Production of recycled manure solids for use as bedding in Canadian dairy farms: II. Composting methods.

Recent technological advances in the dairy industry have enabled Canadian farms with liquid manure systems to use mechanical solid-liquid separation paired with composting of the separated solids for on-farm production of low-cost bedding material. However, because several approaches are available, it is difficult for farmers to select the appropriate one to achieve high quality recycled manure solids (RMS). Whereas 3 solid-liquid manure separators were compared in part I of the series (companion paper in this issue), the present study (part II) aims to assess the performance of 4 composting methods (static or turned windrow and drum composter for 24 or 72 h) under laboratory conditions. Parameters evaluated included temperature, physico-chemical characteristics, and bacterial composition of RMS, as well as airborne microorganisms, dust, and gases associated with composting RMS. Because each treatment attained the desired composting temperature range of 40 to 65°C (either in heaps or in the drum composter), reductions in bacteria were a better indicator of the sanitation efficiency. The treatment of fresh RMS in a drum composter for 24 h showed decreased bacterial counts, especially for Escherichia coli (from 1.0 × 105 to 2.0 × 101 cfu/g of dry matter) and Klebsiella spp. (from 3.2 × 104 to 4.0 × 102 cfu/g of dry matter). Increasing the time spent in the rotating vessel to 72 h did not result in further decreases of these pathogens. Composting in a static or turned windrow achieved similar E. coli and Klebsiella spp. reductions as the 24-h drum composting but in 5 or 10 d, and generally showed the lowest occupational exposure risk for dairy farmers regarding concentrations of airborne mesophilic bacteria, mesophilic and thermotolerant fungi, and total dust. Drum-composted RMS stored in piles exhibited intermediate to high risk. Composting approaches did not have a major influence on the physico-chemical characteristics of RMS and gas emissions. Drum composting for 24 h was the best compromise in terms of product quality, temperature reached, decreased bacterial numbers, and emitted airborne contaminants. However, because levels of pathogenic agents rapidly increase once composted RMS are spread in stalls, bacteriological characteristics of RMS along with milk quality and animal health and welfare features should be monitored in Canadian dairy barns applying recommended separation (part I) and composting (part II) systems to evaluate health risk and optimize management practices.

No effect of scalp cooling on survival among women with breast cancer.

Scalp cooling can prevent chemotherapy-induced alopecia in some cancer patients. It is not used in all countries. No data are available regarding its impact, if any, on survival. The aim of this study was to compare overall survival according to whether or not scalp cooling was used during neoadjuvant or adjuvant chemotherapy for non-metastatic breast cancer. We conducted a retrospective cohort study of 1,370 women with non-metastatic invasive breast carcinoma who received chemotherapy in the neoadjuvant or adjuvant setting. A total of 553 women who used scalp cooling came from a tertiary breast cancer clinic in Quebec City (diagnosed between 1998 and 2002) and 817 were treated in other hospitals in the province of Quebec (between 1998 and 2003) where scalp cooling was not routinely available. Overall survival of women who used scalp cooling and those who did not was compared using Cox proportional hazards models. Median follow-up for the scalp-cooled and the non-scalp-cooled groups was 6.3 years and 8.0 years, respectively. Overall mortality was no different (adjusted hazard ratio 0.89, 95 % confidence interval: 0.68-1.17, p = 0.40) among scalp-cooled women, compared to those not getting scalp cooling. Among women getting neoadjuvant or adjuvant chemotherapy for non-metastatic breast cancer, scalp cooling used to prevent chemotherapy-induced alopecia had no negative effect on survival. To our knowledge, this is the first study to compare survival of women who used scalp cooling to that of women who did not.

Management of hypersensitivity to platinum- and taxane-based chemotherapy: cepo review and clinical recommendations.

