A practical approach to implementing incremental haemodialysis.

The majority of end-stage kidney disease patients are treated with haemodialysis (HD). Starting HD can pose physical, social, and psychological challenges to patients, and mortality rates within the first 6 months are disproportionately high, with intensive HD regimens implicated as a potential factor. Starting HD with an incremental approach, taking residual kidney function (RKF) into account, potentially allows for a gentle start with reduced dialysis intensity. Dialysis intensity (session time or frequency) can then be proportionally increased as RKF reduces. This approach to starting HD has been reported in observational studies to result in better patient self-reported health quality of life and reduced costs, and now several definitive randomised controlled trials are underway comparing an incremental approach to the conventional thrice weekly paradigm. Physician concerns over the risk of inadequate dialysis, with consequent increased emergency admissions, and practical challenges of how to estimate RKF and implement incremental dialysis have impeded widespread adoption. Addressing these challenges is paramount to increasing the uptake of incremental HD. Careful patient selection lies at the heart of a successful incremental HD programme. Generally, patients with a residual urea clearance of > 3 ml/min/1.73 m2 can be considered suitable for starting with incremental HD provided they comply with fluid intake, salt and other dietary recommendations. Calculating RKF from regular interdialytic urine collections and appropriately adjusting sessional HD clearance targets are practical and conceptual challenges. In this report we aim to disentangle these complexities and provide a step-by-step guide for patient selection and adjusting dialysis sessional targets.

Definitive Stereotactic Body Radiation Therapy in Early-Stage Solitary Hepatocellular Carcinoma: An Australian Multi-Institutional Review of Outcomes.

AIMS: Standard curative options for early-stage, solitary hepatocellular carcinoma (HCC) are often unsuitable due to liver dysfunction, comorbidities and/or tumour location. Stereotactic body radiation therapy (SBRT) has shown high rates of local control in HCC; however, limited data exist in the treatment-naïve, curative-intent setting. We report the outcomes of patients with solitary early-stage HCC treated with SBRT as first-line curative-intent therapy. MATERIALS AND METHODS: A multi-institutional retrospective study of treatment-naïve patients with Barcelona Clinic Liver Cancer stage 0/A, solitary ≤5 cm HCC, Child-Pugh score (CPS) A liver function who underwent SBRT between 2010 and 2019 as definitive therapy. The primary end point was freedom from local progression. Secondary end points were progression-free survival, overall survival, rate of treatment-related clinical toxicities and change in CPS >1. RESULTS: In total, 68 patients were evaluated, with a median follow-up of 20 months (range 3-58). The median age was 68 years (range 50-86); 54 (79%) were men, 62 (91%) had cirrhosis and 50 (74%) were Eastern Cooperative Oncology Group 0. The median HCC diameter was 2.5 cm (range 1.3-5) and the median prescription biologically effective dose with a tumour a/b ratio of 10 Gy (BED10) was 93 Gy (interquartile range 72-100 Gy). Two-year freedom from local progression, progression-free survival and overall survival were 94.3% (95% confidence interval 86.6-100%), 59.5% (95% confidence interval 46.3-76.4%) and 88% (95% confidence interval 79.2-97.6%), respectively. Nine patients (13.2%) experienced grade ≥2 treatment-related clinical toxicities. A rise >1 in CPS was observed in six cirrhotic patients (9.6%). CONCLUSION: SBRT is an effective and well-tolerated option to consider in patients with solitary, early-stage HCC. Prospective, randomised comparative studies are warranted to further refine its role as a first-line curative-intent therapy.

An unusual presentation of an adrenal tumour-a case report.

