Animal tissue-based quantitative comparison of dual-energy CT to SPR conversion methods using high-resolution gel dosimetry.

Dual-energy computed tomography (DECT) has been shown to allow for more accurate ion therapy treatment planning by improving the estimation of tissue stopping power ratio (SPR) relative to water, among other tissue properties. In this study, we measured and compared the accuracy of SPR values derived using both dual- and single-energy CT (SECT) based on different published conversion algorithms. For this purpose, a phantom setup containing either fresh animal soft tissue samples (beef, pork) and a water reference or tissue equivalent plastic materials was designed and irradiated in a clinical proton therapy facility. Dosimetric polymer gel was positioned downstream of the samples to obtain a three-dimensional proton range distribution with high spatial resolution. The mean proton range in gel for each tissue relative to the water sample was converted to a SPR value. Additionally, the homogeneous samples were probed with a variable water column encompassed by two ionization chambers to benchmark the SPR accuracy of the gel dosimetry. The SPR values measured with both methods were consistent with a mean deviation of 0.2%, but the gel dosimetry captured range variations up to 5 mm within individual samples.Across all fresh tissue samples the SECT approach yielded significantly greater mean absolute deviations from the SPR deduced using gel range measurements, with an average difference of 1.2%, compared to just 0.3% for the most accurate DECT-based algorithm. These results show a significant advantage of DECT over SECT for stopping power prediction in a realistic setting, and for the first time allow to compare a large set of methods under the same conditions.

Patients' understanding of cellulitis and views about how best to prevent recurrent episodes: mixed-methods study in primary and secondary care.

BACKGROUND: Cellulitis is a common painful infection of the skin and underlying tissues that recurs in approximately one-third of cases. The only proven strategy to reduce the risk of recurrence is long-term, low-dose antibiotics. Given current concerns about antibiotic resistance and the pressure to reduce antibiotic prescribing, other prevention strategies are needed. OBJECTIVES: To explore patients' views about cellulitis and different ways of preventing recurrent episodes. METHODS: Adults aged ≥ 18 years with a history of first-episode or recurrent cellulitis were invited through primary care, hospitals and advertising to complete a survey, take part in an interview or both. RESULTS: Thirty interviews were conducted between August 2016 and July 2017. Two hundred and forty surveys were completed (response rate 17%). Triangulation of quantitative and qualitative data showed that people who have had cellulitis have wide-ranging beliefs about what can cause cellulitis and are often unaware of risk of recurrence or potential strategies to prevent recurrence. Enhanced foot hygiene, applying emollients daily, exercise and losing weight were more popular potential strategies than the use of compression stockings or long-term antibiotics. Participants expressed caution about long-term oral antibiotics, particularly those who had experienced only one episode of cellulitis. CONCLUSIONS: People who have had cellulitis are keen to know about possible ways to prevent further episodes. Enhanced foot hygiene, applying emollients daily, exercise and losing weight were generally viewed to be more acceptable, feasible strategies than compression or antibiotics, but further research is needed to explore uptake and effectiveness in practice.

Prevention of bovine herpesvirus-1 transmission by the transfer of embryos disinfected with recombinant bovine trypsin.

This study deals with the potential for the introduction of infectious agents through the use of animal-derived products. The efficacy of a recombinant bovine trypsin (RBTr) as a replacement for porcine pancreatic trypsin and a disinfectant for bovine herpesvirus-1 (BHV-1)-infected embryos was investigated according to the sanitary guidelines of the International Embryo Transfer Society. Treatment of in vivo and in vitro fertilized embryos contaminated with BHV-1 (10(5) TCID50/mL) in the presence of RBTr (525 U/mL) for 120 s, effectively removed the infectious virus compared with untreated and washed embryos (P < 0.05). Transfer of in vivo fertilized and disinfected embryos to BHV-1 seronegative recipients (n = 24) resulted in 14 pregnancies and 11 calves born free of BHV-1. In contrast, transfer of unwashed or undisinfected embryos to four recipients resulted in seroconversion and no pregnancies at term. It was concluded that the use of RBTr could be considered as an alternative method of rendering embryos free of BHV-1 and thus reduce the potential risk of disease transmission to embryo recipients and offspring.

Embryos produced from fertilization with bovine viral diarrhea virus (BVDV)-infected semen and the risk of disease transmission to embryo transfer (ET) recipients and offspring.

