Underdiagnosis of Borderline oxacillin-resistant Staphylococcus aureus (BORSA) - Case series.

Borderline oxacillin-resistant Staphylococcus aureus (BORSA) are mecA-negative strains with oxacillin minimum inhibitor concentration (MIC) close to the resistance breakpoint of ≥ 4µg/mL. Instead of producing penicillin-binding protein with low affinity to methicillin (oxacillin) mediated by mecA gene as in methicillin-resistant S. aureus (MRSA), BORSA strains are characterised by the hyperproduction of ß-lactamase enzymes, thus able to break down methicillin. Common laboratory methods to detect MRSA such as cefoxitin disk diffusion alone may fail to detect methicillin resistance due to BORSA. We report five cases of BORSA blood-stream infections in a university teaching hospital. All isolates were found to be susceptible to cefoxitin using disk diffusion, resistant to oxacillin using automated MIC method, and did not harbour mecA gene. All patients were suscessfully treated with anti-MRSA antibiotics, and removal of primary sources were done if identified. A more cost-effective method for screening and diagnosis of BORSA is needed in addition to cefoxitin disk diffusion test, in order to monitor the spread, and to enable routine detection and treatment of this pathogen.

Time toxicity associated with early phase clinical trial participation.

BACKGROUND: Early phase cancer clinical trials (EPCTs) involve experimental drugs being used for the first time in humans. These studies are designed for dose determination and safety, and represent the most time intensive of all clinical trials for both clinicians and patients. We sought to quantify the amount of patient time consumed through EPCT participation. PATIENTS AND METHODS: A retrospective audit of patients treated in the EPCT unit at Liverpool Hospital, Sydney was carried out from 2013 to 2023. We defined 'time toxicity' (TT) as a composite measure where time-toxic days were considered days with any health care system contact, including clinic visits, infusions, procedures or blood work. RESULTS: A total of 219 patients across 36 EPCTs were included. The median age was 65 years (range 31-81 years). Patients spent a median of 29% (range 4%-100%) of their days in direct contact with the health care system during their study. Protocol-specified visits accounted for the greatest contribution to total TT in 101 (46%) patients. In 7% (n = 16) of patients, unscheduled visits due to either adverse events or cancer-related symptoms accounted for the greatest TT. TT reduced as patients completed additional cycles of treatment. Patients who completed >10 cycles spent 14% of their days interacting with health care systems compared with 35% for those who completed ≤2 cycles. No statistically significant difference in TT was noted between dose-expansion and dose-escalation studies or trials focusing on immune-oncology versus targeted therapy. CONCLUSIONS: Our study is the first to report TT in EPCTs with an extended follow-up. Clinicians should be aware of TT when discussing risks and benefits. TT also may not be the appropriate term when describing the time patients invest during EPCTs. Toxicity implies a negative impact, but for many patients, trial participation would be seen as positive. There should be efforts to streamline health care visits to limit TT in EPCTs.

Feasibility of virtual reality-delivered pain psychology therapy for cancer-related neuropathic pain: a pilot randomised controlled trial.

Virtual reality-delivered psychological therapies have recently been investigated as non-pharmacological management for acute and chronic pain. However, no virtual reality pain therapy software existed that met the needs of cancer patients with neuropathic pain. We created a bespoke virtual reality-delivered pain therapy software programme to help cancer patients manage neuropathic pain incorporating guided visualisation and progressive muscle relaxation techniques, whilst minimising the risk of cybersickness in this vulnerable patient population. This randomised controlled pilot study evaluated the feasibility, acceptability, recruitment rates and risk of cybersickness of this pain therapy software programme. Clinical outcomes including opioid consumption, pain severity, pain interference and global quality of life scores were secondary aims. Of 87 eligible cancer patients with neuropathic pain, 39 were recruited (47%), allocated to either the intervention (20 patients, virtual reality pain therapy software programme) or control (19 patients, viewing virtual reality videos). Four patients withdrew before the 3-month follow-up (all in the control group). Pre-existing dizziness (Spearman ρ 0.37, p = 0.02) and pre-existing nausea (Spearman ρ 0.81, p < 0.001) were significantly associated with risk of cybersickness in both groups. Patients in the intervention group reported less cybersickness, as well as tolerated and completed all therapy sessions. At 1- and 3-month follow-up, there were trends in the intervention group towards reductions in: oral morphine equivalent daily dose opioid consumption (-8 mg and -4 mg; vs. control: 0 mg and +15 mg respectively); modified Brief Pain Inventory pain severity (-0.4, -0.8; vs. control +0.4, -0.3); and pain interference (-0.9, -1.8; vs. control -0.2, -0.3) scores. The global quality of life subscale from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 was not significantly changed between groups at 1 and 3 months (intervention: -5, -8; vs. control: +3, +4). This newly created virtual reality-delivered pain therapy software programme was shown to be feasible and acceptable to cancer patients with neuropathic pain. These results will aid the design of a definitive multicentre randomised controlled trial.

