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.

Fragment-Based Identification of Ligands for Bromodomain-Containing Factor 3 of Trypanosoma cruzi.

The Trypanosoma cruzi (T. cruzi) parasite is the cause of Chagas disease, a neglected disease endemic in South America. The life cycle of the T. cruzi parasite is complex and includes transitions between distinct life stages. This change in phenotype (without a change in genotype) could be controlled by epigenetic regulation, and might involve the bromodomain-containing factors 1-5 (TcBDF1-5). However, little is known about the function of the TcBDF1-5. Here we describe a fragment-based approach to identify ligands for T. cruzi bromodomain-containing factor 3 (TcBDF3). We expressed a soluble construct of TcBDF3 in E. coli, and used this to develop a range of biophysical assays for this protein. Fragment screening identified 12 compounds that bind to the TcBDF3 bromodomain. On the basis of this screen, we developed functional ligands containing a fluorescence or 19F reporter group, and a photo-crosslinking probe for TcBDF3. These tool compounds will be invaluable in future studies on the function of TcBDF3 and will provide insight into the biology of T. cruzi.

COVID-19: Four Paediatric Cases in Malaysia.

OBJECTIVE: This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia BACKGROUND: COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease. CASES: In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy. DISCUSSION: There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.

Matching-adjusted indirect comparison of efficacy in patients with moderate-to-severe plaque psoriasis treated with ixekizumab vs. secukinumab.

BACKGROUND: Head-to-head randomized studies comparing ixekizumab and secukinumab in the treatment of psoriasis are not available. OBJECTIVES: To assess efficacy and quality of life using matching-adjusted indirect comparisons for treatment with ixekizumab vs. secukinumab. METHODS: Psoriasis Area and Severity Index (PASI) improvement of at least 75%, 90% and 100% and Dermatology Life Quality Index (DLQI) 0/1 response rates for approved dosages of ixekizumab (160 mg at Week 0, then 80 mg every two weeks for the first 12 weeks) and secukinumab (300 mg at Weeks 0, 1, 2, 3 and 4, then 300 mg every 4 weeks) treatment were compared using data from active (etanercept and ustekinumab) and placebo-controlled studies. Comparisons were made using the Bucher (BU) method and two modified versions of the Signorovitch (SG) method (SG total and SG separate). Subsequently, results based on active treatment common comparators were combined using generic inverse-variance meta-analysis. RESULTS: In the meta-analysis of studies with active comparators, PASI 90 response rates were 12·7% [95% confidence interval (CI) 5·5-19·8, P = 0·0005], 10·0% (95% CI 2·1-18·0, P = 0·01) and 11·2% (95% CI 3·2-19·1, P = 0·006) higher and PASI 100 response rates were 11·7% (95% CI 5·9-17·5, P < 0·001), 12·7% (95% CI 6·0-19·4, P < 0·001) and 13·1% (95% CI 6·3-19·9, P < 0·001) higher for ixekizumab compared with secukinumab using BU, SG total and SG separate methods. PASI 75 results were comparable when SG methods were used and favoured ixekizumab when the BU method was used. Week 12 DLQI 0/1 response rates did not differ significantly. CONCLUSIONS: Ixekizumab had higher PASI 90 and PASI 100 responses at week 12 compared with secukinumab using adjusted indirect comparisons.

Primary versus secondary tracheoesophageal puncture: systematic review and meta-analysis.

BACKGROUND: Tracheoesophageal puncture represents the 'gold standard' for voice restoration following laryngectomy. Tracheoesophageal puncture can be undertaken primarily during laryngectomy or in a separate secondary procedure. There is no current consensus on which approach is superior. The current evidence comparing primary and secondary tracheoesophageal puncture was assessed. METHODS: A systematic review and meta-analysis of articles comparing outcomes for primary and secondary tracheoesophageal puncture after laryngectomy were conducted. Outcome measures were: voice success, overall complication rate and pharyngocutaneous fistula rate. RESULTS: Eleven case series met the inclusion criteria, two prospective and nine retrospective. Meta-analysis did not demonstrate statistically significant differences in overall complication rate or voice outcomes, though it suggested a significantly increased risk of pharyngocutaneous fistula in primary compared to secondary tracheoesophageal puncture. CONCLUSION: Primary tracheoesophageal puncture is a safe and efficient approach for voice rehabilitation. However, secondary tracheoesophageal puncture should be preferred where there is a higher risk of pharyngocutaneous fistula.