Bovine diarrhea virus (BVDV) causes a variety of economically important enteric and infertility problems in cattle. For that reason, several countries have eradicated the disease, and some others have schemes in progress to achieve freedom. Although there is a considerable amount of information about the risk of BVDV transmission through contaminated semen used for artificial insemination (AI), there is no evidence to indicate whether the resulting embryos, when used for embryo transfer, can lead to the transmission of BVDV to recipients or offspring. For this experiment, semen from a bull persistently infected with BVDV (10(5) 50% tissue culture infective doses/mL NY strain) was used for insemination (two times at estrus) of BVDV-seronegative, superovulated cows (N = 35). Embryos were collected 7 days after insemination and subsequently were washed according to the International Embryo Transfer Society recommendations or left unwashed. Out of 302 collected oocytes and embryos, 173 (57%) were fertilized and the remaining 129 (43%) had degenerated. Infectious BVDV was detected in 24% (17/71) of unwashed and 10% (8/77) of washed embryos, and in all (N = 11) follicular fluid samples, oviductal epithelial cells, endometrium, and corpora lutea tissues as determined by the virus isolation test. After transfer of 39 washed embryos to 27 BVDV-seronegative recipients, 12 (44%) cows became pregnant and 17 calves free of BVDV and BVDV antibodies, including five sets of twins, were born. After embryo transfer, all pregnant and nonpregnant recipients remained free of BVDV and antibodies. In conclusion, results herein suggest that BVDV can be transmitted by AI resulting in the production of some proportion of contaminated embryos. However, it appears that such embryos, when washed according to International Embryo Transfer Society and the World Organization for Animal Health guidelines do not cause BVDV transmission to recipients or their offspring.

Nontransmission of porcine circovirus 2 (PCV2) by embryo transfer.

Two experiments were conducted to determine the association of porcine circovirus type 2 (PCV2) with embryos and the risk of viral transmission by embryo transfer. In the first experiment, 240 embryos from uninfected donors were exposed to PCV2a 10(4)TCID50/mL in vitro before transfer to seronegative recipients; in the second experiment, 384 embryos recovered from infected donors, 10 days after donor inoculation with PCV2, were transferred to seronegative recipients. In total, 1120 embryos and/or ova were collected from 37 viral-free donors (experiment 1) and 1019 from 59 PCV2-infected donors (experiment 2) (P < 0.01). The washing and/or disinfection procedure recommended by the International Embryo Transfer Society was applied to embryos in both experiments. Transfer of embryos experimentally exposed in vitro to high titers of virus caused seroconversion of recipients (58%; N = 7/12) and their piglets (81%; N = 13/16). Postmortem, PCV2 DNA was detected in various organs of embryo transfer recipients and their embryo transfer-derived piglets. In contrast, the transfer of embryos recovered from infectious PCV2 donors did not result in the seroconversion of embryo recipients (N = 24) or their embryo transfer-derived piglets (N = 76). Neither PCV2 DNA nor infectious virus was detected in the tissues of either recipients or embryo transfer-derived piglets collected postmortem in the second experiment. The results obtained in this study indicate that the transmission of PCV2 from infected donors by embryo transfer is unlikely if the sanitary recommendations of the International Embryo Transfer Society are followed. In practical terms, this means that embryo transfer can be successfully used for the intentional elimination of PCV2 and to create virus-free offspring for the safe exchange of swine genetic materials.

Efficacy of the International Embryo Transfer Society (IETS) washing procedure for rendering oocytes matured in vitro free of bovine viral diarrhea virus (BVDV).

To ensure the freedom of embryos from pathogenic agents prior to embryo transfer (ET), a specific sanitary washing procedure has been recommended by the International Embryo Transfer Society (IETS). In the present study, the efficacy of removing the bovine viral diarrhea virus (BVDV) from cumulus-free matured oocytes at the stage of extruded first polar body (N = 240) was evaluated, using the IETS-recommended 10 sequential wash procedure, after exposure in vitro to BVDV type 2 (strain PA-131, 1 × 10(5.2) TCID(50)/mL for 1 h). In general, the percentage of contaminated oocytes was reduced (P < 0.03) after the first two washes. Nevertheless, after 10 washes, approximately 20% of oocytes still remained infectious or contaminated with virus, as detected by the virus isolation test (VI) and quantitative reverse transcription PCR (qRT-PCR) of viral RNA (on average 13 copies/oocyte). Similarly, a higher percentage of positive washing fluid samples were detected in the first three washes (50-100%). The six subsequent washes had lower but variable proportions of fluid samples contaminated with infectious virus. We concluded that the standard washing procedure may not render all oocytes free from the infectious virus adhered to the zona pellucida (ZP), and application of an additional method of oocyte disinfection was warranted to ensure nontransmission of BVDV to recipients by embryos derived from infected oocytes.

