Herd-level associations between the proportion of elevated prepartum nonesterified fatty acid concentrations and postpartum diseases, reproduction, or culling on dairy farms.

The objectives of this herd-level prospective observational cohort study were to describe the proportion of cows with elevated prepartum nonesterified fatty acid concentrations (PropElevNEFA) in dairy herds and to assess the herd-level associations between PropElevNEFA and postpartum diseases, reproductive performance, and culling. From November 2018 to December 2020, a convenience sample of 49 herds was enrolled in this study. Blood sampling (16 to 29 cows per herd) was performed during the week before and during the 2 wk following calving to quantify the concentration of nonesterified fatty acids (NEFA) and ß-hydroxybutyrate acids (BHBA), respectively. Elevated NEFA was defined as ≥280 µmol/L and hyperketonemia as BHBA ≥1.4 mmol/L. Retained placenta, metritis, purulent vaginal discharge, endometritis, and mastitis were diagnosed on-farm following standardized definitions, and success at first artificial insemination (AI) and culling events were recorded. The associations between PropElevNEFA and each individual disease, success at first AI, and culling were evaluated using Bayesian aggregated binomial regression models with weakly informative priors, from the which odds ratio (OR) and the 95% credible intervals (BCI) were obtained. A total of 981 cows were included in the statistical analyses representing 16 to 29 (median = 19) cows per herd. Cows were enrolled in the prepartum period of their first to tenth (median = third) lactation, and 41% of them had an elevated prepartum NEFA concentration. At the herd level, PropElevNEFA varied between 11% and 78% (median = 39%). The odds of metritis (OR = 1.37, 95% BCI = 1.13-1.67) increased for every 10-point increase in PropElevNEFA, whereas the odds of success at first AI decreased (OR = 0.69, 95% BCI = 0.59-0.80). The PropElevNEFA was not associated with the other tested diseases or culling. Our results suggest that the herd-level proportion of cows having elevated prepartum NEFA concentrations is associated with metritis and poor success at first AI in dairy herds.

Association between prepartum nonesterified fatty acid serum concentrations and postpartum diseases in dairy cows.

The objective of the present study was to quantify the relationships between prepartum nonesterified fatty acid (NEFA) concentrations and the development of subsequent diseases or culling and to identify the optimal thresholds allowing identification of animals at high risk of developing postpartum diseases or being culled. A total of 1,299 Holstein cows from 50 commercial herds located around Saint-Hyacinthe (QC, Canada) were enrolled in this observational study. Blood samples were collected from enrolled cows between 1 and 14 d before calving for serum NEFA quantification. Data concerning postpartum diseases and culling were collected from computerized record systems. The association between prepartum NEFA concentrations and postpartum diseases and culling was quantified using generalized linear mixed models, accounting for parity, season, week of sampling, and herd. Optimal NEFA thresholds were evaluated with receiver operator characteristic curves analysis for all diseases and then confirmed with generalized linear mixed models, considering NEFA as a categorical variable (high or low). Prepartum serum NEFA concentrations were associated with diseases diagnosed during the first 30 d in milk (DIM) and culling within the first 50 DIM. The optimal NEFA threshold associated with diseases was ≥290 µmol/L for retained placenta, ≥300 µmol/L for metritis and abomasal displacement, and ≥280 µmol/L for clinical mastitis and hyperketonemia. The level associated with the occurrence of at least one of these diseases in the first 30 DIM was ≥280 µmol/L, but it was ≥260 µmol/L for culling in the first 50 DIM. No relationship was found between NEFA concentrations and reproductive tract diseases (purulent vaginal discharge or cytological endometritis) or subclinical intramammary infection. Despite the strong relationship between prepartum NEFA concentrations and many diseases, the NEFA optimal threshold accuracy found in our study was low. In conclusion, our results demonstrate a relationship between NEFA concentrations in the 14-d period before calving and the subsequent development of diseases and culling. Prepartum NEFA concentrations thresholds between ≥260 and 300 µmol/L appear to be a strategic choice. However, considering the low accuracy, their use at the cow level should be performed with caution.

A new LC/MS method for specific determination of human systemic exposure to bisphenol A, F and S through their metabolites: Application to cord blood samples.