INTRODUCTION AND IMPORTANCE: Adrenal myelolipomas are rare, benign tumours with an incidence of 0.08-0.2%. They present between the fifth and seventh decade of life [1]. CASE PRESENTATION: Our patient presented with complaints of vomiting and left lumbar pain of four weeks duration. Blood work revealed dyselectrolytemia. Contrast enhanced computed tomography of the abdomen and pelvis confirmed the diagnosis and the patient was planned for an adrenalectomy. Histopathology report revealed the pathology. She is currently on routine follow up and is disease free. Written informed consent was obtained from the patient for publication of this case report and its accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request. This case report has been reported in line with the SCARE criteria [2]. CLINICAL DISCUSSION: With the increased use of imaging modalities of the abdomen, they are now considered to be the second most common cause of adrenal incidentalomas (6-16%) [3]. Most tumours are small, asymptomatic and often go undiagnosed. Large tumours can cause chronic pain and other nonspecific symptoms. CONCLUSION: Though myelolipomas are identified on routine CT scans, on a background of dyselectrolytemia, a further evaluation is of utmost importance to rule out the possibility of a functioning tumour.

Malignant peripheral nerve sheath tumour-A case report.

INTRODUCTION: Malignant peripheral nerve sheath tumors (MPNST) are rare, aggressive sarcomatous tumors that arise from peripheral nerve sheaths and show schwann cell differentiation (Thangadurai, 2017) [1]. They commonly arise among patients with neurofibromatosis I and following radiation therapy (Farid et al., 2014). High resolution PET scans confirm the diagnosis and the definitive treatment is surgical excision. Post operative radiotherapy plays an important role in disease free survival rates. Chemotherapy is offered to people who have a systemic disease. PRESENTATION OF CASE: This case report is on a 47 year old lady, a known case of Von Recklinghausen, who complained of a vague mass in the pelvis with recent history of pain to her right thigh. Pelvic examination revealed a vague mass on the right side of her pelvis. She was planned for excision of the mass. Intraoperative findings were consistent with the clinical and radiological findings. She is currently on regular follow-up and disease free. DISCUSSION: MPNSTs are rare tumours that arise in patients with neurofibromatosis I. Mutations at the genetic level is responsible for the development of MPNST. Early presentation, radiological confirmation, aggressive margin free surgery followed by chemoradiation helps in near complete cure of the disease. CONCLUSION: MPNST are difficult to manage because of their aggressive nature and the limitations in early diagnosis and management. In patients with Von Recklinghausens disease, malignancy must be suspected when a patient presents with the complaints as mentioned in this case report.

Lessons learned from a comprehensive electronic patient record procurement process-implications for healthcare organisations.

BACKGROUND: This study describes learning from procurement of a comprehensive electronic patient record (EPR/electronic health record (EHR)), system for a specialist clinical academic institution. METHOD: Retrospective review of procurement process in addition to evaluation of peer-reviewed literature in the field. RESULTS: Main lessons learned include the importance of detailed preparation of organisational requirements/specifications and organisational 'readiness'. Early staff involvement, resulting in ownership of the selected system by the organisation was a key achievement. The scoring process used required significant resource commitment but, despite being extensive in scope, provided relatively poor distinction between suppliers, despite significant variation in supplier self-scoring. Other elements, such as demonstrations and site visits, provided superior evaluation of functional abilities, and specification requirements should be regarded as threshold evaluation. CONCLUSION: While principles should be followed, the procurement process must be modified to meet the needs of the specific organisation, in terms of its clinical activities, digital maturity, existing infrastructure and budget.

Determination of thiamethoxam residues in banana stem and fruit through LC-MS/MS.

An analytical method based on liquid chromatography coupled with mass spectroscopy/mass spectroscopy was developed and validated for the determination of thiamethoxam residues in banana fruit and stem tissue samples. In this study, Waters Alliance LC and Acquity TQD were used with an electrospray ionization interface in the positive ion mode. An isocratic flow of 0.5% HCOOH in water and 0.05% HCOOH in CH3CN was used for separation. Thiamethoxam residue was extracted from the samples using CH3CN and a dispersive solid-phase extraction method was used for subsequent cleanup. Linearity studies were conducted between 0.001 and 0.1 µg mL-1 of standard solution with three replicates for each concentration. Satisfactory recoveries (107.21 to 115.16% and 90.94 to 109.22%) and high precision (relative standard deviations of 3.71 to 12.83% and 3.24 to 10.78%) were obtained for the banana stem and banana fruit matrix, respectively. The lower limits of detection and quantification achieved were 0.002 and 0.008 µg g-1 for banana stem and 0.001and 0.005 µg g-1for banana fruit, respectively. The developed method was used to analyze the banana stem and fruit samples collected from thiamethoxam-treated fields and stems from the local market.

