Subcutaneous fast-acting insulin analogues, alone or in combination with long-acting insulin, versus intravenous regular insulin infusion in patients with diabetic ketoacidosis: protocol for an updated systematic review and meta-analysis of randomised trials.

INTRODUCTION: Diabetic ketoacidosis (DKA) is traditionally managed using intravenous regular insulin infusion (RII) in intensive care unit (ICU)/high dependency unit (HDU). Subcutaneous fast-acting insulin analogues (FAIAs) may help to manage DKA outside ICU/HDU. Furthermore, combining subcutaneous long-acting insulin (LAI) with subcutaneous FAIAs may accelerate ketoacidosis resolution. The latest (2016) Cochrane review was inconclusive regarding subcutaneous FAIAs versus intravenous RII in DKA. It was limited by small sample sizes, unclear risk of bias (RoB) in primary trials and did not examine subcutaneous FAIAs with subcutaneous LAI versus intravenous RII in DKA. We report the protocol for an updated meta-analysis on the safety and benefits of subcutaneous FAIAs with/without subcutaneous LAI versus intravenous RII in DKA. METHODS AND ANALYSIS: We will search Medline, Embase, CINAHL and Cochrane Library, from inception until December 2022, without language restrictions, for randomised trials on subcutaneous FAIAs with/without subcutaneous LAI versus intravenous RII in DKA. We also search ClinicalTrials.gov, ClinicalTrialsRegister.eu and reference lists of included trials. Primary outcomes include all-cause in-hospital mortality, time to DKA resolution, in-hospital DKA recurrence and hospital readmission for DKA post-discharge. Secondary outcomes include resource utilisation and patient satisfaction. Safety outcomes include important complications of DKA and insulin. Reviewers will extract data, assess overall RoB and quality of evidence using Grading of Recommendations, Assessment, Development and Evaluation. We will assess statistical heterogeneity by visually inspecting forest plots and the I2 statistic. We will synthesise data using the random-effects model. Predefined subgroup analyses are: mild versus moderate versus severe DKA; age <20 vs ≥20 years; pregnant versus non-pregnant; infective versus non-infective DKA precipitating cause; subcutaneous FAIAs alone versus subcutaneous FAIAs and subcutaneous LAI; and high versus low overall RoB. We will also perform trial sequential analysis for primary outcomes. ETHICS AND DISSEMINATION: Ethics board approval is not required. Results will be disseminated through publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022369518.

Assessment of changes in gaze patterns during training in point-of-care ultrasound.

BACKGROUND: Point-of-care ultrasound (POCUS) is a core skill in emergency medicine (EM), however, there is a lack of objective competency measures. Eye-tracking technology is a potentially useful assessment tool, as gaze patterns can reliably discriminate between experts and novices across medical specialties. We aim to determine if gaze metrics change in an independent and predictable manner during ultrasound training. METHODS: A convenience sample of first-year residents from a single academic emergency department was recruited. Participants interpreted 16 ultrasound videos of the focused assessment with sonography for trauma (FAST) scan while their gaze patterns were recorded using a commercially available eye-tracking device. The intervention group then completed an introductory ultrasound course whereas the control group received no additional education. The gaze assessment was subsequently repeated. The primary outcome was total gaze duration on the area of interest (AOI). Secondary outcomes included time to fixation, mean duration of first fixation and mean number of fixations on the AOI. RESULTS: 10 EM residents in the intervention group and 10 non-EM residents in the control group completed the study. After training, there was an 8.8 s increase in the total gaze time on the AOI in the intervention group compared to a 4.0 s decrease in the control group (p = .03). EM residents were also 3.8 s quicker to fixate on the AOI whereas the control group became 2.5 s slower (p = .04). There were no significant interactions on the number of fixations (0.43 vs. 0.18, p = .65) or duration of first fixation on the AOI (0.02 s vs. 0.06 s, p = .63). CONCLUSIONS: There are significant and quantifiable changes in gaze metrics, which occur with incremental learning after an ultrasound course. Further research is needed to validate the serial use of eye-tracking technology in following a learner's progress toward competency in point-of-care ultrasound image interpretation.