Continuous dosing versus interrupted therapy with ixekizumab: an integrated analysis of two phase 3 trials in psoriasis.

BACKGROUND: Continuous treatment is recommended for patients with moderate-to-severe psoriasis; however, treatment may need to be interrupted in routine clinical practice. OBJECTIVE: To assess outcomes in patients continuously treated with ixekizumab versus those who interrupted therapy and were subsequently retreated with ixekizumab (IXE). METHODS: This analysis used data pooled from two phase 3 trials, UNCOVER-1 and UNCOVER-2. Patients were randomized to placebo (PBO), IXE every 4 (Q4W) or IXE every 2 weeks (Q2W) for 12 weeks. Patients with a static Physician's Global Assessment (sPGA) 0, 1 at Week 12 were rerandomized to IXEQ4W, IXE every 12 weeks (not presented) or PBO. We examined outcomes in patients who were continuously treated (IXEQ2W/IXEQ4W; IXEQ4W/IXEQ4W) or withdrawn (IXEQ2W/PBO; IXEQ4W/PBO), and in patients who were withdrawn and retreated with IXEQ4W for 24 weeks after disease relapse (sPGA ≥3). RESULTS: A total of 1226 treated patients achieved an sPGA 0, 1 at Week 12 and entered the maintenance phase; of these patients, 402 and 416 were rerandomized to PBO and IXEQ4W, respectively. Among patients interrupting treatment, 157 (82.2%) of IXEQ4W/PBO and 176 (83.4%) of IXEQ2W/PBO had an sPGA ≥3 by Week 60; median time to relapse was approximately 20 weeks irrespective of induction dose. At Week 60, continuously treated patients maintained high levels of PASI and sPGA responses (90.0% PASI 75 IXEQ2W/IXEQ4W; 81.9% sPGA 0, 1 IXEQ2W/IXEQ4W, non-responder imputation). After 24 weeks of retreatment with IXEQ4W (IXEQ2W/PBO/IXEQ4W and IXEQ4W/PBO/IXEQ4W), 87.0% (107 of 123) and 95.1% (97 of 102) (observed), respectively, of patients recaptured PASI 75 and 70.7% (104 of 147) and 82.3% (107 of 130) (observed) recaptured an sPGA 0, 1. Overall, adverse events in continuously treated and retreated patients were comparable. CONCLUSION: High levels of response were sustained with continuous ixekizumab treatment through 60 weeks. Most patients who were withdrawn experienced disease relapse, and most of those patients recaptured response after 24 weeks of retreatment.

Rational Drug Discovery of HCV Helicase Inhibitor: Improved Docking Accuracy with Multiple Seeding in AutoDock Vina and In Situ Minimization.

BACKGROUND: Hepatitis C is a significant cause for end-stage liver diseases and liver transplantation which affects approximately 3% of the global populations. Despite the current several direct antiviral agents in the treatment of Hepatitis C, the standard treatment for HCV infection is accompanied by several drawbacks, such as adverse side effects, high pricing of medications and the rapid emerging rate of resistant HCV variants. OBJECTIVES: To discover potential inhibitors for HCV helicase through an optimized in silico approach. METHODS: In this study, a homology model (HCV Genotype 3 helicase) was used as the target and screened through a benzopyran-based virtual library. Multiple-seedings of AutoDock Vina and in situ minimization were to account for the non-deterministic nature of AutoDock Vina search algorithm and binding site flexibility, respectively. ADME/T and interaction analyses were also done on the top hits via FAFDRUG3 web server and Discovery Studio 4.5. RESULTS: This study involved the development of an improved flow for virtual screening via implemention of multiple-seeding screening approach and in situ minimization. With the new docking protocol, the redocked standards have shown better RMSD value in reference to their native conformations. Ten benzopyran-like compounds with satisfactory physicochemical properties were discovered to be potential inhibitors of HCV helicase. ZINC38649350 was identified as the most potential inhibitor. CONCLUSION: Ten potential HCV helicase inhibitors were discovered via a new docking optimization protocol with better docking accuracy. These findings could contribute to the discovery of novel HCV antivirals and serve as an alternative approach of in silico rational drug discovery.

