Subject(s)
Breast Neoplasms , Humans , Breast Neoplasms/radiotherapy , Breast Neoplasms/pathology , Female , Radiotherapy DosageABSTRACT
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.
Subject(s)
Breast Neoplasms , COVID-19 , Porcine Reproductive and Respiratory Syndrome , Self-Management , Swine , Animals , Humans , Female , Breast Neoplasms/drug therapy , Quality of LifeABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Consultants , Education, Medical , Medical Oncology/education , Clinical Competence , Humans , Physicians , Radiologists , Surveys and Questionnaires , WorkloadABSTRACT
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.
Subject(s)
Cardiovascular Agents/pharmacokinetics , Cardiovascular Agents/therapeutic use , Electrocardiography/drug effects , Long QT Syndrome/drug therapy , Female , Humans , MaleABSTRACT
AIMS: To seek the views of consultants appointed less than 2 years ago on the appropriateness of their training in fitting them to carry out their present posts, the FRCR examination, experience of research and the prevalence and value of out of programme experience and acting up as a consultant. MATERIALS AND METHODS: All the consultants identified from the Royal College of Radiologists' database as having been appointed to a consultant post in the last 2 years were emailed inviting them to take part in a web-based survey. RESULTS: The response rate was 60% (32 of 53 consultants). Ninety-four per cent agreed or strongly agreed that training had equipped them for clinical work as a consultant, but only 44% agreed or strongly agreed that training had equipped them to fulfil the management roles. Free text answers stressed the importance of management skills, getting involved with trial set-up and producing publications early in their career. Ninety-four per cent agreed or strongly agreed that they had adequate opportunity to develop skills in systemic therapy and radiotherapy planning, but only 56% thought this was the case for intensity-modulated radiotherapy and image-guided radiotherapy. Although 87% agreed or strongly agreed they had sufficient opportunity to develop teaching skills, this was only the case in 62% with regard to research skills. They published a median number of three papers in peer-reviewed journals. Twenty-five per cent of respondents studied for research degrees; 69% of consultants had undertaken out of programme experience and 50% had acted up as a consultant and these were generally found to be valuable experiences. There was strong support for the FRCR examination. CONCLUSIONS: Consultants appointed in the last 2 years are generally satisfied with their training. Training in intensity-modulated radiotherapy and image-guided radiotherapy should be improved and the advanced specialist training requires reviewing to better fit consultants for subspecialisation, management and research.
Subject(s)
Consultants , Medical Oncology/education , Radiation Oncology/education , Attitude of Health Personnel , Data Collection , Education, Medical, Continuing/organization & administration , Humans , Medical Staff, Hospital/education , Professional Competence , Radiotherapy, Image-Guided , Radiotherapy, Intensity-Modulated , SpecializationABSTRACT
BACKGROUND: The risk of recurrence following surgery in women with early breast cancer varies, depending upon prognostic factors. Adjuvant chemotherapy reduces this risk; however, increasingly effective regimens are associated with higher costs and toxicity profiles, making it likely that different regimens may be cost-effective for women with differing prognoses. To investigate this we performed a cost-effectiveness analysis of four treatment strategies: (1) no chemotherapy, (2) chemotherapy using cyclophosphamide, methotrexate, and fluorouracil (CMF) (a first generation regimen), (3) chemotherapy using Epirubicin-CMF (E-CMF) or fluorouracil, epirubicin, and cyclophosphamide (FEC60) (a second generation regimens), and (4) chemotherapy with FEC60 followed by docetaxel (FEC-D) (a third generation regimen). These adjuvant chemotherapy regimens were used in three large UK-led randomised controlled trials (RCTs). METHODS: A Markov model was used to simulate the natural progression of early breast cancer and the impact of chemotherapy on modifying this process. The probability of a first recurrent event within the model was estimated for women with different prognostic risk profiles using a parametric regression-based survival model incorporating established prognostic factors. Other probabilities, treatment effects, costs and quality of life weights were estimated primarily using data from the three UK-led RCTs, a meta-analysis of all relevant RCTs, and other published literature. The model predicted the lifetime costs, quality adjusted life years (QALYs) and cost-effectiveness of the four strategies for women with differing prognoses. Sensitivity analyses investigated the impact of uncertain parameters and model assumptions. FINDINGS: For women with an average to high risk of recurrence (based upon prognostic factors and any other adjuvant therapies received), FEC-D appeared most cost-effective assuming a threshold of £20,000 per QALY for the National Health Service (NHS). For younger low risk women, E-CMF/FEC60 tended to be the optimal strategy and, for some older low risk women, the model suggested a policy of no chemotherapy was cost-effective. For no patient group was CMF chemotherapy the preferred option. Sensitivity analyses demonstrated cost-effectiveness results to be particularly sensitive to the treatment effect estimate for FEC-D and the future price of docetaxel. INTERPRETATION: To our knowledge, this analysis is the first cost-effectiveness comparison of no chemotherapy, and first, second, and third generation adjuvant chemotherapy regimens for early breast cancer patients with differing prognoses. The results demonstrate the potential for different treatment strategies to be cost-effective for different types of patients. These findings may prove useful for policy makers attempting to formulate cost-effective treatment guidelines in the field of early breast cancer.
Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Antineoplastic Agents/economics , Antineoplastic Combined Chemotherapy Protocols/economics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/economics , Chemotherapy, Adjuvant/economics , Cost-Benefit Analysis , Cyclophosphamide/economics , Cyclophosphamide/therapeutic use , Docetaxel , Epirubicin/economics , Epirubicin/therapeutic use , Female , Fluorouracil/economics , Fluorouracil/therapeutic use , Health Care Costs , Humans , Methotrexate/economics , Methotrexate/therapeutic use , Middle Aged , Prognosis , Quality-Adjusted Life Years , Taxoids/economics , Taxoids/therapeutic useABSTRACT
Electrocardiograms (ECGs) in patients with Parkinson's disease are affected by artifacts related to muscle tremor. Malik et al. report methods used in QTc study in patients with Parkinson's disease that markedly reduce the noise and variance of QTc in a sample of ECGs that are undeniably difficult to interpret. This study adds significant experience and novel methods that have the potential to further enhance the evaluation of the effect of a drug on QTc.
Subject(s)
Artifacts , Electrocardiography/standards , Parkinson Disease/physiopathology , Antiparkinson Agents/adverse effects , Antiparkinson Agents/pharmacology , Electrocardiography/drug effects , Electrocardiography/methods , Heart Conduction System/drug effects , Heart Conduction System/physiology , Humans , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Long QT Syndrome/physiopathology , Parkinson Disease/diagnosis , Parkinson Disease/drug therapy , Tremor/diagnosis , Tremor/drug therapy , Tremor/physiopathologySubject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Middle Aged , TrastuzumabABSTRACT
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.
Subject(s)
Evidence-Based Medicine , Testicular Neoplasms/therapy , Adolescent , Adult , Combined Modality Therapy , Follow-Up Studies , Humans , Male , Practice Guidelines as Topic , Recurrence , Testicular Neoplasms/physiopathology , Testicular Neoplasms/psychologyABSTRACT
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.
Subject(s)
Blood Pressure/drug effects , Cholesterol Ester Transfer Proteins/antagonists & inhibitors , Oxazolidinones/toxicity , Quinolines/toxicity , Adrenal Cortex/cytology , Adrenal Cortex/drug effects , Aldosterone/blood , Animals , Anticholesteremic Agents/toxicity , Corticosterone/blood , Dogs , Drug Evaluation, Preclinical , Female , Macaca mulatta , Male , Mice , Mice, Inbred C57BL , Models, Animal , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Rats , Rats, Sprague-Dawley , Species SpecificitySubject(s)
Cholesterol Ester Transfer Proteins/antagonists & inhibitors , Oxazolidinones/pharmacology , Oxazolidinones/pharmacokinetics , Administration, Oral , Adolescent , Adult , Cholesterol Ester Transfer Proteins/administration & dosage , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Humans , Male , Middle Aged , Oxazolidinones/administration & dosage , Reference Values , Risk Factors , Sensitivity and Specificity , Young AdultABSTRACT
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.
Subject(s)
Electrocardiography , HIV Integrase Inhibitors/adverse effects , Pyrrolidinones/adverse effects , Adult , Anti-Infective Agents/adverse effects , Aza Compounds/adverse effects , Cross-Over Studies , Double-Blind Method , Female , Fluoroquinolones , HIV Integrase Inhibitors/pharmacokinetics , Humans , Male , Middle Aged , Moxifloxacin , Pyrrolidinones/pharmacokinetics , Quinolines/adverse effects , Raltegravir Potassium , Time FactorsABSTRACT
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.
Subject(s)
Anti-Infective Agents/adverse effects , Aza Compounds/adverse effects , Long QT Syndrome/chemically induced , Quinolines/adverse effects , Research Design , Adult , Anti-Infective Agents/administration & dosage , Aza Compounds/administration & dosage , Cross-Over Studies , Dose-Response Relationship, Drug , Electrocardiography , Female , Fluoroquinolones , Humans , Long QT Syndrome/physiopathology , Male , Moxifloxacin , Pilot Projects , Quinolines/administration & dosageABSTRACT
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.