BACKGROUND: Although antineoplastic agents are critical in the treatment of cancer, they can potentially cause hypersensitivity reactions that can have serious consequences. When such a reaction occurs, clinicians can either continue the treatment, at the risk of causing a severe or a potentially fatal anaphylactic reaction, or stop the treatment, although it might be the only one available. The objective of the present work was to evaluate the effectiveness of methods used to prevent and treat hypersensitivity reactions to platinum- or taxane-based chemotherapy and to develop evidence-based recommendations. METHODS: The scientific literature published to December 2013, inclusive, was reviewed. RESULTS: Premedication with antihistamines, H2 blockers, and corticosteroids is not effective in preventing hypersensitivity reactions to platinum salts. However, premedication significantly reduces the incidence of hypersensitivity to taxanes. A skin test can generally be performed to screen for patients at risk of developing a severe reaction to platinum salts in the presence of grade 1 or 2 reactions, but skin testing does not appear to be useful for taxanes. A desensitization protocol allows for re-administration of either platinum- or taxane-based chemotherapy to some patients without causing severe hypersensitivity reactions. CONCLUSIONS: Several strategies such as premedication, skin testing, and desensitization protocols are available to potentially allow for administration of platinum- or taxane-based chemotherapy to patients who have had a hypersensitivity reaction and for whom no other treatment options are available. Considering the available evidence, the Comité de l'évolution des pratiques en oncologie made recommendations for clinical practice in Quebec.

The feasibility of implementing an English language version of GLA:D Back.

BACKGROUND: Evidenced-based clinical guidelines for the treatment of low back pain (LBP) consistently suggest educating patients about their back pain, its natural course, and providing advice to keep active and continue working. Despite this evidence, clinicians routinely do not follow these recommendations resulting in ineffective and fragmented care. GLA:D® Back, a standardized care package, was originally developed in Denmark to assist clinicians in implementing evidence-based care. This study will evaluate the feasibility of implementing the English version of the Danish GLA:D® Back program in Alberta, Canada. METHODS: Thirty-five clinicians from nineteen clinics in Alberta, Canada, participated. Feasibility of program implementation, our primary objective, was evaluated within 3 months. Feasibility success was defined as 50% clinician/clinic adoption in addition to 66-88 enrolled participants registered in the database. Our secondary objectives included collecting data pertaining to clinician confidence, attitudes and behaviour of treating patients, perceived barriers and facilitators of program in addition to collecting patient-data regarding pain, function, general health and self-efficacy. RESULTS: The majority of the clinics (15/19, 79%) offered GLA:D® Back to their patients within the study period. Of the participating clinicians, GLA:D® Back was delivered by (25/35, 71%) of clinicians. In total, 78 patients were enrolled in the program and (69/78, 88%) participants attended the final assessment. Secondarily, clinicians demonstrated a biomedical and behavioural orientation along with high confidence when treating LBP patients while patient outcomes trended toward improvement. CONCLUSION: The English translation of the Danish GLA:D Back program was feasible for Albertan clinicians to implement into practice in both urban and rural settings.

The role of HER2-targeted therapies in women with HER2-overexpressing metastatic breast cancer.

The role of targeted therapies in the treatment of women with breast cancer has been rapidly evolving. Trastuzumab, a monoclonal antibody against the human epidermal growth factor receptor 2 (HER2), was the first HER2-targeted therapy that clearly demonstrated a significant clinical benefit for women with HER2-overexpressing metastatic breast cancer (mbc). However, in recent years it has become increasingly apparent that, when trastuzumab is used in the first-line setting in combination with chemotherapy, most women eventually develop progressive disease. Determining the treatment options available to women who have progressed while on trastuzumab therapy has been hampered by a paucity of high-quality published data. In addition, with the standard use of trastuzumab in the adjuvant setting (for eligible HER2-positive patients), the role of anti-HER2 agents for patients who experience a breast cancer relapse has become a clinically relevant question. This manuscript reviews current available data and outlines suggestions from a panel of Canadian oncologists about the use of trastuzumab and other HER2-targeted agents in two key mbc indications:Treatment for women with HER2-positive mbc progressing on trastuzumab (that is, treatment beyond progression)Treatment for women with HER2-positive mbc recurring following adjuvant trastuzumab (that is, re-treatment)The suggestions set out here will continue to evolve as data and future trials with trastuzumab and other HER2-targeted agents emerge.

Value assessment in oncology drugs: funding of drugs for metastatic breast cancer in Canada.

