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.

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.

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.

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.

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.

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.

Endovascular Stent Graft Repair is an Effective and Safe Alternative Therapy for Arteriovenous Graft Pseudoaneurysms.

OBJECTIVE/BACKGROUND: Pseudoaneurysm formation occurs in 2-10% of hemodialysis arteriovenous grafts (AVGs). Surgical repair often requires pseudoaneurysm resection, interposition graft placement, and insertion of a catheter as a bridge. Endovascular stent graft repair is a controversial alternative therapy. This study was performed to examine the effectiveness and mid-term outcomes of stent graft repair for AVG pseudoaneurysms. METHODS: All patients who had undergone stent graft repair for AVG pseudoaneurysms between December 2012 and July 2015 were identified from hospital medical records for retrospective analysis. Outcome measures were technical success, early and late complications, and primary and secondary patency rates. RESULTS: A total of 37 stent graft repairs of AVG pseudoaneurysms were performed in 35 patients (42.9% men; mean age 66.9 years). The mean time from AVG creation to pseudoaneurysm repair was 69 months. The indications of treatment (as per the institutional policy) were large pseudoaneurysm (56.7%), impending rupture (27.1%), and bleeding (16.2%). Mean pseudoaneurysm diameter was 23.0 mm. The most common diameter and length of stent graft used were 7 mm (67.6%) and 50 mm (48.6%), respectively. Technical success was 100%. Only one early complication occurred after stent graft repair, which was due to recurrence of the pseudoaneurysm as a result of a short landing zone. Late complications included infection (17.1%) and thrombosis (37.1%). The 1, 6, and 12 month primary patency rates were 89.2%, 55.5%, and 22.0%, respectively. The 1, 6, and 12 month secondary patency rates were 100%, 88.6%, and 78.6%, respectively. The median follow up was 12.3 months. CONCLUSIONS: The study demonstrates that endovascular stent graft repair is an effective and safe alternative therapy for AVG pseudoaneurysms. However, the rate of thrombosis and infection was high and needs to be balanced against open surgery in future studies.

Engineering versatile protein expression systems mediated by inteins in Escherichia coli.

We have recently employed an intein, Saccharomyces cerevisiae vascular membrane ATPase (VMA), in conjunction with efficient expression and secretory functions formed between the ompA leader sequence and the human epidermal growth factor (EGF) gene (fused at the 5' end of VMA), and the human basic fibroblast growth factor (bFGF) gene (fused at the 3' end of VMA), to engineer an efficient intein-based Escherichia coli system for high-level co-expression of EGF and bFGF as authentic mature products. Both products were found not only excreted to the culture medium but also located, surprisingly, in the cytoplasm (Kwong and Wong 2013). In this study, we employed two structurally varied inteins, VMA and Mycobacterium xenopi GyraseA (GyrA), and further demonstrated that despite acting alone, both VMA and GyrA were able to mediate successful co-expression of two widely different proteins, EGF and an endoglucanase (Eng) in E. coli. Although EGF and Eng were initially expressed as large precursors/intermediates, they were soluble and auto-cleavable to finally yield the desired products in both the cytoplasm and culture media. The results further substantiate our postulation that the aforementioned intein/E. coli approach might lead to the development of cost-effective and versatile host systems, wherein all culture fractions are involved in producing the target proteins.

Primary ventriculoperitoneal shunting outcomes: a multicentre clinical audit for shunt infection and its risk factors.