Due to restriction of the use of BPA, several structural analogues such as BPS and BPF have been proposed for its replacement in many consumer products. This has increased the prevalence of BPS and BPF in urine from tested cohorts. However, these substitutes have similar endocrine disrupting properties to BPA, particularly on reproductive and metabolic functions, which suggests that fetal exposure to these analogues could be of concern for human health. Bisphenols (BPs) are mainly metabolized to glucuronides (BP-Gs), which are considered as inactive but provide a relevant marker of fetal exposure during pregnancy. In most instances, these metabolites are indirectly quantified after hydrolysis and measurement of the corresponding native BPs, which may lead to bias due to spurious BPs contamination during blood collection and/or analyses. We have developed a new method for direct quantification of BP-Gs, which has the advantage of not being affected by errors related to the presence of BPs. First, BP-Gs were extracted from plasma by anion exchange solid phase extraction. They were then labelled with dansyl chloride, using experimentally-optimized incubation conditions, after which the dansyl derivatives were injected into an on-line SPE-UHPLC/MS/MS system. The performance of the method, in terms of sensitivity, precision and accuracy, was evaluated in plasma over a concentration range of 0.05-5 ng/mL. The intra- and inter-day CV% precision were lower than 20% with accuracies ranging from 93% to 115%. The limit of quantification was set at 0.05 ng/mL. The method was then applied to measure BP-Gs in forty-four cord plasma samples. Although no BPF-G was found, BPA-G and BPS-G was determined in almost half of the cord plasma samples with concentration ranges nd-0.089 ng/mL and nd-0.586 ng/mL, respectively.

Basal Ti level in the human placenta and meconium and evidence of a materno-foetal transfer of food-grade TiO2 nanoparticles in an ex vivo placental perfusion model.

BACKGROUND: Titanium dioxide (TiO2) is broadly used in common consumer goods, including as a food additive (E171 in Europe) for colouring and opacifying properties. The E171 additive contains TiO2 nanoparticles (NPs), part of them being absorbed in the intestine and accumulated in several systemic organs. Exposure to TiO2-NPs in rodents during pregnancy resulted in alteration of placental functions and a materno-foetal transfer of NPs, both with toxic effects on the foetus. However, no human data are available for pregnant women exposed to food-grade TiO2-NPs and their potential transfer to the foetus. In this study, human placentae collected at term from normal pregnancies and meconium (the first stool of newborns) from unpaired mothers/children were analysed using inductively coupled plasma mass spectrometry (ICP-MS) and scanning transmission electron microscopy (STEM) coupled to energy-dispersive X-ray (EDX) spectroscopy for their titanium (Ti) contents and for analysis of TiO2 particle deposition, respectively. Using an ex vivo placenta perfusion model, we also assessed the transplacental passage of food-grade TiO2 particles. RESULTS: By ICP-MS analysis, we evidenced the presence of Ti in all placentae (basal level ranging from 0.01 to 0.48 mg/kg of tissue) and in 50% of the meconium samples (0.02-1.50 mg/kg), suggesting a materno-foetal passage of Ti. STEM-EDX observation of the placental tissues confirmed the presence of TiO2-NPs in addition to iron (Fe), tin (Sn), aluminium (Al) and silicon (Si) as mixed or isolated particle deposits. TiO2 particles, as well as Si, Al, Fe and zinc (Zn) particles were also recovered in the meconium. In placenta perfusion experiments, confocal imaging and SEM-EDX analysis of foetal exudate confirmed a low transfer of food-grade TiO2 particles to the foetal side, which was barely quantifiable by ICP-MS. Diameter measurements showed that 70 to 100% of the TiO2 particles recovered in the foetal exudate were nanosized. CONCLUSIONS: Altogether, these results show a materno-foetal transfer of TiO2 particles during pregnancy, with food-grade TiO2 as a potential source for foetal exposure to NPs. These data emphasize the need for risk assessment of chronic exposure to TiO2-NPs during pregnancy.

Does bovine besnoitiosis affect the sexual function of chronically infected bulls?

