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An 11-year-old Belgian shepherd presented with progressive right thoracic limb lameness. Computed tomography and magnetic resonance imaging revealed a brachial plexus neoplasm and cytology was suggestive of a sarcoma. The patient underwent forequarter amputation and hemilaminectomy of the fifth cervical to first thoracic vertebrae with nerve root transection. Histopathology confirmed extraskeletal osteosarcoma. Twelve months post-operatively, the dog was exercising normally, and computed tomography did not identify local recurrence or metastatic disease. This is the first recorded case of canine brachial plexus extraskeletal osteosarcoma.
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OBJECTIVE: To investigate the prevalence of firework-associated fear in dogs in Sydney, owner perception of their dog's response to fireworks, perceived efficacy of interventions to manage fearful behaviours and the frequency of dog owners seeking professional advice for these behaviours. METHODS: Dog owners in the Greater Sydney area were invited to complete an anonymous online survey. RESULTS: From 387 valid responses, 44.4% (171 of 385) reported their dogs were fearful of fireworks. The most common fear-related behaviour was seeking an owner or caretaker (120 of 161, 74.5%). Most owners responded by bringing their dog inside or trying to comfort or reassure their dog. Only 22.5% of owners sought professional advice for their dog's fear of fireworks, but of these, 65.5% considered that advice to be effective. Source and breed group were significantly associated with fear of fireworks (P = 0.011, P = 0.036 respectively). Fear of fireworks was also significantly associated with fear of thunder (P < 0.0001), gunshots (P < 0.0001) and vehicles (P = 0.0009). CONCLUSION: Fear of fireworks and other loud noises negatively impacts canine welfare, yet only a small percentage of owners sought professional advice. There is scope for veterinarians to educate owners and raise awareness about the identification and management of noise-associated fear and reduce the risk of escalation of fearful behaviours.
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BACKGROUND: It is doubtful that any of the treatments proposed for feline leukaemia virus (FeLV) infection are effective, despite the entity being described 60 years ago. METHODS: Eighteen pet cats with progressive FeLV infections were recruited in Australia. One or more antiviral drugs were trialled in 16 cats, while two FeLV-infected cats were not handleable and served as untreated controls. Six cats were administered RetroMAD1™ only (0.5 mg/kg orally twice daily), a commercially available recombinant chimeric protein with proposed antiretroviral activity. Three cats were administered the integrase inhibitor raltegravir only (10-15 mg/kg orally twice daily), a drug used as a component of highly effective antiretroviral therapy for human immunodeficiency virus (HIV-1) infection. Three cats were administered RetroMAD1™ and raltegravir concurrently, and four cats were administered raltegravir and the reverse transcriptase inhibitor zidovudine (AZT, 5 mg/kg orally twice daily) concurrently. FeLV RNA and p27 antigen loads were measured at two timepoints (T1-2 months and T3-5 months) during therapy and compared to baseline (pretreatment) levels, to assess the response to therapy using linear modelling. The median survival time (MST) of the cats from commencement of FeLV treatment to death was also determined and compared between treatments. RESULTS: The MST for the 16 FeLV-positive cats which received antiviral therapy was 634 days, while the MST from FeLV diagnosis to death for the two untreated control cats was 780 days. In cats treated with RetroMAD1™, FeLV viral load decreased from T0 to T1-2 months (median viral load reduced from 1339 × 106 to 705 × 106 copies/mL plasma; P = 0.012), but MST was reduced compared to cats not given RetroMAD1™ (426 days vs 1006 days; P = 0.049). Cats treated with raltegravir and AZT had no significant changes in FeLV viral load over time, but p27 antigen load was decreased from T0 to T3-5 months in cats treated with raltegravir (median p27 antigen level reduced from 50.2% to 42.7%; P = 0.005). All other results were not significantly affected by the treatment provided. Importantly, statistically significant and substantial associations were found between age at FeLV diagnosis and survival time (P = 0.046, R2 = 18.6) and between FeLV viral load at T0 and survival time (P = 0.004, R2 = 44.4). Younger cats, and cats with higher levels of pretreatment FeLV RNA, had reduced survival times. Cats treated with RetroMAD1™ were typically younger (median age 2.0 vs 8.0 years), likely explaining the observed reduction in MST. A significant association was found between FeLV viral load and p27 antigen load at T0 (P = 0.015, R2 = 32.9). CONCLUSIONS: Results from this small case series do not provide convincing support for the use of RetroMAD1™, raltegravir or AZT, alone or in combination, for the treatment of cats progressively infected with FeLV. The changes observed were biologically insignificant. Age and FeLV viral load at diagnosis are useful prognostic markers, and p27 antigen concentration can be used to predict viral load. Larger field trials should be performed examining antiretroviral therapy in FeLV-positive cats with progressive infections, preferably using three or more drugs from at least two classes, as is standard with human antiretroviral therapy. Future studies would be easier in countries with a higher prevalence of FeLV infections than Australia.
