Harnessing the potential of data-driven strategies to optimise transfusion practice.

No one doubts the significant variation in the practice of transfusion medicine. Common examples are the variability in transfusion thresholds and the use of tranexamic acid for surgery with likely high blood loss despite evidence-based standards. There is a long history of applying different strategies to address this variation, including education, clinical guidelines, audit and feedback, but the effectiveness and cost-effectiveness of these initiatives remains unclear. Advances in computerised decision support systems and the application of novel electronic capabilities offer alternative approaches to improving transfusion practice. In England, the National Institute for Health and Care Research funded a Blood and Transplant Research Unit (BTRU) programme focussing on 'A data-enabled programme of research to improve transfusion practices'. The overarching aim of the BTRU is to accelerate the development of data-driven methods to optimise the use of blood and transfusion alternatives, and to integrate them within routine practice to improve patient outcomes. One particular area of focus is implementation science to address variation in practice.

Impacts of climate change on drinking water quality in Norway.

Climate change will lead to higher temperatures, increased precipitation and runoff, as well as more intense and frequent extreme weather events in Norway. More extreme rainfall and increased runoff are historically associated with higher concentrations of indicator bacteria, colour and turbidity in raw water of Norwegian waterworks. Regional information about the risk for drinking water deterioration by the end of the century is essential for evaluating potential treatment capacity upgrades at the waterworks. We combined locally downscaled future climate scenarios with historical associations between weather/runoff and water quality from a wide spread of waterworks in Norway. With continued climate change, we estimate higher concentrations of water quality indicators of raw water by the end of the century. The water quality is estimated to deteriorate mainly due to the projected increase in rainfall, and mainly in the Western and Northern parts of Norway. While large waterworks seem to be able to adapt to future conditions, the degradation of raw water quality may cause future challenges for the treatment processes at smaller waterworks. Combining these results with further studies of treatment effects and microbial risk assessments is needed to ensure sufficient treatment capacities of the raw water in the future.

Impact of national guidelines on use of BRCA1/2 germline testing, risk management advice given to women with pathogenic BRCA1/2 variants and uptake of advice.

BACKGROUND: This nationwide study assessed the impact of nationally agreed cancer genetics guidelines on use of BRCA1/2 germline testing, risk management advice given by health professionals to women with pathogenic BRCA1/2 variants and uptake of such advice by patients. METHODS: Clinic files of 883 women who had initial proband screens for BRCA1/2 pathogenic variants at 12 familial cancer clinics between July 2008-July 2009 (i.e. before guideline release), July 2010-July 2011 and July 2012-July 2013 (both after guideline release) were audited to determine reason given for genetic testing. Separately, the clinic files of 599 female carriers without a personal history of breast/ovarian cancer who underwent BRCA1/2 predictive genetic testing and received their results pre- and post-guideline were audited to ascertain the risk management advice given by health professionals. Carriers included in this audit were invited to participate in a telephone interview to assess uptake of advice, and 329 agreed to participate. RESULTS: There were no significant changes in the percentages of tested patients meeting at least one published indication for genetic testing - 79, 77 and 78% of files met criteria before guideline, and two-, and four-years post-guideline, respectively (χ = 0.25, p = 0.88). Rates of documentation of post-test risk management advice as per guidelines increased significantly from pre- to post-guideline for 6/9 risk management strategies. The strategies with the highest compliance amongst carriers or awareness post-release of guidelines were annual magnetic resonance imaging plus mammography in women 30-50 years (97%) and annual mammography in women > 50 years (92%). Of women aged over 40 years, 41% had a risk-reducing bilateral mastectomy. Amongst women aged > 40 years, 75% had a risk-reducing salpingo-oophorectomy. Amongst women who had not had a risk-reducing bilateral mastectomy, only 6% took risk-reducing medication. Fear of side-effects was cited as the main reasons for not taking these medicines by 73% of women. CONCLUSIONS: Guidelines did not change the percentages of tested patients meeting genetic testing criteria but improved documentation of risk management advice by health professionals. Effective approaches to enhance compliance with guidelines are needed to improve risk management and quality of care.