Bovine besnoitiosis is a reemerging disease in Europe. The clinically Besnoitia besnoiti infection in bulls is characterized by fever, nasal discharge, and orchitis in the acute phase and by scleroderma in the chronic phase. However, in many bulls, B besnoiti infection remains at a subclinical stage. Bull infertility is an economically relevant consequence of besnoitiosis infection. It is not clear, however, if semen quality returns to normal levels when infected animals have clinically recovered. The aim of this study was to examine the relationship between chronic besnoitiosis and bull sexual function in a region of eastern France, where the disease is reemerging, by comparing semen quality and genital lesions in 11 uninfected, 17 subclinically infected, and 12 clinically infected bulls. The presence of anti-B besnoiti antibodies was detected by Western blot test. Semen was collected by electroejaculation. Bulls clinically infected with B besnoiti showed significantly more genital tract alterations than uninfected or subclinically infected bulls. No relationship was evidenced between besnoitiosis infectious status and semen quality, whereas a significant relationship was noted between genital lesions and semen score. This means that in the absence of moderate to severe genital lesions, chronic bovine besnoitiosis is unlikely to alter semen quality. However, as the presence of infected animals could lead to spread of the disease, culling or separation of clinically infected bulls from the remaining healthy animals is strongly recommended.

Bisphenol A in culture media and plastic consumables used for ART.

STUDY QUESTION: Do the embryo culture media and plastic materials used during assisted reproductive technology (ART) laboratory procedures expose embryos to bisphenol A (BPA)? SUMMARY ANSWER: BPA was not detected in embryo culture media or protein supplements at concentrations above those encountered in normal patient serum and follicular fluids. WHAT IS KNOWN ALREADY: BPA is strongly suspected of altering the epigenome during mammalian development. Medical devices have been shown to be a source of BPA exposure in adult and neonatal intensive care units. STUDY DESIGN, SIZE, DURATION: An analytical study of ART culture media and plastic labware products was performed under conditions close to routine practice and if BPA was detected, tests were carried out under more stringent conditions. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two single-step embryo culture media, two sequential media and three different protein supplements [a purified human serum albumin (HSA), a synthetic serum substitute, and a recombinant HSA] were tested for BPA. Thirty-three different plastic consumables, used from oocyte collection through to embryo transfer, were tested for their ability to leach BPA into their surrounding environment.BPA concentrations were measured according to a previously described liquid chromatography/mass spectrometry method. This method is linear over the calibration range from 0.5 to 100 ng/ml using a linear model weighted by 1/X² and validated in terms of selectivity, linearity, repeatability, reproducibility and limit of quantification (0.5 ng/ml). MAIN RESULTS AND THE ROLE OF CHANCE: Neither the culture media nor the protein supplements were shown to contain detectable levels of BPA. None of the plastic materials leached BPA into the surrounding medium at levels higher than the upper limit detected previously in serum and follicular fluids in women (about 2 ng/ml). However, the plastic of the three tested strippers used for oocyte denudation/embryo handling did contain BPA. Two of these strippers are made with polycarbonate, a plastic whose synthesis is known to require BPA. LIMITATIONS, REASONS FOR CAUTION: This study is limited to the ART media and materials tested here and using a BPA assay with a limit of quantification at 0.5 ng/ml. A minimum volume was required for testing, and one type of plastic labware could not be tested in conditions identical to those in routine use. WIDER IMPLICATIONS OF THE FINDINGS: Although we demonstrated that some plastic materials used in ART contain BPA, under routine conditions none appear capable of leaching BPA at levels higher than those from maternal internal exposure. However, BPA is strongly suspected of altering the epigenome. Since important epigenetic modifications occur in the early embryonic stage, it is questionable whether plastics that contain BPA, polycarbonate in particular, should be used in the manufacture of plastic consumables for ART procedures. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a grant from the Agence de Biomédecine (AOR 2012) and by a grant from the French Ministry of Health (Clinical Research Hospital Program 2012; no.12-018-0560). The authors declared no competing interest.

Improving access to cancer guidelines: feedback from health care professionals.

PURPOSE: We examined access to locally developed and other available clinical practice guidelines (cpgs) for the management of cancer and evaluated how to improve uptake. METHODS: A 12-question online survey was administered to 772 members of 12 multidisciplinary tumour teams in a Canadian provincial oncology program. The teams are composed of physicians, surgeons, nurses, allied health professionals, and researchers involved in the provision of cancer care across the province. Many of these individuals construct or provide input into the provincial cpgs. The questionnaires were administered online and were completed voluntarily. RESULTS: Responses were received from 232 individuals, a response rate of 30.1%. Most respondents (75.1%) indicated they actively referenced cpgs for cancer treatment. Of the 177 respondents who identified barriers to cpg access, 24.9% said that the cause was being too busy; 24.3% and 22.6% cited the user-unfriendliness of the Web site and a lack of awareness about the cpgs. When asked about innovative changes that could be made to improve access, the creation of cpg summary documents was identified as the most effective change (46.3%). The creation of summary documents was ranked highest by physicians, surgeons, and nurses. CONCLUSIONS: Clinical practice guidelines are important tools for standardizing treatment protocols and improving outcomes in health care systems, but support for their use is variable among health care professionals. We have identified barriers to-and potential mitigating strategies for-more widespread access to cpgs by the various health professions involved in cancer care. Local creation of succinct and easily accessible cpgs was identified as the single most effective way to enhance access by health care professionals.

