Hospitalization and hospital mortality rates during the first and second waves of the COVID-19 pandemic in Quebec: interrupted time series and decomposition analysis.

OBJECTIVES: We investigated hospitalization and hospital mortality rates by cause during the first year of the COVID-19 pandemic in Quebec, Canada. STUDY DESIGN: Interrupted time series and decomposition analysis. METHODS: We analyzed hospital mortality during the first (February 25-August 22, 2020) and second waves (August 23, 2020-March 31, 2021), compared with 2019. We identified the cause of death and examined trends using: 1) interrupted time series analysis; 2) log-binomial regression; and 3) decomposition of cause-specific mortality. RESULTS: Hospitalization rates decreased; however, the proportion of deaths increased from 27.0 per 1000 in 2019 to 35.0 per 1000 in the first wave, for an excess of 8.0 deaths per 1000 admissions. COVID-19 was the cause of a third of excess deaths (2.6 per 1000). Other drivers of excess deaths included respiratory conditions (1.6 deaths per 1000), circulatory disorders (0.6 deaths per 1000), and cancer (0.9 deaths per 1000). COVID-19 was the cause of 58% of excess deaths in the second wave. Interrupted time series regression indicated that the proportion of deaths increased at the outset of the first wave but returned to prepandemic levels before increasing again in the second wave. Compared with 2019, the first wave was associated with 1.31 times (95% confidence interval [CI] 1.28-1.33) and the second wave with 1.17 times (95% CI 1.15-1.19) the risk of death during hospitalization. CONCLUSIONS: The pandemic was associated with a greater risk of hospital mortality. Excess deaths were driven by COVID-19 but also other causes, including respiratory conditions, circulatory disorders, and cancer.

Predictors and impact of postoperative atrial fibrillation following thoracic surgery: a state-of-the-art review.

This review of 19 studies (39,783 patients) of atrial fibrillation after thoracic surgery addresses the pathophysiology, incidence, and consequences of atrial fibrillation in this population, as well as its prevention and management. Interestingly, atrial fibrillation was most often identified in patients not previously known to have the disease. Rhythm control with amiodarone was the most commonly used treatment and nearly all patients were discharged in sinus rhythm. Major predictors were age; male sex; history of atrial fibrillation; congestive heart failure; left atrial enlargement; elevated brain natriuretic peptide level; and the invasiveness of procedures. Overall, patients with atrial fibrillation stayed 3 days longer in hospital. We also discuss the importance of standardising research on this subject and provide recommendations that might mitigate the impact postoperative atrial fibrillation on hospital resources.

Transcatheter closure of aneurysmal perimembranous ventricular septal defect with the canine duct occluder in two dogs.

Congenital membranous ventricular septal aneurysm has been reported in dogs and can be associated with a perimembranous ventricular septal defect (VSD). The windsock-like ventricular septal aneurysm is formed by tissue of the membranous ventricular septum and portions of the septal leaflet of the tricuspid valve. We report two dogs that underwent transcatheter closure of perimembranous VSD associated with membranous ventricular septal aneurysm using a commercial device marketed for transcatheter closure of patent ductus arteriosus, the canine duct occluder. Partial closure was achieved in the first dog with reduction in left heart dimensions documented on echocardiography both at one day and nine months after procedure. In the second dog, three-dimensional transesophageal echocardiography, cardiac computed tomography, and a three-dimensionally printed whole heart model were used to evaluate feasibility for transcatheter device closure. Complete closure of the VSD was subsequently achieved. Both cases had good short- to medium-term outcomes, no perioperative complications were observed, and both dogs are apparently healthy and receiving no cardiac medications at 34 months and 17 months after procedure. Transcatheter attenuation of perimembranous VSD with membranous ventricular septal aneurysm is clinically feasible using the canine duct occluder, and multimodal cardiac imaging allows accurate assessment and planning prior to transcatheter intervention for structural heart disease in dogs.

Trifoliate left atrioventricular valve with and without intact septal structures in four dogs: echocardiographic findings and surgical repair.