Hong Kong Geriatrics Society and Hong Kong Urological Association consensus on personalised management of male lower urinary tract symptoms in the era of multiple co-morbidities and polypharmacy.

Lower urinary tract symptoms (LUTS) are common complaints of adult men. Benign prostatic hyperplasia (BPH) represents the most common underlying cause. As the incidence of BPH increases with age, and pharmacological treatment is a major part of the disease's management, the majority of patients with LUTS are managed by primary care practitioners. There are circumstances in which specialist care by urologists or geriatricians is required, such as failure of medical treatment, adverse effects from medical treatment, or complications from BPH. Referral choices can be confusing to patients and even practitioners in different specialties under such circumstances. There is currently no local consensus about the diagnosis, medical management, or referral mechanism of patients with BPH. A workgroup was formed by members of The Hong Kong Geriatrics Society (HKGS) and the Hong Kong Urological Association (HKUA) to review evidence for the diagnosis and medical treatment of LUTS. A consensus was reached by HKGS and HKUA on an algorithm for the flow of male LUTS care and the use of uroselective alpha blockers, antimuscarinics, beta-3 adrenoceptor agonists, and 5α-reductase inhibitors in the primary care setting. This consensus by HKGS and HKUA provides a new management paradigm of male LUTS.

The metaphyseal sleeve: an unexplored option in the treatment of complex primary knee osteoarthritis.

BACKGROUND: In an ever-aging society that as a whole has become more affluent, significant emphasis has been accorded to an improved quality of life. Knee osteoarthritis is ever-increasingly treated with total knee arthroplasty. The benefits and satisfaction experienced by those who have undergone total knee replacements (TKR) are well documented in the literature. The issue arises when osteoarthritis of the affected knee is more complex than simple osteoarthritis, i.e. the patient has complex primary osteoarthritis. This collective term encompasses conditions such as massive bone loss, ligamentous laxity, coronal defects and those with contractures. There are various classifications to describe massive bone loss but we utilized the Anderson Orthopaedic Research Institute (AORI) classification. Numerous treatment options are available and we report the use of metaphyseal sleeves as a highly successful treatment option. METHODS: We retrospectively reviewed all the patients at our centre who underwent primary TKR using the metaphyseal sleeves. Patients were assessed on symptoms and functional status, and radiographs were also taken to assess for osseointegration. Only patients who completed 2 years of follow up were included in our study. RESULTS: The updated (2011) Knee Society Score (KSS) was used in conjunction with radiological assessments at each follow up. Mean KSS scores improved from 53.83 preoperatively to 193.39 postoperatively. All patients demonstrated increasing osseointegration throughout follow up. CONCLUSION: The metaphyseal sleeve is an excellent treatment option for complex primary osteoarthritic knees with good results objectively, functionally and radiologically and would be a great choice for all orthopaedic surgeons to include in their armamentarium.

Evaluation of implementation of risk management guidelines for carriers of pathogenic variants in mismatch repair genes: a nationwide audit of familial cancer clinics.

INTRODUCTION: This nationwide study assessed the impact of Lynch syndrome-related risk management guidelines on clinicians' recommendations of risk management strategies to carriers of pathogenic variants in mismatch repair genes and the extent to which carriers took up strategies in concordance with guidelines. MATERIALS AND METHODS: Clinic files of 464 carriers (with and without colorectal cancer) were audited for carriers who received their genetic testing results in July 2008-July 2009 (i.e. before guideline release), July 2010-July 2011 and July 2012-July 2013 (both after guideline release) at 12 familial cancer clinics (FCCs) to ascertain the extent to which carriers were informed about risk management in accordance with guidelines. All carriers captured by the audit were invited to participate in interviews; 215 were interviewed to assess adherence to recommended risk management guidelines. RESULTS: The rates of documentation in clinic files increased significantly from pre- to post-guideline for only two out of eight risk management strategies. The strategies with the highest compliance of carriers post-guidelines were: uptake of one or two-yearly colonoscopy (87%), followed by hysterectomy to prevent endometrial cancer (68%), aspirin as risk-reducing medication (67%) and risk-reducing salpingo-oophorectomy (63%). Interrater reliability check for all guidelines showed excellent agreement (k statistics = 0.89). CONCLUSION: These results indicate that there is scope to further increase provision of advice at FCCs to ensure that all carriers receive recommendations about evidence-based risk management. A multi-pronged behaviour change and implementation science approach tailored to specific barriers is likely to be needed to achieve optimal clinician behaviours and outcomes for carriers.

