Machine learning prediction of refractory ventricular fibrillation in out-of-hospital cardiac arrest using features available to EMS.

Background: Shock-refractory ventricular fibrillation (VF) or ventricular tachycardia (VT) is a treatment challenge in out-of-hospital cardiac arrest (OHCA). This study aimed to develop and validate machine learning models that could be implemented by emergency medical services (EMS) to predict refractory VF/VT in OHCA patients. Methods: This was a retrospective study examining adult non-traumatic OHCA patients brought into the emergency department by Singapore EMS from the Pan-Asian Resuscitation Outcomes Study (PAROS) registry. Data from April 2010 to March 2020 were extracted for this study. Refractory VF/VT was defined as VF/VT persisting or recurring after at least one shock. Features were selected based on expert clinical opinion and availability to dispatch prior to arrival at scene. Multivariable logistic regression (MVR), LASSO and random forest (RF) models were investigated. Model performance was evaluated using receiver operator characteristic (ROC) area under curve (AUC) analysis and calibration plots. Results: 20,713 patients were included in this study, of which 860 (4.1%) fulfilled the criteria for refractory VF/VT. All models performed comparably and were moderately well-calibrated. ROC-AUC were 0.732 (95% CI, 0.695 - 0.769) for MVR, 0.738 (95% CI, 0.701 - 0.774) for LASSO, and 0.731 (95% CI, 0.690 - 0.773) for RF. The shared important predictors across all models included male gender and public location. Conclusion: The machine learning models developed have potential clinical utility to improve outcomes in cases of refractory VF/VT OHCA. Prediction of refractory VF/VT prior to arrival at patient's side may allow for increased options for intervention both by EMS and tertiary care centres.

Increasing neurologically intact survival after out-of-hospital cardiac arrest among elderly: Singapore Experience.

Objectives: With more elderly presenting with Out-of-Hospital Cardiac Arrests (OHCAs) globally, neurologically intact survival (NIS) should be the aim of resuscitation. We aimed to study the trend of OHCA amongst elderly in a large Asian registry to identify if age is independently associated with NIS and factors associated with NIS. Methods: All adult OHCAs aged ≥18 years attended by emergency medical services (EMS) from April 2010 to December 2019 in Singapore was extracted from the Pan-Asian Resuscitation Outcomes Study (PAROS) registry. Cases pronounced dead at scene, non-EMS transported, traumatic OHCAs and OHCAs in ambulances were excluded. Patient characteristics and outcomes were compared across four age categories (18-64, 65-79, 80-89, ≥90). Multivariable logistic regression analysis determined the factors associated with NIS. Results: 19,519 eligible cases were analyzed. OHCA incidence increased with age almost doubling in octogenarians (from 312/100,000 in 2011 to 652/100,000 in 2019) and tripling in those ≥90 years (from 458/100,000 in 2011 to 1271/100,000 in 2019). The proportion of patients with NIS improved over time for the 18-64, 65-79- and 80-89-years age groups, with the greatest improvement in the youngest group. NIS decreased with each increasing year of age and minute of response time. NIS increased in the arrests of presumed cardiac etiology, witnessed and bystander CPR. Conclusions: Survival with good outcomes has increased even amongst the elderly. Regardless of age, NIS is possible with good-quality CPR, highlighting its importance. End-of-life planning is a complex yet necessary decision that requires qualitative exploration with elderly, their families and care providers.

Comparing outcomes of out-of-hospital cardiac arrest patients with initial shockable rhythm in Singapore and Osaka using population-based databases.

BACKGROUND: Previous research indicated outcomes among refractory out-of-hospital cardiac arrest (OHCA) patients with initial shockable rhythm were different in Singapore and Osaka, Japan, possibly due to the differences in access to extracorporeal cardiopulmonary resuscitation. However, this previous study had a risk of selection bias. To address this concern, this study aimed to evaluate the outcomes between Singapore and Osaka for OHCA patients with initial shockable rhythm using only population-based databases. METHODS: This was a secondary analysis of two OHCA population-based databases in Osaka and Singapore, including adult OHCA patients with initial shockable rhythm. A machine-learning-based prediction model was derived from the Osaka data (n = 3088) and applied to the PAROS-SG data (n = 2905). We calculated the observed-expected ratio (OE ratio) for good neurological outcomes observed in Singapore and the expected derived from the data in Osaka by dividing subgroups with or without prehospital ROSC. RESULTS: The one-month good neurological outcomes in Osaka and Singapore among patients with prehospital ROSC were 70% (791/1,125) and 57% (440/773), and among patients without prehospital ROSC were 10% (196/1963) and 2.8% (60/2,132). After adjusting patient characteristics, the outcome in Singapore was slightly better than expected from Osaka in patients with ROSC (OE ratio, 1.067 [95%CI 1.012 to 1.125]), conversely, it was worse than expected in patients without prehospital ROSC (OE ratio, 0.238 [95%CI 0.173 to 0.294]). CONCLUSION: This study showed the outcomes of OHCA patients without prehospital ROSC in Singapore were worse than expected derived from Osaka data even using population-based databases. (249/250 words).

