Survey of Patient Knowledge and Awareness of "Sick Day Rules" in Rheumatology Patients on Long Term Glucocorticoid Therapy.

Aims Rheumatic disease (RMD) patients treated with long-term glucocorticoids (GC) are at risk of developing tertiary adrenal insufficiency. With this survey we aimed to assess the knowledge of RMD patients taking long-term glucocorticoid therapy regarding risk of adrenal insufficiency and understanding of the "steroid sick day rules". Methods RMD patients taking ≥2.5 mg prednisolone daily for ≥3 months were recruited from the Rheumatology outpatient department in Beaumont Hospital, Dublin. Patient knowledge and previous counselling of steroid sick day rules was determined using an 8-point questionnaire carried out face-to-face or via phone call. Results 51 RMD patients on GC therapy were recruited. 3/51 (5.9%) of patients reported that they had been counselled on the Sick Day Rules. 2/51 (3.9%) carried a steroid emergency card or MedicAlert bracelet. Few patients would increase their steroid dose appropriately in response to infection, vomiting or peri-procedure [14/51 (27.5%); 9/51 (17.7%) and 5/51 (7.2%), respectively]. Conclusion We demonstrate a significant deficit of patient knowledge around the precautions for long-term GC use in rheumatic diseases. We suspect that our results may be generalisable to many other RMD units. We are currently reviewing our procedures around healthcare professional and patient education, issuing of information leaflets, emergency cards or MedicAlert bracelets etc. to at risk patients.

The implementation of an advanced practice radiation therapy (APRT) program in Singapore.

BACKGROUND: The exploration of Advanced Practiced Radiation Therapists (APRTs) development in Singapore started in 2011. This study aims to provide an overview of the development of the APRT roles, and to discuss the approaches used to develop and implement these roles in Singapore. MATERIALS AND METHODS: A mixed methods approach was used in the development of the APRT program. A literature review was carried out to define the APRT scope of practice and core responsibilities. A competency and assessment framework were setup to assess the core competency areas. With this framework, a structured 1-year residency training program was developed. RESULTS: The scope of practice and core responsibilities of APRTs were defined with five proposed advanced practice profiles being successfully validated. A competency framework was set up to assess the core competency domains: clinical, technical and professional competencies, research, education and leadership. A 4-point scoring system was developed for the competency assessment based on two criteria; the frequency with which RTTs would demonstrate competency, and the ability of performing the task competently. A 1-year structured APRT residency program was developed and implemented. The programme consisted of structured lectures, and clinical practice-based modules where APRT residents receive structured mentoring under a mentorship program. CONCLUSION: The APRT program in Singapore employed an evidence-based implementation process that tested the feasibility of a new practice model. Multidisciplinary involvements, mentorship and clinical training were important factors for the success of the APRT program.

Minimally Invasive versus Conventional Open Surgery for Fixation of Spinal Fracture in Ankylosed Spine.

INTRODUCTION: This was a retrospective study aimed to investigate the perioperative outcomes of long construct minimally invasive spinal stabilisation (MISt) using percutaneous pedicle screws (PPS) versus conventional open spinal surgery in the treatment of spinal fracture in ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH). MATERIAL AND METHODS: Twenty-one patients with AS and DISH who were surgically treated between 2009 and 2017 were recruited. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union rate. RESULTS: Mean age was 69.2 ± 9.9 years. Seven patients had AS and 14 patients had DISH. 17 patients sustained AO type B3 fracture and 4 patients had type B1 fracture. Spinal trauma among these patients mostly involved thoracic spine (61.9%), followed by lumbar (28.6%) and cervical spine (9.5%). MISt using PPS was performed in 14 patients (66.7%) whereas open surgery in 7 patients (33.3%). Mean number of instrumentation level was 7.9 ± 1.6. Mean operative time in MISt and open group was 179.3 ± 42.3 minutes and 253.6 ± 98.7 minutes, respectively (p=0.028). Mean intra-operative blood loss in MISt and open group was 185.7 ± 86.4ml and 885.7 ± 338.8ml, respectively (p<0.001). Complications and union rate were comparable between both groups. CONCLUSION: MISt using PPS lowers the operative time and reduces intra-operative blood loss in vertebral fractures in ankylosed disorders. However, it does not reduce the perioperative complication rate due to the premorbid status of the patients. There was no significant difference in the union rate between MISt and open surgery.