High seroprevalence of anti-Fasciola antibody among cattle farm workers and dwellers in Kelantan.

Human fascioliasis is a public health problem particularly in areas where ruminants are raised. The aims of this study were to determine the seroprevalence of anti-Fasciola antibody and the associated risk factors among cattle farm workers and dwellers in Kelantan. A total of 90 blood samples were collected in this cross-sectional study. A set of validated questionnaire was used to obtain information on socio-demographic profiles and dietary habits of participants. The sera were subjected to enzyme linked immunosorbent assay (ELISA) for the detection of anti-Fasciola IgG antibody. The association between seropositivity and the significant risk factors were determined via logistic regression. From the result, serological screening revealed 60 (67%) participants positive for anti-Fasciola IgG antibody. The factors found to be significantly associated with seropositivity against anti-Fasciola IgG antibody were the age group of 18 years old and above with calculated odds ratio of 3.2 times (p=0.032) and the duration of farming activities of more than 5 years with calculated odds ratio of 2.6 times (p=0.036). In conclusion, Fasciola infection is prevalent among cattle farm workers and dwellers in Kelantan.

High seroprevalence of anti-Fasciola antibody among cattle farm workers and dwellers in Kelantan

@#Human fascioliasis is a public health problem particularly in areas where ruminants are raised. The aims of this study were to determine the seroprevalence of anti-Fasciola antibody and the associated risk factors among cattle farm workers and dwellers in Kelantan. A total of 90 blood samples were collected in this cross-sectional study. A set of validated questionnaire was used to obtain information on socio-demographic profiles and dietary habits of participants. The sera were subjected to enzyme linked immunosorbent assay (ELISA) for the detection of anti-Fasciola IgG antibody. The association between seropositivity and the significant risk factors were determined via logistic regression. From the result, serological screening revealed 60 (67%) participants positive for anti-Fasciola IgG antibody. The factors found to be significantly associated with seropositivity against anti-Fasciola IgG antibody were the age group of 18 years old and above with calculated odds ratio of 3.2 times (p=0.032) and the duration of farming activities of more than 5 years with calculated odds ratio of 2.6 times (p=0.036). In conclusion, Fasciola infection is prevalent among cattle farm workers and dwellers in Kelantan.

Erysipelothrix Septicaemia and Hepatitis in a Colony of Humboldt Penguins (Spheniscus humboldti).

This report describes an outbreak of erysipelas in a colony of captive Humboldt penguins (Spheniscus humboldti). The only previously reported case in a related species was of an individual little blue penguin (Eudyptula minor). Five Humboldt penguins in a mixed colony displayed non-specific signs of illness, including lethargy, inappetence and regurgitation after movement for exhibit upgrading. There was no improvement after 5 days of treatment with oral enrofloxacin (10 mg/kg q24h). Four Humboldt penguins, including two that were not part of the original five displaying signs of illness, died during this outbreak and Erysipelothrix rhusiopathiae was cultured from organ samples collected post mortem. Oral clavulanic acid/amoxycillin (125 mg/kg q12h) was added to the treatment of the sick Humboldt penguins, as well as itraconazole (8.5 mg/kg q12h) and silymarin (10 mg/kg q24h) for 10 days (both per os), which resolved their clinical signs. The likely source of E. rhusiopathiae was the fish they were fed, but this could not be confirmed. Another contributing factor to the growth of E. rhusiopathiae in the exhibit pool was the increase in water temperature due to a fault in the water circulating system. The temperature of the pool water had increased to 29°C, which was rectified, and the water temperature decreased to 13°C. However, there was one further Humboldt penguin death after the decrease in water temperature. This episode suggests that E. rhusiopathiae infection should be high on the differential list of piscivorous avian species with non-specific clinical signs. A liver biopsy for bacterial culture and sensitivity may be required for definitive diagnosis.