Trifoliate left atrioventricular (AV) valve with common atrioventricular junction is considered part of the spectrum of atrioventricular septal defect. This valve morphology is typically associated with defects in the AV septum resulting in communication at the atrial or ventricular level, but has also been described as an isolated defect in the setting of a common AV junction without AV septal defect. Trifoliate left AV valve exhibits a line of apposition between the bridging leaflets that is directed toward the inlet interventricular septum, distinguishing it from isolated mitral valve cleft in which the orientation of the bridging leaflets are toward the left ventricular outflow tract. The echocardiographic findings of four dogs with trifoliate left AV valve are described; two with intact septal structures and two with large ostium primum defects. Three dogs underwent open surgical repair using different approaches depending on the presence or absence of a septal defect. One of these underwent concurrent surgical repair for right AV valve dysplasia. One dog with intact septal structures underwent interventional closure of a concurrent patent ductus arteriosus. Current terminology associated with trileaflet left AV valve malformations is reviewed.

Medial insertion of the patent ductus arteriosus characterized by computed tomography angiography in a cat and dog.

Surgical ligation of a left-to-right shunting patent ductus arteriosus was attempted in two animals. In both cases, a young cat and dog, ligation was complicated by poor visualization of the ductus resulting in unsuccessful ligation. Post-operatively, both the cat and dog underwent computed tomography angiography to characterize the location and morphology of the patent ductus arteriosus. In both cases, computed tomography angiography revealed a left-to-right shunting patent ductus arteriosus with an insertion location medial to the left pulmonary artery branch compared to the typical location. We hypothesize that this atypical location resulted in a difficult surgical visualization from the left thoracotomy approach. Transvenous coil embolization of the duct from the external jugular vein was performed in both cases and resulted in successful occlusion. Variations in the medial-lateral insertion of the ductus arteriosus may have consequences for surgical intervention. If an atypical location of a patent ductus arteriosus is suspected on transthoracic echocardiography, computed tomography angiography prior to ligation may be useful to further define ductal location and help guide the surgical approach.

Electroluminescence image analysis of a photovoltaic module under accelerated lifecycle testing.

Electroluminescence (EL) imaging of Si-based photovoltaic (PV) modules is used widely to spatially detect and characterize electrical defects, including handling and degradation-induced cracking of the component Si cells that are associated with reductions in module performance. In the present study, a commercial polycrystalline silicon PV module was subjected to accelerated lifecycle test environmental conditions and examined as a function of environmental exposure time using EL imaging. The approach followed pixel intensity distributions over each individual PV cell and confirmed a positive correlation between module conversion efficiency and results of the image analysis. Overall, an average of a 2.5% reduction in normalized EL intensity was correlated to a 0.35% reduction in actual power conversion efficiency (or a 2.3% decrease in relative efficiency). The imaging analysis technique offers a rapid, unsupervised means to assess EL data in lieu of conventional visual interpretation.

Obstetric haemorrhage and risk of cardiovascular disease after three decades: a population-based cohort study.

OBJECTIVE: To investigate the association between obstetric haemorrhage and cardiovascular disease up to three decades after pregnancy. DESIGN: Population-based cohort study. SETTING AND POPULATION: All women who delivered between 1989 and 2016 in Quebec, Canada. METHODS: Using hospital admissions data, 1 224 975 women were followed from their first delivery until March 2018. The main exposure measures were antenatal (placenta praevia, placental abruption, peripartum haemorrhage) or postpartum haemorrhage, with or without transfusion. Adjusted Cox regression models were used to assess the association between obstetric haemorrhage and future cardiovascular disease. MAIN OUTCOME MEASURE: Cardiovascular hospitalisation. RESULTS: Among 104 291 (8.5%) women with haemorrhage, 4612 (4.4%) required transfusion. Women with haemorrhage had a higher incidence of cardiovascular hospitalisation than women without haemorrhage (15.5 versus 14.1 per 10 000 person-years; 2437 versus 28 432 events). Risk of cardiovascular hospitalisation was higher for obstetric haemorrhage, with or without transfusion, compared with no haemorrhage (adjusted hazard ratio [aHR] 1.06, 95% CI 1.02-1.10). Women with haemorrhage and transfusion had a substantially greater risk of cardiovascular hospitalisation (aHR 1.47, 95% CI 1.23-1.76). Among transfused women, placental abruption (aHR 1.79, 95% CI 1.06-3.00) and postpartum haemorrhage (aHR 1.38, 95% CI 1.13-1.68) were both associated with risk of cardiovascular hospitalisation. Antenatal haemorrhage with transfusion was associated with 2.46 times the risk of cardiovascular hospitalisation at 5 years (95% CI 1.59-3.80) and 2.14 times the risk at 10 years (95% CI 1.47-3.12). CONCLUSIONS: Obstetric haemorrhage requiring transfusion is associated with maternal cardiovascular disease. The benefit of cardiovascular risk prevention in pregnant women with obstetric haemorrhage requires further investigation. TWEETABLE ABSTRACT: Risk of future cardiovascular disease is increased for women with obstetric haemorrhage who require transfusion.

