Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study.

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.

Prevalence of Coxiella burnetii seropositivity and shedding in farm, pet and feral cats and associated risk factors in farm cats in Quebec, Canada.

Cats represent a potential source of Coxiella burnetii, the aetiological agent of Q fever in humans. The prevalence and risk factors of C. burnetii infection in farm, pet and feral cats were studied in Quebec, Canada, using a cross-sectional study. Serum samples were tested using a specific enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies against C. burnetii, whereas rectal swabs were assayed using real-time quantitative polymerase chain reaction (qPCR) for the molecular detection of the bacteria. Potential risk factors for farm cats were investigated using clinical examinations, questionnaires and results from a concurrent study on C. burnetii farm status. A total of 184 cats were tested: 59 from ruminant farms, 73 pets and 52 feral cats. Among farm cats, 2/59 (3.4%) were ELISA-positive, 3/59 (5.1%) were ELISA-doubtful and 1/59 (1.7%) was qPCR-positive. All pets and feral cats were negative to C. burnetii ELISA and qPCR. Farm cat positivity was associated with a positive C. burnetii status on the ruminant farm (prevalence ratio = 7.6, P = 0.03). Our results suggest that although pet and feral cats do not seem to pose a great C. burnetii risk to public health, more active care should be taken when in contact with cats from ruminant farms.

Evidence for Differences in the Temporal Progress of Plasmopara viticola Clades riparia and aestivalis Airborne Inoculum Monitored in Vineyards in Eastern Canada Using a Specific Multiplex Quantitative PCR Assay.

Four clades of Plasmopara viticola isolated from wild and cultivated Vitis species were described in 2013. Only P. viticola clades riparia and aestivalis have been detected in eastern Canada. To increase our understanding of the epidemiology of these clades of P. viticola, airborne sporangia were monitored with spore samplers at two experimental vineyards from 2015 to 2018 and at 11, 14, and 15 commercial vineyards in 2016, 2017, and 2018, respectively. At each vineyard and in each year, airborne sporangia were assessed three times weekly from grapevine budbreak to harvest. To accurately monitor airborne inoculum, a specific and sensitive quantitative PCR assay for simultaneous quantification of P. viticola clades riparia and aestivalis was developed. At the experimental site, in the vineyard planted with the hybrid grape variety Chancellor, mostly P. viticola clade riparia was detected. In vineyards planted with multiple grape varieties, airborne sporangia of P. viticola clade riparia were prevalent at the beginning of the season, whereas P. viticola clade aestivalis was mostly detected from midseason to harvest. At the commercial sites, airborne sporangia of P. viticola clade riparia were more prevalent in 2016, whereas P. viticola clade aestivalis was more prevalent in 2017 and 2018. The only significant difference between the inoculum progress curves was the time at which 50% of the seasonal inoculum was reached, with an average for the 3 years of 100.8 and 117.9 days since 1 May for P. viticola clade riparia and clade aestivalis, respectively. When airborne sporangium concentrations were expressed as the proportion of the two clades, in general, the proportion of clade aestivalis to that of clade riparia was low at the beginning of the season and increased to reach approximately 0.9 to 1.0 at the end of the season. These results suggest that both clades of P. viticola coexist, but that clade aestivalis is predominant and that downy mildew epidemics caused by P. viticola clade riparia occur 2 to 3 weeks before those caused by clade aestivalis.

Outcomes of patients with myelofibrosis treated with compassionate use pacritinib: a sponsor-independent international study.

Myelofibrosis (MF) is a chronic yet progressive myeloid neoplasm in which only a minority of patients undergo curative therapy, hematopoietic stem cell transplantation. Ruxolitinib, a JAK1/2 inhibitor, is the lone therapy approved for MF, offering a clear symptom and spleen benefit at the expense of treatment-related cytopenias. Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in MF with minimal myelosuppression. Due to an FDA-mandated full clinical hold, the randomized phase 3 PERSIST trials were abruptly stopped and PAC was immediately discontinued for all patients. Thirty-three patients benefitting from PAC on clinical trial prior to the hold were allowed to resume therapy on an individual, compassionate-use basis. This study reports the detailed outcomes of 19 of these PAC retreatment patients with a median follow-up of 8 months. Despite a median platelet count of 49 × 109/L at restart of PAC, no significant change in hematologic profile was observed. Grade 3/4 adverse events of epistaxis (n = 1), asymptomatic QT prolongation (n = 1), and bradycardia (n = 1) occurred in three patients within the first 3 months of retreatment. One death due to catheter-associated sepsis occurred. The median time to discontinuation of PAC therapy on compassionate use for all 33 patients was 12.2 (95% CI 8.3-NR) months. PAC retreatment was associated with modest improvement in splenomegaly without progressive myelosuppression and supports the continued development of this agent for the treatment of MF second line to ruxolitinib or in the setting of treatment-limiting thrombocytopenia.