Effect of cryopreservation by slow cooling and vitrification on viral contamination of IVF embryos experimentally exposed to bovine viral diarrhea virus and bovine herpesvirus-1.

The objective was to determine the effect of cryopreservation by conventional slow controlled cooling (0.5 degrees C/min) and by vitrification on the presence of bovine viral diarrhea virus (BVDV) and bovine herpesvirus-1 (BHV-1) infectivity associated with frozen-thawed Day 7 bovine embryos. In this study, Day 7 embryos generated by in vitro fertilization (IVF) were exposed in vitro for 1.5h to BVDV (N=393) and BHV-1 (N=242) and subsequently tested before and after cryopreservation for the presence of infectivity. Exposure of embryos to viral agents resulted in 72% of them infected prior to cryopreservation. Stepwise exposure of embryos to cryoprotectants, as well as their removal, substantially reduced the proportion of contaminated embryos (46% vs. 72%, P<0.05). Overall, both freezing methods reduced the percentage of infectious embryos compared with that of embryos similarly exposed to viruses but not cryopreserved (31% vs. 72%, respectively; P<0.001). The percentage of embryos with infectious viruses was not significantly higher after vitrification than after slow cooling (38% vs. 22%). In addition, after cryopreservation, a higher percentage (P<0.002) of embryos exposed to BHV-1 (42%) remained infectious than did embryos exposed to BVDV (24%). In conclusion, cryopreservation reduced the proportion of infected embryos but did not render all of them free from infectious pathogens.

Transmission of bovine viral diarrhea virus (BVDV) via in vitro-fertilized embryos to recipients, but not to their offspring.

The objective was to assess the potential of Day-7, IVP zona pellucida-intact blastocysts to transmit bovine viral diarrhea virus (BVDV) to embryo recipients. Embryos were exposed (1h) to two non-cytopathic (NCP) biotypes, either NY-1 (type 1) or two concentrations of PA-131 (type 2), washed 10 times, and transferred into recipients (two embryos/recipient) free of BVDV and its antibody. Six (30.0%) of the 20 pregnancies were lost after 30 d following transfer of the embryos exposed to the type 1 strain; none of the recipients or their 18 full term offspring seroconverted. Conversely, following exposure to the type 2 strain, 16 (51.6%) of the 31 pregnancies were lost >30 d after embryo transfer. Furthermore, 18 (51.4%) of 35 recipients receiving embryos exposed to type 2 seroconverted; 11 of those were pregnant at 30 d, but only 2 went to full term and gave birth to noninfected (seronegative) calves. Virus isolation tests were performed on single, virus-exposed, washed embryos (not transferred); 3 of 12 (25%) and 17 of 61 (28%) exposed to type 1 and type 2, respectively, were positive for live BVDV. Embryos exposed to type 2 virus had from 0 to 34 viral copies. In conclusion, a large proportion of recipients that received embryos exposed to BVDV, especially those exposed to a high concentration of type 2 virus, became infected after ET, and their pregnancies failed. However, term pregnancies resulted in calves free of both virus and antibody. Therefore, additional disinfection procedures are recommended prior to transferring potentially infected IVP embryos.

Chemical activation of parthenogenetic and nuclear transfer porcine oocytes using ionomycin and strontium chloride.

Effective protocols for oocyte activation are crucial for study of parthenogenetic development and to produce nuclear transfer reconstructed embryos. This study investigated the use of ionomycin (ION) and strontium chloride (Sr(2+)) in the activation of parthenogenetic and nuclear transfer porcine oocytes. In-vitro-matured oocytes with a polar body were treated with varying concentrations of ION, Sr(2+) or its combinations, and then fixed or cultured to assess activation and development rates, respectively. Ionomycin concentrations of 10 and 15 microM resulted in more frequent oocyte activation and the 15 microM in advanced development compared to 5 microM (71.8 and 70%vs. 47.5%; P=0.04, and 43.7%vs. 19.3%; P=0.008, respectively). Oocytes treated with 10, 20 or 30 mM of Sr(2+) for 2 or 4h displayed a pronuclear formation rate ranging from 46.7 to 70%. When employed after a 5 min treatment with 10 or 15 microM ION, exposure to 10 mM Sr(2+) for 4 h resulted in higher pronuclear formation than did the 20 mM concentration (82 and 88.6%vs. 63.3 and 73.2%; P=0.03). Nuclear transfer reconstructed oocytes treated with 15 microM/5 min ION followed by 10 mM/4 h Sr(2+) resulted in a higher development to blastocyst stage compared to those treated with 15 microM ION alone (17.7 vs. 11.3%; P=0.06). In conclusion, we inferred that the inclusion of Sr(2+) in the activation protocol can benefit the development of nuclear transfer reconstructed porcine oocytes.