OBJECTIVES: To determine the frequency of primary ventriculoperitoneal shunt infection among patients treated at neurosurgical centres of the Hospital Authority and to identify underlying risk factors. METHODS: This multicentre historical cohort study included consecutive patients who underwent primary ventriculoperitoneal shunting at a Hospital Authority neurosurgery centre from 1 January 2009 to 31 December 2011. The primary endpoint was shunt infection, defined as: (1) the presence of cerebrospinal fluid or shunt hardware culture that yielded the pathogenic micro-organism with associated compatible symptoms and signs of central nervous system infection or shunt malfunction; or (2) surgical incision site infection requiring shunt reinsertion (even in the absence of positive culture); or (3) intraperitoneal pseudocyst formation (even in the absence of positive culture). Secondary endpoints were shunt malfunction, defined as unsatisfactory cerebrospinal fluid drainage that required shunt reinsertion, and 30-day mortality. RESULTS: A primary ventriculoperitoneal shunt was inserted in 538 patients during the study period. The mean age of patients was 48 years (range, 13-88 years) with a male-to-female ratio of 1:1. Aneurysmal subarachnoid haemorrhage was the most common aetiology (n=169, 31%) followed by intracranial tumour (n=164, 30%), central nervous system infection (n=42, 8%), and traumatic brain injury (n=27, 5%). The mean operating time was 75 (standard deviation, 29) minutes. Shunt reinsertion and infection rates were 16% (n=87) and 7% (n=36), respectively. The most common cause for shunt reinsertion was malfunction followed by shunt infection. Independent predictors for shunt infection were: traumatic brain injury (adjusted odds ratio=6.2; 95% confidence interval, 2.3-16.8), emergency shunting (2.3; 1.0-5.1), and prophylactic vancomycin as the sole antibiotic (3.4; 1.1-11.0). The 30-day all-cause mortality was 6% and none were directly procedure-related. CONCLUSIONS: This is the first Hong Kong territory-wide review of infection in primary ventriculoperitoneal shunts. Although the ventriculoperitoneal shunt infection rate met international standards, there are areas of improvement such as vancomycin administration and the avoidance of scheduling the procedure as an emergency.

Sequence memory based on coherent spin-interaction neural networks.

Sequence information processing, for instance, the sequence memory, plays an important role on many functions of brain. In the workings of the human brain, the steady-state period is alterable. However, in the existing sequence memory models using heteroassociations, the steady-state period cannot be changed in the sequence recall. In this work, a novel neural network model for sequence memory with controllable steady-state period based on coherent spininteraction is proposed. In the proposed model, neurons fire collectively in a phase-coherent manner, which lets a neuron group respond differently to different patterns and also lets different neuron groups respond differently to one pattern. The simulation results demonstrating the performance of the sequence memory are presented. By introducing a new coherent spin-interaction sequence memory model, the steady-state period can be controlled by dimension parameters and the overlap between the input pattern and the stored patterns. The sequence storage capacity is enlarged by coherent spin interaction compared with the existing sequence memory models. Furthermore, the sequence storage capacity has an exponential relationship to the dimension of the neural network.

A cautionary tale: dealing with missing data in clinical trials for rheumatic diseases.

OBJECTIVES: Missing data are found in nearly all clinical trials and it is important to use appropriate statistical techniques to analyse clinical trials with missing data. We discuss common statistical methods for tackling missing data and how to handle results when the analyses give different results. METHODS: Using data from a placebo-controlled, randomised bovine Type I collagen (CI) study in diffuse cutaneous systemic sclerosis (dcSSc), we apply different statistical approaches to handling missing data. We also describe simple ways to ascertain the type of missing data in the data set, to the extent possible. RESULTS: We examine eleven different methods to impute missing data. An analysis based on completers alone (complete case analysis and available case analysis) and the last observation carried forward (LOCF) methods require underlying assumptions which are rarely met in practice. Multiple imputation, mixed effects, and repeated measures try to account for the differences among patients and account for patient's specific response patterns, although the assumption that the missing data is directly related to the observed characteristics may well not be true. The joint likelihood based model combines the mixed effect model and logistic regression model to explicitly handle data not missing at random and so it is more realistic and potentially takes an additional step toward decreasing bias. CONCLUSIONS: We discussed various ways of handling missing data and provide recommendations on how to arrive at a conclusion when different statistical approaches to analyse missing data analysis in clinical trials give conflicting answers.