Programmed cell death-1 pathway inhibition in myeloid malignancies: implications for myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic diseases that belong to the spectrum of myeloid malignancies (MyMs), which also include myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). While hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many MyMs, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification. Immune checkpoint inhibition, in particular along the programmed cell death protein 1 (PD-1)/B7-H1 (PD-L1) axis, is an established strategy in solid tumors with potential as an adjunctive therapy in hematologic malignancies. Seminal studies suggest that the pro-inflammatory microenvironment of MyMs can suppress T lymphocyte-mediated immunity via PD-1 signaling and that response to mainstay epigenetic therapies for MyMs may be governed by PD-1 gene regulation. Although the role of PD-1 signaling in MPN pathogenesis and progression is as yet unclear, research in MPN patients has revealed expansion of myeloid-derived suppressor cells (MDSCs), which may effect host immune tolerance of tumor via temporally and spatially specific activation of PD-1/PD-L1 signaling. The current understanding of immune dysfunction in MPNs and analogous MyMs offers a compelling rationale to study PD-1/PD-L1 inhibition in patients as a novel treatment option.

Identification of the Dominant Genotypes of Phytophthora infestans in Canada Using Real-Time PCR with ASO-PCR Assays.

Phytophthora infestans, a pathogenic oomycete that is the causal agent of potato and tomato late blight, has devastating effects worldwide. The genetic composition of P. infestans populations in Canada has changed considerably over the last few years, with the appearance of several new genotypes showing different mating types and sensitivity to the fungicide metalaxyl. Genetic markers allowing for a rapid assessment of genotypes from small amounts of biological material would be beneficial for the early detection and control of this pathogen throughout Canada. Mining of the P. infestans genome revealed several regions containing single-nucleotide polymorphisms (SNP) within both nuclear genes and flanking sequences of microsatellite loci. Allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) assays were developed from 14 of the 50 SNP found by sequencing. Nine optimized ASO-PCR assays were validated using a blind test comprising P. infestans and other Phytophthora spp. The assays revealed diagnostic profiles unique to each of the five dominant genotypes present in Canada. The markers developed in this study can be used with environmental samples such as infected leaves, and will contribute to the genomic toolbox available to assess the genetic diversity of P. infestans at the intraspecific level. For late blight management, early warning about P. infestans genotypes present in potato and tomato fields will help growers select the most appropriate fungicides and application strategies.

Bacterial biofilm-derived antigens: a new strategy for vaccine development against infectious diseases.

INTRODUCTION: Microorganisms can develop into a social organization known as biofilms and these communities can be found in virtually all types of environment on earth. In biofilms, cells grow as multicellular communities held together by a self-produced extracellular matrix. Living within a biofilm allows for the emergence of specific properties for these cells that their planktonic counterparts do not have. Furthermore, biofilms are the cause of several infectious diseases and are frequently inhabited by multi-species. These interactions between microbial species are often critical for the biofilm process. Despite the importance of biofilms in disease, vaccine antigens are typically prepared from bacteria grown as planktonic cells under laboratory conditions. Vaccines based on planktonic bacteria may not provide optimal protection against biofilm-driven infections. AREAS COVERED: In this review, we will present an overview of biofilm formation, what controls this mode of growth, and recent vaccine development targeting biofilms. EXPERT OPINION: Previous and ongoing research provides evidence that vaccine formulation with antigens derived from biofilms is a promising approach to prevent infectious diseases and can enhance the protective efficacy of existing vaccines. Therefore, research focusing on the identification of biofilm-derived antigens merits further investigations.

Low-volume walking HIIT: Efficient strategy to improve physical capacity and reduce the risk of cardiovascular disease in older women with type 2 diabetes.

