Pre-procedural pacing bias among transcatheter aortic valves with higher post-procedure pacing rates: evidence from the UK TAVI Registry.

Rates of permanent pacemaker (PPM) implantation following transcatheter aortic valve implantation (TAVI) are higher than following surgery and are dependent on patient factors and valve type. There is an increasing trend towards pre-emptive PPM insertion in patients with significant conduction disease prior to TAVI. We report results from the British Cardiovascular Intervention Society (BCIS) on pre- and post-procedural PPM implantation in the TAVI population. All centres in the United Kingdom performing TAVI are required to submit data on all TAVI procedures to the National database which are then reported annually. During 2015, there were 2373 TAVI procedures in the UK. 22.4% of TAVI patients had a PPM implanted either pre-procedure (including the distant past), or during the in-hospital procedural episode. Of these, 7.9% were pre-procedure and 14.5% post-procedure. Overall PPM rates were Edwards Sapien (13.5%), Medtronic CoreValve (28.2%) and Boston Lotus (42.1%; p < 0.01). Pre-procedure pacing rates were Edwards Sapien (6.0%), Medtronic CoreValve (9.1%) and Boston Lotus (12.3%; p < 0.01). Pre-procedural pacing rates for the Boston Lotus valve have risen year-on-year from 5.8% (2013) to 8.6% (2014) to 12.3% (2015). The UK TAVI Registry demonstrates a pre-procedural permanent pacing bias amongst patients receiving transcatheter valves with higher post-procedure pacing rates. Pre-emptive permanent pacing is likely to be responsible for this difference.

A randomized controlled trial of a walking training with simultaneous cognitive demand (dual-task) in chronic stroke.

BACKGROUND AND PURPOSE: The aim was to evaluate the tolerability of, adherence to and efficacy of a community walking training programme with simultaneous cognitive demand (dual-task) compared to a control walking training programme without cognitive distraction. METHODS: Adult stroke survivors at least 6 months after stroke with a visibly obvious gait abnormality or reduced 2-min walk distance were included in a two-arm parallel randomized controlled trial of complex intervention with blinded assessments. Participants received a 10 week, bi-weekly, 30 min treadmill programme at an aerobic training intensity (55%-85% heart rate maximum), either with or without simultaneous cognitive demands. Outcome was measured at 0, 11 and 22 weeks. The primary assessment involved 2-min walk tests with and without cognitive distraction to investigate the dual-task effect on walking and cognition; secondary results were the Short Form Health Survey 36, EuroQol-5D-5L, the Physical Activity Scale for the Elderly (PASE) and step activity. RESULTS: Fifty stroke patients were included; 43 received allocated training and 45 completed all assessments. The experimental group (n = 26) increased their mean (SD) 2-min walking distance from 90.7 (8.2) to 103.5 (8.2) m, compared with 86.7 (8.5) to 92.8 (8.6) m in the control group, and their PASE score from 74.3 (9.1) to 89.9 (9.4), compared with 94.7 (9.4) to 77.3 (9.9) in the control group. Statistically, only the change in the PASE differed between the groups (P = 0.029), with the dual-task group improving more. There were no differences in other measures. CONCLUSIONS: Walking with specific additional cognitive distraction (dual-task training) might increase activity more over 12 weeks, but the data are not conclusive.

Thyroid hormone receptor beta-1 expression in early breast cancer: a validation study.

PURPOSE: Preliminary data suggest that high expression of the TRß1 tumor suppressor is associated with longer survival among women with early breast cancer. We undertook this study to validate these findings. METHODS: In this prospective cohort study, we analyzed the prognostic significance of TRß1 protein expression in the breast tumors of 796 women who had undergone breast surgery in the Henrietta Banting Breast Cancer database. All women were recruited after undergoing primary surgical therapy at Women's College Hospital (Toronto, ON, Canada) between January 1987 and December 2000. Details regarding patient age at diagnosis, systemic, and local therapies, as well as pathological features of their tumor have been systematically recorded. Clinical outcomes including breast cancer recurrence and death have been updated at least once each year with a median follow-up of 9.6 years (range 0.1-21 years). RESULTS: High TRß1 expression (> 4 on the Allred score) was associated with a longer breast cancer-specific survival with a HR 0.45 (95% CI 0.33-0.61), p < 0.0001 in a univariable Cox regression model. This was maintained in a multivariable model adjusted for age, tumor size, nodal status, chemotherapy, hormone therapy, radiotherapy, surgery, and ER status with a HR of 0.61 (95% CI 0.44-0.85), p = 0.004. CONCLUSIONS: High expression of TRß1 is associated with longer breast cancer-specific survival independent of other prognostic factors. Given that low TRß expression is associated with chemotherapy resistance in-vitro, TRß1 may also serve as a predictive biomarker or even a therapeutic target given the availability of TRß agonists.