Background: Life expectancy for women with metastatic breast cancer has improved since the early 2000s, in part because of the introduction of novel therapies, including chemotherapy, hormonal therapy, and targeted agents. However, those treatments can come at a cost for the patient (short- and long-term toxicities from treatment) and at a financial cost for the health care system. Given the increase in the number of costly anticancer agents being introduced into the clinical setting, the American Society of Clinical Oncology (asco) and the European Society for Medical Oncology (esmo) have developed a system to quantify the value of new cancer treatments in terms of benefit, toxicities, and costs. Methods: In our value-assessment analysis, we included drugs that were funded in Canada between 2012 and 2017 for metastatic breast cancer. We reviewed the clinical benefit of those agents (survival, progression, quality of life), their costs, their value according to the asco and esmo value frameworks, and their assessments from the pan-Canadian Oncology Drug Review [pcodr (in Canada, except Quebec)] and the Institut national d'excellence en santé et en services sociaux [iness (in Quebec)]. Results: Drugs funded in Canada showed variation in their asco net health benefit scores and esmo magnitude of clinical benefit scores, but all had a cost-effectiveness ratio greater than $100,000 per quality-adjusted life-year. The strength and magnitude of the clinical benefit (for example, overall survival benefit vs. progression-free survival benefit) was not necessarily associated with a higher value score. Conclusions: Although great progress has been made in developing value frameworks, use of those frameworks has to be refined to help patients and health care providers make informed decisions about the benefit of novel cancer therapies and to help policymakers make decisions about the societal benefit of funding those therapies.

Real-world patient- and caregiver-reported outcomes in advanced breast cancer.

Background: Advanced breast cancer (abc) represents a substantial burden for patients and caregivers. In the present study, we aimed to estimate quality of life (qol), utility, productivity loss, pain, health care resource utilization, and costs for patients with abc, and qol, utility, and productivity loss for their caregivers. Methods: This multicentre prospective non-interventional study was conducted in Canada. Eligible participants were postmenopausal women with estrogen receptor-positive, her2-negative unresectable abc and their caregivers. Validated questionnaires were used to measure qol, utility, productivity loss, and pain. Patients and caregivers were classified into 4 health states typically used in oncology economic modelling: first-line progression-free (1l-pf), first-line progressive disease (1l-pd), second- or subsequent-line progression-free (≥2l-pf), and second- or subsequent-line progressive disease (≥2l-pd). Results: Most patients and caregivers accepted to participate, with total recruitment of 202 patients and 78 caregivers. Compared with patients in pf, patients in pd had lower mean qol scores (52.9 ± 29.9 for 1l-pd vs. 68.2 ± 23.2 for 1l-pf, and 54.0 ± 23.6 for ≥2l-pd vs. 66.0 ± 22.1 for ≥2l-pf), lower mean utility values (0.64 ± 0.22 for 1l-pd vs. 0.73 ± 0.20 for 1l-pf, and 0.65 ± 0.25 for ≥2l-pd vs. 0.74 ± 0.18 for ≥2l-pf), and greater productivity loss (39.4 ± 27.7 for 1l-pd vs. 27.5 ± 30.1 for 1l-pf, and 37.6 ± 29.2 for ≥2l-pd vs. 32.0 ± 29.0 for ≥2l-pf). Compared with caregivers of patients in pf, caregivers of patients in pd had lower qol scores and utility values, and greater productivity loss. Conclusions: Study results indicate that, for patients and caregivers, pd health states are associated with a deterioration of qol and utility and a decrease in productivity in both 1l and ≥2l.

Regulation of physiological rates in Caenorhabditis elegans by a tRNA-modifying enzyme in the mitochondria.