Paraneoplastic relapsing minimal change disease associated with type A thymoma in an elderly patient: A case report and literature review.

Thymoma is a rare mediastinal tumour that can be accompanied by different paraneoplastic syndromes. Here we report a case of Type A thymoma associated with relapsing minimal change disease (MCD). This case highlights: (1) The need to balance rapid prednisolone weaning against risk for relapse in an elderly patient at risk for steroid-induced complications. (2) The addition of calcineurin inhibitor in relapsed thymoma-related MCD, to achieve steroid sparing effects. Resection of the offending tumour and prompt immunosuppressive therapy are critical in getting best renal and overall outcomes in this rare entity.

Assessing the medical workforces perceived barriers to the prescription of risk-reducing medication for women at high-risk of breast cancer.

This study aims to determine the attitudes and barriers of Australian oncology health professionals towards using tamoxifen as a breast cancer risk-reducing medication (RRM). Our target group was health professionals involved in breast cancer risk assessment or treatment. Members of relevant medical organizations in Australia and New Zealand were invited to participate in a web-based survey assessing: their attitudes towards tamoxifen as a RRM; which health professionals they felt were responsible for initiating and monitoring women on RRM and their views on workforce issues related to RRM prescription. There were 100 respondents, including 33 genetic health professionals, 32 medical oncologists and 20 surgeons. Respondents perceived tamoxifen to be effective as a RRM (99%). However, only 41% of prescribing health professionals (n = 64) had ever prescribed tamoxifen as a RRM. Overall, survey respondents felt that the initiation of RRM was the role of specialists. Assessing a patient's risk of breast cancer was reported to be the role of cancer geneticists/familial cancer clinicians (74%) and medical oncologists (66%). Discussion about the use of RRM was reported to be the role of these same groups (84% and 85% respectively). Medical oncologists (83%) and breast physicians (70%) were most frequently considered to be responsible for initiating the prescription and monitoring women once commenced on RRM (72% and 71% respectively). Oncology health professionals express confidence in the effectiveness of tamoxifen as a RRM despite reporting low prescription rates. Findings demonstrate that these oncology health professionals felt that initiation of RRM was the role of cancer specialists, despite preventative medicine being seen as a primary care activity. If uptake among at-risk women increases, this will put a significant burden on cancer services and GPs will need to take on a greater role in the delivery of RRM.

Evaluation of an online communication skills training programme for oncology nurses working with patients from minority backgrounds.

OBJECTIVE: This study aimed to develop and assess the feasibility of an online communication skills training intervention to increase cultural competence amongst oncology nurses working with individuals from minority backgrounds. METHODS: The intervention provided examples of communication strategies using vignette-based, professionally produced videos, developed through an iterative process with input from a large multidisciplinary team. Fifty-three oncology nurses completed all three questionnaires at baseline, within 2 weeks and then 3 months after accessing the programme. RESULTS: The online intervention was well received by the majority of participants, and was endorsed as clearly presented, informative, relevant and useful by more than 90% of participants. Eighty-seven percent of participants reported increased confidence in communicating with patients via an interpreter, and 93% agreed that skills they gained would be useful in providing better patient care. Participants reported significant improvements in practice while interacting with people with limited English proficiency 2 weeks and 3 months after accessing the website (X2 = 13.66, P < 0.001). CONCLUSION: This online communication training programme can now be tested for its utility in improving patient care for oncology nurses working with patients from minority backgrounds.

Novel strategy for expression of authentic and bioactive human basic fibroblast growth factor in Bacillus subtilis.

Inteins, also known as "protein introns," have been found to be present in many microbial species and widely employed for the expression and purification of recombinant proteins in Escherichia coli. However, interestingly, until now there has not been much information on the identification and application of inteins to protein expression in Bacillus subtilis. In this article, for the first time, despite the likelihood of absence of inteins in B. subtilis, this bacterium was shown to be able to facilitate auto-catalytic cleavages of fusions formed between inteins and recombinant proteins. Employing a construct expressing the intein, Ssp DnaB, (DnaB), which was fused at its N-terminus with the cellulose-binding domain (CellBD) of an endoglucanase encoded by the cenA gene of Cellulomonas fimi, the construct was demonstrated to be capable of mediating intracellular expression of basic fibroblast growth factor (bFGF), followed by auto-processing of the CellBD-DnaB-bFGF fusion to result in bFGF possessing the 146-residue authentic structure. The mentioned fusion was shown to result in a high yield of 84 mg l-1 of biologically active bFGF. Future work in improving the growth of B. subtilis may enable the use of this bacterium, working in cooperation with inteins, to result in a new platform for efficient expression of valuable proteins.