Advance care planning: identifying system-specific barriers and facilitators.

BACKGROUND: Advance care planning (acp) is an important process in health care today. How to prospectively identify potential local barriers and facilitators to uptake of acp across a complex, multi-sector, publicly funded health care system and how to develop specific mitigating strategies have not been well characterized. METHODS: We surveyed a convenience sample of clinical and administrative health care opinion leaders across the province of Alberta to characterize system-specific barriers and facilitators to uptake of acp. The survey was based on published literature about the barriers to and facilitators of acp and on the Michie Theoretical Domains Framework. RESULTS: Of 88 surveys, 51 (58%) were returned. The survey identified system-specific barriers that could challenge uptake of acp. The factors were categorized into four main domains. Three examples of individual system-specific barriers were "insufficient public engagement and misunderstanding," "conflict among different provincial health service initiatives," and "lack of infrastructure." Local system-specific barriers and facilitators were subsequently explored through a semi-structured informal discussion group involving key informants. The group identified approaches to mitigate specific barriers. CONCLUSIONS: Uptake of acp is a priority for many health care systems, but bringing about change in multi-sector health care systems is complex. Identifying system-specific barriers and facilitators to the uptake of innovation are important elements of successful knowledge translation. We developed and successfully used a simple and inexpensive process to identify local system-specific barriers and enablers to uptake of acp, and to identify specific mitigating strategies.

Effect of gonadorelin, lecirelin, and buserelin on LH surge, ovulation, and progesterone in cattle.

Analogs of gonadoliberin (GnRH) are widely used in cattle to synchronize estrus and to induce ovulation, as well as for the treatment of ovarian cysts. The aim of this study was to compare the plasma profiles of LH and progesterone and the follicular dynamics in response to the administration of gonadorelin, lecirelin, or buserelin at the dose recommended to induce ovulation. In addition, the biological response to a half dose of lecirelin was assessed. Twelve healthy Holstein female cows were divided into four sequence groups, according to a Latin square design and received the four treatments during the four periods of the study. Before each period, the estrous cycle was synchronized, and on Day 6 or 7 of the ensuing cycle, the time at which it was most likely to have a dominant follicle, 100 µg of gonadorelin, 25 µg of lecirelin, 50 µg of lecirelin, or 10 µg of buserelin was administered to the cows. Blood samples were regularly collected for up to 4 days after the GnRH administrations. The plasma LH response was evaluated for up to 6 hours after administration, and the plasma progesterone response and ovarian follicular dynamics were evaluated for up to 4 days. There was a significantly lower LH release after gonadorelin treatment compared to lecirelin at the doses of 25 or 50 µg and the buserelin treatment. The mean maximal LH concentration after gonadorelin treatment was 2.5 lower than after lecirelin or buserelin treatment and was reached 1 hour earlier. Four days after the GnRH administration (i.e., at Days 10-11 of the estrous cycle), the overall mean increase in plasma progesterone concentration was 70% and did not differ between the treatment groups. The percentage of disappearance of the dominant follicle (84.8% of ovulation and 4.3% of luteinization) after GnRH treatment was high (73%, 82%, 100%, and 100%, for gonadorelin, lecirelin at the doses of 25 and 50 µg, and buserelin, respectively) and did not differ between the GnRH treatments. The follicle disappearance was followed by the emergence of a synchronous follicle wave within 2 days in almost all the heifers. Altogether, our data show that the three GnRH analogs, at the doses indicated for the induction of ovulation or at a half dose for lecirelin, are almost equally effective to induce the disappearance of the dominant follicle at Day 6 to 7 of the estrous cycle.

Recommendations for the referral of patients for proton-beam therapy, an Alberta Health Services report: a model for Canada?