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OBJECTIVE: To describe ophthalmic findings in hospitalized canine and feline patients with tick paralysis (TP) and investigate possible predisposing factors. ANIMALS STUDIED: Forty-seven dogs and 28 cats hospitalized with TP assessed with an ophthalmic examination performed by an ABVO resident. METHODS: Dogs and cats were hospitalized with TP from October 2021 to January 2022 and had an ophthalmic examination performed by an ABVO resident. Patient signalment data, information regarding tick number and location, hospitalization duration, medications used, and patient paralysis grades were recorded. Statistical analysis was performed to correlate findings. RESULTS: Corneal ulcers developed in up to 34.8% of dogs and up to 42.9% of cats hospitalized with TP. An absent palpebral reflex ipsilaterally increased the odds of a concurrent corneal ulcer being present by 14.7× in dogs and 20.1× in cats (p < .0001). Palpebral reflexes were absent in 38.3% of dogs and 35.7% of cats hospitalized with TP and were correlated with more severe gait paralysis (p = .01) and respiratory paralysis (p = .005) in dogs, and respiratory paralysis in cats (p = .041). STT-1 findings <10 mm/min were present in 27.7% of dogs and 57.1% of cats examined and were associated with increasing gait paralysis (p = .017) and respiratory paralysis (p = .007) in dogs, and increasing gait paralysis in cats (p = .017). CONCLUSIONS: Simple corneal ulcers, loss of a complete palpebral reflex, and reduced STT-1 scores frequently occurred in dogs and cats hospitalized for TP. The frequency of these findings increased as the degree of patient paralysis increased.
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OBJECTIVE: To investigate the incidence and predisposing factors leading to the development of corneal ulcers and the loss of a palpebral reflex in hospitalised canine and feline patients with tick paralysis (TP). ANIMALS STUDIED: A total of 102 dogs and 100 cats retrospectively were assessed from previously hospitalised patients. METHODS: A retrospective cohort study was performed on 102 different canine and 100 different feline patients who were hospitalised for TP from October 2020-January 2022. Patient data were collected, and logistic regression was conducted to determine factors affecting the palpebral reflex and the development of corneal ulcers. RESULTS: Corneal ulcers occurred in 23/102 (22.5%) dogs during hospitalisation and were strongly associated with an incomplete palpebral reflex ipsilaterally during hospitalisation (P < 0.001), hospitalisation ≥3 days (P = 0.004), mechanical ventilation ≥3 days (P = 0.015) or a tick location cranial to C1 (P = 0.003). An incomplete palpebral reflex during hospitalisation was observed in 29/102 (28.4%) dogs and was significantly associated with decreasing patient weight (P = 0.018), increasing days hospitalised (P = 0.001), having a tick found cranial to C1 (P = 0.004), highest recorded GP grade (P = 0.01), highest recorded RP grade (P = 0.005), use of amoxycillin-clavulanic acid during hospitalisation (P = 0.002) and use of piperacillin/tazobactam during hospitalisation (P = 0.003). There was a significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in dogs (OR = 4.5, P = 0.029). Corneal ulcers occurred in 10/100 (10.0%) cats during hospitalisation, and was significantly more likely to occur to an eye if an incomplete palpebral reflex was observed ipsilaterally during hospitalisation (OR = 20.1, P < 0.0001) and with increasing patient age (P = 0.019). The absence of a complete palpebral reflex during hospitalisation was observed in 18/10 (18.0%) cats and was significantly associated with increasing days hospitalised (P = 0.034). There was no significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in cats. CONCLUSIONS: The frequency of corneal ulcers and loss of palpebral reflexes were significant in dogs and cats hospitalised by TP, with many factors contributing to the risk of these developing.