Rapid passage signals induced by chirped quantum cascade laser radiation: K state dependent-delay effects in the nu2 band of NH3.

In this Letter, a 10 microm quantum cascade laser operating in the intrapulse mode is used observe rapid passage (RP) effects within a 40 cm single-pass gas cell containing low pressures of NH(3). The laser tuning range allows the rotational states J=2 with K=0, 1, and 2 to be probed. We show that the RP structures change as a function of optical density and that the magnitude of the delay in the switch from absorption to emission as a function of increased gas pressure is dependent upon the initial value of K. These measurements are qualitatively well modeled using the Maxwell-Bloch equations.

Digital subtraction angiography of the superior mesenteric artery: identifying arterial branches.

This "problem in diagnostic imaging" provides an overview of the technique of digital subtraction angiography. The possibility of artefacts arising from movement subsequent to the taking of the masking image is discussed. It is also important that contrast medium is allowed to backflow into the parent vessel (in this case the aorta) to ensure that there has been filling of the proximal branches of the vessel of interest (in this case the superior mesenteric artery). An accessory middle colic artery is demonstrated. Detection of such variant vessels is important not only to surgeons but also to specialist radiologists carrying out therapeutic embolization.

Prospective randomized trial of laparoscopic gastrojejunostomy versus duodenal stenting for malignant gastric outflow obstruction.

BACKGROUND: We prospectively compared laparoscopic gastrojejunostomy with duodenal stenting as a means of palliating malignant gastric outflow obstruction. METHODS: A total of 27 patients with malignant gastric outflow obstruction were randomized to either laparoscopic gastrojejunostomy (LGJ) or duodenal stenting (DS) over a 3-year period. RESULTS: Thirteen patients underwent successful LGJ and 10 had successful DS. Eight patients had complications after LGJ, but none had complications after DS. Patients who underwent LGJ had a significant increase in visual analog pain score at day 1 (p = 0.05), and also had a longer hospital stay compared to those who underwent DS (11.4 vs. 5.2 days, p = 0.02). After DS, patients experienced an improvement in physical health at 1 month as measured using the Short Form-36 (SF-36) questionnaire (p < 0.01). There was no change following LGJ. CONCLUSION: Duodenal stenting is a safe means of palliating malignant gastric outflow obstruction. It offers significant advantages for patients compared with minimal-access surgery.

Effectiveness, costs, and cost-effectiveness of recruitment strategies for a mammographic screening program to detect breast cancer.

BACKGROUND AND PURPOSE: Since effective and affordable recruitment methods are essential for the widespread implementation of mammographic screening for detection of breast cancer, we studied the effectiveness, the costs, and the cost-effectiveness of various recruitment strategies in the population targeted by a pilot Australian program that offered free mammography screening between 1988 and 1990. METHODS: We evaluated three public recruitment strategies--local newspaper articles, community promotion, and promotion to physicians--and five personal strategies--invitation letters with or without specified appointment times, either alone or with a follow-up letter, or telephone call to nonattenders. The effectiveness of public recruitment strategies was estimated from monthly attendance rates by Poisson regression analysis, while the probability of attendance in response to personal strategies was calculated using logistic regression analysis. Costs were determined by resource usage studies. The cost-effectiveness ratios for personal strategies were determined using decision analysis. RESULTS: The costs in 1988-1989 Australian dollars per woman recruited were $22 for local newspaper articles and $106 for community promotion. No detectable increase in attendance resulted from promotion to physicians. When the cost of reserving an appointment was considered, the most cost-effective personal recruitment strategy was an invitation letter without a specified appointment time, followed by a second letter to nonattenders. This strategy recruited 35.6% of women in the sample targeted and cost $10.52 per attendee. In comparison, the most effective personal recruitment strategy was a letter with a specified appointment time followed by a second letter to nonattenders, which recruited 44.1% of women at an average cost of $19.99 and a marginal cost of $59.71 per additional attendee. CONCLUSIONS: Personal recruitment strategies were more cost-effective than public strategies. The most cost-effective personal strategy was an invitation letter without a specified appointment time, followed by a second letter to nonattenders.