BACKGROUND: Compared with photon therapy, proton-beam therapy (pbt) offers compelling advantages in physical dose distribution. Worldwide, gantry-based proton facilities are increasing in number, but no such facilities exist in Canada. To access pbt, Canadian patients must travel abroad for treatment at high cost. In the face of limited access, this report seeks to provide recommendations for the selection of patients most likely to benefit from pbt and suggests an out-of-country referral process. METHODS: The medline, embase, PubMed, and Cochrane databases were systematically searched for studies published between January 1990 and May 2014 that evaluated clinical outcomes after pbt. A draft report developed through a review of evidence was externally reviewed and then approved by the Alberta Health Services Cancer Care Proton Therapy Guidelines steering committee. RESULTS: Proton therapy is often used to treat tumours close to radiosensitive tissues and to treat children at risk of developing significant late effects of radiation therapy (rt). In uncontrolled and retrospective studies, local control rates with pbt appear similar to, or in some cases higher than, photon rt. Randomized trials comparing equivalent doses of pbt and photon rt are not available. SUMMARY: Referral for pbt is recommended for patients who are being treated with curative intent and with an expectation for long-term survival, and who are able and willing to travel abroad to a proton facility. Commonly accepted indications for referral include chordoma and chondrosarcoma, intraocular melanoma, and solid tumours in children and adolescents who have the greatest risk for long-term sequelae. Current data do not provide sufficient evidence to recommend routine referral of patients with most head-and-neck, breast, lung, gastrointestinal tract, and pelvic cancers, including prostate cancer. It is recommended that all referrals be considered by a multidisciplinary team to select appropriate cases.

Information needs and sources of information for patients during cancer follow-up.

BACKGROUND: Now more than ever, cancer patients want health information. Little has been published to characterize the information needs and preferred sources of that information for patients who have completed cancer treatment. METHODS: We used a nationally validated instrument to prospectively survey patients attending a cancer clinic for a post-treatment follow-up visit. All patients who came to the designated clinics between December 2011 and June 2012 were approached (N = 648), and information was collected only from those who agreed to proceed. RESULTS: The 411 patients who completed the instrument included individuals with a wide range of primary malignancies. Their doctor or health professional was overwhelmingly the most trusted source of cancer information, followed by the Internet, family, and friends. The least trusted sources of information included radio, newspaper, and television. Patients most preferred to receive personalized written information from their health care provider. CONCLUSIONS: Cancer survivors are keenly interested in receiving information about cancer, despite having undergone or finished active therapy. The data indicate that, for patients, their health care provider is the most trusted source of cancer information. Cancer providers should ask patients about the information they want and should direct them to trusted sources.

Bidirectional placental transfer of Bisphenol A and its main metabolite, Bisphenol A-Glucuronide, in the isolated perfused human placenta.

The widespread human exposure to Bisphenol A (BPA), an endocrine disruptor interfering with developmental processes, raises the question of the risk for human health of BPA fetal exposure. In humans, highly variable BPA concentrations have been reported in the feto-placental compartment. However the human fetal exposure to BPA still remains unclear. The aim of the study was to characterize placental exchanges of BPA and its main metabolite, Bisphenol A-Glucuronide (BPA-G) using the non-recirculating dual human placental perfusion. This high placental bidirectional permeability to the lipid soluble BPA strongly suggests a transport by passive diffusion in both materno-to-fetal and feto-to-maternal direction, leading to a calculated ratio between fetal and maternal free BPA concentrations of about 1. In contrast, BPA-G has limited placental permeability, particularly in the materno-to-fetal direction. Thus the fetal exposure to BPA conjugates could be explained mainly by its limited capacity to extrude BPA-G.

No detection of Besnoitia besnoiti DNA in the semen of chronically infected bulls.

Bovine besnoitiosis is a chronic and debilitating disease observed in many European countries that may cause important economic losses in cattle. The recent widespread of the parasite in Europe had led the European Food Safety Authority to declare bovine besnoitiosis as a re-emerging disease in Europe. Many aspects of the epidemiology of bovine besnoitiosis such as the main routes of transmission are still unclear and need to be further studied. Among the different hypotheses, a sexual transmission has not yet been investigated. Therefore, the aim of this study was to evaluate the presence of Besnoitia besnoiti DNA in the semen of naturally infected bulls by using a highly sensitive method (real-time qPCR). Both pre-sperm and sperm fractions of 40 bulls, including seronegative (n = 11), seropositive subclinically (n = 17), and seropositive clinically (n = 12) infected animals, were collected by electroejaculation and analyzed by real-time qPCR. No B. besnoiti DNA was detected in 27 pre-sperm and 28 sperm fractions of the 40 examined bulls, suggesting that the transmission of B. besnoiti infection by the semen of chronically infected bulls is very unlikely.