Discovery of novel genic-SSR markers from transcriptome dataset of an important non-human primate, Macaca fascicularis.

Macaca fascicularis, also known as the cynomolgus macaque, is an important non-human primate animal model used in biomedical research. It is an Old-World primate widely distributed in Southeast Asia and is one of the most abundant macaque species in Malaysia. However, the genetic structure of wild cynomolgus macaque populations in Malaysia has not been thoroughly elucidated. In this study, we developed genic-simple sequence repeat (genic-SSR) markers from an in-house transcriptome dataset generated from the Malaysian cynomolgus macaque via RNA sequencing, and applied these markers on 26 cynomolgus macaque individuals. A collection of 14,751 genic-SSRs were identified, where 13,709 were perfect SSRs. Dinucleotide repeats were the most common repeat motifs with a frequency of 65.05%, followed by trinucleotide repeats (20.55%). Subsequently, we designed 300 pairs of primers based on perfect di- and trinucleotide SSRs, in which 105 SSRs were associated with functional genes. A subset of 30 SSR markers were randomly selected and validated, yielding 19 polymorphic markers with an average polymorphism information content value of 0.431. The development of genic-SSR markers in this study is indeed timely to provide useful markers for functional and population genetic studies of the cynomolgus macaque and other related non-human primate species.

Evaluating the concurrent validity of body mass index (BMI) in the identification of malnutrition in older hospital inpatients.

BACKGROUND: Nutrition screening and assessment tools often include body mass index (BMI) as a component in identifying malnutrition risk. However, rising obesity levels will impact on the relevancy and applicability of BMI cut-off points which may require re-evaluation. This study aimed to explore the relationship between commonly applied BMI cut-offs and diagnosed malnutrition. METHODS: Data (age, gender, BMI and Subjective Global Assessment (SGA) ratings) were analysed for 1152 inpatients aged ≥65 years across annual malnutrition audits (2011-2015). The receiver operation characteristic (ROC) curve analysed the optimal BMI cut-off for malnutrition and concurrent validity of commonly applied BMI cut-offs in nutritional screening and assessment tools. RESULTS: Malnutrition prevalence was 36.0% (n = 372) using SGA criteria (not malnourished, moderate or severe malnutrition). Median age was 78.7 (IQR 72-85) years, median BMI 25.4 (IQR 21.8-29.7) kg/m2; 52.1% male and 51.2% overweight/obese. ROC analysis identified an optimal BMI cut-off of <26 kg/m2, 80.8% sensitivity and 61.5% specificity (AUC 0.802, 95% CI 0.773, 0.830; p < 0.0001). Commonly applied BMI cut-offs (between 18.5 and 23 kg/m2) failed to meet the alpha-priori requirement of 80% sensitivity and 60% specificity. However, BMI <23 kg/m2 had the highest agreement (κ = 0.458) with malnutrition diagnosed using the SGA. CONCLUSIONS: Both malnutrition and overweight/obesity are common in older inpatients. Continuing increases in the prevalence of overweight and obesity will impact on the sensitivity of BMI as a screening component for malnutrition risk. The current study suggests tools developed over a decade ago may need to be revisited in future.

Does intentional weight loss improve daytime sleepiness? A systematic review and meta-analysis.