Subject(s)
Cat Diseases , Corneal Ulcer , Dog Diseases , Ixodes , Tick Paralysis , Animals , Dogs , Cats , Dog Diseases/drug therapy , Retrospective Studies , Cat Diseases/drug therapy , Tick Paralysis/veterinary , Female , Male , Corneal Ulcer/veterinary , Hospitalization/statistics & numerical data , Cohort Studies , Incidence , Risk FactorsABSTRACT
Nitrogen (N) availability is one of the principal drivers of primary productivity across aquatic ecosystems. However, the microbial communities and emergent metabolisms that govern N cycling in tropical lakes are both distinct from and poorly understood relative to those found in temperate lakes. This latitudinal difference is largely due to the warm (>20°C) temperatures of tropical lake anoxic hypolimnions (deepest portion of a stratified water column), which result in unique anaerobic metabolisms operating without the temperature constraints found in lakes at temperate latitudes. As such, tropical hypolimnions provide a platform for exploring microbial membership and functional diversity. To better understand N metabolism in warm anoxic waters, we combined measurements of geochemistry and water column thermophysical structure with genome-resolved metatranscriptomic analyses of the water column microbiome in Lake Yojoa, Honduras. We sampled above and below the oxycline in June 2021, when the water column was stratified, and again at the same depths and locations in January 2022, when the water column was mixed. We identified 335 different lineages and significantly different microbiome membership between seasons and, when stratified, between depths. Notably, nrfA (indicative of dissimilatory nitrate reduction to ammonium) was upregulated relative to other N metabolism genes in the June hypolimnion. This work highlights the taxonomic and functional diversity of microbial communities in warm and anoxic inland waters, providing insight into the contemporary microbial ecology of tropical ecosystems as well as inland waters at higher latitudes as water columns continue to warm in the face of global change.IMPORTANCEIn aquatic ecosystems where primary productivity is limited by nitrogen (N), whether continuously, seasonally, or in concert with additional nutrient limitations, increased inorganic N availability can reshape ecosystem structure and function, potentially resulting in eutrophication and even harmful algal blooms. Whereas microbial metabolic processes such as mineralization and dissimilatory nitrate reduction to ammonium increase inorganic N availability, denitrification removes bioavailable N from the ecosystem. Therefore, understanding these key microbial mechanisms is critical to the sustainable management and environmental stewardship of inland freshwater resources. This study identifies and characterizes these crucial metabolisms in a warm, seasonally anoxic ecosystem. Results are contextualized by an ecological understanding of the study system derived from a multi-year continuous monitoring effort. This unique data set is the first of its kind in this largely understudied ecosystem (tropical lakes) and also provides insight into microbiome function and associated taxa in warm, anoxic freshwaters.