Impact of sepsis education for healthcare professionals and students on learning and patient outcomes: a systematic review.

BACKGROUND: Sepsis is an important global healthcare problem that is a key challenge faced by healthcare professionals face worldwide. One key effort aimed at reducing the global burden of sepsis is educating healthcare professionals about early identification and management of sepsis. AIM: To provide a comprehensive evaluation of sepsis education among healthcare professionals and students. METHODS: Six databases (PubMed, CINAHL, Embase, MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus) were searched. We included studies that described and evaluated any form of education or training on sepsis delivered to healthcare professionals and students. Study outcomes were summarized according to the adapted Kirkpatrick model of training evaluation. RESULTS: Thirty-two studies were included in the review. The learning contents were reported to be in accordance with the Surviving Sepsis Campaign guidelines. Seven studies included the topic of interprofessional teamwork and communication in their sepsis education content. Most educational programmes were effective and reported positive effects on immediate knowledge outcomes. Interventions that were delivered through an active learning approach such as simulation and game-based learning generally produced greater gains than didactic teaching. Improvements in patient care processes and patient outcomes were associated with the concomitant existence or implementation of a hospital sepsis care bundle. CONCLUSION: Incorporating active learning strategies into sepsis education interventions has the potential to improve learners' long-term outcomes. In addition, sepsis education and a protocol-based sepsis care bundle act in synergy to augment greater improvements in care processes and patient benefits.

Prevalence, Risk Factors and Microbiological Profile of Orthopaedic Surgical Site Infection in North-Eastern Peninsular Malaysia.

Introduction: The devastating outcome of orthopaedic surgical site infections (SSI) are largely preventable if its risk factors, causative organisms and antimicrobial susceptibility patterns in the regional area are known. Materials and methods: We conducted a retrospective study to address the lack of epidemiological and microbiological data on orthopaedic SSI in Malaysia. All the 80 patients diagnosed and treated for microbiologically proven orthopaedic SSIs in a tertiary hospital in Malaysia from April 2015 to March 2019 were included in a 1:2 case control study. Results: The prevalence of SSI in clean and clean-contaminated surgeries was 1.243%, which is consistent with most of the studies worldwide, but is low compared to other studies done in Malaysia. The most common type of orthopaedics SSI were internal fixation infections (46.25%), superficial SSIs (25.2%) and Prosthetic joint infections (18.75%). Obesity and tobacco use were found to be significant risk factors of orthopaedic SSI. The most common perioperative prophylaxis used was IV cefuroxime. Majority of the cases (86.5%) received prolonged prophylactic antibiotics. The most common causative agent was Staphylococcus aureus (31.25%), followed by Pseudomonas aeruginosa (26.25%) and Enterobacter spp (7.5%). Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 20% of the S. aureus infections. Up to 19.4% of the Gram-negative organisms are multidrug resistant. The higher rate of isolation of organisms resistant to the prophylactic antibiotics being used may be related to the prolonged use of prophylactic antibiotics, which exerted selective pressure for the acquisition of resistant organisms. Conclusion: Despite its relatively low prevalence in our local institution and worldwide, the prevention of SSI in orthopaedic practice is crucial to avoid morbidity, mortality and high healthcare cost. This may be achieved by control of modifiable risk factors such as obesity and tobacco use, appropriate use of prophylactic antibiotics and implementation of good surgical and infection control practices.

Lipidomic Analysis of Archival Pathology Specimens Identifies Altered Lipid Signatures in Ovarian Clear Cell Carcinoma.

Cancer metabolism is associated with the enhanced lipogenesis required for rapid growth and proliferation. However, the magnitude of dysregulation of diverse lipid species still requires significant characterization, particularly in ovarian clear cell carcinoma (OCCC). Here, we have implemented a robust sample preparation workflow together with targeted LC-MS/MS to identify the lipidomic changes in formalin-fixed paraffin-embedded specimens from OCCC compared to tumor-free ovarian tissue. We quantitated 340 lipid species, representing 28 lipid classes. We observed differential regulation of diverse lipid species belonging to several glycerophospholipid classes and trihexosylceramide. A number of unsaturated lipid species were increased in OCCC, whereas saturated lipid species showed a decrease in OCCC compared to the controls. We also carried out total fatty acid analysis and observed an increase in the levels of several unsaturated fatty acids with a concomitant increase in the index of stearoyl-CoA desaturase (SCD) in OCCC. We confirmed the upregulation of SCD (the rate-limiting enzyme for the synthesis of monounsaturated fatty acids) by immunohistochemistry (IHC) assays. Hence, by carrying out a mass spectrometry analysis of archival tissue samples, we were able to provide insights into lipidomic alterations in OCCC.

