What affected UK adults' adherence to medicines during the COVID-19 pandemic? Cross-sectional survey in a representative sample of people with long-term conditions.

Aim: Medicines non-adherence is associated with poorer outcomes and higher costs. COVID-19 affected access to healthcare, with increased reliance on remote methods, including medicines supply. This study aimed to identify what affected people's adherence to medicines for long-term conditions (LTCs) during the pandemic. Subject and methods: Cross-sectional online survey of UK adults prescribed medicines for LTCs assessing self-reported medicines adherence, reasons for non-adherence (using the capability, opportunity and motivation model of behaviour [COM-B]), medicines access and COVID-19-related behaviours. Results: The 1746 respondents reported a mean (SD) of 2.5 (1.9) LTCs, for which they were taking 2.4 (1.9) prescribed medicines, 525 (30.1%) reported using digital tools to support ordering or taking medicines and 22.6% reported medicines non-adherence. No access to at least one medicine was reported by 182 (10.4%) respondents; 1048 (60.0%) reported taking at least one non-prescription medicine as a substitute; 409 (23.4%) requested emergency supply from pharmacy for at least one medicine. Problems accessing medicines, being younger, male, in the highest socioeconomic group and working were linked to poorer adherence. Access problems were mostly directly or indirectly related to the COVID-19 pandemic. Respondents were generally lacking in capabilities and opportunities, but disruptions to habits (automatic motivation) was the major reason for non-adherence. Conclusion: Navigating changes in how medicines were accessed, and disruption of habits during the COVID-19 pandemic, was associated with suboptimal adherence. People were resourceful in overcoming barriers to access. Solutions to support medicines-taking need to take account of the multiple ways that medicines are prescribed and supplied remotely. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-022-01813-0.

Development of an intervention to increase adherence to nebuliser treatment in adults with cystic fibrosis: CFHealthHub.

BACKGROUND: Cystic fibrosis (CF) is a life-limiting genetic condition in which daily therapies to maintain lung health are critical, yet treatment adherence is low. Previous interventions to increase adherence have been largely unsuccessful and this is likely due to a lack of focus on behavioural evidence and theory alongside input from people with CF. This intervention is based on a digital platform that collects and displays objective nebuliser adherence data. The purpose of this paper is to identify the specific components of an intervention to increase and maintain adherence to nebuliser treatments in adults with CF with a focus on reducing effort and treatment burden. METHODS: Intervention development was informed by the Behaviour Change Wheel (BCW) and person-based approach (PBA). A multidisciplinary team conducted qualitative research to inform a needs analysis, selected, and refined intervention components and methods of delivery, mapped adherence-related barriers and facilitators, associated intervention functions and behaviour change techniques, and utilised iterative feedback to develop and refine content and processes. RESULTS: Results indicated that people with CF need to understand their treatment, be able to monitor adherence, have treatment goals and feedback and confidence in their ability to adhere, have a treatment plan to develop habits for treatment, and be able to solve problems around treatment adherence. Behaviour change techniques were selected to address each of these needs and were incorporated into the digital intervention developed iteratively, alongside a manual and training for health professionals. Feedback from people with CF and clinicians helped to refine the intervention which could be tailored to individual patient needs. CONCLUSIONS: The intervention development process is underpinned by a strong theoretical framework and evidence base and was developed by a multidisciplinary team with a range of skills and expertise integrated with substantial input from patients and clinicians. This multifaceted development strategy has ensured that the intervention is usable and acceptable to people with CF and clinicians, providing the best chance of success in supporting people with CF with different needs to increase and maintain their adherence. The intervention is being tested in a randomised controlled trial across 19 UK sites.

A supervised machine learning approach to characterize spinal network function.