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Ammonium Compounds , Ecosystem , Nitrates/analysis , Lakes/chemistry , Organic Chemicals , Water , NitrogenABSTRACT
Escalating environmental threats to coral reefs coincides with global advancements in coral restoration programs. To improve long-term efficacy, practitioners must consider incorporating genotypes resilient to ocean warming and disease while maintaining genetic diversity. Identifying such genotypes typically occurs under long-term exposures that mimic natural stressors, but these experiments can be time-consuming, costly, and introduce tank effects, hindering scalability for hundreds of nursery genotypes used for outplanting. Here, we evaluated the efficacy of the acute Coral Bleaching Automated Stress System (CBASS) against long-term exposures on the bleaching response of Acropora cervicornis, the dominant restoration species in Florida's Coral Reef. Comparing bleaching metrics, Fv/Fm, chlorophyll, and host protein, we observed similar responses between the long-term heat and the CBASS treatment of 34.3 °C, which was also the calculated bleaching threshold. This suggests the potential of CBASS as a rapid screening tool, with 90% of restoration genotypes exhibiting similar bleaching tolerances. However, variations in acute bleaching phenotypes arose from measurement timing and experiment heat accumulation, cautioning against generalizations solely based on metrics like Fv/Fm. These findings identify the need to better refine the tools necessary to quickly and effectively screen coral restoration genotypes and determine their relative tolerance for restoration interventions.
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Anthozoa , Animals , Anthozoa/genetics , Coral Reefs , Benchmarking , Biological Assay , ChlorophyllABSTRACT
The National Health Service strategy for the delivery of proton beam therapy (PBT) in the UK provides a unique opportunity to deliver high-quality evidence for PBT through randomised controlled trials (RCTs). We present a summary of three UK PBT RCTs in progress, including consideration of their key design characteristics and outcome assessments, to inform and support future PBT trial development. The first three UK multicentre phase III PBT RCTs (TORPEdO, PARABLE and APPROACH), will compare PBT with photon radiotherapy for oropharyngeal squamous cell carcinoma, breast cancer and oligodendroglioma, respectively. All three studies were designed by multidisciplinary teams, which combined expertise from clinicians, clinical trialists and scientists with strong patient advocacy and guidance from national radiotherapy research networks and international collaborators. Consistent across all three studies is a focus on the reduction of long-term radiotherapy-related toxicities and an evaluation of patient-reported outcomes and health-related quality of life, which will address key uncertainties regarding the clinical benefits of PBT. Innovative translational components will provide insights into mechanisms of toxicity and help to frame the key future research questions regarding PBT. The UK radiotherapy research community is developing and delivering an internationally impactful PBT research portfolio. The combination of data from RCTs with prospectively collected data from a national PBT outcomes registry will provide an innovative, high-quality repository for PBT research and the platform to design and deliver future trials of PBT.
Subject(s)
Breast Neoplasms , Proton Therapy , Female , Humans , Breast Neoplasms/radiotherapy , Randomized Controlled Trials as TopicABSTRACT
Blooms of the harmful algae species Karenia brevis are frequent off the southwest coast of Florida despite having relatively slow growth rates. The regional frequency of these harmful algal blooms led to the examination of the dominant estuarine outflows for effects on both K. brevis and the phytoplankton community in general. There is comparatively little information on the growth rates of non-Karenia taxonomic groups other than diatoms. A seasonally based series (Fall, Winter, and Spring) of bioassay experiments were conducted to determine the nutrient response of the coastal phytoplankton community. Treatments included estuarine waters (Tampa Bay, Charlotte Harbor, and the Caloosahatchee River) applied in a 1:25 dilution added to coastal water to mimic the influence of estuarine water in a coastal environment. Other treatments were 5-15 µM additions of nitrogen (N), phosphorus (P), and silica (Si) species, amino acids, and N (urea) + P added to coastal water. Incubations were conducted under ambient conditions with shading for 48 h. Analyses of dissolved and particulate nutrients were coupled with HPLC analysis of characteristic photopigments and taxonomic assignments of biomass via CHEMTAX. The coastal phytoplankton community, dominated by diatoms, cyanophytes and prasinophytes, was significantly different both by bioassay and by season, indicating little seasonal fidelity in composition. Specific growth rates of chlorophyll a indicated no significant difference between any controls, any estuarine treatment, P, or Si treatments. Conditions were uniformly N-limited with the highest growth rates in diatom biomass. Despite differing initial communities, however, there were seasonally reproducible changes in community due to the persistent growth or decline of the various taxa, including haptophytes, cyanophytes, and cryptophytes. For the one bioassay in which K. brevis was present, the slow growth of K. brevis relative to diatoms in a mixed community was evident, indicating that identifying the seasonally based behavior of other taxa in response to nutrients is critical for the simulation of phytoplankton competition and the successful prediction of the region's harmful algal blooms.