We show that the phenotype associated with gro-1(e2400) comprises the whole suite of features that characterize the phenotype of the clk mutants in Caenorhabditis elegans, including deregulated developmental, behavioral, and reproductive rates, as well as increased life span and a maternal effect. We cloned gro-1 and found that it encodes a highly conserved cellular enzyme, isopentenylpyrophosphate:tRNA transferase (IPT), which modifies a subset of tRNAs. In yeast, two forms of the enzyme are produced by alternative translation initiation, one of which is mitochondrial. In the gro-1 transcript there are also two possible initiator ATGs, between which there is a sequence predicted to encode a mitochondrial localization signal. A functional GRO-1::GFP fusion protein is localized diffusely throughout the cytoplasm and nucleus. A GRO-1::GFP initiated from the first methionine is localized exclusively to the mitochondria and rescues the mutant phenotype. In contrast, a protein initiated from the second methionine is localized diffusely throughout the cell and does not rescue the mutant phenotype. As oxygen consumption and ATP concentration have been reported to be unaffected in gro-1 mutants, our observations suggest that GRO-1 acts in mitochondria and regulates global physiology by unknown mechanisms.

A novel DR beta 1*03 allele identified by polymerase chain reaction-restriction fragment length polymorphism.

This report describes a new MHC class II allele, HLA-DR beta 1*0306, discovered in a 31-year-old Norwegian male. The allele typed serologically as DRw52 (DR3) and amplified in PCR using DR52-associated group primers. This product could not be identified using established restriction digests, however. Use of Asp 700, Msp I, Hha I, Bse RI, Mnl I, Hph I, and Bsrb I gave banding patterns expected for a DR beta 1*03011 allele, but Rsa I had an additional site at codon 47. Sequencing showed a single base change at this position, with the substitution of tyrosine for phenylanine in this new allele. The biologic impact of this substitution remains to be determined.

Regulation of 2',3'-cyclic nucleotide phosphodiesterase gene expression in experimental peripheral neuropathies.

2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNPase) is an enzyme associated with central nervous system myelination. Although present in the mammalian peripheral nerve, it is not clear what its role is during myelination nor how the expression of this gene is regulated in the PNS. In this study, CNPase gene expression was studied in the crushed and permanently transected rat sciatic nerve, two models of peripheral nerve neuropathy. The Schwann cells of the crushed nerve initially demyelinate, remain in a non-myelinating condition until active regeneration induces remyelination (10-21 days after injury), whereas those of the permanently transected nerve remain in a quiescent, non-myelinating state after the initial demyelination. An increase of CNPase mRNA levels is observed during degeneration and remains high whether the peripheral nerve is regenerating or not, suggesting transcriptional activation of CNPase mRNA and/or increased CNPase mRNA stability as a response to nerve injury. In contrast, the steady state level of CNPase protein did not increase during degeneration or regeneration suggesting either negative translational regulation of CNPase gene expression or a higher turnover of this protein in the injured peripheral nerve. Furthermore, CNPase activity dropped sharply during early degeneration and remained low in the quiescent cells of the permanently transected nerve while it increased in the regenerating nerve. The results suggest that although transcriptional or post-transcriptional regulation of CNPase gene expression is not dependent on Schwann cell-axonal contact, the activity of CNPase appears to be dependent on myelination and indirectly dependent on the presence of axons in the peripheral nerve.

Topographical evolution of spike-wave complexes.

Computer-generated 3-dimensional field potential maps of spike-wave complexes from two 4 X 4 electrode grids on the scalp were studied. A visual analysis of these field maps throughout the spike-wave evolution permitted quantification of the spike, trough and slow wave components in terms of distribution, origin and propagation. In addition, a more objective morphological analyzer also quantified the discriptive parameters of distribution, origin and propagation for the spike component of the patients' spike-wave complexes. We found that field distributions of spikes differed from that of waves. Succeeding positive troughs evolved more symmetrically than did spikes but less than ensuing negative waves. Negative waves were more diffuse, more symmetrical in evolution, and more posteriorly centred than either spikes or troughs. Unlike the troughs and slow waves whose fields tended to remain stationary during their evolution, spikes always moved from their points of origin. Spikes originated at the most lateral points of the grids and propagated laterally and anteriorly in one of two ways: a simultaneous origin at both lateral positions, then propagation toward the midline, and then usually anteriorly, a clearly unilateral origin with spread contralaterally to the homologous electrode position of the contralateral hemisphere followed again by anterior propagation. Interhemispheric lag times of spikes ranged from 0 to 25 ms with an average of 10.5 ms. Inter- and intrapatient variability was considerable. This type of analysis reveals properties of spike-wave complexes which may not be appreciated by standard paper writeout.