The predictive and prognostic significance of liquid biopsy in advanced epidermal growth factor receptor-mutated non-small cell lung cancer: A prospective study.

OBJECTIVE: To determine the predictive and prognostic roles of three blood-based biomarkers: circulating tumour DNA (ctDNA), circulating tumour cells (CTC) and carcinoembryonic antigen (CEA), in patients with advanced epidermal growth factor receptor-mutated (EGFR+) lung cancer. MATERIALS AND METHODS: We recruited 28 patients with 103 serial blood samples. We performed mutational analyses for EGFR mutations using droplet digital PCR (ddPCR) on ctDNA. We evaluated the accuracy of EGFR mutation detection in ctDNA compared with tissue biopsy. We also quantified CTCs, ctDNA and CEA in serially collected blood samples, and evaluated the baseline and changes in these blood-based biomarkers with clinical outcomes. RESULTS: EGFR mutation detection in plasma was highly concordant as compared with tissue biopsy. Detectable baseline ctDNA was associated with higher disease burden (p < 0.01). Early disappearance of ctDNA at 4 weeks was associated with radiological response at 12 weeks of treatment (p = 0.01) and improved progression free survival (PFS) (HR 5.47, 95%CI 1.32-22.72, p = 0.02) and overall survival (OS) (HR 5.46, 95%CI 1.28-23.22, p = 0.02). A decrease in CTC count at 4 weeks was associated with improved PFS (HR 3.81, 95%CI 1.13-12.79, p = 0.03) but not OS. 85% of patients with radiological progression had a ctDNA rise compared with 22% of patients with stable disease (p=0.01). ctDNA rise was seen on average 170 days prior to radiological progression. There is a significant association between the rise of CEA level with radiological progression (p=0.001). CONCLUSION: Early change in ctDNA, CTC and CEA levels may be long-term predictors of treatment benefit and failure prior to availability of radiological response data.

A survey of first-year biology student opinions regarding live lectures and recorded lectures as learning tools.

A cohort of first-year biology students was surveyed regarding their opinions and viewing habits for live and recorded lectures. Most respondents (87%) attended live lectures as a rule (attenders), with 66% attending more than two-thirds of the lectures. In contrast, only 52% accessed recordings and only 13% viewed more than two-thirds of the available recordings. Respondents regarded lectures as efficient for information delivery (75%), and 89% enjoyed live lectures because they were useful for learning (89%), understanding coursework (94%), and keeping up with the subject (93%). Lecture enjoyment was driven less by entertainment (34%) or interaction with the lecturers (47%), although most students preferred an entertaining lecturer to a factual expert (72%). Exam marks were positively correlated with the number of lectures attended (P < 0.001) and negatively correlated with the number of recordings viewed (P < 0.05), although marks were similar for lecture attenders and nonattenders (P > 0.05). Lecture attenders mostly missed lectures to complete assessments during the same week (68%), whereas nonattenders were more likely to miss lectures due to outside commitments or preference for study from books or recorded lectures (P < 0.001). Recordings were used to replace missed lectures (64%), rather than for revision, and were viewed mostly alone (96%) in one sitting (65%). Only 22% of respondents agreed that some lectures could be replaced by recordings, but 59% agreed with having some videoconference lectures from experts on another campus. Overall, this cohort showed a clear preference for live lectures over recordings, with limited support for synchronous videoconference lectures.

Calf Compartment Syndrome associated with the Use of an Intra-osseous Line in an Adult Patient: A Case Report.

We present a case of a lower limb compartment syndrome associated with the use of an intra-osseous line inserted into the proximal tibia in an adult patient. An unconscious 59-year old male with multiple injuries presented to our Emergency Department after a road traffic accident. Bilateral proximal tibial intra osseous-lines were inserted due to poor venous access. After resuscitation his left leg was noted to be tense and swollen with absent pulses. Acute compartment syndrome was diagnosed both clinically and with compartment pressure measurement. Two incision fasciotomy on his left lower leg was performed. Intra osseous-lines in the proximal tibia are increasingly used in adult patients in the pre-hospital setting by paramedics and emergency physicians. Their use, along with the possible complications of these devices, such as the development of compartment syndrome or osteomyelitis leading to amputation, is well reported in the paediatric literature. To the best of our knowledge, there have not been any previous reports of complications in the adult patient. We present a case of lower leg compartment syndrome developing from the use of an intra-osseous line in the proximal tibia in an adult patient. With the increasing use of intra-osseous lines in adult patients, clinicians should be aware of the possibility of developing compartment syndrome which may lead to disability or amputation in severe cases.