Spontaneous activity is a common feature of immature neuronal networks throughout the central nervous system and plays an important role in network development and consolidation. In postnatal rodents, spontaneous activity in the spinal cord exhibits complex, stochastic patterns that have historically proven challenging to characterize. We developed a software tool for quickly and automatically characterizing and classifying episodes of spontaneous activity generated from developing spinal networks. We recorded spontaneous activity from in vitro lumbar ventral roots of 16 neonatal [postnatal day (P)0-P3] mice. Recordings were DC coupled and detrended, and episodes were separated for analysis. Amplitude-, duration-, and frequency-related features were extracted from each episode and organized into five classes. Paired classes and features were used to train and test supervised machine learning algorithms. Multilayer perceptrons were used to classify episodes as rhythmic or multiburst. We increased network excitability with potassium chloride and tested the utility of the tool to detect changes in features and episode class. We also demonstrate usability by having a novel experimenter use the program to classify episodes collected at a later time point (P5). Supervised machine learning-based classification of episodes accounted for changes that traditional approaches cannot detect. Our tool, named SpontaneousClassification, advances the detail in which we can study not only developing spinal networks, but also spontaneous networks in other areas of the nervous system. NEW & NOTEWORTHY Spontaneous activity is important for nervous system network development and consolidation. Our software uses machine learning to automatically and quickly characterize and classify episodes of spontaneous activity in the spinal cord of newborn mice. It detected changes in network activity following KCl-enhanced excitation. Using our software to classify spontaneous activity throughout development, in pathological models, or with neuromodulation, may offer insight into the development and organization of spinal circuits.

Tumour stage and resection margin status are independent survival factors following partial pancreatoduodenectomy for duodenal adenocarcinoma.

INTRODUCTION: There is limited published evidence on duodenal carcinoma due to its rarity. This study aimed to evaluate gastric outlet obstruction and obstructive jaundice along with pathological variables as survival factors in patients with duodenal adenocarcinoma following resection. METHODS: Survival factor analysis was undertaken in patients undergoing duodenal cancer surgery from 1997 to 2015 in a single centre. RESULTS: There were 57 patients of whom 18 had gastric outlet obstruction and 14 had obstructive jaundice. Fifty-three had a partial pancreatoduodenectomy and four had palliative bypass. Perioperative mortality and morbidity were 4% (2/53) and 47% (25/53) respectively in resected patients. With a median (95% confidence interval, CI) follow-up of 72 (57-86) months, median overall and recurrence-free survival was 38 months (95% CI 28-113) and 27 months (95% CI 18-83) respectively. The 1 and 3-year overall survival rates were 84% (95% CI 74-95) and 52% (95% CI 39-69) respectively. Median overall survival was 19 months in patients with gastric outlet obstruction vs 53 months in those without (p = 0.026) and 28 months in patients with obstructive jaundice vs 38 months in those without (p = 0.611). Univariate analysis revealed that tumour stage, resection margin status, pre-operative albumin status, gastric outlet obstruction and age were associated with poorer overall and recurrence-free survival but multivariate analysis confirmed only tumour stage and resection margin status to be significant. CONCLUSION: Whereas gastric outlet obstruction in duodenal cancer appeared to be an important survival factor following partial pancreatoduodenectomy, multivariate analysis showed that only tumour stage and resection margin status were the key independent survival factors. Further multicentre studies are required to elucidate further characteristics of duodenal carcinoma and develop neoadjuvant/adjuvant management strategies.

Differentiation of Autoimmune Pancreatitis from Pancreatic Cancer Remains Challenging.

BACKGROUND: Autoimmune pancreatitis (AIP) is an uncommon form of chronic pancreatitis. Whilst being corticosteroid responsive, AIP often masquerades radiologically as pancreatic neoplasia. Our aim is to appraise demographic, radiological and histological features in our cohort in order to differentiate AIP from pancreatic malignancy. METHODS: Clinical, biochemical, histological and radiological details of all AIP patients 1997-2016 were analysed. The initial imaging was re-reviewed according to international guidelines by three blinded independent radiologists to evaluate features associated with autoimmune pancreatitis and pancreatic cancer. RESULTS: There were a total of 45 patients: 25 in type 1 (55.5%), 14 type 2 (31.1%) and 6 AIP otherwise not specified (13.3%). The median (IQR) age was 57 (51-70) years. Thirty patients (66.6%) were male. Twenty-six patients (57.8%) had resection for suspected malignancy and one for symptomatic chronic pancreatitis. Three had histologically proven malignancy with concurrent AIP. Two patients died from recurrent pancreatic cancer following resection. Multidisciplinary team review based on radiology and clinical history dictated management. Resected patients (vs. non-resected group) were older (64 vs. 53, p = 0.003) and more frequently had co-existing autoimmune pathologies (22.2 vs. 55.6%, p = 0.022). Resected patients also presented with less classical radiological features of AIP, which are halo sign (0/25 vs. 3/17, p = 0.029) and loss of pancreatic clefts (18/25 vs. 17/17, p = 0.017). There were no differences in demographic features other than age. CONCLUSION: Despite international guidelines for diagnosing AIP, differentiation from pancreatic cancer remains challenging. Resection remains an important treatment option in suspected cancer or where conservative treatment fails.