Active mode locking of quantum cascade lasers in an external ring cavity.

Stable ultrashort light pulses and frequency combs generated by mode-locked lasers have many important applications including high-resolution spectroscopy, fast chemical detection and identification, studies of ultrafast processes, and laser metrology. While compact mode-locked lasers emitting in the visible and near infrared range have revolutionized photonic technologies, the systems operating in the mid-infrared range where most gases have their strong absorption lines, are bulky and expensive and rely on nonlinear frequency down-conversion. Quantum cascade lasers are the most powerful and versatile compact light sources in the mid-infrared range, yet achieving their mode-locked operation remains a challenge, despite dedicated effort. Here we report the demonstration of active mode locking of an external-cavity quantum cascade laser. The laser operates in the mode-locked regime at room temperature and over the full dynamic range of injection currents.

Should women take part in clinical trials in breast cancer? Issues and some solutions.

PURPOSE: The purpose of this review is to consider the issues for women related to participation in clinical trials that evaluate the management of breast cancer and provide some recommendations for future initiatives to address the identified areas of concern. METHODS: The National Health and Medical Research Council (NHMRC) National Breast Cancer Centre hosted an international workshop to address the question "Clinical Trials in Breast Cancer: Should Women Take Part?" We also reviewed the literature on informed participation in clinical trials that was identified in a broadly based search that covered Medline, PsycLIT, and HealthPlan from 1986 to 1996. RESULTS AND CONCLUSION: When women are asked to participate in a clinical trial, they are faced with a number of questions and dilemmas. These include issues related to the conduct and ethical considerations of the trial; the effect of participation or nonparticipation on treatment; the roles of the doctor as clinician and as researcher; the process of informed consent; the timing of the request for participation; and the benefits and costs of participation. A number of steps are identified that could help women decide whether to participate in clinical trials. These include provision of community information about clinical trials; establishment of independent brokers and registers for clinical trials; consumer review of information and protocols and involvement in trials; review of the role of ethics committees; collection of data about the proportion of women currently recruited to clinical trials, their reasons for participating or declining, and their views about the process of recruitment and participation; models for optimal practice in recruiting women to clinical trials and encouraging ongoing participation in trials; evidence-based communication skills training for clinicians to teach skills to inform women adequately of clinical trial participation; and auspicing and promotion of trials by an independent agency.

Development and validation of an instrument to measure satisfaction of participants at breast screening programmes.

A reliable and valid questionnaire has been developed to measure the satisfaction of participants with service offered at mammography screening programmes. The questionnaire measures five specific aspects: convenience and accessibility, staffs' interpersonal skills, information transfer between staff and client, physical surroundings and perceived technical competence of staff. A general satisfaction dimension was also included. Systematic procedures were followed to ensure that the initial pool of items met the criteria for satisfactory content validity. These procedures included extensive literature review and interviews with participants and service providers. Discriminant validity was assessed by a modified Q-sort procedure, where eight expert judges sorted items into relevant dimensions. The sample for other validity and reliability testing consisted of 584 women who were participants at a breast X-ray programme in Melbourne, Australia. Concurrent validity was demonstrated by considering the correlation of the sum of the subscale scores for each respondent with their score on the general subscale (r = 0.76; P less than 0.001). Multiple regression was used to provide further evidence for the discriminant validity of the proposed subscales and support for the multidimensional conceptualism of satisfaction. Scores on the general satisfaction subscale were used as an outcome variable and other subscale scores were predictor variables. All subscale scores significantly contributed to the prediction of satisfaction, over and above that of other subscales (R2 = 0.59). This indicates that these subscales are measuring distinct dimensions of satisfaction. Cronbach's alpha of each subscale was over 0.50, indicating that the subscales are reliable. The instrument is a potentially useful tool for assessing the quality of care at mammographic screening services and could be used routinely by such services to monitor satisfaction.