Rare case of Torsades de Pointes in severe hypothyroidism: literature review and challenges in management.

BACKGROUND: Hypothyroidism can manifest as several important cardiac abnormalities. There are few reports of ventricular dysrhythmias (VDs) in hypothyroidism. We described a rare case of VDs in severe hypothyroidism and reviewed the literature behind its management. CASE PRESENTATION: A 67-year-old gentleman, with poor compliance to treatment for Hashimoto's thyroiditis, presented with palpitations to the Emergency Department. He had runs of non-sustained ventricular tachycardia (NSVT). He was treated with intravenous (IV) amiodarone and admitted to the intensive care unit for observation. He then developed recurrent Torsades de Pointes (Tdp) despite treatment with several anti-arhythmics. He required electrical cardioversion and eventual transvenous overdrive pacing (OP). VT recurred while he was on OP. VT resolved and he was weaned off OP only after adequate thyroid hormone replacement. CONCLUSIONS: VDs, including NSVT, Tdp, and VT, are rare and potentially lethal in hypothyroidism. Our case demonstrates important challenges in the management of severe hypothyroidism. Here, VDs are often refractory to treatment with drugs and electrical means. The choice(s) of anti-arrhthymics requires careful consideration and can be difficult before thyroid function tests are known. Amiodarone use should be cautioned as it is associated with thyroid dysfunction and QT interval prolongation. There is no literature to guide thyroid hormone replacement in this disease. Aggressive replacement is associated with adverse cardiovascular effects. Our case showed a fine balance between the risk of rapid thyroid hormone replacement and the urgency to terminate VDs. Its administration should be carefully monitored amidst bridging strategies like electrical cardioversion and OP to manage life-threatening VDs.

Benefits and safety of transdermal glyceryl trinitrate in acute stroke: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Transdermal glyceryl trinitrate (GTN) has potential beneficial properties in acute stroke including intracerebral hemorrhage (ICH) and possible clinical benefits suggested in ultra-early stroke (≤6 h). Our meta-analysis updated the evidence on its safety and benefits in acute stroke. METHODS: We searched major electronic databases for randomized trials comparing transdermal GTN versus placebo/control in acute stroke. Primary outcomes were mortality, 90-day modified Rankin Scale (mRS), and blood pressure (BP) effects. Secondary outcomes included early, late, resource utilization, and surrogate outcomes. Safety outcomes were adverse events. Reviewers identified studies, extracted data, and assessed risk of bias (RoB) using a modified Cochrane RoB instrument and quality of evidence (QoE) using GRADE. We also performed a priori subgroup and trial sequential analyses (TSA) on primary outcomes. These subgroup analyses were ICH versus ischemic stroke, minor (NIHSS ≤5) versus major (NIHSS >5) ischemic stroke, ischemic stroke with versus without thrombolysis, prehospital versus non prehospital settings, time from stroke to randomization ≤6 h versus >6 h, and high versus low overall RoB studies. RESULTS: Seven eligible primary trials enrolled 5363 patients. GTN reduced BP (mean difference [MD] = -4.74 mm Hg, 95% confidence interval [CI] = -6.03 to -3.45 mm Hg] and diastolic BP (MD = -2.94 mm Hg, 95% CI = -3.74 to -2.13 mm Hg) 24 h posttreatment but did not affect 4- to 10-day mortality (relative risk [RR] = 1.11, 95% CI = 0.82 to 1.49), 90-day mortality (RR = 0.96, 95% CI = 0.77 to 1.19), and 90-day mRS >2 (RR = 0.98, 95% CI = 0.93 to 1.03) compared to control/placebo. The QoE was high for primary outcomes with no subgroup effects detected. GTN did not affect secondary outcomes and increased risk of headache and hypotension. TSA generally supported our conclusions regarding primary outcomes. CONCLUSIONS: Transdermal GTN reduces BP in acute stroke but does not alter clinical outcomes even in ultra-early stroke (≤6 h).

A potential microbiological approach to the evaluation of earthquake-induced soil liquefaction.

