin lymphoma. Quality of reporting was assessed using a 14-item questionnaire based on the CONSORT checklist. Reporting was studied in two pre-CONSORT periods (1966-1988 and 1989-1995) and one post-CONSORT period (1996-2002). RESULTS: Only six of the 14 items were addressed in 75% or more of the studies in all three time periods. Most items that are necessary to assess the methodologic quality of a study were reported by fewer than 20% of the studies. Improvements over time were seen for some items, including the description of statistics methods used, reporting of primary research outcomes, performance of power calculations, method of randomization and concealment allocation, and having performed intention-to-treat analysis. CONCLUSIONS: Despite recent improvements, reporting levels of CONSORT items in RCTs involving patients with Hodgkin lymphoma remain unsatisfactory. Further concerted action by journal editors, learned societies, and medical schools is necessary to make authors even more aware of the need to improve the reporting RCTs in medical journals to allow assessment of validity of published clinical research.

The influence of intention on masked priming: A study with semantic classification of words

Unconscious perception is commonly described as a phenomenon that is not under intentional control and relies on automatic processes. We challenge this view by arguing that some automatic processes may indeed be under intentional control, which is implemented in task-sets that define how the task is to be performed. In consequence, those prime attributes that are relevant to the task will be most effective. To investigate this hypothesis, we used a paradigm which has been shown to yield reliable short-lived priming in tasks based on semantic classification of words. This type of study uses fast, well practised classification responses, whereby responses to targets are much less accurate if prime and target belong to a different category than if they belong to the same category. In three experiments, we investigated whether the intention to classify the same words with respect to different semantic categories had a differential effect on priming. The results suggest that this was indeed the case: Priming varied with the task in all experiments. However, although participants reported not seeing the primes, they were able to classify the primes better than chance using the classification task they had used before with the targets. When a lexical task was used for discrimination in experiment 4, masked primes could however not be discriminated. Also, priming was as pronounced when the primes were visible as when they were invisible. The pattern of results suggests that participants had intentional control on prime processing, even if they reported not seeing the primes.

Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies

OBJECTIVE: To estimate the prognosis over 5 years of HIV-1-infected, treatment-naive patients starting HAART, taking into account the immunological and virological response to therapy. DESIGN: A collaborative analysis of data from 12 cohorts in Europe and North America on 20,379 adults who started HAART between 1995 and 2003. METHODS: Parametric survival models were used to predict the cumulative incidence at 5 years of a new AIDS-defining event or death, and death alone, first from the start of HAART and second from 6 months after the start of HAART. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. RESULTS: During 61 798 person-years of follow-up, 1005 patients died and an additional 1303 developed AIDS. A total of 10 046 (49%) patients started HAART either with a CD4 cell count of less than 200 cells/microl or with a diagnosis of AIDS. The 5-year risk of AIDS or death (death alone) from the start of HAART ranged from 5.6 to 77% (1.8-65%), depending on age, CD4 cell count, HIV-1-RNA level, clinical stage, and history of injection drug use. From 6 months the corresponding figures were 4.1-99% for AIDS or death and 1.3-96% for death alone. CONCLUSION: On the basis of data collected routinely in HIV care, prognostic models with high discriminatory power over 5 years were developed for patients starting HAART in industrialized countries. A risk calculator that produces estimates for progression rates at years 1 to 5 after starting HAART is available from www.art-cohort-collaboration.org.

Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia

Early allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as primary treatment modality for patients with chronic myeloid leukemia (CML). This concept has been challenged by transplantation mortality and improved drug therapy. In a randomized study, primary HSCT and best available drug treatment (IFN based) were compared in newly diagnosed chronic phase CML patients. Assignment to treatment strategy was by genetic randomization according to availability of a matched related donor. Evaluation followed the intention-to-treat principle. Six hundred and twenty one patients with chronic phase CML were stratified for eligibility for HSCT. Three hundred and fifty four patients (62% male; median age, 40 years; range, 11-59 years) were eligible and randomized. One hundred and thirty five patients (38%) had a matched related donor, of whom 123 (91%) received a transplant within a median of 10 months (range, 2-106 months) from diagnosis. Two hundred and nineteen patients (62%) had no related donor and received best available drug treatment. With an observation time up to 11.2 years (median, 8.9 years), survival was superior for patients with drug treatment (P = .049), superiority being most pronounced in low-risk patients (P = .032). The general recommendation of HSCT as first-line treatment option in chronic phase CML can no longer be maintained. It should be replaced by a trial with modern drug treatment first.