Retracing your footsteps: developmental insights to spinal network plasticity following injury.

During development of the spinal cord, a precise interaction occurs between descending projections and sensory afferents, with spinal networks that lead to expression of coordinated motor output. In the rodent, during the last embryonic week, motor output first occurs as regular bursts of spontaneous activity, progressing to stochastic patterns of episodes that express bouts of coordinated rhythmic activity perinatally. Locomotor activity becomes functionally mature in the 2nd postnatal wk and is heralded by the onset of weight-bearing locomotion on the 8th and 9th postnatal day. Concomitantly, there is a maturation of intrinsic properties and key conductances mediating plateau potentials. In this review, we discuss spinal neuronal excitability, descending modulation, and afferent modulation in the developing rodent spinal cord. In the adult, plastic mechanisms are much more constrained but become more permissive following neurotrauma, such as spinal cord injury. We discuss parallel mechanisms that contribute to maturation of network function during development to mechanisms of pathological plasticity that contribute to aberrant motor patterns, such as spasticity and clonus, which emerge following central injury.

Modulatory and plastic effects of kinins on spinal cord networks.

KEY POINTS: Inflammatory kinins are released following spinal cord injury or neurotrauma. The effects of these kinins on ongoing locomotor activity of central pattern generator networks are unknown. In the present study, kinins were shown to have short- and long-term effects on motor networks. The short-term effects included direct depolarization of interneurons and motoneurons in the ventral horn accompanied by modulation of transient receptor potential vanilloid 1-sensitive nociceptors in the dorsal horn. Over the long-term, we observed a bradykinin-mediated effect on promoting plasticity in the spinal cord. In a model of spinal cord injury, we observed an increase in microglia numbers in both the dorsal and ventral horn and, in a microglia cell culture model, we observed bradykinin-induced expression of glial-derived neurotrophic factor. ABSTRACT: The expression and function of inflammatory mediators in the developing spinal cord remain poorly characterized. We discovered novel, short and long-term roles for the inflammatory nonapeptide bradykinin (BK) and its receptor bradykinin receptor B2 (B2R) in the neuromodulation of developing sensorimotor networks following a spinal cord injury (SCI), suggesting that BK participates in an excitotoxic cascade. Functional expression of B2R was confirmed by a transient disruptive action of BK on fictive locomotion generated by a combination of NMDA, 5-HT and dopamine. The role of BK in the dorsal horn nociceptive afferents was tested using spinal cord attached to one-hind-limb (HL) preparations. In the HL preparations, BK at a subthreshold concentration induced transient disruption of fictive locomotion only in the presence of: (1) noxious heat applied to the hind paw and (2) the heat sensing ion channel transient receptor potential vanilloid 1 (TRPV1), known to be restricted to nociceptors in the superficial dorsal horn. BK directly depolarized motoneurons and ascending interneurons in the ventrolateral funiculus. We found a key mechanism for BK in promoting long-term plasticity within the spinal cord. Using a model of neonatal SCI and a microglial cell culture model, we examined the role of BK in inducing activation of microglia and expression of glial-derived neurotrophic factor (GDNF). In the neonatal SCI model, we observed an increase in microglia numbers and increased GDNF expression restricted to microglia. In the microglia cell culture model, we observed a BK-induced increased expression of GDNF via B2R, suggesting a novel mechanism for BK spinal-mediated plasticity.