Sanitation marketing: A systematic review and theoretical critique using the capability approach.

Sanitation is a human right that benefits health. As such, technical and behavioural interventions are widely implemented to increase the number of people using sanitation facilities. These include sanitation marketing interventions (SMIs), in which external support agencies (ESAs) use a hybrid of commercial and social marketing tools to increase supply of, and demand for, sanitation products and services. However, there is little critical discourse on SMIs, or independent rigorous analysis on whether they increase or reduce well-being. Most available information is from ESAs about their own SMI implementation. We systematically reviewed the grey and peer-reviewed literature on sanitation marketing, including qualitatively analysing and calculating descriptive statistics for the parameters measured, or intended to be measured, in publications reporting on 33 SMIs. Guided by the capability approach to development we identified that publications for most SMIs (n = 31, 94%) reported on commodities, whilst fewer reported on parameters related to impacts on well-being (i.e., functionings, n = 22, 67%, and capabilities, n = 20, 61%). When evaluating future SMIs, it may be useful to develop a list of contextualised well-being indicators for the particular SMI's location, taking into account local cultural norms, with this list ideally co-produced with local stakeholders. We identified two common practices in SMIs that can reduce well-being and widen well-being inequalities; namely, the promotion of conspicuous consumption and assaults on dignity, and we discuss the mechanisms by which such impacts occur. We recommend that ESAs understand sanitation marketing's potential to reduce well-being and design SMIs to minimize such detrimental impacts. Throughout the implementation phase ESAs should continuously monitor for well-being impacts and adapt practices to optimise well-being outcomes for all involved.

Improving community health through marketing exchanges: A participatory action research study on water, sanitation, and hygiene in three Melanesian countries.

Diseases related to poor water, sanitation and hygiene (WaSH) are major causes of mortality and morbidity. While pursuing marketing approaches to WaSH to improve health outcomes is often narrowly associated with monetary exchange, marketing theory recognises four broad marketing exchange archetypes: market-based, non-market-based, command-based and culturally determined. This diversity reflects the need for parameters broader than monetary exchange when improving WaSH. This study applied a participatory action research process to investigate how impoverished communities in Melanesian urban and peri-urban informal settlements attempt to meet their WaSH needs through marketing exchange. Exchanges of all four archetypes were present, often in combination. Motivations for participating in the marketing exchanges were based on social relationships alongside WaSH needs, health aspirations and financial circumstances. By leveraging these motivations and pre-existing, self-determined marketing exchanges, WaSH practitioners may be able to foster WaSH marketing exchanges consistent with local context and capabilities, in turn improving community physical, mental and social health.

Comparison of resting and total energy expenditure in peritoneal dialysis patients and body composition measured by dual-energy X-ray absorptiometry.