Comparison between the effects of torsemide and furosemide on the renin-angiotensin-aldosterone system of normal dogs.

INTRODUCTION/OBJECTIVES: We hypothesized that torsemide and furosemide, at approximately equipotent dosages (similar diuresis), would have comparable effects on the circulating renin-angiotensin-aldosterone system. ANIMALS, MATERIALS AND METHODS: Six, healthy, middle-aged, male Beagles were randomized to receive torsemide (0.1 mg/kg PO q 12 h), furosemide (2.0 mg/kg PO q 12 h), or placebo for 10 days during three separate periods, separated by a 10-day washout period, in a crossover design. Blood was collected on days 1, 5, and 9 and 24-h urine collection ended on days 2, 6, and 10. After repeated measures analysis and Bonferonni correction, variables with an adjusted p<0.05 were investigated further, using Tukey's method. RESULTS: Twenty-four-hour urine production differed significantly between the diuretics only on day 10, with torsemide causing a 38% greater diuresis than furosemide. There was, however, no significant difference in average 3-day diuresis. There were no significant differences between diuretics in the 24-h urinary excretion of sodium, chloride, or potassium, though furosemide caused less kaliuresis than torsemide. Serum renin, angiotensin II, and aldosterone and the urine aldosterone-to-creatinine ratio were significantly increased in the diuretic groups, as compared to placebo on days 5/6 and 9/10. There were no significant differences in these values between diuretics. Creatinine and blood urea nitrogen concentrations rose comparably in the diuretic groups, remaining within reference intervals in all dogs. CONCLUSIONS: At approximately equipotent dosages (20:1), torsemide and furosemide produced comparable renin-angiotensin-aldosterone system activation. Torsemide's similar potassium excretion profile to furosemide decreases support for a hypothesized mineralocorticoid-receptor blocking capability.

Upper rate behavior in six dogs with dual-chamber pacemakers.

INTRODUCTION: This report provides clinical examples of upper rate behavior in dogs with dual-chamber pacemakers, with suggestions for programming alterations to avoid detrimental upper rate behavior. ANIMALS: Six dogs with dual-chamber pacemakers displaying upper rate behavior at upper atrial tracking rates. METHODS: Medical records of dogs with dual-chamber pacemakers with evidence of upper rate behavior were reviewed retrospectively from two institutions. Two of the six dogs were followed prospectively, and 24 h Holter monitors were placed to evaluate upper rate behavior correlated to programming settings. RESULTS: Pacemaker Wenckebach or 2:1 atrioventricular block was documented in four of six dogs, and automatic mode switch was documented in two of six dogs. Twenty-four-hour Holter monitors placed on two dogs after pacemaker optimization documented a pacemaker Wenckebach window at increased atrial rates with neither dog reaching their respective 2:1 block point throughout the recording period. CONCLUSIONS: Clinicians who implant dual-chamber pacemakers should be aware of upper rate behavior in animal species with high heart rates. Optimal programming of dual-chamber pacemakers can be achieved by selecting programmed timing intervals to limit deleterious upper rate behavior and create a more physiologic ventricular response at maximum tracking rates.

Structure of ZnCl2 Melt. Part II: Fragile-to-Strong Transition in a Tetrahedral Liquid.

The fraction of edge- and corner-sharing tetrahedra in liquid ZnCl2 is quantified as a function of temperature using Raman spectroscopy and ab initio molecular dynamic simulations. Two distinct regimes are found in the temperature dependence of the change in these structural units. This behavior is consistent with the existence of a fragile-to-strong transition in liquid ZnCl2 as suggested by calorimetric and viscosity measurements. The structural origin of this transition is rationalized in terms of a constraint counting formalism. It is suggested that the ratio of edge- to corner-sharing tetrahedra controls the configurational entropy and in turn the viscosity of the melt. The temperature dependence of this ratio above the melting point is also found to be qualitatively consistent with neutron diffraction data. The observation of a similar fragile-to-strong transition in the isostructural GeSe2 melt indicates that it may be a common feature of tetrahedral liquids.