Characterizing distress, the 6th vital sign, in an oncology pain clinic.

CONTEXT: The delineation of populations of cancer patients with complex symptoms can inform the planning and delivery of supportive care services. OBJECTIVES: We explored the physical, psychosocial, and practical concerns experienced by patients attending an ambulatory oncology symptom control clinic. METHODS: Patients attending a Pain Clinic at a large tertiary cancer centre were invited to complete screening measures assessing distress, pain, fatigue, anxiety, depression, and practical and psychosocial problems. A matched sample of patients who did not attend the Pain Clinic were selected as a comparison group. RESULTS: Of all eligible Pain Clinic patients, 46 (77%) completed the measures; so did 46 comparison group patients. The percentages of patients reporting distress (78.3%), pain (93.5%), and fatigue (93.5%) were higher among Pain Clinic patients than among the comparison patients. A higher percentage of Pain Clinic patients also reported multiple, severe, concurrent symptoms: 87% scored 7 or higher in at least one of the pain, fatigue, or distress scales, and 30.4% of the patients scored 7 or higher on all three. The most common problem areas were feeling a burden to others, trouble talking with friends and family, spirituality, and sleep difficulties. CONCLUSIONS: Higher levels of multiple, concurrent symptoms and psychosocial problems were found in Pain Clinic patients than in a group of patients who did not attend the Pain Clinic. Routine screening and triaging of cancer patients using a comprehensive and standardized panel of questions can facilitate symptom assessment and management, and can inform program planning.

Quantitative comparison between full-spectrum and filter-based imaging in hyperspectral fluorescence microscopy.

We implement a filterless illumination scheme on a hyperspectral fluorescence microscope to achieve full-range spectral imaging. The microscope employs polarisation filtering, spatial filtering and spectral unmixing filtering to replace the role of traditional filters. Quantitative comparisons between full-spectrum and filter-based microscopy are provided in the context of signal dynamic range and accuracy of measured fluorophores' emission spectra. To show potential applications, a five-colour cell immunofluorescence imaging experiment is theoretically simulated. Simulation results indicate that the use of proposed full-spectrum imaging technique may result in three times improvement in signal dynamic range compared to that can be achieved in the filter-based imaging.

Hyperbaric oxygen therapy for late radiation tissue injury in gynecologic malignancies.

BACKGROUND: Late radiation tissue injury is a serious complication of radiotherapy for patients with gynecologic malignancies. Strategies for managing pain and other clinical features have limited efficacy; however, hyperbaric oxygen therapy (HBO(2)) may be an effective option for some patients. METHODS: In a systematic review of the literature, the Ovid medline, embase, Cochrane Library, National Guidelines Clearinghouse, and Canadian Medical Association Infobase databases were searched to June 2009 for clinical practice guidelines, systematic reviews, randomized controlled trials, or other relevant evidence. Studies that did not evaluate soft tissue necrosis, cystitis, proctitis, bone necrosis, and other complications were excluded. RESULTS: Two randomized trials, eleven nonrandomized studies, and five supporting documents comprise the evidence base. In addition, information on the harms and safety of treatment with HBO(2) were reported in three additional sources. There is modest direct evidence and emerging indirect evidence that the use of HBO(2) is broadly effective for late radiation tissue injury of the pelvis in women treated for gynecologic malignancies. CONCLUSIONS: Based on the evidence and expert consensus opinion, HBO(2) is likely effective for late radiation tissue injury of the pelvis, with demonstrated efficacy specifically for radiation damage to the anus and rectum;the main indication for HBO(2) therapy in gynecologic oncology is in the management of otherwise refractory chronic radiation injury;HBO(2) may provide symptomatic benefit in certain clinical settings (for example, cystitis, soft-tissue necrosis, and osteonecrosis); andHBO(2) may reduce the complications of gynecologic surgery in patients undergoing surgical removal of necrosis.

Establishing a multicentre clinical research network: lessons learned.