Immune cell infiltrates and prognosis in primary carcinoma of the lung.

The prognostic significance of immune cell infiltrates in surgically resected human lung cancer was investigated in 710 patients. Lymphoid infiltrates were quantified on both standard H&E stained sections and, in a subset of 95 cases, using immunohistochemistry and antibodies to CD3, CD8, CD57, CD68, CD79a and S100 to identify various immune cell types. Subjective grading (low, moderate, high) of lymphoid cell infiltrates on H&E sections of tumour and measurement, using image analysis, of overall level of tumour infiltration by any of the immunohistochemically labelled specific immune cell types of the stained sections showed no prognostic significance. However, when a distinction between peritumoural and intratumoural infiltration by particular cell types was made, intratumoural infiltration by high levels of CD3+ and S100+ cells was associated with longer post-operative survival (P = 0.02 and P = 0.045, respectively). In lung cancer, subjective assessment of tumour lymphoid infiltration and overall levels of infiltration by particular immune cell types carries no prognostic significance. Intratumoural infiltration by relatively high numbers of CD3+ T-lymphocytes and Langerhans cells (S100+) is associated with a better patient outcome.

Preoperative histological classification of primary lung cancer: accuracy of diagnosis and use of the non-small cell category.

AIMS: To compare the preoperative classification of lung carcinoma made on cytological and histological specimens with the postoperative classification made on the resected specimen. In addition, to find out how often the term "non-small cell lung cancer, not otherwise specified" (NSCLC) was used, and in such cases to note the final diagnosis. METHODS: Between 1991 and 1995, 303 patients had a lung resection in Aberdeen for primary carcinoma. For each patient, the departmental records were examined for preoperative specimens (cytological and histological). A note was made of whether each specimen was positive or negative for malignancy and, if positive, what the cell type was. Where patients had more than one sample submitted, the most specific result was taken. RESULTS: Fifty four per cent of patients had a correct specific preoperative diagnosis of malignancy, whereas 34% were labelled as NSCLC. Patients with squamous carcinoma were more likely to have a diagnosis of malignancy (88%) that was specifically correct (75%). Patients who had adenocarcinoma were less likely to have a preoperative diagnosis of malignancy (64%) that was specifically correct (35%). For those in whom a diagnosis of NSCLC was made, 55% turned out to have adenocarcinoma whereas 24% had squamous carcinoma. CONCLUSIONS: By adhering strictly to criteria, a high accuracy of diagnosis can be achieved for squamous carcinoma, but the diagnosis of adenocarcinoma seems to be more of a challenge. NSCLC is a useful and appropriate classification, the use of which reduces the rate of inaccurate specific diagnosis. There are occasions when pathologists can provide a more accurate diagnosis by being less precise.

Can compliance with nonpharmacologic treatments for cardiovascular disease be improved?

OBJECTIVE: To critically review the literature regarding the effectiveness of interventions aimed at improving cardiovascular patient compliance with nonpharmacologic treatments. METHODS: We searched Medline, Healthplan, and Psychlit from 1985 to 1996; searched the bibliographies of located studies; contacted Australian government departments and nongovernment organizations; and two experts examined the resulting study list. We selected 27 studies, which randomly allocated patients to groups and were published in English, and we evaluated interventions aimed at increasing compliance with nonpharmacologic treatments for cardiovascular disease. These trials were critically appraised against eight methodologic criteria and, subsequently, classified as of good, fair, or poor quality. Information about target groups, samples, trial intervention strategies and their effectiveness were extracted from the 18 good- and fair-quality trials. Interrater reliability was high on the 20% of references that were double-coded. The 18 studies reviewed described the effectiveness of 27 intervention strategies at improving compliance with dietary, smoking-cessation, exercise, weight-loss, stress-reduction, general lifestyle, relaxation, and blood pressure screening programs. RESULTS: Tentative recommendations were made for or against most trial strategies: partner-focused and structural strategies showed the most consistent benefits, physician-focused strategies were unanimously unsuccessful, and patient-focused strategies were of mixed benefit. CONCLUSIONS: The methodologic quality of many of the located trials was less than optimal. Therefore, further good-quality, randomized trials are necessary to clarify the effectiveness of those strategies identified as potentially useful in this review.