Palliative and supportive care in head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It provides recommendations on the assessments and interventions for this group of patients receiving palliative and supportive care. Recommendations • Palliative and supportive care must be multidisciplinary. (G) • All core team members should have training in advanced communication skills. (G) • Palliative surgery should be considered in selected cases. (R) • Hypofractionated or short course radiotherapy should be considered for local pain control and for painful bony metastases. (R) • All palliative patients should have a functional endoscopic evaluation of swallowing (FEES) assessment of swallow to assess for risk of aspiration. (G) • Pain relief should be based on the World Health Organization pain ladder. (R) • Specialist pain management service involvement should be considered early for those with refractory pain. (G) • Constipation should be avoided by the judicious use of prophylactic laxatives and the correction of systemic causes such as dehydration, hypercalcaemia and hypothyroidism. (G) • Organic causes of confusion should be identified and corrected where appropriate, failing this, treatment with benzodiazepines or antipsychotics should be considered. (G) • Patients with symptoms suggestive of spinal metastases or metastatic cord compression must be managed in accordance with the National Institute for Health and Care Excellence guidance. (R) • Cardiopulmonary resuscitation is inappropriate in the palliative dying patient. (R) • 'Do not attempt cardiopulmonary resuscitation' orders should be completed and discussed with the patient and/or the family unless good reasons exist not to do so where appropriate. This is absolutely necessary when a patient's care is to be managed at home. (G).

Organisation and provision of head and neck cancer surgical services in the United Kingdom: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the surgical specialty associations involved in the care of head and neck cancer patients in the UK. This paper summarises the current state of play in the organisation and provision of head and neck cancer surgical services in the UK.

Emergency presentations of head and neck cancer: a modern perspective.

BACKGROUND: Head and neck cancer emergency presentations are uncommon but persistent. However, there is little published literature on this aspect of cancer and patient demographics. This study aimed to assess the incidence, patient profile, tumour site and stage of emergency cancer presentations in our region. METHOD: Retrospective review of regional cancer database over a five-year period. RESULTS: Emergency presentations accounted for 7 per cent of all cases. There was no difference in patient age and risk factors between the emergency and non-emergency presentations. The emergency presentation group showed a greater proportion of female patients compared to the non-emergency presentation group (30 vs 15 per cent). In all emergency presentations, the cancer was at advanced stages. Oropharyngeal cancer was the commonest emergency presentation of cancer, but the third commonest in the non-emergency group. CONCLUSION: Emergency presentations are increasing annually. Female patients and oropharyngeal cancer showed greater representation compared to male patients and laryngeal cancer.

Lung ultrasound training: curriculum implementation and learning trajectory among respiratory therapists.

PURPOSE: Guidelines recommend teaching of lung ultrasound for critical care, though little information exists on how much training is required for independent practice, especially for non-physician trainees. We thus aimed to elucidate a threshold number of cases above which competency for independent practice may be attained for respiratory therapists (RTs). METHODS: We conducted a prospective audit of lung ultrasound training between July 2014 and April 2015 in our 20-bed medical intensive care unit. Following theoretical instruction and self-learning, trainees acquired images from 12 lung zones under direct supervision and classified images into six patterns. Assistance during image acquisition and correct interpretation of ultrasound images were recorded. RESULTS: Eleven ultrasound-naïve RTs scanned an average of 15 patients each (170 patients in total). Among supervisor-adjudicated lung ultrasound findings, 35.5% were abnormal. Blinded verification of the adjudicated findings was done for the first 92 patients (1104 images), with an agreement of 95.4%. As RTs scanned more patients, there was a significant decrease in the proportion of images requiring supervisor assistance (Cuzick's P < 0.001), and a significant increase in the proportion of correctly identified images (Cuzick's P = 0.008). After trainees performed at least ten scans, less than 2% of images required assistance with acquisition and less than 5% were wrongly interpreted. CONCLUSIONS: Our training method allowed RTs to independently perform lung ultrasound after at least ten directly supervised scans. Given that RTs are likely to have less ultrasound knowledge and less clinical know-how compared to physicians, we believe that the same threshold number of scans may be also safely applied to the latter.

