The SWAP Filter: A Simple Azimuthally Varying Radial Filter for Wide-Field EUV Solar Images.

We present the SWAP Filter: an azimuthally varying, radial normalizing filter specifically developed for EUV images of the solar corona, named for the Sun Watcher with Active Pixels and Image Processing (SWAP) instrument on the Project for On-Board Autonomy 2 (PROBA2) spacecraft. We discuss the origins of our technique, its implementation and key user-configurable parameters, and highlight its effects on data via a series of examples. We discuss the filter's strengths in a data environment in which wide field-of-view observations that specifically target the low signal-to-noise middle corona are newly available and expected to grow in the coming years. Supplementary Information: The online version contains supplementary material available at 10.1007/s11207-023-02183-w.

Patients' experiences of a suppoRted self-manAGeMent pAThway In breast Cancer (PRAGMATIC): quality of life and service use results.

PURPOSE: To describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway. METHODS: Participants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary). RESULTS: 99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy. The chemotherapy group had poorer QoL; FACT-B total score mean differences were 8.53 (95% CI: 3.42 to 13.64), 5.38 (95% CI: 0.17 to 10.58) and 8.00 (95% CI: 2.76 to 13.24) at 6, 9 and 12 months, respectively. The odds of psychological morbidity (GHQ12 >4) were 5.5-fold greater for those treated with chemotherapy. Financial and caring burdens (PRRS) were worse for this group (mean difference in change at 9 months 3.25 (95% CI: 0.42 to 6.07)). GSE and GHQ-12 scores impacted FACT-B total scores, indicating QoL decline for those with high baseline psychological morbidity. Chemotherapy patients or those with high psychological morbidity or were unable to carry out normal activities had the highest service costs. Over the 12 months, 68.2% participants phoned/emailed breast care nurses, and 53.3% visited a hospital breast clinician. CONCLUSION: The data suggest that chemotherapy patients and/or those with heightened psychological morbidity might benefit from closer monitoring and/or supportive interventions whilst on the SSM/PIFU pathway. Reduced access due to COVID-19 could have affected service use.

Understanding the Physical Nature of Coronal "EIT Waves".

For almost 20 years the physical nature of globally propagating waves in the solar corona (commonly called "EIT waves") has been controversial and subject to debate. Additional theories have been proposed over the years to explain observations that did not agree with the originally proposed fast-mode wave interpretation. However, the incompatibility of observations made using the Extreme-ultraviolet Imaging Telescope (EIT) onboard the Solar and Heliospheric Observatory with the fast-mode wave interpretation was challenged by differing viewpoints from the twin Solar Terrestrial Relations Observatory spacecraft and data with higher spatial and temporal resolution from the Solar Dynamics Observatory. In this article, we reexamine the theories proposed to explain EIT waves to identify measurable properties and behaviours that can be compared to current and future observations. Most of us conclude that the so-called EIT waves are best described as fast-mode large-amplitude waves or shocks that are initially driven by the impulsive expansion of an erupting coronal mass ejection in the low corona.

The effect of moxifloxacin on QTc and implications for the design of thorough QT studies.

A number of issues have remained unanswered in the design of "thorough QT"(TQT) studies. In this randomized, placebo-controlled, two-period crossover study in 20 healthy subjects, replicate electrocardiograms (ECGs) were recorded on a digital 12-lead Holter recorder, extracted in a core ECG laboratory, and interpreted manually by a cardiologist. The observed within-subject variability was slightly greater when time-matched baselines were employed than when predose baselines were employed, whereas the magnitude of the increase in QTc was similar for both. Moxifloxacin 400 mg was associated with an observed 7.5-12.5 ms increase in the mean placebo- and baseline-corrected QTc interval. A PK-QTc model estimated a 3.9 ms increase in the QTc interval for every 1,000 ng/ml increase in moxifloxacin concentration. The QTc increases associated with moxifloxacin support the appropriateness of its use as a positive control in TQT studies. This crossover study failed to justify the use of time-matched baselines rather than the less resource-intensive predose definition of baseline.

Evidence-based pragmatic guidelines for the follow-up of testicular cancer: optimising the detection of relapse.

Testicular germ cell tumours (TGCTs) are the most common cause of cancer in men between the ages of 15 and 40 years, and, overall, the majority of patients should expect to be cured. The European Germ Cell Cancer Consensus Group has provided clear guidelines for the primary treatment of both seminoma and nonseminomatous germ cell tumours. There is, however, no international consensus on how best to follow patients after their initial management. This must promptly and reliably identify relapses without causing further harm. The standardising of follow-up would result in optimising risk-benefit ratios for individual patients, while ensuring economic use of resources. We have identified the seven common scenarios in managing seminomas and nonseminomas of the various stages and discuss the pertinent issues around relapse and follow-up. We review the available literature and present our comprehensive TGCT follow-up guidelines. Our protocols provide a pragmatic, easily accessible user-friendly basis for other centres to use or to adapt to suit their needs. Furthermore, this should enable future trials to address specific issues around follow-up giving meaningful and useful results.

Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone.

BACKGROUND AND PURPOSE: Inhibition of cholesteryl ester transfer protein (CETP) with torcetrapib in humans increases plasma high density lipoprotein (HDL) cholesterol levels but is associated with increased blood pressure. In a phase 3 clinical study, evaluating the effects of torcetrapib in atherosclerosis, there was an excess of deaths and adverse cardiovascular events in patients taking torcetrapib. The studies reported herein sought to evaluate off-target effects of torcetrapib. EXPERIMENTAL APPROACH: Cardiovascular effects of the CETP inhibitors torcetrapib and anacetrapib were evaluated in animal models. KEY RESULTS: Torcetrapib evoked an acute increase in blood pressure in all species evaluated whereas no increase was observed with anacetrapib. The pressor effect of torcetrapib was not diminished in the presence of adrenoceptor, angiotensin II or endothelin receptor antagonists. Torcetrapib did not have a contractile effect on vascular smooth muscle suggesting its effects in vivo are via the release of a secondary mediator. Treatment with torcetrapib was associated with an increase in plasma levels of aldosterone and corticosterone and, in vitro, was shown to release aldosterone from adrenocortical cells. Increased adrenal steroid levels were not observed with anacetrapib. Inhibition of adrenal steroid synthesis did not inhibit the pressor response to torcetrapib whereas adrenalectomy prevented the ability of torcetrapib to increase blood pressure in rats. CONCLUSIONS AND IMPLICATIONS: Torcetrapib evoked an acute increase in blood pressure and an acute increase in plasma adrenal steroids. The acute pressor response to torcetrapib was not mediated by adrenal steroids but was dependent on intact adrenal glands.

Raltegravir thorough QT/QTc study: a single supratherapeutic dose of raltegravir does not prolong the QTcF interval.

Raltegravir is a novel HIV-1 integrase inhibitor with potent in vitro activity (IC(95) = 31 nM in 50% human serum). A double-blind, randomized, placebo-controlled, double-dummy, 3-period, single-dose crossover study was conducted; subjects received single oral doses of 1600 mg raltegravir, 400 mg moxifloxacin, and placebo. The upper limit of the 2-sided 90% confidence interval for the QTcF interval placebo-adjusted mean change from baseline of raltegravir was less than 10 ms at every time point. For the raltegravir and placebo groups, there were no QTcF values >450 ms or change from baseline values >30 ms. A mean C(max) of approximately 20 muM raltegravir was attained, approximately 4-fold higher than the C(max) at the clinical dose. Moxifloxacin demonstrated an increase in QTcF at the 2-, 3-, and 4-hour time points. Administration of a single supratherapeutic dose of raltegravir does not prolong the QTcF interval. A single supratherapeutic dose design may be appropriate for crossover thorough QTc studies.

Training in Clinical Oncology and the Transition from Trainee to Consultant: Results of the Royal College of Radiologists' 2015 Post-Certificate of Completion of Training Survey.

AIMS: To seek feedback from clinical oncologists as to their experiences of specialty training and, where applicable, the transition to working as a consultant in the National Health Service. MATERIALS AND METHODS: All clinical oncologists gaining a Certificate of Completion of Training between 1 July 2012 and 30 June 2014 were identified through records held by the Royal College of Radiologists and approached in May 2015 to take part in an online survey. RESULTS: The survey was completed by 38 of 80 clinical oncologists invited to take part (48% response rate). Most respondents (>87%) agreed that specialty training equipped them well with clinical skills in radiotherapy planning, systemic therapy and tumour site diagnosis and treatment. This fell to 58% with advanced radiotherapy techniques. Of the non-clinical skills, respondents felt training had equipped them less to deal with leadership and management (53%) and research (48%) than clinical governance (61%). Despite wanting to do so, 42% of respondents did not undertake any out-of-programme (OOP) activity to gain new skills. Most of those respondents who did undertake OOP activity agreed that it helped to prepare them for their first consultant post. There is broad support for the FRCR Examination. The First FRCR Examination modules in physics, pharmacology, tumour biology and radiobiology were seen to be very relevant to clinical practice by 50% or more of respondents. The Final FRCR Examination was seen as essential in a technical specialty like clinical oncology by 92% of respondents. Working as a new consultant, the survey revealed a heavy workload for most respondents, with 69% always or almost always working beyond contracted hours. Other issues of concern identified were discrepancies in advertised consultant job plans and ineffectiveness of the job plan review process. The trainee-consultant transition is often a difficult time, yet only 19% of respondents were allocated a formal mentor. Most respondents had to rely on informal arrangements in seeking support and advice from medical colleagues. CONCLUSIONS: In general, respondents were satisfied with their specialty training and the transition from training to working as a new consultant. Areas for possible improvement have been identified for employers as well as those involved in organising specialty training.