Obesity is associated with excessive daytime sleepiness, but its causality remains unclear. We aimed to assess the extent to which intentional weight loss affects daytime sleepiness. Electronic databases were searched through 24 October 2016. Studies involving overweight or obese adults, a weight loss intervention and repeated valid measures of daytime sleepiness were included in the review. Two independent reviewers extracted data on study characteristics, main outcome (change in daytime sleepiness score standardized by standard deviation of baseline sleepiness scores), potential mediators (e.g. amount of weight loss and change in apnoea-hypopnoea index) and other co-factors (e.g. baseline demographics). Forty-two studies were included in the review. Fifteen before-and-after studies on surgical weight loss interventions showed large improvements in daytime sleepiness, with a standardized effect size of -0.97 (95% confidence interval [CI] -1.21 to -0.72). Twenty-seven studies on non-surgical weight loss interventions showed small-to-moderate improvement in daytime sleepiness, with a standardized effect size of -0.40 (95%CI -0.52 to -0.27), with no difference between controlled and before-and-after studies. We found a nonlinear association between amount of weight loss and change in daytime sleepiness. This review suggests that weight loss interventions improve daytime sleepiness, with a clear dose-response relationship. This supports the previously hypothesized causal effect of obesity on daytime sleepiness. It is important to assess and manage daytime sleepiness in obese patients.

Estimation of an optimal chemotherapy utilisation rate for cancer: setting an evidence-based benchmark for quality cancer care.

There is wide variation in the proportion of newly diagnosed cancer patients who receive chemotherapy, indicating the need for a benchmark rate of chemotherapy utilisation. This study describes an evidence-based model that estimates the proportion of new cancer patients in whom chemotherapy is indicated at least once (defined as the optimal chemotherapy utilisation rate). The optimal chemotherapy utilisation rate can act as a benchmark for measuring and improving the quality of care. Models of optimal chemotherapy utilisation were constructed for each cancer site based on indications for chemotherapy identified from evidence-based treatment guidelines. Data on the proportion of patient- and tumour-related attributes for which chemotherapy was indicated were obtained, using population-based data where possible. Treatment indications and epidemiological data were merged to calculate the optimal chemotherapy utilisation rate. Monte Carlo simulations and sensitivity analyses were used to assess the effect of controversial chemotherapy indications and variations in epidemiological data on our model. Chemotherapy is indicated at least once in 49.1% (95% confidence interval 48.8-49.6%) of all new cancer patients in Australia. The optimal chemotherapy utilisation rates for individual tumour sites ranged from a low of 13% in thyroid cancers to a high of 94% in myeloma. The optimal chemotherapy utilisation rate can serve as a benchmark for planning chemotherapy services on a population basis. The model can be used to evaluate service delivery by comparing the benchmark rate with patterns of care data. The overall estimate for other countries can be obtained by substituting the relevant distribution of cancer types. It can also be used to predict future chemotherapy workload and can be easily modified to take into account future changes in cancer incidence, presentation stage or chemotherapy indications.

Circulating tumour cells and the epithelial mesenchymal transition in colorectal cancer.

Circulating tumour cells (CTCs) hold great potential as liquid biopsies to prognosticate disease and guide treatment in colorectal cancer. However, their emerging role in determining the molecular phenotype of tumour metastasis carries even more promising clinical use in the provision of comprehensive biomarker detection for targeted therapies and determination of drug resistance. The isolation of CTCs is technology dependent, and in the case of epithelial cell adhesion molecule-based platforms, the ability to detect cells that have undergone the epithelial to mesenchymal transition (EMT) is ineffective. CTCs displaying a mesenchymal phenotype are believed to have an increased metastatic potential. The rarity of CTCs provides another challenge in the enumeration of these cells. The future will likely involve the analysis of individual CTCs at any stage of the EMT in order to provide real-time phenotypic and molecular snapshots capable of tracking the dynamic evolution of tumour progression over time.

Accuracy and reliability of the i-STAT point-of-care device for the determination of haemoglobin concentration before and after major blood loss.