Earthquakes occur thousands of times every day around the world. They are naturally destructive seismic events and often result in soil liquefaction. Soil microbiota plays a vital role in soil environments and may serve as an effective indicator to assess soil liquefaction after earthquakes. This study aimed to detect the microbial community abundance and composition in soil samples of different depths. Soil samples were collected in Southern Taiwan immediately after the 2010 earthquake. Their physical characteristics were determined, and their microbial communities were analyzed through 16S amplicon sequencing. The results revealed that Nitrospirae phylum dominated in the liquefied layer. In particular, the genus HB118, dominant in the liquefied layer, was not detected at other soil depths or in the expelled liquefied soil. This finding not only provides valuable insights into changes in microbial community composition at different soil depths after earthquakes but also suggests a useful indicator for monitoring liquefied soil.

Excellent Outcome in Living Donor Liver Transplantation: Treating Patients With Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a fatal condition, and liver transplantation (LT) is a vital option for these patients. However, the result of living donor LT (LDLT) for ACLF is not well investigated. This study investigated the outcomes of LDLT in patients with ACLF compared with patients without ACLF. This was a single-center, retrospective, matched case-control study. From July 2002 to March 2017, a total of 112 patients with ACLF who underwent LDLT were enrolled according to the consensus of the Asian Pacific Association for the Study of the Liver. A total of 224 patients were selected for control comparison (non-ACLF) with demographic factors (sex, age, and body mass index) matched (1:2). Patients with ACLF were stratified into ACLF 1, 2, and 3 categories according to the number of organ failures based on the Chronic Liver Failure-Sequential Organ Failure Assessment score. Survival and surgical outcomes after LDLT were analyzed. The Model for End-Stage Liver Disease and Child-Turcotte-Pugh scores in the ACLF group were significantly higher than those in the non-ACLF group (P < 0.001). The 90-day, 3-year, and 5-year survival rates in the ACLF and non-ACLF groups were 97.3%, 95.5%, 92.9%, respectively, and 96.9%, 94.2%, and 91.1%, respectively (P = 0.58). There was more intraoperative blood loss in the ACLF group than in the non-ACLF group (P < 0.001). The other postoperative complications were not significantly different between the groups. A total of 20 patients (17.9%) in the ACLF group presented with 3 or more organ system dysfunctions (ACLF 3), and the 90-day, 3-year, and 5-year survival rates were comparable with those of ACLF 1 and ACLF 2 (P = 0.25). In carefully selected patients, LDLT gives excellent outcomes in patients with ACLF regardless of the number of organs involved. Comprehensive perioperative care and timely transplantation play crucial roles in saving the lives of patients with ACLF.

Exploring Eye-tracking Technology as an Assessment Tool for Point-of-care Ultrasound Training.

OBJECTIVES: Eye-tracking technology has emerged as a potentially useful learner assessment tool in several medical specialties. In the fields of general surgery and anesthesiology, it has been shown to reliably differentiate between different levels of expertise in procedural skills. In the field of radiology, it has been shown to be a valid assessment tool for diagnostic test interpretation. Current methods of competency assessment in point-of-care ultrasound (POCUS) remain a challenge, because they require significant direct observation time by an instructor. The purpose of this study was to determine if eye-tracking technology can accurately distinguish between novice and experts in the interpretation of POCUS clips, specifically of the focused assessment using sonography in trauma (FAST) scan. METHODS: A convenience sample of medical students, residents, and emergency physicians from a single academic emergency department were invited to participate. Participants included both novices and experts in POCUS. Each participant completed a baseline questionnaire and viewed 16 video clips of a FAST ultrasound examination while their gaze patterns were recorded by a commercially available eye-tracking device. The primary outcome was total gaze time on the area of interest (AOI). Secondary outcomes included total time to fixation, mean number of fixations, and mean duration of first fixation on the AOI. RESULTS: Fifteen novices and 15 experts completed this study. For total gaze time on the AOI, experts fixated their gaze significantly longer than novices (75.8 ± 16.2 seconds vs. 56.6 ± 12.8 seconds, p = 0.001). Similarly, experts were significantly faster to fixate on the AOI and had a higher fixation count on the AOI (8.5 ± 4.0 seconds vs. 15.1 ± 6.8 seconds, p = 0.003; and 170 ± 30 vs. 143 ± 28 seconds, p = 0.016). There were no differences on the mean duration of first fixation on the AOI (0.42 ± 0.12 seconds vs. 0.39 ± 0.09 seconds, p = 0.467). CONCLUSION: Eye-tracking technology shows the potential to differentiate between experts and novices by their gaze patterns on video clips of FAST examinations. The total gaze time on the AOI may be a useful metric to help in the assessment of competency in POCUS image interpretation. In addition, the evaluation of gaze patterns may help educators identify causes of interpretation errors. Future studies are needed to further validate these metrics in a larger cohort.