The changing pattern of management for hormone-refractory, metastatic prostate cancer.

Prostate cancer responds initially to hormonal manipulation by androgen withdrawal and peripheral androgen blockade. The inevitable progression to a hormone-refractory state is accompanied by an exacerbation of local symptoms and metastatic spread, principally to the bones, which has a considerable impact on quality of life and survival. Treatment of hormone-refractory prostate cancer is palliative, and surgery and radiotherapy are used for the relief of lower urinary tract symptoms and localized painful bony metastases. Systemic treatments are not widely accepted in this setting, but clinical trials have demonstrated the potential for bone targeting agents such as strontium-89 and the bisphosphonates to palliate painful bone metastases and to delay progression in certain settings. Chemotherapy with mitozantrone in combination with steroids has previously been shown to have palliative benefits and to delay progression. The additional costs incurred by the use of chemotherapy or bone-targeting therapies may be offset by gains in overall care with fewer in-patient admissions compared with steroid monotherapy. Recent clinical trials have demonstrated that docetaxel significantly improves patient quality of life, and importantly, increases survival. Future studies investigating the timing of chemotherapy, combinations with existing treatments or other novel therapies are underway.

Should bisphosphonates be part of the standard therapy of patients with multiple myeloma or bone metastases from other cancers? An evidence-based review.

PURPOSE: To review objectively the evidence for the use of bisphosphonates for the reduction of skeletal events or the management of pain due to multiple myeloma or bone metastases from other types of cancer. METHODS: MEDLINE was searched from 1976 onwards using the MeSH terms "exp diphosphonates/," "exp bone neoplasms/," "exp multiple myeloma/," and "bone metastases" as text words. Bibliographies of reports on these topics and major medical and scientific journals were searched. Experts in the field were approached. The question was defined and the evidence stratified in a hierarchical manner according to classification of study design. There were sufficient studies to enable the use of randomized trials only to address the questions. Effectiveness was defined and the evidence reviewed in a systematic manner. RESULTS AND CONCLUSION: Eighteen randomized trials were identified. No meta-analyses are available. There is level I evidence (defined as an appropriately conducted randomized clinical trial with a statistically significant result) for the use of bisphosphonates to reduce both skeletal events and pain in multiple myeloma and in breast cancer patients with metastatic bone disease. There is also level I evidence for their use as part of a pain management program for bone metastases from carcinoma of the breast, lung, and prostate, and for symptomatic myeloma. The bisphosphonates appear to be well tolerated.

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation.

In a trial of prophylactic implantation of a defibrillator, a mortality benefit was seen among patients with previous myocardial infarction and a left-ventricular ejection fraction of 0.30 or less. We identified 129 similar patients from two previously published clinical trials in which microvolt T-wave alternans testing was prospectively assessed. At 24 months of follow-up, no sudden cardiac death or cardiac arrest was seen among patients who tested T-wave alternans negative, compared with an event rate of 15.6% among the remaining patients. Testing of T-wave alternans seems to identify patients who are at low risk of ventricular tachyarrhythmic event and who may not benefit from defibrillator therapy.

A comparison of T-wave alternans, signal averaged electrocardiography and programmed ventricular stimulation for arrhythmia risk stratification.