Contribution of solid fuel, gas combustion, or tobacco smoke to indoor air pollutant concentrations in Irish and Scottish homes.

UNLABELLED: There are limited data describing pollutant levels inside homes that burn solid fuel within developed country settings with most studies describing test conditions or the effect of interventions. This study recruited homes in Ireland and Scotland where open combustion processes take place. Open combustion was classified as coal, peat, or wood fuel burning, use of a gas cooker or stove, or where there is at least one resident smoker. Twenty-four-hour data on airborne concentrations of particulate matter<2.5 µm in size (PM2.5), carbon monoxide (CO), endotoxin in inhalable dust and carbon dioxide (CO2), together with 2-3 week averaged concentrations of nitrogen dioxide (NO2) were collected in 100 houses during the winter and spring of 2009-2010. The geometric mean of the 24-h time-weighted-average (TWA) PM2.5 concentration was highest in homes with resident smokers (99 µg/m3--much higher than the WHO 24-h guidance value of 25 µg/m3). Lower geometric mean 24-h TWA levels were found in homes that burned coal (7 µg/m3) or wood (6 µg/m3) and in homes with gas cookers (7 µg/m3). In peat-burning homes, the average 24-h PM2.5 level recorded was 11 µg/m3. Airborne endotoxin, CO, CO2, and NO2 concentrations were generally within indoor air quality guidance levels. PRACTICAL IMPLICATIONS: Little is known about indoor air quality (IAQ) in homes that burn solid or fossil-derived fuels in economically developed countries. Recent legislative changes have moved to improve IAQ at work and in enclosed public places, but there remains a real need to begin the process of quantifying the health burden that arises from indoor air pollution within domestic environments. This study demonstrates that homes in Scotland and Ireland that burn solid fuels or gas for heating and cooking have concentrations of air pollutants generally within guideline levels. Homes where combustion of cigarettes takes place have much poorer air quality.

Diversification of intrinsic motoneuron electrical properties during normal development and botulinum toxin-induced muscle paralysis in early postnatal mice.

During early postnatal development, between birth and postnatal days 8-11, mice start to achieve weight-bearing locomotion. In association with the progression of weight-bearing locomotion there are presumed developmental changes in the intrinsic electrical properties of spinal -motoneurons. However, these developmental changes in the properties of -motoneuron properties have not been systematically explored in mice. Here, data are presented documenting the developmental changes of selected intrinsic motoneuron electrical properties, including statistically significant changes in action potential half-width, intrinsic excitability and diversity (quantified as coefficient of variation) of rheobase current, afterhyperpolarization half-decay time, and input resistance. In various adult mammalian preparations, the maintenance of intrinsic motoneuron electrical properties is dependent on activity and/or transmission-sensitive motoneuron-muscle interactions. In this study, we show that botulinum toxin-induced muscle paralysis led to statistically significant changes in the normal development of intrinsic motoneuron electrical properties in the postnatal mouse. This suggests that muscle activity during early neonatal life contributes to the development of normal motoneuron electrical properties.

Locomotor networks are targets of modulation by sensory transient receptor potential vanilloid 1 and transient receptor potential melastatin 8 channels.

It is well recognized that proprioceptive afferent inputs can control the timing and pattern of locomotion. C and Adelta afferents can also affect locomotion but an unresolved issue is the identity of the subsets of these afferents that encode defined modalities. Over the last decade, the transient receptor potential (TRP) ion channels have emerged as a family of non-selective cation conductances that can label specific subsets of afferents. We focus on a class of TRPs known as ThermoTRPs which are well known to be sensor receptors that transduce changes in heat and cold. ThermoTRPs are known to help encode somatosensation and painful stimuli, and receptors have been found on C and Adelta afferents with central projections onto dorsal horn laminae. Here we show, using in vitro neonatal mouse spinal cord preparations, that activation of both spinal and peripheral transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential melastatin 8 (TRPM8) afferent terminals modulates central pattern generators (CPGs). Capsaicin or menthol and cooling modulated both sacrocaudal afferent (SCA) evoked and monoaminergic drug-induced rhythmic locomotor-like activity in spinal cords from wild type but not TRPV1-null (trpv1(-/-)) or TRPM8-null (trpm8(-/-)) mice, respectively. Capsaicin induced an initial increase in excitability of the lumbar motor networks, while menthol or cooling caused a decrease in excitability. Capsaicin and menthol actions on CPGs involved excitatory and inhibitory glutamatergic mechanisms, respectively. These results for the first time show that dedicated pathways of somatosensation and pain identified by TRPV1 or TRPM8 can target spinal locomotor CPGs.