Benefits and safety of transdermal glyceryl trinitrate in acute stroke: a systematic review and meta-analysis of randomised trials (protocol).

INTRODUCTION: High blood pressure (BP) in acute stroke has adverse outcomes. Transdermal glyceryl trinitrate (GTN) has beneficial properties in controlling BP. The 2016 meta-analysis and 2017 Cochrane review showed that transdermal GTN was beneficial in a small patient subgroup with stroke onset ≤6 hours. Larger studies focusing on this patient subgroup have since been conducted. We report the protocol for an updated systematic review and meta-analysis on the safety and benefits of transdermal GTN in acute stroke. METHODS AND ANALYSIS: We will search Medline, Pubmed, Embase, CINAHL and Cochrane Library from inception until June 2020 for randomised trials that report the efficacy and safety of transdermal GTN versus placebo/control therapy among adult patients with acute stroke. Primary outcomes include in-hospital mortality, BP lowering and late functional status. Secondary outcomes include early, late, resource utilisation and surrogate outcomes. Safety outcomes include reported adverse events. Reviewers will first screen titles and abstracts, and then full texts, to identify eligible studies. Independently and in duplicate, they will extract data, assess risk of bias (RoB) using a modified Cochrane RoB tool and quality of evidence using Grading of Recommendations, Assessment, Development and Evaluation. Disagreement will be resolved by discussion and consultation with an external reviewer if necessary. Using a random-effects model, we will report effect sizes using relative risks and 95% CIs. We will perform predefined subgroup analyses: intracerebral haemorrhage versus ischaemic stroke; minor (NIHSS (National Institutes of Health Stroke Scale) ≤five) versus major (NIHSS >five) ischaemic stroke; ischaemic stroke with versus without thrombolysis; prehospital versus non-prehospital settings; time from stroke to randomisation ≤6 versus >6 hours and high versus low overall RoB studies. We will also perform trial sequential analysis for the primary outcomes. ETHICS AND DISSEMINATION: Ethics board approval is unnecessary. PROSPERO registration has been obtained. The results will be disseminated through publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020173093.

Comparative analysis of the drug-drug interaction between immunosuppressants, safety and efficacy of rifabutin from rifampicin-based Anti-TB treatment in living donor liver transplant recipients with active tuberculosis.

BACKGROUND: The Interaction between anti-tuberculous and immunosuppressive drugs which may increase the risk of graft rejections is a major challenge in managing transplant recipients with tuberculosis (TB). Instead of rifampicin (RFM), most guidelines recommended the use of rifabutin (RFB) because of its reduced capacity to induce immunosuppressant metabolism while maintaining the same efficacy as RFM against TB. However, there has been no available data directly comparing the outcome of RFB from RFM-based anti-TB regimens in liver transplant patients with TB. This study aimed to compare the effects of RFB from RFM-based treatment in terms of the drug interaction with immunosuppressants, as well as the safety, efficacy and clinical outcomes of living donor liver transplant (LDLT) recipients with active TB. METHODS: A retrospective study was conducted on all adult LDLT recipients diagnosed with active TB from June 1994 to May 2016 that had concurrently and continuously received either RFB or RFM-based treatment and immunosuppressants. RESULTS: Twenty-two patients were included. Twelve (55%) patients were in the RFM group. Ten (45%) patients were in the RFB group. RFB group showed a lesser rate of immunosuppressant trough level reduction (20% vs 50%, p = 0.009) during TB treatment. There was no TB recurrence and no significant change in platelet or leukocyte count in either group. Acute cellular rejection (ACR), rate of TB-treatment completion and overall survival, rates were excellent and statistically similar in both groups. CONCLUSION: The use of RFB in LDLT recipients with active TB, had a lesser drug interaction than when RFM was used. However, RFB did not significantly reduced the rate of ACR. RFB and RFM are both effective and safe to use in LDLT recipients with active TB.