BACKGROUND AND AIMS: To compare the effect of a low-volume walking high-intensity interval training (HIIT) to moderate-intensity continuous training (MICT) on risk of cardiovascular diseases and physical capacity in older women with type 2 diabetes (T2D). METHODS: Thirty inactive older women with T2D were randomized into either HIIT (75 min/week) or MICT (150 min/week). Cardiovascular risk profile (lipid profile; waist circumference and fat mass; resting, post-exercise and ambulatory blood pressure [BP]; VO2 peak; UKPDS score; ABC's) and physical capacity were assessed before and after a 12-week intervention. RESULTS: While resting systolic and diastolic BP (all p ≤ 0.01) were reduced, ambulatory BP (p ≥ 0.49) and lipid profile (p ≥ 0.40) remained unchanged after the intervention. Although VO2 peak increased to a similar extent in both groups (p = 0.015), the distance covered during the 6MWT (p = 0.01) and grip strength (p = 0.02) increased to a greater extend in HIIT. The UKPDS risk score decreased in both groups after the intervention (p = 0.03) and 31% of the participants reached the ABC's compared to 24% at baseline. CONCLUSION: Low-volume walking HIIT is an efficient exercise intervention for older women with T2D as it improved some CVD risk factors and physical capacity. Nevertheless, neither low-volume HIIT nor MICT is sufficient to affect ambulatory blood pressure in T2D patients.

The EcoChip 2: An Autonomous Sensor Platform for Multimodal Bio-environmental Monitoring of the Northern Habitat.

This paper presents the EcoChip 2, an autonomous multimodal bio-environmental sensor platform for the monitoring of microorganisms in the northern habitat. The EcoChip 2 prototype includes an array of 96-wells for the continuous monitoring of microbiological growth through a multichannel electrochemical impedance analyzer circuit. In addition, the platform includes luminosity, humidity, temperature sensors and monitoring. The developed electronic board uses an ultra-low-power microcontroller unit, a custom power management unit, a low-power wireless ISM-2.45 GHz transceiver, and a flash memory to accumulate and store the sensor data over extended monitoring periods. When a wireless base station is placed within the transmission range of the EcoChip 2, an embedded low-power wireless transceiver transmits the 96-wells impedance data and the other sensor data stored in the flash memory to the user interface. We present the measured performance of the prototype, along with laboratory test results of bacterial growth measurements inside the 96 wells in parallel. We show that the EcoChip 2 can successfully measure the impedances associated with bacterial growth over several hours using an excitation frequency of 2 kHz with power consumption of 114.6 mW under operating mode.

Development of a TaqMan real-time PCR assay for quantification of airborne conidia of Botrytis squamosa and management of botrytis leaf blight of onion.

The use of a DNA-based method for quantifying airborne inoculum of Botrytis squamosa, a damaging pathogen of onion, was investigated. A method for purifying DNA from conidia collected using rotating-arm samplers and quantifying it using a TaqMan real-time quantitative polymerase chain reaction (qPCR) assay is described. The sensitivity of the qPCR assay was high, with a detection limit of 2 conidia/rod. A linear relationship between numbers of conidia counted with a compound microscope and those determined with the qPCR assay was obtained. Receiver operating characteristic curve analysis was used to evaluate the reliability of the two methods of conidia quantification (microscope examination and qPCR assay) to predict the risk of disease being below or above a damage threshold (D(th)). In total, 142 field samples from commercial onion fields were analyzed. At damage thresholds of 5 or 10 lesions/leaf, conidia quantification with the qPCR assay was more reliable at predicting disease risk than conidia quantification based on microscope counts. The proportion of decisions where the disease was present and predicted was higher for the qPCR assay than for the microscope counts, with values of 0.95 and 0.89 compared with 0.79 and 0.81 for D(th) of 5 and 10 lesions/leaf, respectively. The proportion of decisions where the disease was present but not predicted was lower for the qPCR assay than for microscope counts, with values of 0.05 and 0.11 compared with 0.20 and 0.19 for D(th) of 5 and 10 lesions/leaf, respectively. The results demonstrated that this new qPCR assay was reliable for quantifying B. squamosa airborne inoculum in commercial onion fields and that molecular conidia quantification could be used as a component of a risk management system for Botrytis leaf blight.

Gaps and delays in survivorship care in the return-to-work pathway for survivors of breast cancer-a qualitative study.