Under basal resting conditions muscle metabolism is reduced, whereas metabolism increases with physical activity. We wished to determine whether there was an association between resting energy expenditure (REE) and total energy expenditure (TEE) in peritoneal dialysis (PD) patients and lean body mass (LBM). We determined REE and TEE by recently validated equations, using doubly labelled isotopic water, and LBM by dual-energy X-ray absorptiometry (DXA) scanning. We studied 87 patients, 50 male (57.4%), 25 diabetic (28.7%), mean age 60.3±17.6 years, with a median PD treatment of 11.4 (4.7-29.5) months. The mean weight was 70.1±17.7 kg with a REE of 1509±245 kcal/day and TEE 1947±378 kcal/day. REE was associated with body size (weight r=0.78 and body mass index (BMI) r=0.72) and body composition (LBM r=0.77, lean body mass index (LBMI) r=0.76, r=0.62), all P<0.001). For TEE, there was an association with weight r=0.58, BMI r=0.49 and body composition (LBM r=0.64, LBMI (r=0.54), all P<0.001). We compared LBMI measured by DXA and that estimated by the Boer equation using anthropomorphic measurements, which overestimated and underestimated LBM for smaller patients and heavier patients, respectively. Muscle metabolism is reduced at rest and increases with physical activity. Whereas previous reports based on REE did not show any association with LBM, we found an association between both REE and TEE, using a recently validated equation derived from dialysis patients, and LBM measured by DXA scanning. Estimation of muscle mass from anthropomorphic measurements systematically overestimated LBM for small patients and conversely underestimated for heavier patients.

Comparison of energy estimates in chronic kidney disease using doubly-labelled water.

BACKGROUND: Total energy expenditure (TEE) is estimated in clinical practice as a combined measure of resting energy expenditure and physical activity level. Commonly available questionnaires to estimate physical activity level have not been validated in patients with kidney disease using the doubly-labelled water method. METHODS: This prospective, cross-sectional study was conducted on 40 patients with chronic kidney disease stages 1-5 with the objective of validating two physical activity questionnaires: the Recent Physical Activity Questionnaire (RPAQ) and the Stanford 7-day recall questionnaire. TEE was measured using doubly-labelled water technique. TEE was also estimated using predicted resting energy expenditure and estimated physical activity measures from the questionnaires. RESULTS: Measured TEE correlated better with TEE estimated from RPAQ compared to that from the Stanford questionnaire. In Bland-Altman analysis, TEE estimated from RPAQ had the least bias and narrower limits of agreement compared to the measured TEE. A metabolic equivalent of task value of 1.3 for the unaccounted time in RPAQ provided the best approximation of estimated TEE to the measured TEE. CONCLUSIONS: RPAQ is an acceptable questionnaire tool for assessing physical activity level in patients with chronic kidney disease.

Metallothionein Expression in Dogs With Chronic Hepatitis and Its Correlation With Hepatic Fibrosis, Inflammation, and Ki-67 Expression.

The chronic form of primary hepatitis occurs commonly in dogs, and the etiology is rarely found. Metallothionein (MT) is a heavy metal-binding protein found in many organs, including the liver. MT was recently shown to enhance liver regeneration and decrease hepatic fibrosis in human beings. This study examined the expression of MT in 24 cases of chronic hepatitis in dogs using immunohistochemistry. To understand the role of MT as a determinant of hepatic inflammation, fibrosis, bile duct proliferation, and regeneration, we correlated its expression with histologic lesions of chronic hepatitis, such as hepatic inflammation, fibrosis, and bile duct proliferation, as well as hepatocellular growth fraction as measured by Ki67 immunolabeling. Hepatocellular growth fraction was used as a measure of hepatic regeneration. Regression analysis revealed a significant positive correlation between MT labeling intensity and growth fraction (r(2) = 0.29, P < .05). The percentage of MT-positive cells and the overall MT expression were both positively correlated with growth fraction (r(2) = 0.25 and 0.26, respectively; P < .05). A negative correlation was found between the overall MT labeling and fibrosis (r(2) = 0.18, P < .05). A similar trend of negative correlation was also found between the percentage of MT-positive cells and fibrosis, but the P value was not statistically significant (r(2) = 0.14, P = .0684). These findings suggest a protective role of MT in dogs affected by chronic hepatitis, similar to its role in human beings. These dogs may respond to treatment modules focusing on enhancing the expression of MT.

Effects of surgical stress on early nonspecific immune response in children.