Modulation of AMPA currents by D(1)-like but not D(2)-like receptors in spinal motoneurons.

Dopamine can modulate and excite spinal locomotor networks, affect afferent transmission and increase motoneuronal excitability. One of the mechanisms whereby dopamine increases motoneuronal excitability is to potentiate AMPA channel-mediated glutamatergic transmission onto motoneurons. However, it is not known which dopaminergic receptor subtypes or the intracellular mechanisms contribute to these effects. In this study, we used whole-cell patch clamp techniques to record chemically evoked AMPA currents in neonatal mouse motoneurons. Bath application of D(1)-like receptor agonist (SKF 39383) increased the AMPA current amplitude and prolonged the decay time constant. In the presence of D(1) receptor antagonist LE300, the effects of DA on AMPA currents were blocked. In contrast, bath-application of the D(2)-like receptor agonist quinpirole did not modulate AMPA currents. In the presence of D(2) receptor antagonist L-741626, dopaminergic modulation of AMPA currents was unaffected. These results suggest that augmentation of AMPA transmission by dopamine is accomplished by D(1) receptor-based mechanisms. This short-term modulation does not appear to involve cycling of AMPA receptor into the membrane, since blocking insertion with botulinum toxin C did not affect the augmentation of AMPA currents after activating D(1) receptors. On the other hand, blocking protein kinase A (PKA) with H-89 completely abolished the effects of D(1) agonists. In addition, we used cell-attached single channel recording to demonstrate that stimulating D(1) receptors increased individual AMPA channel open probability and open duration. Our data demonstrate that dopamine increases the efficacy of glutamatergic transmission onto motoneurons by increasing AMPA conductances via a D(1) PKA-based signaling system.

A comparison of Aedes vigilax larval population densities and associated vegetation categories in a coastal wetland, Northern Territory, Australia.

Darwin's northern suburbs border an extensive coastal reed and upper mangrove wetland recognized as an important larval habitat for Aedes vigilax (Skuse), the northern salt marsh mosquito, an established vector for Ross River and Barmah Forest viruses and an appreciable pest species. We sought to identify the most important vegetation categories associated with Ae. vigilax breeding to maximize the efficiency of mosquito control efforts. Using a generalized linear model with negative binominal distribution and log link, this study compares larval densities, determined by focused dipping, between 13 discernable vegetation categories. The incidence rate ratios (RR) generated can be used to compare the magnitude of larval densities for each vegetation category, compared with the reference category. Aedes vigilax larval densities were almost ten times greater in artificial drainage areas (RR=9.82), followed by tide-affected reticulate (Sporobolus/Xerochloa) areas (RR=8.15), then Schoenoplectus/mangroves (RR=2.29), compared with the reference vegetation category "lower mangroves." Furthermore, larval densities were highest in May, due to tidal inundation, for drainage areas and tide-affected reticulates (RR=12.2, 11.7, respectively) compared with March, the reference month. Thus, to maximize the efficiency of aerial salt marsh mosquito control operations in this wetland, larval control is best accomplished by concentrating on drains, Schoenoplectus/mangroves, and tide-affected reticulate areas, commencing early after the wet season. These results should apply to other areas of salt marsh mosquito breeding across northern Australia.

A geospatial evaluation of Aedes vigilax larval control efforts across a coastal wetland, Northern Territory, Australia.