OBJECTIVES: The goal of this study was to compare T-wave alternans (TWA), signal-averaged electrocardiography (SAECG) and programmed ventricular stimulation (EPS) for arrhythmia risk stratification in patients undergoing electrophysiology study. BACKGROUND: Accurate identification of patients at increased risk for sustained ventricular arrhythmias is critical to prevent sudden cardiac death. T-wave alternans is a heart rate dependent measure of repolarization that correlates with arrhythmia vulnerability in animal and human studies. Signal-averaged electrocardiography and EPS are more established tests used for risk stratification. METHODS: This was a prospective, multicenter trial of 313 patients in sinus rhythm who were undergoing electrophysiologic study. T-wave alternans, assessed with bicycle ergometry, and SAECG were measured before EPS. The primary end point was sudden cardiac death, sustained ventricular tachycardia, ventricular fibrillation or appropriate implantable defibrillator (ICD) therapy, and the secondary end point was any of these arrhythmias or all-cause mortality. RESULTS: Kaplan-Meier survival analysis of the primary end point showed that TWA predicted events with a relative risk of 10.9, EPS had a relative risk of 7.1 and SAECG had a relative risk of 4.5. The relative risks for the secondary end point were 13.9, 4.7 and 3.3, respectively (p < 0.05). Multivariate analysis of 11 clinical parameters identified only TWA and EPS as independent predictors of events. In the prespecified subgroup with known or suspected ventricular arrhythmias, TWA predicted primary end points with a relative risk of 6.1 and secondary end points with a relative risk of 8.0. CONCLUSIONS: T-wave alternans is a strong independent predictor of spontaneous ventricular arrhythmias or death. It performed as well as programmed stimulation and better than SAECG in risk stratifying patients for life-threatening arrhythmias.

The effects of adjuvant chemotherapy on cognition in women with breast cancer--preliminary results of an observational longitudinal study.

Several studies have reported that chemotherapy-treated patients have impaired cognition function relative to control groups. We are conducting a longitudinal study with cognitive assessments at baseline, 6 and 18 months. A planned preliminary analysis of data from 50 chemotherapy patients and 43 healthy controls at baseline and post-treatment found a significant group by time interaction on three measures of verbal and working memory. Chemotherapy patients were more likely to show cognitive decline than controls (OR 2.25). Patients were significantly more likely to have GHQ(12) scores indicative of possible psychological morbidity and showed significant increases in endocrine symptoms and fatigue post-treatment however neither GHQ(12) nor quality-of-life variables were related to cognitive performance.

Incorporating exposure-response modeling into the assessment of QTc interval: A potential alternative to the thorough QT study.

ICH E14 mandates that a thorough QTc study (TQT) is conducted as part of the clinical drug development program to provide an accurate and precise estimate of a drug's effect on the QTc. In the April issue of CPT, Darpo et al. report the results of a study which validated an alternative approach to evaluating the effect of a drug on QTc using exposure-response modeling in phase I which has the potential to make the TQT study obsolete.

Indications, methodology, and classification of results of tilt-table testing.

Tilt-table testing has become an important part of the evaluation of patients with unexplained syncope, although not every patient with vasovagal syncope requires it. Studies have attested to the effectiveness of the technique for providing direct diagnostic evidence of a patient's susceptibility to vasovagal syncope. This article reviews the need for tilt-table testing and the recommended methods for performing a test. In addition, a detailed classification of the hemodynamic patterns of collapse displayed over the course of a tilt-table study is provided. These distinctive collapse patterns document the evolution of a syncopal event and are particularly important to identify because they can influence the selection of therapy.

Effects of age on outcome of tilt-table testing.

Although neurally mediated syncope is thought to be common in the young and rare in the elderly, there are few data evaluating the effects of age on the outcome of tilt-table testing (TTT), especially in patients aged > or =80 years. We examined the results of TTT in 352 subjects with unexplained syncope including 133 patients >65 years of age and 43 patients >80 years of age. The average age was 54 +/- 20.8 years (range 11 to 99) and 51% were men. The TTT protocol included at least 45 minutes of upright tilt in the drug-free state with or without repeat TTT with isoproterenol or 15 minutes of upright tilt in the drug-free state followed by repeat TTT with isoproterenol. One hundred sixty-four subjects (47%) had a positive TTT. As expected, there was an age-related decline in positive TTT. A high proportion of elderly patients with unexplained syncope had a positive TTT (37% of patients aged > or =65, and 23% patients aged > or =80). Thus, TTT is a useful diagnostic test in patients aged > or =65 years with unexplained syncope.

Correlation between the signal-averaged electrocardiogram from Holter tapes and from real-time recordings.

Signal-averaged electrocardiograms obtained from 3-channel Holter recordings were compared, using the same skin electrodes, with signal-averaged real-time recordings in 32 subjects. The numeric late potential parameters and morphologic appearances correlated closely between the 2 methods. The restricted high frequency response of Holter systems appears not to militate against clinically useful late potential analysis from Holter tape. This study suggests that diagnostic accuracy using real-time 25 to 250-Hz criteria is acceptable for clinical use until criteria derived specifically for Holter applications become available. Holter analysis may confer significant benefits resulting from an ability to perform late potential analysis on the same tape used for conventional arrhythmia analysis, and would allow future studies of possible dynamic changes of late potentials in relation to transient ischemia and spontaneous ventricular tachyarrhythmias.