Patient safety in women's health-care: professional colleges can make a difference. The Society of Obstetricians and Gynaecologists of Canada MORE(OB) program.

The Society of Obstetricians and Gynaecologists of Canada has played a leadership role in advancing patient safety at the national level with the launching of their obstetric patient safety program 'Managing Obstetric Risks Efficiently' (MORE(OB)). Developed over a 2-year period and launched as a pilot in 2002, the program has extended to 126 hospitals in five provinces that provide care for 48% of the births in Canada. The end-point for the program is to change the culture of blame to a focused and sustained patient safety culture, where patient safety is everyone's responsibility, with observed reductions in events and improved quality of care. The program has integrated the principles of high reliability organizations (HROs), systems error theory, team function, and communities of practice (CoPs) as values for the work environment. In this chapter we describe how the program was developed, the role of the national specialty society in the development, and the funding, structure and implementation of the program, and we report on the impact of the program over the first 3 years. In these first 3 years, knowledge enhancement in all disciplines and in all practice environments, with a significant reduction in variance among the disciplines, has been demonstrated. Culture change has occurred in all practice settings and has continued to improve over time. Using liability claims information from the hospitals, a reduction trend has been observed in liability carrier (hospital) incurred costs.

Postpartum hemorrhage today: ICM/FIGO initiative 2004-2006.

Postpartum hemorrhage (PPH) is the main cause of maternal mortality. Yet, even though solutions have been identified, governments and donor countries have been slow to implement programs to contain the problem. While poverty and low educational level remain the underlying cause of PPH, the current literature suggests that active management of the third stage of labor can prevent it. The International Confederation of Midwives (ICM) and the International Federation of Gynecology and Obstetrics (FIGO) are attempting to address the chronic PPH crisis by educating their members on best practices and on troubleshooting where resources are inadequate. Some studies found oxytocin to be preferable to misoprostol in settings where active management is the norm. However, secondary clinical effects may prove more troublesome with oxytocin than with misoprostol, and misoprostol may prove to be more practical and equally effective in low-resource settings. Two new interventions are also proposed, the anti-shock garment and the balloon tamponade.

Reducing postpartum hemorrhage in Africa.

Postpartum hemorrhage (PPH) is the leading cause of maternal mortality in sub-Saharan Africa. This is being addressed by leading professional organizations, which point to the importance of a skilled attendant at birth. But they also emphasize that the active management of the third stage of labor is proven to reduce the incidence of PPH. In low-income settings, the prostaglandin misoprostol should be considered as it is low-cost, stable at room temperature and easy to administer.

The role of professional associations in reducing maternal mortality worldwide.

The death of hundreds of thousands of women due to pregnancy-related complications casts a shadow over the modern obstetrical world. This paper examines the potential roles and responsibilities of professional obstetrical and midwifery associations in addressing this tolerated tragedy of maternal deaths. We examine the successes and challenges of obstetrical and midwifery associations and encourage the growth and development of active associations to address maternal mortality within their own borders. Professional associations can play a vital role in the reduction of maternal mortality worldwide. Their roles include lobbying for women's health and rights, setting standards of practice, raising awareness and team building. Associations from developed countries can influence and strengthen their colleagues within developing countries; for example, the FIGO Save the Mothers initiative. Professional associations should be encouraged to play an active role in reducing maternal mortality within their own country and abroad.

The FIGO Save the Mothers Initiative: the Uganda-Canada collaboration.

In 1998, the ob/gyn associations of Uganda and Canada launched, under the umbrella of the FIGO Save the Mothers Initiative, a district-wide intervention which aimed to increase the availability and utilization of emergency obstetric care (EmOC) services in a rural district of Uganda. The article describes the experience of two professional ob/gyn associations in the development, implementation, monitoring and evaluation of the project. Preliminary results after 24 months of intervention indicate important gains in the capacity of health professionals to deliver EmOC, the availability of emergency transportation services and met need for EmOC.

Medical classification systems in Canada: moving toward the year 2000.

The use of different standards for coding diagnoses and procedures has been identified as a major obstacle to the collection and analysis of data across the various jurisdictions in Canada. In this article the authors briefly describe the current and future situation of medical classification systems in Canada and discuss some of the potential benefits and implications of adopting the 10th revision of the International Statistical Classification of Diseases and Related Health Problems and a revised procedure classification, the Canadian Classification of Health Interventions, as national standards for classification systems in Canada. They further describe some of the key features of the proposed new classification systems and highlight some of the actions being taken by the Canadian Institute for Health Information to support implementation of these standards in Canada over the next few years.