Health care indicators.

Contained in this regular feature of the journal is a section on each of the following five topics: community hospital statistics; employment, hours, and earnings in the private health sector; health care prices; hospital skill mix changes: 1980s; and national economic indicators.

Projections of national health expenditures through the year 2000.

In this article, the authors present a scenario for health expenditures during the 1990s. Assuming that current laws and practices remain unchanged, the Nation will spend $1.6 trillion for health care in the year 2000, an amount equal to 16.4 percent of that year's gross national product. Medicare and Medicaid will foot an increasing share of the Nation's health bill, rising to more than one-third of the total. The factors accounting for growth in national health spending are described as well as the effects of those factors on spending by type of service and by source of funds.

Measuring hospital input price increases: the rebased hospital market basket.

The input prices indexes used in part to set payment rates for Medicare inpatient hospital services in both prospective payment system (PPS) and PPS-excluded hospitals were rebased from 1982 to 1987 beginning with payments for fiscal year 1991. In this article, the issues and evidence used to determine the composition of the revised hospital input price indexes are discussed. One issue is the need for a separate market basket for PPS-excluded hospitals. Also, the payment implications of using hospital-industry versus economywide measures of wage rates as price proxies for the growth in hospital wage rates are addressed.

Effects of a commercial canine gonadotropin releasing hormone vaccine on estrus suppression and estrous behavior in mares.

We investigated the effect of immunization against gonadotropin releasing hormone (GnRH) using a commercial canine GnRH vaccine on estrus suppression and unwanted estrous behavior in mares. In experiment 1, mares were immunized (n = 6) twice with vaccine (5 mL) given intramuscularly 4 weeks apart or received a control diluent (n = 5). Transrectal ultrasonographic examination of the reproductive tracts was performed three days a week for 40 weeks after initial vaccination. Blood samples were collected weekly for GnRH antibody titer and progesterone concentration determination. In experiment 2, privately-owned mares (n = 12) were immunized twice with vaccine (1 mL) given intramuscularly 4 weeks apart. Blood samples were collected prior to each vaccination as well as 12 and 20 weeks after initial treatment, and transrectal ultrasonographic examinations of the reproductive tracts were performed 12 weeks after the first vaccination. Vaccinated mares in experiment 1 responded with a GnRH antibody titer, progesterone concentrations significantly lower than controls, and cessation of ovarian activity. Vaccinated mares in experiment 2 also responded with a GnRH antibody titer, progesterone concentrations that remained basal for the duration of the study, and cessation of ovarian activity. Owners of vaccinated mares in experiment 2 reported that the number of unwanted estrous behaviors present before vaccination significantly decreased following vaccination. In conclusion, GnRH immunization using a canine GnRH vaccine is an effective method for suppressing estrus and unwanted estrous behavior.

Optimizing the management of HER2-positive early breast cancer: the clinical reality.

Breast cancer positive for HER2 (human epidermal growth factor receptor 2) is associated with a poor prognosis for patients with both early-stage and metastatic breast cancer. Trastuzumab has been shown to be effective and is now considered the standard of care for early-stage patients with HER2-positive breast cancer. In that population, trastuzumab has been studied in six randomized clinical trials. Overall, use of this agent leads to a significant reduction in risk of disease recurrence and improvement in overall survival. Despite the strong evidence for the use of trastuzumab in managing HER2-positive early breast cancer (EBC), a number of clinical controversies remain. The authors of this paper undertook a review of the available scientific literature on adjuvant trastuzumab to produce practical considerations from Canadian oncologists. The panel focused their discussion on five key areas: Management of node-negative disease with tumours 1 cm or smaller in size. Management of HER2-positive EBC across the spectrum of the disease (that is, nodal and steroid hormone receptor status, tumour size) Timing of trastuzumab therapy with chemotherapy for early-stage disease: concurrent or sequential. Treatment duration of trastuzumab for EBC. The role of non-anthracycline trastuzumab-based regimens.