A revolutionary approach facilitating co-expression of authentic human epidermal growth factor and basic fibroblast growth factor in both cytoplasm and culture medium of Escherichia coli.

During secretory or excretory production of heterologous proteins in Escherichia coli, peptidase processing cleaves the signal peptide off from a premature protein, which is then secreted as a mature product. Many proteins have been successfully expressed as secreted/excreted products in E. coli. However, basic fibroblast growth factor (bFGF), despite its suitability for secretory/excretory production in E. coli, has never been successfully expressed using such an approach. In this communication, we report the application of a revolutionary E. coli system to the efficient expression of not only bFGF, but also human epidermal growth factor (EGF) concurrently, as authentic products in the culture supernatant (SN). More interestingly, both polypeptides were also shown to be present at high levels as authentic products in the cell lysate (CL). The manifestation of this unusual phenomenon required a collaborative action between construct pWKW2, an efficient excretion vector engineered by our group to facilitate extracellular production of EGF, and the Sce VMA intein, which enables self-cleavage of protein sequences fused to it. Both bFGF and EGF derived from SN and CL were characterized to be bioactive. Moreover, despite employing only shake-flask cultivation, the total yields of bFGF and EGF recovered from both SN and CL were impressive, amounting to 103 and 74 mg l(-1) of culture, respectively. The novel expression approach introduced herein may prove to be practically useful for the production of a wide range of proteins in the future.

Authentic human basic fibroblast growth factor produced by secretion in Bacillus subtilis.

Bacillus subtilis is generally accepted as an inborn host candidate employed for secretory production of heterologous proteins. However, this ideal host system has never been employed for commercial production of medically useful proteins. In this communication, we report for the first time the employment of an engineered B. subtilis system, in conjunction with a facile cell-wall destabilization protocol, to successfully obtain an alluring yield of 40 mg l(-1) of secreted human basic fibroblast growth factor (hbFGF) in the culture supernatant. The product was not only shown to exhibit potent bioactivity but also revealed to possess a protein sequence identical to that of mature native hbFGF (Mat-hbFGF). Our findings may pave way for the development of a cost-effective process for producing Mat-hbFGF, which is currently sold at an unusually expensive price of over US $1 million g(-1), for medical and skin care applications.

Men's experiences of sexuality after cancer: a material discursive intra-psychic approach.

Men can experience significant changes to their sexuality following the onset of cancer. However, research on men's sexuality post-cancer has focused almost exclusively on those with prostate and testicular cancer, despite evidence that the diagnosis and treatment for most cancers can impact on men's sexuality. This Australian qualitative study explores the experiences of changes to sexuality for 21 men across a range of cancer types and stages, sexual orientations and relationship contexts. Semi-structured interviews were analysed with theoretical thematic analysis guided by a material discursive intra-psychic approach, recognising the materiality of sexual changes, men's intrapsychic experience of such changes within a relational context and the influence of the discursive construction of masculine sexuality. Material changes included erectile difficulty, decreased desire, and difficulty with orgasm. The use of medical aids to minimise the impact of erectile difficulties was shaped by discursive constructions of 'normal' masculine sexuality. The majority of men reported accepting the changes to their sexuality post-cancer and normalised them as part of the natural ageing process. Men's relationship status and context played a key role managing the changes to their sexuality. We conclude by discussing the implications for clinical practice.

Pinning controllability of complex networks with community structure.

In this paper, we study the controllability of networks with different numbers of communities and various strengths of community structure. By means of simulations, we show that the degree descending pinning scheme performs best among several considered pinning schemes under a small number of pinned nodes, while the degree ascending pinning scheme is becoming more powerful by increasing the number of pinned nodes. It is found that increasing the number of communities or reducing the strength of community structure is beneficial for the enhancement of the controllability. Moreover, it is revealed that the pinning scheme with evenly distributed pinned nodes among communities outperforms other kinds of considered pinning schemes.