Adjacent to the northern suburbs of Darwin is a coastal wetland that contains important larval habitats for Aedes vigilax (Skuse), the northern salt marsh mosquito. This species is a vector for Ross River virus and Barmah Forest virus, as well as an appreciable human pest. In order to improve aerial larval control efforts, we sought to identify the most important vegetation categories and climatic/seasonal aspects associated with control operations in these wetlands. By using a generalized linear model to compare aerial control for each vegetation category, we found that Schoenoplectus/mangrove areas require the greatest amount of control for tide-only events (30.1%), and also extensive control for tide and rain events coinciding (18.2%). Our results further indicate that tide-affected reticulate vegetation indicated by the marsh grasses Sporobolus virginicus and Xerochloa imberbis require extensive control for Ae. vigilax larvae after rain-only events (44.7%), and tide and rain events coinciding (38.0%). The analyses of vector control efforts by month indicated that September to January, with a peak in November and December, required the most control. A companion paper identifies the vegetation categories most associated with Aedes vigilax larvae population densities in the coastal wetland. To maximize the efficiency of aerial salt marsh mosquito control operations in northern Australia, aerial control efforts should concentrate on the vegetation categories with high larval densities between September and January.

Preoperative resolution of jaundice following biliary stenting predicts more favourable early survival in resected pancreatic ductal adenocarcinoma.

INTRODUCTION: Despite the widespread use of endoscopic biliary stenting in patients presenting with potentially resectable pancreatic cancer, there is no general consensus regarding whether this represents a superior management approach over expeditious surgical intervention. The objective of this study was to investigate the influence of preoperative biliary stenting and resolution of jaundice on subsequent postoperative survival following resection for pancreatic cancer. METHODS: 155 patients undergoing partial pancreatoduodenectomy for pancreatic ductal adenocarcinoma between January 1997 and August 2007 were identified from a prospectively maintained database. RESULTS: There was no survival difference when comparing patients undergoing preoperative biliary drainage (n = 130) with those who did not (n = 25) (log rank, P = 0.981). When analysing individual prognostic factors as continuous variables in univariate Cox analysis, lower albumin levels (P = 0.016), elevated alkaline phosphatase levels (P = 0.011) and elevated CRP levels (P = 0.021) were associated with poorer overall survival. Multivariable Cox regression demonstrated that both albumin (P = 0.008) and CRP (P = 0.038) remained significant independent predictors of overall survival alongside lymph node ratio (P = 0.018). Although preoperative bilirubin levels were not associated with overall survival when analysed as a continuous variable (Cox, P = 0.786), the presence of jaundice (i.e., bilirubin >35 micromol/l) at the time of surgery was a significant adverse predictor of early survival in patients undergoing preoperative biliary drainage (Breslow-Gehan-Wilcoxon, P = 0.013) and remained a significant predictor of early survival when included in a further Cox analysis with censoring of cases who survived beyond 6 months (Cox, P = 0.017). CONCLUSION: These results suggest that the presence of jaundice at the time of resection has an adverse impact on early, but not overall, postoperative survival in pancreatic cancer patients undergoing preoperative biliary drainage.

Automatic seed initialization for the expectation-maximization algorithm and its application in 3D medical imaging.

Statistical partitioning of images into meaningful areas is the goal of all region-based segmentation algorithms. The clustering or creation of these meaningful partitions can be achieved in number of ways but in most cases it is achieved through the minimization or maximization of some function of the image intensity properties. Commonly these optimization schemes are locally convergent, therefore initialization of the parameters of the function plays a very important role in the final solution. In this paper we perform an automatically initialized expectation-maximization algorithm to partition the data in medical MRI images. We present analysis and illustrate results against manual initialization and apply the algorithm to some common medical image processing tasks.

[Link between rheumatoid arthritis and cancer]. / Der Zusammenhang zwischen rheumatoider Arthritis und Krebs.