The pharmacokinetic profile of fesoterodine: similarities and differences to tolterodine

BACKGROUND: Fesoterodine is a new antimuscarinic agent developed for the treatment of overactive bladder. Fesoterodine itself is inactive and is rapidly and extensively converted by ubiquitous esterases to its principal active moiety, 5-hydroxymethyl tolterodine (5-HMT). 5-HMT is formed via biotransformation of both fesoterodine and tolterodine, albeit by different metabolising enzymes, viz. esterases and CYP2D6 respectively. Tolterodine is a potent muscarinic receptor antagonist and has been used for the treatment of overactive bladder for over ten years. The objective of this study was to establish the pharmacokinetic profile of fesoterodine and to highlight ist potential pharmacokinetic advantages over tolterodine. DESIGN: Single-centre, open-label, randomised, 4-way crossover study in a total of 24 healthy male volunteers. Single oral doses of 4, 8, or 12 mg fesoterodine were administered after an overnight fast. In addition, the 8 mg dose was also administered after a standard high-fat and high-calorie breakfast. Blood and urine samples for the analysis of 5-HMT were collected before and multiple times after drug administration for pharmacokinetic analysis. RESULTS: The mean peak plasma concentration (Cmax) of 5-HMT and the mean area under the time versus concentration curve (AUC) increased proportionally with the fesoterodine dose. These two parameters were some 2-fold higher in CYP2D6 poor metabolisers, whereas the time to peak plasma concentration (tmax) and half life (t1/2) were not influenced by the dose or the CYP2D6 metaboliser status. If fesoterodine was taken following a high-fat breakfast, we observed small increases in Cmax and AUC. In spite of these modest genetic influences and food effects on the pharmacokinetics of fesoterodine, the overall interindividual variability in Cmax levels was relatively little compared to previously published reports using tolterodine. CONCLUSIONS: Due to the esterase-mediated cytochrome P450-independent formation of 5-HMT and involvement of multiple metabolic and renal excretion pathways in the elimination of 5-HMT, the effects of patient-intrinsic and -extrinsic factors on the pharmacokinetics of fesoterodine are only modest, with some 2-fold higher 5-HMT exposure. Therefore, in contrast to tolterodine, no reduction of fesoterodine dosage is required under conditions of reduced elimination. In most cases of drug interaction or renal/hepatic impairment, the fesoterodine dose may be increased to 8 mg/day based on individual patients' response, or patients may be required to remain at the initial recommended dose of 4 mg/day.

Adolescents' value of children and their intentions to have children: A cross-cultural and multilevel analysis

This study contributes to research regarding the value of children (VOC) by comparing adolescents' VOC and their intentions to have children across 12 cultures and by exploring the relations between these constructs at the individual and cultural levels using multilevel modeling. A total of 3,348 adolescents from 12 cultures participated in this study. On average, adolescents reported that they intended to have about two children and also reported emotional VOC as being highly important. Adolescents from cultures with a low as compared to a high level of economic development reported a higher importance of the utilitarian-normative VOC. Results of the multilevel analyses showed that the reported emotional VOC was positively related to the number of children adolescents intended to have at the individual level, whereas the utilitarian-normative VOC was not related to adolescents' intention to have children. At the cultural level, the VOC dimensions were only partly related to adolescents' intention to have children. The results are discussed with regard to adolescents' future family orientation and in relation to the VOC approach.