We investigated the accuracy of i-STAT(®) (Abbott Point of Care Inc., Princeton, NJ, USA) haemoglobin (Hb) measurement in surgical patients with an estimated blood loss of ≥25% of total blood volume. Blood tests for i-STAT(®) Hb, laboratory Hb (Sysmex XE-2100(™), Sysmex Corporation, Kobe, Japan) and total plasma proteins were obtained at the start of surgery (T=0) and when an estimated 25% total blood volume loss had occurred (T=1). Thirty-one patients were recruited. The coefficient of variation of the paired i-STAT(®) Hb estimates was 2.8% and 2.9% at T=0 and T=1, respectively. The mean difference between i-STAT(®) and laboratory Hb was -7.6 g/l (standard deviation 6.5) at T=0 and -5.1 g/l (standard deviation 12) at T=1. The mean total plasma protein difference (total plasma protein T=0 minus T=1) was 13.6 g/l (95% confidence interval 10.2 to 17.0). There was poor correlation between total plasma protein and bias in i-STAT(®) measurements. The i-STAT(®) Hb had an acceptable coefficient of variation, but the Hb levels were lower than those estimated by the laboratory. The standard deviation of i-STAT(®) Hb was greater after ≥25% estimated total blood volume loss. Clinicians should not use the i-STAT(®) Hb in isolation for clinical decision-making when considering blood transfusion in a situation of 25% or greater blood loss.

Improving team information sharing with a structured call-out in anaesthetic emergencies: a randomized controlled trial.

BACKGROUND: Sharing information with the team is critical in developing a shared mental model in an emergency, and fundamental to effective teamwork. We developed a structured call-out tool, encapsulated in the acronym 'SNAPPI': Stop; Notify; Assessment; Plan; Priorities; Invite ideas. We explored whether a video-based intervention could improve structured call-outs during simulated crises and if this would improve information sharing and medical management. METHODS: In a simulation-based randomized, blinded study, we evaluated the effect of the video-intervention teaching SNAPPI on scores for SNAPPI, information sharing, and medical management using baseline and follow-up crisis simulations. We assessed information sharing using a probe technique where nurses and technicians received unique, clinically relevant information probes before the simulation. Shared knowledge of probes was measured in a written, post-simulation test. We also scored sharing of diagnostic options with the team and medical management. RESULTS: Anaesthetists' scores for SNAPPI were significantly improved, as was the number of diagnostic options they shared. We found a non-significant trend to improve information-probe sharing and medical management in the intervention group, and across all simulations, a significant correlation between SNAPPI and information-probe sharing. Of note, only 27% of the clinically relevant information about the patient provided to the nurse and technician in the pre-simulation information probes was subsequently learnt by the anaesthetist. CONCLUSIONS: We developed a structured communication tool, SNAPPI, to improve information sharing between anaesthetists and their team, taught it using a video-based intervention, and provide initial evidence to support its value for improving communication in a crisis.

OCT4 as a target of miR-34a stimulates p63 but inhibits p53 to promote human cell transformation.

Human cell transformation is a key step for oncogenic development, which involves multiple pathways; however, the mechanism remains unclear. To test our hypothesis whether cell oncogenic transformation shares some mechanisms with the process of reprogramming non-stem cells to induced pluripotent stem cells (iPSC), we studied the relationship among the key factors for promoting or inhibiting iPSC in radiation-transformed human epithelial cell lines derived from different tissues (lung, breast and colon). We unexpectedly found that p63 and OCT4 were highly expressed (accompanied by low expressed p53 and miR-34a) in all transformed cell lines examined when compared with their non-transformed counterparts. We further elucidated the relationship of these factors: the 3p strand of miR-34a directly targeted OCT4 by binding to the 3' untranslated region (3'-UTR) of OCT4 and, OCT4, in turn, stimulated p63 but inhibited p53 expression by binding to a specific region of the p63 or p53 promoter. Moreover, we revealed that the effects of OCT4 on promoting cell oncogenic transformation were by affecting p63 and p53. These results support that a positive loop exists in human cells: OCT4 upregulation as a consequence of inhibition of miR-34a, promotes p63 but suppresses p53 expression, which further stimulates OCT4 upregulation by downregulating miR-34a. This functional loop contributes significantly to cell transformation and, most likely, also to the iPSC process.