Clinical Outcomes of Tuberculosis in Recipients After Living Donor Liver Transplantation.

BACKGROUND This study aimed to determine clinical outcomes using various drugs during tuberculosis (TB) treatment among living donor liver transplant (LDLT) recipients with TB and to assess the impact of performing LDLT in patients with active TB at the time of LDLT. MATERIAL AND METHODS Out of 1313 LDLT performed from June 1994 to May 2016, 26 (2%) adult patients diagnosed with active TB were included in this study. Active TB was diagnosed using either TB culture, PCR, and/or tissue biopsy. RESULTS The median age was 56 years and the male/female ratio was 1.6: 1. Most patients had pulmonary TB (69.2%), followed by extrapulmonary and disseminated TB (15.4% each). Fourteen (53.8%) patients underwent LDLT even with the presence of active TB. All patients concurrently received anti-TB [Rifampicin-based: 13 (50%); Rifabutin-based: 12 (46.2%); INH-based: 1 (3.8%)] and immunosuppressive drugs [Tacrolimus-based: 6 (23%); Sirolimus/Everolimus-based: 20 (77%)]. During treatment, adverse drug reactions (ADR) occurred in 34.6% of patients: acute rejection in 6 (23.1%), hepatotoxicity in 2 (7.7%), and blurred vision in 1 (3.8%). Twenty-three (88%) patients completed their TB treatment. Neither TB recurrence nor TB-specific mortality were observed. Three (11.5%) patients died of non-TB-related causes. The overall 5-year survival rate was 86.2%. Patients with ADRs had a higher incidence of incomplete TB treatment (log-rank: p=0.012). Furthermore, patients with incomplete treatment were significantly associated with decreased overall survival (log-rank: p<0.001). Immunosuppressive and anti-TB drugs used during TB treatment and performing LDLT in patients with active TB at the time of LDLT were not associated with ADRs and overall survival. CONCLUSIONS Outcomes are generally favorable with intensive peri-operative evaluation and surveillance. ADRs and incomplete TB treatment may result in poor prognosis and increased mortality rates.

Peri-mortem caesarean section after traumatic arrest: Crisis resource management.

Peri-mortem caesarean section (PMCS) is a very rare procedure performed to improve the chances of survival for both mother and fetus following cardiorespiratory arrest. Non-obstetricians including Emergency Physicians (EPs) are often called upon to perform this procedure under challenging and suboptimal circumstances. We reported a case of PMCS performed timely after traumatic cardiorespiratory arrest that resulted in fetal survival. A 25-year-old primigravida female and six-month pregnant presented to the Emergency Department (ED) of an adult tertiary hospital. She experienced traumatic cardiorespiratory arrest for nearly 27 min following a high-speed motor vehicle crash. Upon ED arrival, she was in pulseless electrical activity. She was immediately intubated with continuation of cardiopulmonary resuscitation. She received bilateral tube thoracostomies as well as intravenous (IV) transfusion of blood products, adrenaline and tranexamic acid. Her fundal height was two centimeters above the umbilicus on palpation. The EP performed a PMCS via a midline laparotomy 3-4 min upon ED arrival. The baby was bradycardic and cyanosed with no spontaneous respiration at birth and was resuscitated by a second EP. She was intubated and the EP gained IV access using a cannula introduced into the umbilical vein. Neonatal hypothermia was avoided using cling wrap. The baby was transported to a nearby neonatal intensive unit. She survived and is currently one year old. The mother, however, did not respond to our resuscitation and succumbed to her multiple injuries. We reviewed the limited literature regarding this potentially life-saving emergency procedure and highlighted the challenges facing our resuscitation team.