The Compress® transcutaneous implant for rehabilitation following limb amputation.

Amputation is an unfortunate outcome of a variety of orthopedic conditions. Many amputees can be functionally fitted with conventional suspension sockets. A substantial subset, however, fails this conventional treatment and is unable to function. In Europe, an alternative to socket-based prostheses has been available for 25 years. Patients there who are unable to functionally use socket-based prostheses have been offered the possibility for transcutaneous osseointegration. With this technology, the prosthetic limb can be rigidly attached to the residual bone, and the socket is eliminated, in many cases enabling improved function and patient satisfaction. In the United States, regulatory barriers have greatly limited the adoption and acceptance of transdermal osseointegration. The Compress® device was developed as an alternate means of fixation for massive endoprostheses, such as distal femoral replacements. A uniquely designed prosthesis is rigidly anchored to the end of the cortical bone and is then subjected to a large axial stress. The bone then grows avidly into the device, providing permanent osseointegration. We have recently adopted this device for transcutaneous use. These procedures have been performed in the United States on a custom regulatory basis. Results of this have been encouraging, and we are planning to begin a regulatory trial in the near future.

Effectiveness of foot fasciotomies in foot and ankle trauma.

BACKGROUND: Foot compartment syndrome (FCS) has been reported to cause neuropathic pain, claw or hammer toes, and motor and sensory disturbances. The optimal treatment of FCS is controversial. The purpose of this study was to determine if foot fasciotomies improve patient outcomes in high-energy, combat-related lower extremity trauma. METHODS: Medical records of patients with documented FCS from May 2007 to January 2009 were retrospectively reviewed. Consecutive, matched control patients were identified based on similar hindfoot, mid-foot and/or forefoot injuries who did not undergo foot fasciotomy during the same period. The primary outcomes analysed were the development of claw or hammer toes and neuropathic pain. RESULTS: 19 patients with foot fasctiotomies were identified and matched with 19 controls. Median follow-up was 19.5 months (range, 3.5-47.5 months) for the combined cohorts. The most common mechanism of injury was an explosive blast. Nine fasciotomy and nine control patients sustained open foot fractures. Significantly more patients with foot fasciotomies developed claw toes (50% vs 17%, p=0.03). There were no significant differences in the development of neuropathic pain, sensory deficits, motor deficits, chronic pain, stiffness or infection. The fasciotomy patients underwent an average of 5.5 surgeries per patient versus 4 surgeries per patient in the control group. CONCLUSIONS: Fasciotomy of the foot did not prevent neuropathic pain and deformities in patients with FCS in this study.

Transcutaneous direct current cardioversion in a foal with lone atrial fibrillation.

There are rare published reports of atrial fibrillation (AF) in foals, all of which are associated with structural heart disease or within the adaptive period of newborns. This report describes a 3-month-old Thoroughbred filly with AF and a structurally normal heart on echocardiography. Medical cardioversion of the foal's AF was attempted with three 20mg/kg doses of quinidine sulfate therapy without success. Timed, transcutaneous, direct current cardioversion was successfully performed using adhesive patches on the midthorax in conjunction with intravenous procainamide at a total dose of 20mg/kg. A normal sinus rhythm was maintained through discharge from the hospital and at recheck 5 months after cardioversion. Transcutaneous direct current cardioversion presents a feasible alternative to quinidine sulfate or transvenous electrical cardioversion in young or lower body weight equids.

Structure of ZnCl2 Melt. Part I: Raman Spectroscopy Analysis Driven by Ab Initio Methods.

The structure of molten ZnCl2 is investigated using a combination of computer simulation and experimental methods. Ab initio molecular dynamics (AIMD) is used to model the structure of ZnCl2 at 600 K. The structure factors and pair distribution functions derived from AIMD show a good match with those previously measured by neutron diffraction (ND). In addition, Raman spectroscopy is used to investigate the structure of liquid ZnCl2 and identify the relative fractions of constituent structural units. To ascertain the assignment of each Raman mode, a series of ZnCl2 crystalline prototypes are modeled and the corresponding Raman modes are derived by first-principles calculations. Curve fitting of experimental Raman spectra using these mode assignments shows excellent agreement with both AIMD and ND. These results confirm the presence of significant fractions of edge-sharing tetrahedra in liquid ZnCl2. The presence of these structural motifs has significant impact on the fragility of this tetrahedral glass-forming liquid. The assignment of Raman bands present in molten ZnCl2 is revised and discussed in view of these results.