BACKGROUND: Within many health care disciplines, research networks have emerged to connect researchers who are physically separated, to facilitate sharing of expertise and resources, and to exchange valuable skills. A multicentre research network committed to studying difficult cancer pain problems was launched in 2004 as part of a Canadian initiative to increase palliative and end-of-life care research capacity. Funding was received for 5 years to support network activities. METHODS: Mid-way through the 5-year granting period, an external review panel provided a formal mid-grant evaluation. Concurrently, an internal evaluation of the network by survey of its members was conducted. Based on feedback from both evaluations and on a review of the literature, we identified several components believed to be relevant to the development of a successful clinical cancer research network. RESULTS: THESE COMMON ELEMENTS OF SUCCESSFUL CLINICAL CANCER RESEARCH NETWORKS WERE IDENTIFIED: shared vision, formal governance policies and terms of reference, infrastructure support, regular and effective communication, an accountability framework, a succession planning strategy to address membership change over time, multiple strategies to engage network members, regular review of goals and timelines, and a balance between structure and creativity. CONCLUSIONS: In establishing and conducting a multi-year, multicentre clinical cancer research network, network members were led to reflect on the factors that contributed most to the achievement of network goals. Several specific factors were identified that seemed to be highly relevant in promoting success. These observations are presented to foster further discussion on the successful design and operation of research networks.

Simultaneous quantification of bisphenol A and its glucuronide metabolite (BPA-G) in plasma and urine: applicability to toxicokinetic investigations.

Bisphenol A (BPA) is a widely used plasticizer that can contaminate food and the wider environment and lead to human exposure. In humans, it is mainly metabolized to bisphenol A-glucuronide (BPA-G) and eliminated in the urine. As BPA causes adverse physiological effects at low doses, it is necessary to document the toxicokinetics of both molecules for risk assessment. Because BPA-G is not available as an analytical standard, it is usually quantified after the assay of BPA, following an enzymatic hydrolysis with ß-glucuronidase. With this approach, two separate assays are required for BPA and BPA-G quantification, which can lead to critical pitfalls in terms of accuracy and analysis time. To overcome this problem, we have developed a new method for the isolation and purification of BPA-G from urine by flash chromatography. Large amounts of BPA-G (1g) were isolated and characterized by mass spectrometry and NMR. This BPA-G is suitable for an use as analytical standard and enabled us to develop a novel method for the simultaneous quantification of BPA and BPA-G in biological matrices by UPLC/MS/MS. It has also been used for in vivo toxicokinetic studies in sheep. The method of quantification was validated according FDA guidelines and used to monitor the time course of plasma and urine concentrations of BPA or BPA-G following their administration. The simultaneous quantification of BPA and BPA-G was compared to the commonly used method for urine and plasma samples. For plasma samples, the results obtained with the direct assay of BPA-G were similar to those obtained by quantification after enzymatic hydrolysis. With urine samples, the simultaneous quantification appeared to be more suitable than the hydrolysis method for the BPA-G determination.

A multicentre open-label safety and efficacy study of tetrodotoxin for cancer pain.

BACKGROUND: Cancer pain is highly prevalent, and existing treatments are often insufficient to provide adequate relief. OBJECTIVES: We assessed the long-term safety and efficacy of subcutaneous tetrodotoxin treatment in reducing the intensity of chronic cancer-related pain. METHODS: In this multicentre open-label longitudinal trial, 30 µg tetrodotoxin was administered subcutaneously twice daily for 4 days in a heterogeneous cohort of patients with persistent pain despite opioids and other analgesics. "Responder" was defined as a mean reduction of 30% or more in pain intensity from baseline; and "clinical responder" as some pain reduction, but less than 30%, plus agreement on the part of both the patient and the physician that a meaningful analgesic response to treatment had occurred. RESULTS: Of 45 patients who entered the longitudinal trial, 41 had sufficient data for analysis. Of all 45 patients, 21 (47%) met the criteria for "responder" [16 patients (36%)] or "clinical responder" [5 patients (11%)]. Onset of pain relief was typically cumulative over days, and after administration ended, the analgesic effect subsided over the course of a few weeks. No evidence of loss of analgesic effect was observed during subsequent treatments (2526 patient-days in total and a maximum of 400 days in 1 patient). One patient withdrew from the study because of adverse events. Toxicity was usually mild (82%) or moderate (13%), and remained so through subsequent treatment cycles, with no evidence of cumulative toxicity or tolerance. CONCLUSIONS: Long-term treatment with tetrodotoxin is associated with acceptable toxicity and, in a substantial minority of patients, resulted in a sustained analgesic effect. Further study of tetrodotoxin for moderate-to-severe cancer pain is warranted.