Introduction: The number of survivors of breast cancer (bca) in Canada has steadily increased thanks to major advances in cancer care. But the resulting clientele face new challenges related to survivorship. The lack of continuity of care and the side effects of treatment affect the resumption of active life by survivors of bca, including return to work (rtw). The goal of the present article was to outline gaps and delay in survivorship care in the rtw pathway of survivors of bca. Methods: This qualitative interpretative descriptive study recruited 9 survivors of bca in the province of Quebec. Interviews were conducted at the end of cancer treatments (n = 9), 1 month before rtw (n = 9), and after rtw (n = 5). In an iterative process, a content analysis was performed. Results: The interviews highlighted gaps in survivorship care and the paucity of dedicated resources for cancer survivors. Participants received neither a survivorship care plan nor information about cancer survivorship (for example, transition to a new normal, side effects, rtw). Conclusions: Support for survivors of bca resuming their active lives has to be optimized. We suggest that health professionals have to intervene at 1, 3, and 6 months after cancer treatment. At those points, survivors of bca need support for side-effects management, the rtw decision, resource navigation, and reintegration of daily activities. Also, delay in clinical pathways seems to be longer, and much attention is needed to accompany the transition to a "normal life" after cancer.

Incidence and Significance of Iprodione-Insensitive Isolates of Botrytis squamosa.

Botrytis leaf blight, caused by Botrytis squamosa, is an economically important disease of onion. The principal means of controlling the disease is by applying fungicides. Typical fungicide programs include applications of dithiocarbamates, chloronitriles, carboxamides, and dicarboximides such as iprodione (Rovral). Onion fields were surveyed in 2002, 2003, and 2004 for insensitivity to iprodione. Tests for insensitivity to iprodione were conducted on 62, 58, and 60 monoconidial field isolates using the automated quantitative (AQ) method with a discriminatory dose of 1.78 ppm of iprodione active ingredient (a.i.) in 2002, 2003, and 2004, respectively. Overall, insensitive isolates were detected in 51% of the fields, and the proportions of insensitive isolates were 8.1, 20.7, and 18.3% in 2002, 2003, and 2004, respectively. The aggressiveness of 10 insensitive and 18 sensitive isolates and the efficacy of iprodione was tested in planta. Onion leaves were inoculated with 750 µl of a conidial suspension of 75,000 conidia per ml and incubated in a growth chamber at 15°C. Aggressiveness was measured as lesion density (average number of lesions per cm2 of onion leaf). Lesion density varied from 2.82 to 8.04 lesions per cm2 of leaf. There was a significant effect (P < 0.0001) of isolates on lesion density. However, there was no significant correlation between lesion density and sensitivity to iprodione (r = 0.08). When onion leaves were sprayed with 1,875, 3,750, and 7,500 ppm of iprodione, percent inhibition of lesion density was higher for sensitive isolates with means of 43.04, 61.42, and 74.59, respectively. Accordingly, percent inhibition was lower for insensitive isolates with means of 13.81, 28.26, and 44.37 for iprodione concentrations of 1,875, 3,750, and 7,500, respectively. It was concluded that the incidence of insensitive isolates was relatively low, but insensitive isolates were capable of infecting onion leaves. There was a good relationship between insensitivity to iprodione in B. squamosa populations measured in vitro with the AQ method, and the reduced efficacy of iprodione in controlling Botrytis leaf blight.

Efficacy of a single oral dose of a live bivalent E. coli vaccine against post-weaning diarrhea due to F4 and F18-positive enterotoxigenic E. coli.

F4- and F18-positive enterotoxigenic E. coli strains (F4-ETEC and F18-ETEC) are important causes of post-weaning diarrhea (PWD) in pigs. F4 (antigenic variant ac) and F18 (ab and ac) fimbriae are major antigens that play an important role in the early stages of infection. Herein, the efficacy of a live oral vaccine consisting of two non-pathogenic E. coli strains, one F4ac- and one F18ac-positive, was evaluated using F4ac-ETEC and F18ab-ETEC challenge models. A randomized, masked, placebo-controlled, block design, parallel-group confirmatory study with two different vaccination-challenge intervals (7 and 21 days) was conducted for each challenge model. The vaccine was administered in one dose, to ≥18-day-old piglets via drinking water. Efficacy was assessed by evaluating diarrhea, clinical observations, weight gain and fecal shedding of F4-ETEC or F18-ETEC. Anti-F4 and anti-F18 immunoglobulins in blood were measured. The vaccination resulted in significant reductions in clinical PWD and fecal shedding of F4-ETEC and F18-ETEC after the 7- and 21-day-post-vaccination heterologous challenges, except for after the 21-day-post-vaccination F4-ETEC challenge, when the clinical PWD was too mild to demonstrate efficacy. A significant reduction of mortality and weight loss by vaccination were observed following the F18-ETEC challenge. The 7-day protection was associated with induction of anti-F4 and anti-F18 IgM, whereas the 21-day protection was mainly associated with anti-F4 and anti-F18 IgA. The 7-day onset and 21-day duration of protection induced by this vaccine administered once in drinking water to pigs of at least 18days of age were confirmed by protection against F4-ETEC and F18-ETEC, and induction of F4 and F18-specific immunity. Cross protection of the vaccine against F18ab-E. coli was demonstrated for both the 7- and 21-day F18-ETEC challenges.