Link Between Clinical Predictors of Heterotopic Ossification and Histological Analysis in Combat-Injured Service Members.

BACKGROUND: Heterotopic ossification (HO) is a debilitating condition that occurs following traumatic injury and may restrict range of motion and delay rehabilitation. The timing and efficacy of surgical resection have varied widely, and there is a gap in knowledge between clinical predictors of HO recurrence and histological analysis. METHODS: Thirty-three service members seen at Walter Reed National Military Medical Center for symptomatic HO were enrolled in an institutional review board-approved study. Participants took oxytetracycline on four scheduled days prior to HO resection to determine the mineral apposition rate (bone growth rate). RESULTS: Detailed histological analyses included scanning electron microscopy with backscattered electron imaging and light microscopy. Data indicated that the mineral apposition rate of trauma-induced HO was approximately 1.7 µm/day at the time of operative intervention, which was 1.7 times higher than the rate in non-pathological human bone. The mineral apposition rate and postoperative alkaline phosphatase values were demonstrated to be positively and significantly related (ρ = 0.509, p = 0.026, n = 19). When the analysis was limited to patients with no more than a two-year period from injury to excision (thereby removing outliers who had a longer time period than their counterparts) and traumatic brain injury and nonsteroidal anti-inflammatory drugs (known correlates with HO development) were controlled for in the statistical analysis, the mineral apposition rate and recurrence severity were significantly related (ρ = -0.572, p = 0.041, n = 11). CONCLUSIONS: Data demonstrated a link between benchtop research and bedside care, with the mineral apposition rate elevated in patients with HO and correlated with recurrence severity; however, a larger sample size and more clinical factors are needed to refine this model. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

The development of a rat model to investigate the formation of blast-related post-traumatic heterotopic ossification.

Currently, there is no animal model in which to evaluate the underlying physiological processes leading to the heterotopic ossification (HO) which forms in most combat-related and blast wounds. We sought to reproduce the ossification that forms under these circumstances in a rat by emulating patterns of injury seen in patients with severe injuries resulting from blasts. We investigated whether exposure to blast overpressure increased the prevalence of HO after transfemoral amputation performed within the zone of injury. We exposed rats to a blast overpressure alone (BOP-CTL), crush injury and femoral fracture followed by amputation through the zone of injury (AMP-CTL) or a combination of these (BOP-AMP). The presence of HO was evaluated using radiographs, micro-CT and histology. HO developed in none of nine BOP-CTL, six of nine AMP-CTL, and in all 20 BOP-AMP rats. Exposure to blast overpressure increased the prevalence of HO. This model may thus be used to elucidate cellular and molecular pathways of HO, the effect of varying intensities of blast overpressure, and to evaluate new means of prophylaxis and treatment of heterotopic ossification.

A long-term study examining the antibacterial effectiveness of Agion silver zeolite technology on door handles within a college campus.

Laboratory studies have shown that small concentrations of silver are effective at inhibiting the growth micro-organisms through the disruption of important cell structures and processes. The additional ability to incorporate silver into surfaces has increased the usage of silver in the medical field and expanded its use into the consumer market. To understand the impact of increased silver-containing antimicrobial use, it is important to determine whether silver-based consumer goods are effective at reducing bacterial populations. Our study examined the antibacterial effectiveness of Agion silver zeolite technology applied to 25 silver- and control-coated door handles across a college campus. Door handles were sampled for 6 week periods in both the fall and spring semester, and bacteria were cultured and enumerated on tryptic soy agar (TSA), MacConkey agar (MAC) and mannitol salt agar (MSA). A significant difference was observed between the bacterial populations isolated from silver- and control-coated door handles after 3 years. However, bacteria were consistently isolated from silver-coated door handles suggesting that the silver zeolite was only effective against a portion of the bacterial populations, and further studies are necessary to determine the identities of the isolated bacteria and the prevalence of silver resistance.

Stakeholder attitudes towards the role and application of informed consent for newborn bloodspot screening: a study protocol.