Circulating tumour cells and circulating free nucleic acid as prognostic and predictive biomarkers in colorectal cancer.

The detection of circulating tumour cells or circulating free tumour nucleic acids can potentially guide treatment and inform prognosis in colorectal cancer using minimally invasive "liquid biopsies". Current literature supports the notion that high circulating tumour cell counts or presence of tumour nucleic acid correlate with inferior clinical outcomes for patients, but they are not yet part of routine clinical care. Future research evolves around the examination of the molecular phenotype of circulating tumour cells. The key unanswered areas include differentiating between circulating tumour cell presence and their proliferative capacity and dormancy, identifying tumour heterogeneity and understanding the epithelial-mesenchymal transition.

Morphometric sex determination of Milky and Painted Storks in captivity.

Logistic regression was applied to develop a morphometric sexing method of two closely related stork species that were previously sexed through amplification of the CHD gene. Tarsus length (TL) and bill length (BL) measurements were recorded from captive populations of adult Milky Stork (Mycteria cinerea) (n = 60) and Painted Stork (Mycteria leucocephala) (n = 58) at Zoo Negara Malaysia. Despite having monomorphic plumages, both stork species exhibited normal sexual size dimorphism in which males were significantly larger than females in the tested variables. Based on logistic regression analysis, BL correctly classified the sex of sampled individuals from Painted and Milky stork with an overall predicted accuracy of 94.8 and 90.0%, respectively. However, TL measurements generated a lower predicted accuracy level of 86.2% and a same accuracy level of 90% on the sex classification of individuals from Painted and Milky stork, respectively. By comparing the measurements of both species, only the average BL measurements of the Milky storks were significantly lower than that of Painted storks (t-test, P80.001). The logistic regression equation in this study may serve as a simple and more practical option for sexing Milky and Painted storks for their breeding and conservation programmes.

The efficacy of oral ondansetron and dexamethasone for the prevention of acute chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy - a retrospective audit.

The optimal dose of oral ondansetron for the prevention of acute chemotherapy-induced nausea and vomiting (CINV) resulting from moderately emetogenic chemotherapy (MEC) is unknown. This retrospective audit was conducted to determine the efficacy of 8 mg oral ondansetron plus 8 mg oral dexamethasone as pre-chemotherapy anti-emetic regimen for patients receiving MEC. The efficacy outcomes analysed were the proportion of patients with no acute vomiting, proportion of patients with no acute nausea and the incidence of grade 3 or 4 CINV. A total of 81 patients were identified. The most frequent chemotherapy regimens received in the study population were anthracycline- (48%) and carboplatin-based (28%). No acute vomiting and nausea rates in the study population were 75% and 44% respectively. The incidence of grade 3 CINV was 1%. Patients who received anthracycline-based regimens had a significantly higher incidence of acute emesis (P= 0.001) and nausea (P < 0.0001) when compared with patients who received non-anthracycline-based regimens. In this study, the use of 8 mg oral ondansetron plus 8 mg oral dexamethasone achieved control of acute emesis in 75% of all patients receiving MEC which is comparable to previously reported rates of 70-80%. The benefits of using oral pre-chemotherapy anti-emetics include reduction in the costs of drugs and nursing administration time.

Successful treatment of leflunomide-induced acute pneumonitis with cholestyramine wash-out therapy.

Drug-induced acute pneumonitis is a rare but potentially fatal adverse drug reaction. A high index of suspicion is needed for early diagnosis as it mimics community acquired pneumonia and interstitial lung disease that can occur in rheumatoid arthritis. We report a 32-year-old Chinese lady who suffered from leflunomide-induced pneumonitis and improved dramatically after receiving cholestyramine wash-out therapy. This case illustrates the need for clinical alertness to this potentially fatal complication. When in doubt, discontinuation of leflunomide and empirical wash-out therapy should be administered without delay.

Very long-term outcome of pure lupus membranous nephropathy treated with glucocorticoid and azathioprine.