Diversity of Streptococcus thermophilus phages in a large-production cheese factory in Argentina.

Phage infections still represent a serious risk to the dairy industry, in which Streptococcus thermophilus is used in starter cultures for the manufacture of yogurt and cheese. The goal of the present study was to analyze the biodiversity of the virulent S. thermophilus phage population in one Argentinean cheese plant. Ten distinct S. thermophilus phages were isolated from cheese whey samples collected in a 2-mo survey. They were then characterized by their morphology, host range, and restriction patterns. These phages were also classified within the 2 main groups of S. thermophilus phages (cos- and pac-type) using a newly adapted multiplex PCR method. Six phages were classified as cos-type phages, whereas the 4 others belonged to the pac-type group. This study illustrates the phage diversity that can be found in one factory that rotates several cultures of S. thermophilus. Limiting the number of starter cultures is likely to reduce phage biodiversity within a fermentation facility.

[Development and application of a clinical vignette to assess the quality of cancer care]. / Développement et application d'une vignette clinique pour apprécier la qualité des soins en oncologie.

BACKGROUND: In conjunction with a study focusing on the implementation and effect of an integrated care network for cancer patients in the Monteregie region in Quebec, the vignette research strategy was adopted to assess the quality of care provided by the interdisciplinary teams working with this clientele. This research strategy has only recently been used to assess professional practices. This article adopts a resolutely methodological angle in order to describe a rigorous, innovative, transferable experience from the standpoint of the elaboration of a vignette. METHODS: We adopted a six-step approach to elaborate the vignette. This vignette includes the description of collaboration with clinicians. The approach assured us of attaining high content validity from the standpoint of facets of its relevance, completeness and intelligibility to respondents. Our clinical vignette describes a sequence of events stemming from the care coordination of a 58-year-old man suffering from rectal cancer. Data were collected through group interviews with the interdisciplinary teams (n=5) under study. The professionals present were asked to describe their usual practices with respect to the events described in the vignette. We adopted two data analysis strategies: (i) a comparison of practices revealed through the interviews with anticipated responses in light of the guidelines of the "Programme québécois de lutte contre le cancer"; and (ii) an analysis according to facets of the quality of care. RESULTS: Team professional practices seem to evolve towards the care package valued by the "Programme québécois de lutte contre le cancer". Differences were also observed between the teams from the standpoint of the continuity of care. CONCLUSION: Our study shows that it is possible to develop a vignette that enables us to understand professional practices in an interdisciplinary context provided that a rigorous approach is adopted. This approach, which can be transferred to the study of similar phenomena, makes it possible to document the care offered and contribute to the renewal of professional practices.

Local failure is responsible for the decrease in survival for patients with breast cancer treated with conservative surgery and postoperative radiotherapy.

PURPOSE: The aim of the present study was to evaluate the role of local failure (LF) in the survival of patients treated with lumpectomy and postoperative radiotherapy and to investigate whether LF is not only a marker for distant metastasis (DM) but also a cause. METHODS: Charts of patients treated with breast conservative surgery between 1969 and 1991 were reviewed retrospectively. There were 2,030 patients available for analysis. The median duration of follow-up was 6 years. A Cox regression multivariate analysis was performed using LF as a time-dependent covariate. RESULTS: Local control (LC) was 87% at 10 years. Local failure led to poorer survival at 10 years than local control (55% v 75%, P < .00). In a Cox model, local failure was a powerful predictor of mortality. The relative risk associated with LF was 3.6 for mortality and 5.1 for DM (P < .00). In patients with LF, the rate of DM peaked at 5 to 6 years, whereas it peaked at 2 years for patients with LC. The mean time between surgery and DM was 1,050 days for patients without LF and 1,650 days for patients with LF (P < .00). CONCLUSION: Our results show that local failure is associated with an increase in mortality. The difference in the time distribution of distant metastasis for LF and LC could imply distinct mechanisms of dissemination. Local failure should be considered not only as a marker of occult circulating distant metastases but also as a source for new distant metastases and subsequent mortality.