Combination of FDG-PET and UCSF Criteria for Predicting HCC Recurrence After Living Donor Liver Transplantation.

BACKGROUND: F-18 fluorodeoxyglucose (FDG) uptake in hepatocellular carcinoma (HCC) is related to tumor biology and has predictive value for tumor recurrence after liver transplantation. This retrospective study assessed whether the degree of FDG uptake in positron emission tomography (PET) can be used to predict HCC recurrence after living donor liver transplantation (LDLT). METHODS: One hundred forty-seven patients with HCC underwent FDG-PET studies before LDLT. The semiquantification of FDG uptake in FDG-positive HCC was done with maximum standardized uptake value (SUVmax) and tumor to nontumor ratio (TNR). Recurrence-free survivals (RFS) were calculated using the Kaplan-Meier method. RESULTS: In univariable analysis, T stage, presence of microvascular invasion, being FDG-positive, SUVmax, and TNR were significant predictors for worse RFS. The optimal cutoff values of SUVmax and TNR were 4.8 and 2.0, respectively. The high FDG uptake HCC (TNR ≥ 2) was a strong predictor for worse RFS (hazard ratio, 13.52; 95% confidence interval, 4.77-38.29; P < 0.001). Using a combination of FDG-PET and University of California San Francisco (UCSF) criteria, the patients can be divided into low-risk (within UCSF criteria and FDG-negative), intermediate-risk (beyond UCSF criteria and FDG-negative; FDG-positive and TNR < 2), and high-risk (FDG-positive and TNR ≥ 2) groups. The estimated 5-year RFS in these groups were 85.5%, 83.9%, and 29.6% according to the combination of FDG-PET and clinical UCSF criteria, and 94.0%, 75.8%, and 29.6% according to the combination of FDG-PET and pathologic UCSF criteria, respectively. CONCLUSIONS: Combination of FDG-PET and UCSF criteria can be used to predict the risk of HCC recurrence after LDLT.

The Little India riot: experience of an emergency department in Singapore.

INTRODUCTION: Singapore experienced its second riot in 40 years on 8 December 2013, in the area known as Little India. A retrospective review of 36 casualties treated at the emergency department was conducted to evaluate injury patterns. METHODS: Characteristics including the rate of arrival, injury severity, type and location, and disposition of the casualties were analysed. RESULTS: The injuries were predominantly mild (97.2%), with the most common injuries involving the head (50.0%) and limbs (38.9%). 97.2% of the casualties were managed as outpatient cases. CONCLUSION: The majority of the injuries in this incident were mild and could be managed as outpatient cases. Important lessons were learnt from the incident about the utilisation of manpower and safety of staff in the emergency department.

Hand-assisted laparoscopic splenectomy--preliminary experience in southern Taiwan.

BACKGROUND: A hand-assisted laparoscopic procedure allows the surgeon to insert the nondominant hand into the abdomen, and helps to recover the tactile sensation. For a massively enlarged spleen, this technique overcomes difficulty in conventional laparoscopic splenectomy. The advantages of minimally-invasive surgery can still be preserved. We describe our preliminary experience in hand-assisted laparoscopic splenectomy. METHODS: The data of 5 patients who presented with splenomegaly and underwent hand-assisted laparoscopic splenectomy between April 2000 and January 2004 were reviewed retrospectively for analysis. RESULTS: The mean age was 45.4 +/- 6.6 years, and the hospital stay was 6.6 +/- 1.0 days. The splenic length and weight averaged 20.6 +/- 5.9 cm and 1084.2 +/- 647.8 g. The operative time and blood loss averaged 218.2 +/- 40.2 minutes and 220 +/- 166.1 ml. There was no conversion to open splenectomy. No mortality or morbidity was noted in our series. CONCLUSION: Hand-assisted laparoscopic splenectomy is a safe and feasible procedure, even in our initial experience. It helps in exploration of the surgical field and handling of a fragile spleen, especially in patients with massively enlarged spleens. Although another incision is necessary, the advantages of laparoscopic surgery are still retained.