Surgery alters the body's homeostatic balance and defense mechanisms. In adults transient postoperative cellular and humoral immunosuppression after different degrees of operative stress has been reported. In children the immunologic consequences of operations are not elaborated. This study investigates the effect of minor and major surgery on early nonspecific immune response in terms of neutrophil counts and function. Forty-three children undergoing minor and major elective procedures were studied. Blood samples were collected before, immediately after, and 72 h after surgery. Total white cell count, differential neutrophil count, and neutrophil phagocytic function were studied using nitroblue tetrazolium test. Children were divided into two groups-group 1 underwent minor surgery and group 2 major surgery. In group 1 there was a significant drop in total counts after surgery, but in group 2 total counts were not affected. In both groups, the percentage of neutrophils increased immediately after surgery but fell to near or less than preoperative levels 72 h after surgery. However, the assessment of neutrophil functions by nitroblue tetrazolium test in both unstimulated and stimulated forms revealed it to be unchanged in group 1. In group 2 the unstimulated neutrophil function was elevated 72 h after surgery, whereas stimulated function was elevated immediately after surgery. Minor surgery does not alter the early nonspecific immune response. However, major surgery seems to induce a transient increase in neutrophil phagocytic activity.

Rates of serious infections, opportunistic infections, inflammatory bowel disease, and malignancies in subjects receiving etanercept vs. controls from clinical trials in ankylosing spondylitis: a pooled analysis.

OBJECTIVES: Therapies involving anti-tumour necrosis factor are associated with increased risk of serious infections, opportunistic infections, and some types of malignancies in subjects with rheumatic diseases. However, limited data have been collected for subjects with ankylosing spondylitis (AS). The aim of this retrospective analysis of all sponsor-conducted trials was to examine the rates of serious infections, inflammatory bowel disease (IBD), malignancies, and non-malignant skin cancers during treatment in subjects with AS. METHOD: Data from five randomized controlled trials (one sulfasalazine-controlled, four placebo-controlled) and four open-label studies evaluating etanercept were pooled for analyses. All randomized subjects who received at least one dose of treatment were included in the study. RESULTS: Analyses included 1323 subjects (> 1500 subject-years of treatment). Rate ratios of serious infections and IBD events for etanercept vs. placebo/sulfasalazine during the double-blind studies were 2.19 [95% confidence interval (CI) 0.22-107.79] and 1.09 (95% CI 0.06-64.56), respectively. There were no reports of opportunistic infections. Using the Surveillance, Epidemiology and End Results database, the standardized incidence ratio for malignancies was 1.47 (95% CI 0.54-3.21). CONCLUSIONS: These data suggest that etanercept is well tolerated in subjects with AS. Despite the large number of patients, the 95% CI data all cross 1.0, limiting possible conclusions. No new safety signals were observed.

Locally advanced prostate cancer: current controversies and optimisation opportunities.

Prostate cancer is the most common malignancy in men worldwide. The rate of patients presenting with locally advanced prostate cancer has declined in recent decades, mainly due to prostate-specific antigen screening, but the management of these patients still remains controversial. Current literature suggests that the standard of care for these patients is a combination approach with radiation therapy and androgen deprivation therapy. However, there remain many unresolved issues, including the role of dose-escalated radiation therapy, the additional benefit of surgery and the role of systemic therapy, both standard chemotherapeutic agents and novel agents. Furthermore, in the era of personalised medicine, additional research is needed to evaluate the role of biomarkers to better predict the risk of local and systemic relapse in this population.

In the Pursuit of Effective Affective Computing: The Relationship Between Features and Registration.