INTRODUCTION: Newborn bloodspot screening (NBS) involves testing a small sample of blood taken from the heel of the newborn for a number of serious and life-limiting conditions. In Canada, newborn screening programmes fall under provincial and territorial jurisdiction with no federal coordination. To date, we know very little about the underlying beliefs around different consent practices or how terminology is interpreted by different individuals. Differences in attitudes may have important healthcare consequences. This study will provide empirical data comparing stakeholder opinions on their understanding of consent-related terminology, the perceived applicability of different consent approaches to newborn screening, and the requirements of these different approaches. METHODS AND ANALYSIS: Parents, healthcare professionals and policymakers will be recruited in the provinces of Ontario and Newfoundland and Labrador. Parents will be identified through records held by each provincial screening programme. Healthcare professionals will be purposively sampled on the basis of engagement with newborn screening. Within each province we will identify policymakers who have policy analysis or advisory responsibilities relating to NBS. Data collection will be by qualitative interviews. We will conduct 20 interviews with parents of young children, 10 interviews with key healthcare professionals across the range of appropriate specialties and 10 with policymakers at each site (40 per site, total, N=80). The examination of the transcripts will follow a thematic analysis approach. Recruitment started in June 2014 and is expected to be complete by June 2015. ETHICS AND DISSEMINATION: This study received ethics approval from the Ottawa Health Science Network Research Ethics Board, the Children's Hospital of Eastern Ontario Research Ethics Board (both Ontario), and the Health Research Ethics Authority (Newfoundland and Labrador). RESULTS: These will be reported in peer-reviewed publications and conference presentations. The results will have specific application to the development of parent education materials for newborn screening.

One gene versus two: a regional study on the efficacy of single gene versus pyramided resistance for soybean aphid management.

The soybean aphid (Aphis glycines Matsumura) is a threat to soybean production in the Midwestern United States. Varieties containing the Rag1 soybean aphid resistance gene have been released with limited success in reducing aphid populations. Furthermore, virulent biotypes occur within North America and challenge the durability of single-gene resistance. Pyramiding resistance genes has the potential to improve aphid population suppression and increase resistance gene durability. Our goal was to determine if a pyramid could provide improved aphid population suppression across awide range of environments. We conducted a small-plot field experiment across seven states and three years. We compared soybean near-isolines for the Rag1 or Rag2 gene, and a pyramid line containing both genes for their ability to decrease aphid pressure and protect yield compared with a susceptible line. These lines were evaluated both with and without a neonicitinoid seed treatment. All aphid-resistant lines significantly decreased aphid pressure at all locations but one. The pyramid line experienced lower aphid pressure than both single-gene lines at eight of 23 location-years. Soybean aphids significantly reduced soybean yield for the susceptible line by 14% and for both single-gene lines by 5%; however, no significant yield decrease was observed for the pyramid line. The neonicitinoid seed treatment reduced plant exposure to aphids across all soybean lines, but did not provide significant yield protection for any of the lines. These results demonstrate that pyramiding resistance genes can provide sufficient and consistent yield protection from soybean aphid in North America.

In vivo and in vitro properties of STX2484: a novel non-steroidal anti-cancer compound active in taxane-resistant breast cancer.

BACKGROUND: STX2484 is a novel non-steroidal compound with potent anti-proliferative activity. These studies aimed to identify STX2484's mechanism of action, in vivo efficacy and activity in taxane-resistant breast cancer models. METHODS: Effects of STX2484 and paclitaxel on proliferation, cell cycle and apoptosis were assessed in vitro in drug-resistant (MCF-7(DOX)) and non-resistant cells (MCF-7(WT)). STX2484 efficacy in ßIII tubulin overexpression in MCF-7 cells was also determined. Anti-angiogenic activity was quantified in vitro by a co-culture model and in vivo using a Matrigel plug assay. An MDA-MB-231 xenograft model was used to determine STX2484 efficacy in vivo. RESULTS: STX2484 is a tubulin disruptor, which induces p53 expression, Bcl2 phosphorylation, caspase-3 cleavage, cell cycle arrest and apoptosis. In addition, STX2484 is a potent anti-angiogenic agent in vitro and in vivo. In breast cancer xenografts, STX2484 (20 mg kg(-1) p.o.) suppressed tumour growth by 84% after 35 days of daily dosing, with limited toxicity. In contrast to paclitaxel, STX2484 efficacy was unchanged in two clinically relevant drug-resistant models. CONCLUSIONS: STX2484 is an orally bioavailable microtubule-disrupting agent with in vivo anti-angiogenic activity and excellent in vivo efficacy with no apparent toxicity. Crucially, STX2484 has superior efficacy to paclitaxel in models of clinical drug resistance.