Predictive and prognostic biomarkers for neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Locally advanced rectal cancer is regularly treated with trimodality therapy consisting of neoadjuvant chemoradiation, surgery and adjuvant chemotherapy. There is a need for biomarkers to assess treatment response, and aid in stratification of patient risk to adapt and personalise components of the therapy. Currently, pathological stage and tumour regression grade are used to assess response. Experimental markers include proteins involved in cell proliferation, apoptosis, angiogenesis, the epithelial to mesenchymal transition and microsatellite instability. As yet, no single marker is sufficiently robust to have clinical utility. Microarrays that screen a tumour for multiple promising candidate markers, gene expression and microRNA profiling will likely have higher yield and it is expected that a combination or panel of markers would prove most useful. Moving forward, utilising serial samples of circulating tumour cells or circulating nucleic acids can potentially allow us to demonstrate tumour heterogeneity, document mutational changes and subsequently measure treatment response.

Upregulated Polo-Like Kinase 1 Expression Correlates with Inferior Survival Outcomes in Rectal Cancer.

BACKGROUND: Human polo-like kinase 1 (PLK1) expression has been associated with inferior outcomes in colorectal cancer. Our aims were to analyse PLK1 in rectal cancer, and its association with clinicopathological variables, overall survival as well as tumour regression to neoadjuvant treatment. METHODS: PLK1 expression was quantified with immunohistochemistry in the centre and periphery (invasive front) of rectal cancers, as well as in the involved regional lymph nodes from 286 patients. Scores were based on staining intensity and percentage of positive cells, multiplied to give weighted scores from 1-12, dichotomised into low (0-5) or high (6-12). RESULTS: PLK1 scores in the tumour periphery were significantly different to adjacent normal mucosa. Survival analysis revealed that low PLK1 score in the tumour periphery had a hazard ratio of death of 0.59 in multivariate analysis. Other predictors of survival included age, tumour depth, metastatic status, vascular and perineural invasion and adjuvant chemotherapy. There was no statistically significant correlation between PLK1 score and histological tumour regression in the neoadjuvant cohort. CONCLUSION: Low PLK1 score was an independent predictor of superior overall survival, adjusting for multiple clinicopathological variables including treatment.

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.

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.

Front line nurses' experiences with deteriorating ward patients: a qualitative study.

BACKGROUND: Nurses in the general ward are faced with patients who are at high risk of clinical deterioration. Having the key role in performing routine vital signs monitoring, non-registered nurses such as enrolled nurses are the front line nurses who play a pivotal role in detecting and responding to the deteriorating ward patient. AIMS: (1) To explore the experience of enrolled nurses with deteriorating patients in pre-cardiac arrest situations and (2) to identify strategies to enhance their role in caring for deteriorating ward patients. METHOD: A qualitative study using critical incident technique was conducted. Fifteen enrolled nurses who had encountered deteriorating ward patients were interviewed. Data were analysed using content analysis. FINDINGS: Three themes emerged describing enrolled nurse's experience with deteriorating patients: recognizing deterioration, responding to deterioration and taking responsibility. Two themes, including educational development and modifying clinical processes, were strategies identified to enhance the ability of enrolled nurses in recognizing and managing deteriorating patients. CONCLUSION: The study highlighted a need to enhance the ability of front line nurses in recognizing and responding to patient deterioration through nursing education and modifications of clinical processes. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nursing education could focus on increasing the awareness of the importance of performing complete vital signs monitoring and undertaking accurate interpretation of vital signs. Strategies to improve clinical processes could include the need for registered nurses to provide supervision of enrolled nurses in the interpretation of vital signs readings and share the responsibility of performing vital signs monitoring.

Intra-articular correction of extra-articular tibial deformities with total knee arthroplasty.

INTRODUCTION: Extra-articular leg deformities may occur in the femur or tibia from mal-unions from previous trauma or metabolic bone disease. Secondary osteoarthritis at the knee occurs due to loss of mechanical alignment of the limb. At surgery for total knee arthroplasty, mechanical alignment can be restored intra-articularly with appropriate bone cuts and soft tissue balancing. PRESENTATION OF CASE: We describe 2 case studies with extra-articular tibial deformities (9° and 24° varus deformity) which were corrected with a 1 stage procedure of total knee arthroplasty with intra-articular deformity correction. DISCUSSION: Patient selection, pre-operative considerations and surgical technique are discussed with reference to the literature. CONCLUSION: One stage intra-articular correction of extra-articular deformity is suitable for mild degrees of varus deformities (<30°). Staged corrective procedures with larger deformities in the tibia or femur can be performed with extra-articular osteotomies on top of intra-articular corrections. Consideration should be given to the use of computer navigation when conventional jigs cannot be applied to deformed bone.