A mixed methods analysis of experiences and expectations among early-career medical oncologists in Australia.

AIM: A viable and sustainable medical oncology profession is integral for meeting the increasing demand for quality cancer care. The aim of this study was to explore the workforce-related experiences, perceptions and career expectations of early-career medical oncologists in Australia. METHODS: A mixed-methods design, including a survey (n  =  170) and nested qualitative semistructured interviews (n  =  14) with early-career medical oncologists. Recruitment was through the Medical Oncology Group of Australia. Qualitative data were thematically analyzed and for the survey results, logistic regression modeling was conducted. RESULTS: Early-career medical oncologists experienced uncertainty regarding their future employment opportunities. The competitive job market has made them cautious about securing a preferred job leading to a perceived need to improve their qualifications through higher degree training and research activities. The following themes and trends were identified from the qualitative and quantitative analyses: age, career stage and associated early-career uncertainty; locale, professional competition and training preferences; participation in research and evolving professional expectations; and workload and career development opportunities as linked to career uncertainty. CONCLUSION: Perceived diminished employment opportunities in the medical oncology profession, and shifting expectations to be "more qualified," have increased uncertainty among junior medical oncologists in terms of their future career prospects. Structural factors relating to adequate funding of medical oncology positions may facilitate or inhibit progressive change in the workforce and its sustainability. Workforce planning and strategies informed by findings from this study will be necessary in ensuring that both the needs of cancer patients and of medical oncologists are met.

Cloning and characterization of two novel ß-glucosidase genes encoding isoenzymes of the cellobiase complex from Cellulomonas biazotea.

Enzymatic degradation of cellulosic waste to generate renewable biofuels has offered an attractive solution to the energy problem. Synergistic hydrolysis of cellulose residues requires the participation of three different types of cellulases - endoglucanases, exoglucanases, and ß-glucosidases (Bgl). Our group has been interested in using Bgl of Cellulomonas biazotea in studies designed to investigate cooperative action among different cellulases. We previously have cloned bgl genes encoding Cba and Cba3, which are C. biazotea Bgl isozymes representing two different Bgl families, respectively; specifically, Glycoside Hydrolase Family 3 (GH3) and Glycoside Hydrolase Family 1 (GH1). To gain an understanding of the complexity of Bgl in C. biazotea, we analyzed E. coli clones containing plasmids into which C. biazotea DNA had been inserted; these clones could hydrolyze 4-methylumbelliferyl ß-d-glucopyranoside (MUG) supplemented in solid agar media, suggesting they might contain bgl genes. Through restriction analysis and DNA sequencing, two novel bgl genes, designated cba4 and cba5 and encoding Cba4 (484 amino acids) and Cba5 (758 amino acids) were identified. Cba4 and Cba5 appear to be members of GH1 and GH3, respectively. Both Cba4 and Cba5 were concluded to be genuine cellobiases as each was found to enable their E. coli hosts to survive on media in which cellobiose was the sole carbon source. Despite lacking a typical secretory signal sequence, Cba4 and Cba5 are secretory proteins. Although they are isoenzymes, Cba, Cba3, Cba4, and Cba5 were shown to possess distinct substrate specificities. These four Bgl members may play important roles in hydrolyzing a wide variety of ß-glucosides including cellobiose and non-cellulosic substrates.

Motivators and barriers of tamoxifen use as risk-reducing medication amongst women at increased breast cancer risk: a systematic literature review.