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Cyanobacteria , Diatoms , Dinoflagellida , Phytoplankton/metabolism , Seasons , Chlorophyll A/metabolism , Florida , Diatoms/metabolism , Nutrients , WaterABSTRACT
Obesity is an escalating global health problem affecting both humans and companion animals. In cats it is associated with increased mortality and multiple diseases, including diabetes mellitus. Two genes coding for proteins known to play a critical role in energy homeostasis across species are the proopiomelanocortin (POMC) gene and the melanocortin-4 receptor (MC4R) gene. A missense variant in the coding sequence of the feline MC4R (MC4R:c.92C>T) has been reported to be associated with diabetes and overweight in domestic shorthair cats, and while variants in the POMC gene are known to cause obesity in humans and dogs, variants in POMC and their association with feline obesity and diabetes mellitus have not been investigated to date. The current study aimed to assess the association between the previously described MC4R variant and body condition score (BCS), as well as body fat content (%BF) in 89 non-diabetic domestic shorthair cats. Furthermore, we investigated the feline POMC gene as a potential candidate gene for obesity. Our results indicate that the MC4R:c.92C>T polymorphism is not associated with BCS or %BF in non-diabetic domestic shorthair cats. The mutation analysis of all POMC exons identified two missense variants, with a variant in exon 1 (c.28G>C; p.G10R) predicted to be damaging. The variant was subsequently assessed in all 89 cats, and cats heterozygous for the variant had a significantly increased body condition score (p = 0.03) compared with cats homozygous for the wild-type allele. Results from our study provide additional evidence that the previously described variant in MC4R is not associated with obesity in domestic shorthair cats. More importantly, we have identified a novel variant in the POMC gene, which might play a role in increased body condition score and body fat content in domestic shorthair cats.
Subject(s)
Cat Diseases , Diabetes Mellitus , Receptor, Melanocortin, Type 4 , Animals , Cats/genetics , Dogs , Humans , Alleles , Cat Diseases/genetics , Diabetes Mellitus/genetics , Dog Diseases/genetics , Obesity/genetics , Obesity/veterinary , Pro-Opiomelanocortin/genetics , Pro-Opiomelanocortin/metabolism , Receptor, Melanocortin, Type 4/genetics , Receptor, Melanocortin, Type 4/metabolismABSTRACT
AIMS: Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination. MATERIALS AND METHODS: Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests. RESULTS: Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts. CONCLUSION: Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.
Subject(s)
Brachytherapy , Carcinoma, Transitional Cell , Radiation Oncology , Urinary Bladder Neoplasms , Humans , Aged , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/radiotherapy , Mitomycin , GemcitabineABSTRACT
Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including after SARS-CoV-2 mRNA vaccines. However, the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated a cohort of patients who developed myocarditis and/or pericarditis with elevated troponin, B-type natriuretic peptide, and C-reactive protein levels as well as cardiac imaging abnormalities shortly after SARS-CoV-2 mRNA vaccination. Contrary to early hypotheses, patients did not demonstrate features of hypersensitivity myocarditis, nor did they have exaggerated SARS-CoV-2-specific or neutralizing antibody responses consistent with a hyperimmune humoral mechanism. We additionally found no evidence of cardiac-targeted autoantibodies. Instead, unbiased systematic immune serum profiling revealed elevations in circulating interleukins (IL-1ß, IL-1RA, and IL-15), chemokines (CCL4, CXCL1, and CXCL10), and matrix metalloproteases (MMP1, MMP8, MMP9, and TIMP1). Subsequent deep immune profiling using single-cell RNA and repertoire sequencing of peripheral blood mononuclear cells during acute disease revealed expansion of activated CXCR3+ cytotoxic T cells and NK cells, both phenotypically resembling cytokine-driven killer cells. In addition, patients displayed signatures of inflammatory and profibrotic CCR2+ CD163+ monocytes, coupled with elevated serum-soluble CD163, that may be linked to the late gadolinium enhancement on cardiac MRI, which can persist for months after vaccination. Together, our results demonstrate up-regulation in inflammatory cytokines and corresponding lymphocytes with tissue-damaging capabilities, suggesting a cytokine-dependent pathology, which may further be accompanied by myeloid cell-associated cardiac fibrosis. These findings likely rule out some previously proposed mechanisms of mRNA vaccine--associated myopericarditis and point to new ones with relevance to vaccine development and clinical care.