Perceived sensitivity of mammographic screening: women's views on test accuracy and financial compensation for missed cancers.

OBJECTIVES: To estimate women's expectations of the accuracy of screening mammography and to explore attitudes towards compensation for missed cancers. DESIGN: Cross sectional survey (by telephone). SETTING: Australia; population-based survey conducted in April 1996. PARTICIPANTS: Random sample of women aged 30-69 years. A total of 2935 women completed the Breast Health Survey (adjusted response rate 65%). A random sample of 115 completed this sub-survey on perceived sensitivity of mammographic screening and compensation for missed cancers. RESULTS: About one third of women (32.2%, 95% CI 23.7, 40.7) had an unrealistically high expectation of the sensitivity of screening mammography, reporting it to be 95% or higher. Approximately 40% of the women (43.5%, 95% CI 34.4, 52.6) thought that screening mammography should pick up all cancers (should have a sensitivity of 100%). Just under half the women (45.2%, 95% CI 36.1, 54.3) said financial compensation should be awarded for a cancer missed by screening mammography even if the cancer was missed as a consequence of the small failure rate of the test. Younger women living in metropolitan areas and women who had realistic expectations of the accuracy of the tests were more likely to favour financial compensation. CONCLUSION: Unrealistically high expectations of the sensitivity of screening mammography were common in this group of women. Many women favoured financial compensation for missed cancers even if the cancer was missed solely because of the failure rate of the test. Public education is required to inform women of the limited sensitivity of breast cancer tests but this may not reduce claims for financial compensation when cancers are missed.

Predictors of returning for second round screening at a population based mammographic screening programme in Melbourne, Australia.

OBJECTIVE: To examine factors associated with returning for second round mammography screening. SETTING: This was a population based mammographic screening programme in Melbourne, Australia. DESIGN: A cohort design was used whereby 668 women were interviewed before the screening programme began and attendance for both first and second round screening was ascertained from programme records. The cohort sample was drawn from two regions of a defined area (close to and distant from the screening centre). MAIN RESULTS: Of the 315 women who attended for first round screening, 75% from the proximal sample and 70% from the distal sample returned for second round screening. Attendance at the second round was predicted by the following: the method of recruitment for first round screening, with women who required a letter of invitation and a reminder being less likely to reattend than those who initially attended in response to a community campaign (OR = 0.34; CI 0.19, 0.61); mammographic history before the initial screen, with women who reported previous diagnostic mammography being more likely to reattend than those who did not (OR = 2.97; CI 1.01, 8.9); stated intention of attending for the initial screen, with those with weakest intention of attending for their first round being less likely to attend for second round (OR = 0.44; CI 0.23, 0.85); and increasing scores on a scale that measured preventive orientation to health (OR = 1.24; CI 1.02, 1.50). CONCLUSION: Our findings corroborate other findings of reduced long term attendance for screening from people who are "reluctant participants" initially.

Behavioural dynamics of a clinical trial of sunscreens for reducing solar keratoses in Victoria, Australia.

OBJECTIVE: To determine whether the behaviour of participants based on perception of treatment group in a randomised trial contributed to clinical outcome. DESIGN: A double blind randomised controlled trial of the effect of daily application of SPF 17 broad spectrum sunscreen cream (or placebo) on solar keratoses. SETTING: A rural city in Victoria, Australia. Residents aged 40 years or over were invited by letter to attend for a skin cancer screening check. Of these, 588 people with between one and 30 solar keratoses enrolled in the trial and 431 completed the trial, which extended over a six month period that included summer. Participants' perceptions of their treatment allocation, adherence with the treatment regimen, adoption of other sun protection behaviours, side effects, and perceptions of change in condition were measured at two monthly intervals. RESULTS: There were no significant differences between those who completed the study and those that did not for sex, age, treatment group, skin type, number of solar keratoses or correct perception of treatment group. Thirty per cent of those completing the study correctly guessed their treatment allocation, and people were just as likely to be right as to be wrong when they stated their opinion about their treatment allocation (z = 1.04; p = 0.15). Study group, skin type, amount of time spent outdoors, presence of side effects, perceptions of change in skin condition did not significantly predict correct perception of treatment allocation. Multivariate analysis of variance indicated that adoption of other sun protection and adherence with cream use were not significantly affected by actual treatment allocation, correct perception of treatment allocation nor by their interaction. Poisson regression analysis showed a significantly lower difference ratio of solar keratoses in the sunscreen group compared with the placebo base cream group (OR 0.55; CI = 0.46, 0.64), and for women compared with men (OR = 0.76; CI = 0.63, 0.93) but no independent effect of any of the indices of other sun protection or adherence. CONCLUSIONS: A sufficient level of commitment to study procedures was achieved, so that trial participants did not adopt other behaviours that affected treatment outcomes. It is recommended that the potential threat to validity posed by the behaviour of participants be recognised at an early stage in planning of clinical trials, so that strategies to deal with this can be integrated into study protocols.