Evidence for Endovascular Simulation Training: A Systematic Review.

BACKGROUND: Simulation training in endovascular surgery provides opportunities for trainees to practice and learn from non-patient based experience. Several types of endovascular simulators are available commercially. Previous studies on endovascular simulation training can be categorized into trials in which only a simulator was used when measuring performance metrics or "trials within simulation"; patient specific procedure rehearsals; and randomized, controlled trials (RCTs) or translational studies. OBJECTIVES: To examine whether endovascular simulation training can improve surgeon techniques and patient outcomes in real clinical settings. METHODS: A literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. All searches were done via PubMed and Embase. Review articles, and papers that were not related to endovascular surgery and not within the scope of interest were excluded. References of review articles were further screened according to the exclusion criteria. RESULTS: In total, 909 records were identified and 290 duplicates were removed. Thirty-one were included in the qualitative analysis. Twenty-three were trials within simulation and most of them found statistically significant improvements in procedure time, fluoroscopy time, and contrast volume. Five were patient specific procedure rehearsals and showed that simulation significantly affected the fluoroscopy angle and improved performance metrics. Three were RCTs and revealed mainly positive results on a Global Rating Scale and procedure specific rating scale. CONCLUSIONS: Contemporary evidence shows that performance metrics within endovascular simulations improve with simulation training. Successful translation to in vivo situations is observed in patient specific procedure rehearsals and RCTs on real procedures. However, there is no level I evidence to show that predictive validity of simulation can definitively improve patient outcomes. Current literature supports the idea that there is a beneficial role of simulation in endovascular training. Future studies are needed to confirm the efficacy of simulation in endovascular surgical training and to see if simulation is superior to traditional training in the operating theatre.

Evidenced-based management of haemoptysis by otolaryngologists.

BACKGROUND: Haemoptysis is an uncommon presenting symptom to the ENT clinic and ward, but has potentially sinister aetiology. This article aims to provide a systematic and evidence-based method of managing patients with haemoptysis. METHODS: The data in this article are based on a literature search performed using PubMed in August 2013. The keywords used included 'haemoptysis' in combination with 'otolaryngology', 'ENT', 'head & neck', 'diagnosis', 'management', 'investigations' and 'treatment'. RESULTS: The majority of published literature on the subject is level IV evidence. However, this can guide ENT specialists in assessing, investigating and managing presentations of haemoptysis. CONCLUSION: Understanding the different causes of haemoptysis is important for the otolaryngologist. The main concern is the detection of a malignant lesion in the upper aerodigestive tract or tracheobronchial tree. A thorough history and systematic examination can aid diagnosis.

Enhanced recovery programmes in head and neck surgery: systematic review.

OBJECTIVE: To review the literature on enhanced recovery programmes in head and neck surgery. METHOD: A systematic review was performed in May 2013. RESULTS: Thirteen articles discussing enhanced recovery after laryngectomy, neck dissection, major ablative surgery and microvascular reconstruction were identified. Articles on general pre-operative preparation and post-operative care were also reviewed. CONCLUSION: Considerable evidence is available supporting enhanced recovery in head and neck surgery that could be of benefit to patients and which surgeons should be aware of.

Experimental heart failure modelled by the cardiomyocyte-specific loss of an epigenome modifier, DNMT3B.

Differential DNA methylation exists in the epigenome of end-stage failing human hearts but whether it contributes to disease progression is presently unknown. Here, we report that cardiac specific deletion of Dnmt3b, the predominant DNA methyltransferase in adult mouse hearts, leads to an accelerated progression to severe systolic insufficiency and myocardial thinning without a preceding hypertrophic response. This was accompanied by widespread myocardial interstitial fibrosis and myo-sarcomeric disarray. By targeted candidate gene quantitative RT-PCR, we discovered an over-activity of cryptic splice sites in the sarcomeric gene Myh7, resulting in a transcript with 8 exons missing. Moreover, a region of differential methylation overlies the splice site locus in the hearts of the cardiac-specific conditional knockout (CKO) mice. Although abundant and complex forms of alternative splice variants have been reported in diseased hearts and the contribution of each remains to be understood in further detail, our results demonstrate for the first time that a link may exist between alternative splicing and the cardiac epigenome. In particular, this gives the novel evidence whereby the loss of an epigenome modifier promotes the development and progression of heart disease.