Because it is a systemic disorder, rheumatoid arthritis (RA) is known to predispose affected individuals to other organ manifestations as well as arthritic problems. The serious complications include pericarditis, pulmonary and cutaneous nodules, episcleritis, and rheumatoid vasculitis. Of late, a significantly increased incidence of lymphoma has also accumulated. The overall risk is about double than in the general population, but that in patients with the most severe arthritis is dramatically higher. Men with RA appear to have an extremely elevated risk of Hodgkin's disease, which has also been observed at a higher incidence among the children of affected patients. These lymphomas are not typically infected with EBV, though RA patients have a defective capacity to control systemic EBV infection. Increasing attention is being paid to the effect of RA treatments on development of lymphoma, and some patients with EBV-positive tumors who have been taking methotrexate have shown a positive response after just discontinuing this drug. More controversial is the question of whether anti-TNF alpha agents involve an increased risk of lymphoma; in light of the conflicting evidence this matter is still unresolved.

Left-ventricle myocardium segmentation using a coupled level-set with a priori knowledge.

This paper presents a coupled level-set segmentation of the myocardium of the left ventricle of the heart using a priori information. From a fast marching initialisation, two fronts representing the endocardium and epicardium boundaries of the left ventricle are evolved as the zero level-set of a higher dimension function. We introduce a novel and robust stopping term using both gradient and region-based information. The segmentation is supervised both with a coupling function and using a probabilistic model built from training instances. The robustness of the segmentation scheme is evaluated by performing a segmentation on four unseen data-sets containing high variation and the performance of the segmentation is quantitatively assessed.

Automatic segmentation of the left ventricle cavity and myocardium in MRI data.

A novel approach for the automatic segmentation has been developed to extract the epi-cardium and endo-cardium boundaries of the left ventricle (lv) of the heart. The developed segmentation scheme takes multi-slice and multi-phase magnetic resonance (MR) images of the heart, transversing the short-axis length from the base to the apex. Each image is taken at one instance in the heart's phase. The images are segmented using a diffusion-based filter followed by an unsupervised clustering technique and the resulting labels are checked to locate the (lv) cavity. From cardiac anatomy, the closest pool of blood to the lv cavity is the right ventricle cavity. The wall between these two blood-pools (interventricular septum) is measured to give an approximate thickness for the myocardium. This value is used when a radial search is performed on a gradient image to find appropriate robust segments of the epi-cardium boundary. The robust edge segments are then joined using a normal spline curve. Experimental results are presented with very encouraging qualitative and quantitative results and a comparison is made against the state-of-the art level-sets method.

Phase III trial of satraplatin, an oral platinum plus prednisone vs. prednisone alone in patients with hormone-refractory prostate cancer.

Satraplatin is a novel oral platinum (IV) complex that shows activity against hormone-refractory prostate cancer (HRPC) in cisplatin-resistant human tumor lines in phase I and phase II trials. A randomized multicenter phase III trial with a target sample size of 380 patients was initiated in men with HRPC. After 50 randomized patients, the trial was closed to further accrual by the sponsoring company. An ad hoc analysis of all available data is reported here. Eligibility criteria included pathological proof of prostate cancer, documented progression despite prior hormonal manipulation, WHO PS 0-2, and no daily intake of narcotic analgesics. Patients were randomized between satraplatin 100 mg/m(2) for 5 days plus prednisone 10 mg orally BID or prednisone alone. Compliance was excellent. 48/50 patients have progressed and 42 have died, mostly due to prostate cancer. Median overall survival was 14.9 months (95% CI: 13.7-28.4) on the satraplatin plus prednisone arm and 11.9 months (95% CI: 8.4-23.1) on prednisone alone (hazard ratio, HR = 0.84, 95% CI: 0.46-1.55). A >50% decrease in prostrate specific antigen (PSA) was seen in 9/27 (33.3%) in the satraplatin plus prednisone arm vs. 2/23 (8.7%) on the prednisone alone arm. Progression-free survival was 5.2 months (95% CI: 2.8-13.7) on the satraplatin plus prednisone arm as compared to 2.5 months (95% CI: 2.1- 4.7) on the prednisone alone arm (HR = 0.50, 95% CI: 0.28-0.92). This difference is statistically significant (p = 0.023). Toxicity was generally minimal in both arms. This randomized comparison of a combination of satraplatin and prednisone versus prednisone alone supports the antitumor activity of the combination. Its role in the treatment of HPRC remains to be elucidated in an appropriate phase III setting.