Subject(s)
Antineoplastic Agents , COVID-19 , Myocarditis , Humans , Myocarditis/etiology , SARS-CoV-2 , Leukocytes, Mononuclear , COVID-19 Vaccines/adverse effects , Contrast Media , COVID-19/prevention & control , Gadolinium , Killer Cells, Natural , CytokinesABSTRACT
Cyclones are a poorly described disturbance in tropical lakes, with the potential to alter ecosystems and compromise the services they provide. In November 2020, Hurricanes Eta and Iota made landfall near the Nicaragua-Honduras border, inundating the region with a large amount of late-season precipitation. To understand the impact of these storms on Lake Yojoa, Honduras, we compared 2020 and 2021 conditions using continuous (every 16 days) data collected from five pelagic locations. The storms resulted in increased Secchi depth and decreased algal abundance in December 2020, and January and February 2021, and lower-than-average accumulation of hypolimnetic nutrients from the onset of stratification (April 2021) until mixus in November 2021. Despite the reduced hypolimnetic nutrient concentrations, epilimnetic nutrient concentrations returned to (and in some cases exceeded) pre-hurricane levels following annual water column turnover in 2021. This response suggests that Lake Yojoa's trophic state had only an ephemeral response to the disturbance imposed by the two hurricanes, likely due to internal input of sediment derived nutrients. These aseasonal storms acted as a large-scale experiment that resulted in nutrient dilution and demonstrated the resilience of Lake Yojoa's trophic state to temporary nutrient reductions.
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Cyclonic Storms , Ecosystem , Lakes , Honduras , Water , Phosphorus/analysis , Environmental Monitoring/methodsABSTRACT
AIMS: To evaluate whether there is sufficient correlation between patient-reported outcomes (PROs) and clinician-reported outcomes (CROs) in bladder cancer follow-up post-radiotherapy to streamline data collection and to reduce trial follow-up burden on patients, clinicians and trial programmes. MATERIALS AND METHODS: PROs data were collected within the BC2001 trial using the Functional Assessment of Cancer Therapy specific to bladder cancer (FACT-BL) questionnaire. CROs data were collected by clinicians using Late Effects in Normal Tissues Subjective, Objective and Management (LENT/SOM). Data were collected at baseline, post-treatment, at 6 and 12 months post-randomisation and then annually to 5 years. The percentage agreement between CROs and PROs measures was evaluated at 2 and 5 years post-randomisation. Concordance was tested using the weighted Kappa statistic with 95% confidence intervals. RESULTS: Correlation was evaluated between six categories of the FACT-BL and LENT/SOM scores. At 2 years the percentage agreement across these domains ranged from 45 to 78%, with the weighted Kappa statistic between 0.07 and 0.35. Results were similar in year 5 with 48-83% agreement and kappa statistics between -0.02 and 0.21. CONCLUSION: The correlation between CROs and PROs in patients treated with radiotherapy for bladder cancer were generally poor. PROs appear to be more sensitive, with higher grade events reported. Further work is needed to evaluate whether PROs alone can be used to evaluate toxicity-related outcomes in randomised controlled trials.