For facial expression recognition systems to be applicable in the real world, they need to be able to detect and track a previously unseen person's face and its facial movements accurately in realistic environments. A highly plausible solution involves performing a "dense" form of alignment, where 60-70 fiducial facial points are tracked with high accuracy. The problem is that, in practice, this type of dense alignment had so far been impossible to achieve in a generic sense, mainly due to poor reliability and robustness. Instead, many expression detection methods have opted for a "coarse" form of face alignment, followed by an application of a biologically inspired appearance descriptor such as the histogram of oriented gradients or Gabor magnitudes. Encouragingly, recent advances to a number of dense alignment algorithms have demonstrated both high reliability and accuracy for unseen subjects [e.g., constrained local models (CLMs)]. This begs the question: Aside from countering against illumination variation, what do these appearance descriptors do that standard pixel representations do not? In this paper, we show that, when close to perfect alignment is obtained, there is no real benefit in employing these different appearance-based representations (under consistent illumination conditions). In fact, when misalignment does occur, we show that these appearance descriptors do work well by encoding robustness to alignment error. For this work, we compared two popular methods for dense alignment-subject-dependent active appearance models versus subject-independent CLMs-on the task of action-unit detection. These comparisons were conducted through a battery of experiments across various publicly available data sets (i.e., CK+, Pain, M3, and GEMEP-FERA). We also report our performance in the recent 2011 Facial Expression Recognition and Analysis Challenge for the subject-independent task.

The importance of local control in high-risk locally advanced prostate cancer.

Prostate cancer is a common malignancy worldwide, and in Canada, it is the most frequently diagnosed cancer in men. The stratification of prostate cancer into risk categories has allowed for improved counselling of patients and provides guidance for treatment selection. However, the exact definition of high-risk prostate cancer remains controversial, and that lack of consensus remains a barrier to assessing available data from various institutions and from clinical trials. The proportion of patients with locally advanced high-risk disease has fallen in the last 20 years largely because of screening for prostate-specific antigen, but management in this population continues to be an important clinical problem. A factor that has emerged in recent years is the importance of local disease control, with data from multiple randomized trials suggesting that local therapy improves progression-free survival, disease-free survival, and overall survival. Further research in this population is necessary to improve outcomes.

Epitope mapping and key amino acid identification of anti-CD22 immunotoxin CAT-8015 using hybrid ß-lactamase display.

Monoclonal antibodies are a commercially successful class of drug molecules and there are now a growing number of antibodies coupled to toxic payloads, which demonstrate clinical efficacy. Determining the precise epitope of therapeutic antibodies is beneficial in understanding the structure-activity relationship of the drug, but in many cases is not done due to the structural complexity of, in particular, conformational protein epitopes. Using the immunotoxin CAT-8015 as a test case, this study demonstrates that a new methodology, hybrid ß-lactamase display, can be employed to elucidate a complex epitope on CD22. Following insertion of random CD22 gene fragments into a permissive site within ß-lactamase, proteins expressed in Escherichia coli were first screened for correct folding by resistance to ampicillin and then selected by phage display for affinity to CAT-8015. The optimal protein region recognised by CAT-8015 could then be used as a tool for fine epitope mapping, using alanine-scanning analysis, demonstrating that this technology is well suited to the rapid characterisation of antibody epitopes.

AFP-Pred: A random forest approach for predicting antifreeze proteins from sequence-derived properties.

Some creatures living in extremely low temperatures can produce some special materials called "antifreeze proteins" (AFPs), which can prevent the cell and body fluids from freezing. AFPs are present in vertebrates, invertebrates, plants, bacteria, fungi, etc. Although AFPs have a common function, they show a high degree of diversity in sequences and structures. Therefore, sequence similarity based search methods often fails to predict AFPs from sequence databases. In this work, we report a random forest approach "AFP-Pred" for the prediction of antifreeze proteins from protein sequence. AFP-Pred was trained on the dataset containing 300 AFPs and 300 non-AFPs and tested on the dataset containing 181 AFPs and 9193 non-AFPs. AFP-Pred achieved 81.33% accuracy from training and 83.38% from testing. The performance of AFP-Pred was compared with BLAST and HMM. High prediction accuracy and successful of prediction of hypothetical proteins suggests that AFP-Pred can be a useful approach to identify antifreeze proteins from sequence information, irrespective of their sequence similarity.