BACKGROUND: Selective estrogen receptor modulators, such as tamoxifen, reduce breast cancer risk by up to 50% in women at increased risk for breast cancer. Despite tamoxifen's well-established efficacy, many studies show that most women are not taking up tamoxifen. This systematic literature review aimed to identify the motivators and barriers to tamoxifen use 's amongst high-risk women. METHODS: Using MEDLINE, PsycINFO, and Embase plus reviewing reference lists of relevant articles published between 1995 and 2016, 31 studies (published in 35 articles) were identified, which addressed high-risk women's decisions about risk-reducing medication to prevent breast cancer and were peer-reviewed primary clinical studies. RESULTS: A range of factors were identified as motivators of, and barriers to, tamoxifen uptake including: perceived risk, breast-cancer-related anxiety, health professional recommendation, perceived drug effectiveness, concerns about side-effects, knowledge and access to information about side-effects, beliefs about the role of risk-reducing medication, provision of a biomarker, preference for other forms of breast cancer risk reduction, previous treatment experience, concerns about randomization in clinical trial protocols and finally altruism. CONCLUSIONS: Results indicate that the decision for high-risk women regarding tamoxifen use or non-use as a risk-reducing medication is not straightforward. Support of women making this decision is essential and needs to encompass the full range of factors, both informational and psychological.

Filmless methods for quality assurance of Tomotherapy using ArcCHECK.

PURPOSE: Tomotherapy delivers an intensity-modulated radiation therapy (IMRT) treatment by the synchronization of gantry rotation, multileaf collimator (MLC), and couch movement. This dynamic nature makes the quality assurance (QA) important and challenging. The purpose of this study is to develop some methodologies using an ArcCHECK for accurate QA measurements of the gantry angle and speed, MLC synchronization and leaf open time, couch translation per gantry rotation, couch speed and uniformity, and constancy of longitudinal beam profile for a Tomotherapy unit. METHODS: Four test plans recommended by AAPM Task Group 148 (TG148) and the manufacturer were chosen for this study. Helical and static star shot tests are used for checking the leaves opened at the expected gantry angles. Another helical test is to verify the couch traveled the expected distance per gantry rotation. The final test is for checking the couch speed constancy with a static gantry. ArcCHECK can record the detector signal every 50 ms as a movie file, and has a virtual inclinometer for gantry angle measurement. These features made the measurement of gantry angle and speed, MLC synchronization and leaf open time, and longitudinal beam profile possible. A shaping parameter was defined for facilitating the location of the beam center during the plan delivery, which was thereafter used to calculate the couch translation per gantry rotation and couch speed. The full width at half maximum (FWHM) was calculated for each measured longitudinal beam profile and then used to evaluate the couch speed uniformity. Furthermore, a mean longitudinal profile was obtained for constancy check of field width. The machine trajectory log data were also collected for comparison. Inhouse programs were developed in MATLAB to process both the ArcCHECK and machine log data. RESULTS: The deviation of our measurement results from the log data for gantry angle was calculated to be less than 0.4°. The percentage differences between measured and planned leaf open time were found to be within 0.5% in all the tests. Our results showed mean values of MLC synchronization of 0.982, 0.983, and 0.995 at static gantry angle 0°, 45°, and 135°, respectively. The mean value of measured couch translation and couch speed by ArcCHECK had less than 0.1% deviation from the planned values. The variation in the value of FWHM suggested the couch speed uniformity was better than 1%. The mean of measured longitudinal profiles was suitable for constancy check of field width. CONCLUSION: Precise and efficient methods for measuring the gantry angle and speed, leaf open time, couch translation per gantry rotation, couch speed and uniformity, and constancy of longitudinal beam profile of Tomotherapy using ArcCHECK have been developed and proven to be accurate compared with machine log data. Estimation of the Tomotherapy binary MLC leaf open time is proven to be precise enough to verify the leaf open time as small as 277.8 ms. Our method also makes the observation and quantification of the synchronization of leaves possible.

Optimal designs for active controlled dose-finding trials with efficacy-toxicity outcomes.

We derive optimal designs to estimate efficacy and toxicity in active controlled dose-finding trials when the bivariate continuous outcomes are described using nonlinear regression models. We determine upper bounds on the required number of different doses and provide conditions under which the boundary points of the design space are included in the optimal design. We provide an analytical description of minimally supported optimal designs and show that they do not depend on the correlation between the bivariate outcomes.