Subject(s)
Radiotherapy, Conformal , Urinary Bladder Neoplasms , Humans , Patient Reported Outcome Measures , Radiotherapy, Conformal/methods , Radiotherapy Dosage , Surveys and Questionnaires , Urinary Bladder Neoplasms/radiotherapy , Quality of LifeABSTRACT
AIMS: BC2001, a randomised trial of treatment for muscle-invasive bladder cancer, demonstrated no difference in health-related quality of life (HRQoL) or late toxicity between patients receiving radical radiotherapy with and without chemotherapy. This secondary analysis explored sex-based differences in HRQoL and toxicity. MATERIALS AND METHODS: Participants completed the Functional Assessment of Cancer Therapy Bladder (FACT-BL) HRQoL questionnaires at baseline, end of treatment, 6 months and annually until 5 years. Clinicians assessed toxicity with the Radiation Therapy Oncology Group (RTOG) and Late Effects in Normal Tissues Subjective, Objective and Management (LENT/SOM) scoring systems at the same timepoints. The impact of sex on patient-reported HRQoL was evaluated using multivariate analyses of change in FACT-BL subscores from baseline to the timepoints of interest. For clinician-reported toxicity, differences were compared by calculating the proportion of patients with grade 3-4 toxicities occurring over the follow-up period. RESULTS: For both males and females, all FACT-BL subscores had a reduction in HRQoL at the end of treatment. For males, the mean bladder cancer subscale (BLCS) score remained stable through to year 5. For females, there was a decline in BLCS from baseline at years 2 and 3 with a return to baseline at year 5. At year 3, females had a statistically significant and clinically meaningful worsening of mean BLCS score (-5.18; 95% confidence interval -8.37 to -1.99), which was not seen in males (0.24; -0.76 to 1.23). RTOG toxicity was more frequent in females than males (27% versus 16%, P = 0.027). CONCLUSION: Results suggest that female patients treated with radiotherapy ± chemotherapy for localised bladder cancer report worse treatment-related toxicity in post-treatment years 2 and 3 than males.
Subject(s)
Radiation Injuries , Urinary Bladder Neoplasms , Humans , Male , Female , Quality of Life , Radiotherapy Dosage , Urinary Bladder Neoplasms/radiotherapy , Urinary Bladder/radiation effectsABSTRACT
Rotavirus vaccination has been shown to reduce rotavirus burden in many countries, but the long-term magnitude of vaccine impacts is unclear, particularly in low-income countries. We use a transmission model to estimate the long-term impact of rotavirus vaccination on deaths and disability adjusted life years (DALYs) from 2006 to 2034 for 112 low- and middle-income countries. We also explore the predicted effectiveness of a one- vs two- dose series and the relative contribution of direct vs indirect effects to overall impacts. To validate the model, we compare predicted percent reductions in severe rotavirus cases with the percent reduction in rotavirus positivity among gastroenteritis hospital admissions for 10 countries with pre- and post-vaccine introduction data. We estimate that vaccination would reduce deaths from rotavirus by 49.1 % (95 % UI: 46.6-54.3 %) by 2034 under realistic coverage scenarios, compared to a scenario without vaccination. Most of this benefit is due to direct benefit to vaccinated individuals (explaining 69-97 % of the overall impact), but indirect protection also appears to enhance impacts. We find that a one-dose schedule would only be about 57 % as effective as a two-dose schedule 12 years after vaccine introduction. Our model closely reproduced observed reductions in rotavirus positivity in the first few years after vaccine introduction in select countries. Rotavirus vaccination is likely to have a substantial impact on rotavirus gastroenteritis and its mortality burden. To sustain this benefit, the complete series of doses is needed.