Trade-offs between voice and silence: a qualitative exploration of oncology staff's decisions to speak up about safety concerns

BACKGROUND Research suggests that "silence", i.e., not voicing safety concerns, is common among health care professionals (HCPs). Speaking up about patient safety is vital to avoid errors reaching the patient and thus to prevent harm and also to improve a culture of teamwork and safety. The aim of our study was to explore factors that affect oncology staff's decision to voice safety concerns or to remain silent and to describe the trade-offs they make. METHODS In a qualitative interview study with 32 doctors and nurses from 7 oncology units we investigated motivations and barriers to speaking up towards co-workers and supervisors. An inductive thematic content analysis framework was applied to the transcripts. Based on the individual experiences of participants, we conceptualize the choice to voice concerns and the trade-offs involved. RESULTS Preventing patients from serious harm constitutes a strong motivation to speaking up but competes with anticipated negative outcomes. Decisions whether and how to voice concerns involved complex considerations and trade-offs. Many respondents reflected on whether the level of risk for a patient "justifies" the costs of speaking up. Various barriers for voicing concerns were reported, e.g., damaging relationships. Contextual factors, such as the presence of patients and co-workers in the alarming situation, affect the likelihood of anticipated negative outcomes. Speaking up to well-known co-workers was described as considerably easier whereas "not knowing the actor well" increases risks and potential costs of speaking up. CONCLUSIONS While doctors and nurses felt strong obligation to prevent errors reaching individual patients, they were not engaged in voicing concerns beyond this immediacy. Our results offer in-depth insight into fears and conditions conducive of silence and voicing and can be used for educational interventions and leader reinforcement.

Do Increasing Rates of Loss to Follow-up in Antiretroviral Treatment Programs Imply Deteriorating Patient Retention?

In several studies of antiretroviral treatment (ART) programs for persons with human immunodeficiency virus infection, investigators have reported that there has been a higher rate of loss to follow-up (LTFU) among patients initiating ART in recent years than among patients who initiated ART during earlier time periods. This finding is frequently interpreted as reflecting deterioration of patient retention in the face of increasing patient loads. However, in this paper we demonstrate by simulation that transient gaps in follow-up could lead to bias when standard survival analysis techniques are applied. We created a simulated cohort of patients with different dates of ART initiation. Rates of ART interruption, ART resumption, and mortality were assumed to remain constant over time, but when we applied a standard definition of LTFU, the simulated probability of being classified LTFU at a particular ART duration was substantially higher in recently enrolled cohorts. This suggests that much of the apparent trend towards increased LTFU may be attributed to bias caused by transient interruptions in care. Alternative statistical techniques need to be used when analyzing predictors of LTFU-for example, using "prospective" definitions of LTFU in place of "retrospective" definitions. Similar considerations may apply when analyzing predictors of LTFU from treatment programs for other chronic diseases.

Immunologic response to the survivin-derived multi-epitope vaccine EMD640744 in patients with advanced solid tumors

PURPOSE Survivin is a member of the inhibitor-of-apoptosis family. Essential for tumor cell survival and overexpressed in most cancers, survivin is a promising target for anti-cancer immunotherapy. Immunogenicity has been demonstrated in multiple cancers. Nonetheless, few clinical trials have demonstrated survivin-vaccine-induced immune responses. EXPERIMENTAL DESIGN This phase I trial was conducted to test whether vaccine EMD640744, a cocktail of five HLA class I-binding survivin peptides in Montanide(®) ISA 51 VG, promotes anti-survivin T-cell responses in patients with solid cancers. The primary objective was to compare immunologic efficacy of EMD640744 at doses of 30, 100, and 300 μg. Secondary objectives included safety, tolerability, and clinical efficacy. RESULTS In total, 49 patients who received ≥2 EMD640744 injections with available baseline- and ≥1 post-vaccination samples [immunologic-diagnostic (ID)-intention-to-treat] were analyzed by ELISpot- and peptide/MHC-multimer staining, revealing vaccine-activated peptide-specific T-cell responses in 31 patients (63 %). This cohort included the per study protocol relevant ID population for the primary objective, i.e., T-cell responses by ELISpot in 17 weeks following first vaccination, as well as subjects who discontinued the study before week 17 but showed responses to the treatment. No dose-dependent effects were observed. In the majority of patients (61 %), anti-survivin responses were detected only after vaccination, providing evidence for de novo induction. Best overall tumor response was stable disease (28 %). EMD640744 was well tolerated; local injection-site reactions constituted the most frequent adverse event. CONCLUSIONS Vaccination with EMD640744 elicited T-cell responses against survivin peptides in the majority of patients, demonstrating the immunologic efficacy of EMD640744.