Respiratory pathogens in Québec dairy calves and their relationship with clinical status, lung consolidation, and average daily gain.

BACKGROUND: Bovine respiratory disease (BRD) is 1 of the 2 most important causes of morbidity and mortality in dairy calves. Surprisingly, field data are scant concerning the prevalence of respiratory pathogens involved in BRD in preweaned dairy calves, especially in small herds. OBJECTIVES: To identify the main respiratory pathogens isolated from calves in Québec dairy herds with a high incidence of BRD, and to determine if there is an association between the presence of these pathogens and clinical signs of pneumonia, lung consolidation, or average daily gain. ANIMALS: Cross-sectional study using a convenience sample of 95 preweaned dairy calves from 11 dairy herds. METHODS: At enrollment, calves were weighed, clinically examined, swabbed (nasal and nasopharyngeal), and lung ultrasonography was performed. One month later, all calves were reweighed. RESULTS: Twenty-two calves had clinical BRD and 49 had ultrasonographic evidence of lung consolidation. Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni were isolated in 54, 17, and 12 calves, respectively. Mycoplasma bovis was identified by PCR testing or culture in 19 calves, and 78 calves were found to be positive for Mycoplasma spp. Bovine coronavirus was detected in 38 calves and bovine respiratory syncytial virus in 1. Only the presence of M. bovis was associated with higher odds of clinical signs, lung consolidation, and lower average daily gain. CONCLUSIONS AND CLINICAL IMPORTANCE: Results suggested that nasopharyngeal carriage of M. bovis was detrimental to health and growth of dairy calves in small herds with a high incidence of BRD.

Optimization of permanent 125I prostate implants using fast simulated annealing.

PURPOSE: Treatment planning of ultrasound-guided transperineal 125I permanent prostatic implants is a time-consuming task, due to the large number of seeds used and the very large number of possible source arrangements within the target volume. The goal of this work is to develop an algorithm based on fast simulated annealing allowing consistent and automatic dose distribution optimization in permanent 125I prostatic implants. METHODS AND MATERIALS: Fast simulated annealing is used to optimize the dose distribution by finding the best seed distribution through the minimization of a cost function. The cost function includes constraints on the dose at the periphery of the planned target volume and on the dose uniformity within this volume. Adjustment between peripheral dose and the dose uniformity can be achieved by varying the weight factor in the cost function. RESULTS: Fast simulated annealing algorithm finds very good seed distributions within 20,000 iterations. The computer time needed for the optimization of a typical permanent implant involving 60 seeds and 14 needles is approximately 15 min. An additional 5 min are necessary for isodose distribution computations and miscellaneous outputs. CONCLUSION: The use of fast simulated annealing allows for an efficient and rapid optimization of dose distribution. This algorithm is now routinely used at our institution in the clinical planning of 125I permanent transperineal prostate implants for early stage prostatic carcinoma.

Seed misplacement and stabilizing needles in transperineal permanent prostate implants.

BACKGROUND AND PURPOSE: Seed misplacement occurring in transperineal permanent implants contributes to the degradation in dose coverage. It has been suggested that needles could be used to immobilize the prostate and help reduce misplacement. This study investigates the effects of parallel stabilizing needles on seed misplacement. MATERIALS AND METHODS: A group of ten patients implanted with stabilizing needles was compared with a group of 20 patients implanted without stabilization. Measurements were performed on the displacement of individual seeds and needles. The needle measurements are: insertion angle, the ratio of post-implant over pre-implant lengths and the clustering tendency, a measure of relative misplacement among the seeds of the same needle. RESULTS: No difference was observed in seed misplacement. No difference was observed in needle insertion angle, a measure which was expected to improve with the use of stabilizing needles. CONCLUSION: None of the expected effects from the use of parallel stabilizing needles have been observed. This method of prostate contention appears to be without benefits. Seed misplacement is most pronounced along the insertion axis and is caused by friction between prostatic tissues and implantation needles. Reducing friction could be a promising alternative to prostate contention in trying to reduce misplacement.