Subject(s)
Gastroenteritis , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Humans , Infant , Rotavirus Infections/prevention & control , Gastroenteritis/prevention & control , Vaccination , Cost-Benefit AnalysisABSTRACT
Most dogs with immune mediated haemolytic anaemia (IMHA) are hypercoagulable, as measured by thromboelastography (TEG). Thromboelastography-platelet mapping (TEG-PM) has been used to assess platelet function in human patients treated with aspirin or clopidogrel. The aim of this study was to compare platelet thromboxane A2-receptor inhibition (TXA2-RI) and platelet adenosine diphosphate (ADP)-receptor inhibition (ADP-RI) as measured by TEG-PM in dogs with primary IMHA receiving aspirin or clopidogrel to determine if TEG-PM might be useful to monitor treatment. Eighteen client-owned dogs with IMHA were enroled in a prospective double blinded study. Dogs were randomised to receive aspirin or clopidogrel in addition to standard therapy. Thromboelastography was measured before, and 1 and 4 days after commencing treatment. Thromboelastography-PM was performed on days 1 and 4. Non-responders were defined as < 50 % platelet thromboxane A2-receptor inhibition (TXA2-RI) in the aspirin group and < 50 % platelet adenosine diphosphate (ADP)-receptor inhibition (ADP-RI) in the clopidogrel group, on day 4. Mean platelet TXA2-RI and platelet ADP-RI were not significantly different between groups at any timepoint (P > 0.05). The overall mean percentage inhibition of TXA2-receptor was 25 % (aspirin 33 %, clopidogrel 15 %), and of ADP-receptor was 82 % (aspirin 83 %, clopidogrel 80 %). On day 4, 6/9 dogs (66 %) in the aspirin group and 2/8 dogs (25 %) in the clopidogrel group were non-responders (P = 0.086). Two dogs defined as responders based on TEG-PM developed thromboembolism. Overall, there was no significant difference in efficacy between aspirin and clopidogrel based on measurement of receptor inhibition using TEG-PM (P > 0.05), and routine TEG was not reliable for monitoring treatment response in dogs with IMHA. In some dogs, there was a discrepancy between TEG-PM results and clinical response. Further investigation of TEG-PM use in dogs, including its usefulness to monitor treatment response and adjust treatment in individual dogs and any effect of anaemia, is warranted.
Subject(s)
Anemia, Hemolytic, Autoimmune , Dog Diseases , Adenosine Diphosphate/pharmacology , Anemia, Hemolytic, Autoimmune/veterinary , Animals , Aspirin/pharmacology , Aspirin/therapeutic use , Blood Platelets , Clopidogrel/pharmacology , Clopidogrel/therapeutic use , Dog Diseases/chemically induced , Dog Diseases/drug therapy , Dogs , Humans , Platelet Aggregation , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Platelet Function Tests/methods , Platelet Function Tests/veterinary , Prospective Studies , Thrombelastography/veterinary , Thromboxanes/pharmacologyABSTRACT
OBJECTIVES: To examine the prescribing habits for omeprazole in a veterinary teaching hospital and to evaluate the effect of a clinical audit on omeprazole prescription. MATERIAL AND METHODS: Observational study with retrospective clinical audit followed by a prospective study. The evaluated data about omeprazole prescription included the dose, frequency and indication. These were assessed according to published guidelines. A seminar about the audit and current guidelines on the use of omeprazole was organised for all members of clinical staff. Prospective data collection was conducted after the seminar. A comparison of the collected data before and after the clinical audit was made. RESULTS: A total of 301 dogs were prescribed omeprazole in the veterinary teaching hospital during the study period (including the retrospective and prospective parts). Complete data were acquired from 240 patients. The prescribed frequency of omeprazole was inappropriate in 23 (16.5%) of the prescriptions in the retrospective section but in only five (5.0%) in the prospective study. Inappropriate indications were reported in 12 (8.6%) patients in the retrospective section and in two patients (2.0%) in the prospective study. Overall inappropriate omeprazole prescription was identified in 34 (24.5%) patients in the retrospective part and in seven (6.9%) patients in the prospective part. There was a statistically significant difference between the two groups in frequency, indication and overall prescription of omeprazole. CLINICAL SIGNIFICANCE: This study details the frequency of inappropriate prescription of omeprazole in a veterinary teaching hospital and provides some evidence that dissemination of guidelines based on clinical audit can improve prescribing habits.