The case for mistletoe in the treatment of laryngeal cancer.

INTRODUCTION: Complementary and alternative medicine usage, though rising, remains largely devoid of a sound scientific basis; however, there is increasing evidence to support its use in cancer therapy. AIM: To present the case of a patient with laryngeal carcinoma who made a full recovery following mistletoe therapy, despite failing to respond to chemoradiotherapy and salvage laryngectomy. DESIGN: Case report with relevant literature review. RESULTS: The patient developed extensive, unresectable stomal recurrence, and it was deemed appropriate to supply palliative care only. Following treatment with mistletoe extract injections after palliative radiotherapy, he recovered fully and was eventually discharged from care. CONCLUSION: The benefit of mistletoe in laryngeal cancer treatment requires further investigation, and might be considered in selected patients, as an adjunct or when other conventional therapies have failed.

Trans-oral resection of large parapharyngeal space tumours.

The aim of this study is to describe minimally invasive trans-oral approach for resection of parapharyngeal space (PPS) tumours and to demonstrate surgical technique, resection, repair and outcomes. Five cases were prospectively included in the study. The data collected include age, sex, site, size, pathology, radiological investigations, surgical excision, complications and outcomes. Three females and two male patients underwent trans-oral resection of PPS tumours sized 4-8 cm. The pathology included two deep lobe parotid tumours, one schwannoma, one hibernoma and one primary adenocarcinoma arising form the minor salivary gland. All tumours were resected completely without any technical difficulty. The healing was quick and by primary intention. Patients resumed oral feeding on recovery from general anaesthesia and did not require any significant analgesia beyond the first 2 days. Patient with adenocarcinoma received postoperative radiotherapy and remained disease-free during 4 years post-treatment. No recurrences were observed in patients with benign tumours. No neurovascular injury occurred during surgery and no secondary bleeding was observed. We have demonstrated successful and safe execution of trans-oral resection of large PPS tumours. There were no intra and post-operative complications and there has been no recurrence during the follow-up period. In our experience, it appears to be efficient, safe and minimally invasive compared to the established techniques.

Risk factors for hospital and long-term mortality of critically ill elderly patients admitted to an intensive care unit.

BACKGROUND: Data on long-term outcomes of elderly (≥65 years) patients in ICU are sparse. MATERIALS AND METHODS: Adult patients (n = 1563, 45.4% elderly) admitted over 28 months were analyzed by competing risks regression model to determine independent factors related to in-hospital and long-term mortality. RESULTS: 414 (26.5%) and 337 (21.6%) patients died in-hospital and during the 52 months following discharge, respectively; the elderly group had higher mortality during both periods. After discharge, elderly patients had 2.3 times higher mortality compared to the general population of the same age-group. In-hospital mortality was independently associated with mechanical ventilation (subdistribution hazard ratio (SHR) 2.74), vasopressors (SHR 2.56), neurological disease (SHR 1.77), and Mortality Prediction Model II score (SHR 1.01) regardless of age and with malignancy (SHR, hematological 3.65, nonhematological 3.4) and prior renal replacement therapy (RRT, SHR 2.21) only in the elderly. Long-term mortality was associated with low hemoglobin concentration (SHR 0.94), airway disease (SHR 2.23), and malignancy (SHR hematological 1.11, nonhematological 2.31) regardless of age and with comorbidities especially among the nonelderly. CONCLUSIONS: Following discharge, elderly ICU patients have higher mortality compared to the nonelderly and general population. In the elderly group, prior RRT and malignancy contribute additionally to in-hospital mortality risk. In the long-term, comorbidities (age-related), anemia, airway disease, and malignancy were significantly associated with mortality.