Task interruption in prospective memory: a frontal lobe function?

Prospective memory involves remembering an intention to do something as well as remembering the content of the task. It also shares common features with executive skills that are argued to be mediated by the frontal lobes. This paper describes performance on tests of prospective memory by a subject with bilateral frontal lobe infarcts and good retrospective memory but who displayed impairments of planning, initiation and inhibition of ongoing behaviour. The results lend some support to the suggestion that separate neuroanatomical pathways underly retrospective and prospective memory. They also indicate dissociable features within prospective memory that may reflect differences in utilisation of attentional resources and inhibitory control mechanisms.

How do old dogs learn new tricks: teaching a technological skill to brain injured people.

Little is known about the way people learn technological skills. This investigation was carried out to see how 100 brain injured, 50 controls and two amnesic patients performed on a task requiring them to learn a six-step programme for an electronic memory aid. Performance was correlated with other measures of memory to determine whether the technological skill was similar to a procedural learning task, a spatial memory task, a visual task, a verbal task or an amalgam of these. All controls but only 59 percent of the patients learned the task within three trials. The two amnesic patients also failed to learn the new skill. There was a high correlation between overall performance on a standardized test of everyday memory (the Rivermead Behavioural Memory Test) but little evidence that the technological skill was similar to a procedural learning task; nor was it specifically related to visual, verbal or spatial memory. It is concluded that a combination of skills is required to learn the technological task. Implications for the concept of procedural learning are discussed.

Why are amnesic judgements of recency and frequency made in a qualitatively different way from those of normal people?

The Huppert and Piercy (1978) test of recency and frequency judgements was given to a group of 12 non-Korsakoff amnesics of mixed aetiology and to four non-amnesic patients with selective frontal lobe lesions. The results confirmed that non-Korsakoff amnesics show a significant tendency to base their recency and frequency judgements on memory strength and that amnesics with medial temporal lobe damage show this tendency at least with recency judgements. The patients with frontal lobe lesions performed like normal subjects. Patients who were dysexecutive or impaired in cognitive resources were less likely to base recency judgements on trace strength. Such a recency bias was not however, correlated with measures of amnesic severity. The tendency to base frequency judgements on memory strength was not related to either degree of amnesia or reduction of cognitive resources.

Development and validation of the PCQ: a questionnaire to measure the psychological consequences of screening mammography.

We have developed a reliable and valid questionnaire to measure the psychological consequences of screening mammography. The questionnaire measures the effect of screening on an individual's functioning on emotional, social, and physical life domains. Content validity was ensured by extensive review of the relevant literature, discussion with professionals and interviews with attenders at a pilot Breast X-ray Screening Program in Melbourne, Australia. Discriminant validity was assessed by having expert judges sort items into dimensions which they appeared to be measuring. Acceptable levels of concordance (above 80%) with a priori classifications were found. Concurrent validity was demonstrated by comparison of subscale scores of 53 attenders at the Breast X-ray Program with an independent interview assessment of dysfunction on each of the emotional, social and physical dimensions. There was over 79% agreement between interview scores and questionnaire scores for each dimension. Construct validity was confirmed by showing that subscale scores varied in predicted ways. For women who were recalled for further investigation, scores on each subscale measuring negative consequences, were higher at the recall clinic than at screening clinic (emotional: t = -7.28; df = 70; P less than 0.001; physical: t = -2.53; df = 70; P = 0.014; social: t = -2.49; df = 70; P = 0.015). The internal consistency of all subscales was found to be acceptable. This questionnaire is potentially useful for assessing the psychological consequences of the screening process and should have wide application.