The aim of this study is to report the long-term outcome of pure membranous lupus nephropathy (MLN) treated with glucocorticoid and azathioprine (AZA). A cohort of patients with SLE who had biopsy-confirmed pure MLN was treated initially with prednisone (0.8-1.0 mg/kg/day) and AZA (targeted to 2 mg/kg/day). Patients were followed for the following outcomes: remission rate at 12 months, renal flares, extra-renal flares and renal function deterioration. The cumulative risks of renal flares and renal function decline were studied by Kaplan-Meier analysis. Thirty-eight patients were studied (31 women; age 35.0 +/- 9.2 years; mean SLE duration 48.5 +/- 59 months; WHO Class Va 45%, Vb 55%). Twenty-two (58%) patients were nephrotic and four (11%) were hypertensive at presentation. All patients were treated with prednisolone (0.85 +/- 0.24 mg/kg/day) and AZA (1.72 +/- 0.43 mg/kg/day). At 12 months, 24 (67%) patients achieved complete response (CR), 8 (22%) had partial response (PR) and 4 (11%) were treatment resistant. After a follow-up of 12 +/- 5.8 years, 19 episodes of renal flares (15 proteinuric and 4 nephritic) occurred in 13 (34%) patients. The cumulative risks of renal flares at 5, 10 and 15 years were 19.4, 32.0 and 36.8%, respectively. Retreatment with an augmented dosage of prednisolone, +/- another immunosuppressive agent, resulted in CR and PR in 15 (79%) and 4 (21%) of these flare episodes, respectively. At last visit, three (8%) patients had doubling of serum creatinine, whereas six (16%) patients had decline of creatinine clearance by >/=30% (none developed end stage renal failure). Seven episodes of thromboembolic complications occurred in five (13%) patients and 11 episodes of infective complications (five major, six minor) were reported in seven (18%) patients. In the absence of co-existing proliferative lesions, MLN runs a relatively benign course with low risk of renal function deterioration. Treatment with high-dose prednisolone and AZA is effective, inexpensive and well-tolerated. Prolonged observation shows that one of three patients develop renal flares, which are often proteinuric and responsive to reinduction therapy.

Nodular regenerative hyperplasia of the liver associated with systemic lupus erythematosus: three cases.

Nodular regenerative hyperplasia of the liver, characterised by regenerative nodules distributed throughout the liver in the absence of fibrosis, is a rare but important complication of systemic lupus erythematosus. The main consequence of nodular regenerative hyperplasia of the liver is non-cirrhotic portal hypertension. This condition is probably underdiagnosed, as many of these patients may remain asymptomatic. Furthermore, nodular regenerative hyperplasia of the liver may be misdiagnosed as cirrhosis. We describe three female patients with nodular regenerative hyperplasia of the liver associated with systemic lupus erythematosus. All three patients have clinical manifestations of portal hypertension, and all were initially misdiagnosed as having cryptogenic cirrhosis.

Spontaneous intra-hepatic haemorrhage in a patient with fever of unknown origin.

Polyarteritis nodosa is a systemic necrotising vasculitis that affects the small- and medium-sized arteries. Multifocal aneurysmal formation in the renal, hepatic, and mesenteric vasculature is a hallmark of this condition, and spontaneous aneurysmal rupture may occur, resulting in life-threatening haemorrhage. We describe a 42-year-old man who initially presented with fever of unknown origin. A diagnosis could not be reached at that time despite extensive investigations. The fever subsided spontaneously after 8 weeks, and the patient remained well for 6 years until he was admitted again for evaluation of fever. During his hospital stay, he developed a spontaneous massive intra-hepatic haemorrhage resulting in hepatic rupture and a haemoperitoneum. The bleeding was controlled at emergency laparotomy. An abdominal angiography demonstrated multiple microaneurysms in the hepatic and mesenteric arterial vasculature. The clinical findings suggested polyarteritis nodosa, and the source of bleeding was probably a ruptured intra-hepatic artery aneurysm.