Can we predict sputum eosinophilia from clinical assessment in patients referred to an adult asthma clinic?

BACKGROUND: There is overwhelming evidence that asthma guidelines aimed at reducing airway inflammation are superior to those based on clinical symptoms alone. This involves targeting eosinophilic inflammation with inhaled corticosteroids. AIM: Because induced sputum is not readily available, our study set out to investigate whether the collective or singular use of routine asthma investigations can predict sputum eosinophilia. METHODS: Eighty patients underwent skin prick testing, blood tests (IgE, full blood count), spirometry, exhaled fraction nitric oxide (FeNO), PD15 to hypertonic saline, and induced sputum testing at first assessment. A predictive model for sputum eosinophilia (defined as ≥3% eosinophils) was sought using routinely available tests. RESULTS: Fifty-four subjects underwent both induced sputum and FeNO testing. Seventeen (30%) revealed eosinophilic inflammation, nine (16%) neutrophilic, four (7%) mixed granulocytic and 26 (46%) paucigranulocytic. Positive predictors for sputum eosinophilia included low forced expiratory volume in 1 s (FEV(1))% predicted, raised serum eosinophil, positive smoking history, Polynesian ethnicity and negative asthma family history. There was a non-statistically significant trend for FeNO predicting sputum eosinophilia. The best combination of predictors was low FEV(1)% predicted, raised serum eosinophil, positive smoking history and negative family history of asthma. CONCLUSION: This study demonstrates that the serum eosinophil count and FEV(1) combined with aspects of a clinical history may provide a simple and practical alternative to assessment of airway (sputum) eosinophilia in the clinical setting. A full blood count can be performed at a substantially lesser cost and with greater accessibility than induced sputum. We feel the time has come for the clinical utility of the serum eosinophil count to be revisited.

Effectiveness of frequency mapping on 28 nm device broken scan chain failures.

Frequency mapping methodology is an effective diagnostic tool for detection of manufacturing defects in scan chains. It analyses reflected laser modulations from toggling scan cells to localize defective scan path or scan cell. In this paper, we demonstrate experimentally that the use of solid immersion lens technology to enhance signal and spatial resolution is not a prerequisite for this technique up till 28 nm technology node. We present case studies to show the effectiveness of frequency mapping for detecting systematic and random broken scan chain failures on a 28 nm technology node test chip. We achieved 81% success rate in this methodology.

Reporting clinical trial information: colorectal cancer trials at Sydney Cancer Centre.

BACKGROUND: Clinical trial units are integral to the functioning of a medical oncology department with patient access to clinical trials an important component in patient care. There has been a paucity of potential key performance indicators in medical oncology and clinical trial information may be utilised for this purpose. The aim of this study was to record retrospectively and collate prospectively collected information regarding basic demographics, response rate, progression and survival plus grade 3 or 4 toxicity in patients enrolled in clinical trials for metastatic colorectal cancer at the Sydney Cancer Centre between 1999 and 2007. METHODS: Baseline patient demographics, clinical response, progression dates, grade 3 or 4 toxicities plus treatment-related fatalities were collected from individual clinical trials. Outcome measures were clinical response, progression-free survival and overall survival. RESULTS: There was a total of 14 trials undertaken during the defined period for patients with metastatic colorectal cancer. There was available information for 243 patient trials with sufficient information regarding response rates, toxicity, progression and survival. Tumour response rates ranged from 27% to 66% for first line chemotherapy trials and 0% to 20% for non-first line chemotherapy trials. The overall progression-free survival was 6.4 months and overall survival 14.0 months for all trials. There was one treatment-related fatality on clinical trial during this period. CONCLUSIONS: Results of our clinical database have been used here to illustrate the concept and value of reporting clinical trial information in medical oncology. Public reporting of such information may allow for comparisons between units and for quality improvement.

Ministry of Health clinical practice guidelines: schizophrenia.

The Ministry of Health (MOH) has updated the clinical practice guidelines on Schizophrenia to provide doctors and patients in Singapore with evidence-based treatment for schizophrenia. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Schizophrenia, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov. sg/mohcorp/publications.aspx?id=26138. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.