Outcome assessment for out-of-hospital cardiac arrest patients in Singapore and Japan with initial shockable rhythm.

BACKGROUND: Singapore and Osaka in Japan have comparable population sizes and prehospital management; however, the frequency of ECPR differs greatly for out-of-hospital cardiac arrest (OHCA) patients with initial shockable rhythm. Given this disparity, we hypothesized that the outcomes among the OHCA patients with initial shockable rhythm in Singapore were different from those in Osaka. The aim of this study was to evaluate the outcomes of OHCA patients with initial shockable rhythm in Singapore compared to the expected outcomes derived from Osaka data using machine learning-based prediction models. METHODS: This was a secondary analysis of two OHCA databases: the Singapore PAROS database (SG-PAROS) and the Osaka-CRITICAL database from Osaka, Japan. This study included adult (18-74 years) OHCA patients with initial shockable rhythm. A machine learning-based prediction model was derived and validated using data from the Osaka-CRITICAL database (derivation data 2012-2017, validation data 2018-2019), and applied to the SG-PAROS database (2010-2016 data), to predict the risk-adjusted probability of favorable neurological outcomes. The observed and expected outcomes were compared using the observed-expected ratio (OE ratio) with 95% confidence intervals (CI). RESULTS: From the SG-PAROS database, 1,789 patients were included in the analysis. For OHCA patients who achieved return of spontaneous circulation (ROSC) on hospital arrival, the observed favorable neurological outcome was at the same level as expected (OE ratio: 0.905 [95%CI: 0.784-1.036]). On the other hand, for those who had continued cardiac arrest on hospital arrival, the outcomes were lower than expected (shockable rhythm on hospital arrival, OE ratio: 0.369 [95%CI: 0.258-0.499], and nonshockable rhythm, OE ratio: 0.137 [95%CI: 0.065-0.235]). CONCLUSION: This observational study found that the outcomes for patients with initial shockable rhythm but who did not obtain ROSC on hospital arrival in Singapore were lower than expected from Osaka. We hypothesize this is mainly due to differences in the use of ECPR.

Does witness type affect the chance of receiving bystander CPR in out-of-hospital cardiac arrest?

OBJECTIVES: The relationship between the bystander witness type and receipt of bystander CPR (BCPR) is not well understood. Herein we compared BCPR administration between family and non-family witnessed out-of-hospital cardiac arrest (OHCA). BACKGROUND: In many communities, interventions in the past decade have contributed to an increased receipt of BCPR, for example in Singapore from 15% to 60%. However, BCPR rates have plateaued despite sustained and ongoing community-based interventions, which may be related to gaps in education or training for various witness types. The purpose of this study was to investigate the association between witness type and BCPR administration. METHODS: Singapore data from 2010-2020 was extracted from the Pan-Asian Resuscitation Outcomes Study (PAROS) network registry (n = 25,024). All adult, layperson witnessed, non-traumatic OHCAs were included in this study. RESULTS: Of 10,016 eligible OHCA cases, 6,895 were family witnessed and 3,121 were non-family witnessed. After adjustment for potential confounders, BCPR administration was less likely for non-family witnessed OHCA (OR 0.83, 95% CI 0.75, 0.93). After location stratification, non-family witnessed OHCAs were less likely to receive BCPR in residential settings (OR 0.75, 95% CI 0.66, 0.85). In non-residential settings, there was no statistically significant association between witness type and BCPR administration (OR 1.11, 95% CI 0.88, 1.39). Details regarding witness type and bystander CPR were limited. CONCLUSION: This study found differences in BCPR administration between family and non-family witnessed OHCA cases. Elucidation of witness characteristics may be useful to determine populations that would benefit most from CPR education and training.

A developmental approach to diversifying neuroscience through effective mentorship practices: perspectives on cross-identity mentorship and a critical call to action.

Many early-career neuroscientists with diverse identities may not have mentors who are more advanced in the neuroscience pipeline and have a congruent identity due to historic biases, laws, and policies impacting access to education. Cross-identity mentoring relationships pose challenges and power imbalances that impact the retention of diverse early career neuroscientists, but also hold the potential for a mutually enriching and collaborative relationship that fosters the mentee's success. Additionally, the barriers faced by diverse mentees and their mentorship needs may evolve with career progression and require developmental considerations. This article provides perspectives on factors that impact cross-identity mentorship from individuals participating in Diversifying the Community of Neuroscience (CNS)-a longitudinal, National Institute of Neurological Disorders and Stroke (NINDS) R25 neuroscience mentorship program developed to increase diversity in the neurosciences. Participants in Diversifying CNS were comprised of 14 graduate students, postdoctoral fellows, and early career faculty who completed an online qualitative survey on cross-identity mentorship practices that impact their experience in neuroscience fields. Qualitative survey data were analyzed using inductive thematic analysis and resulted in four themes across career levels: (1) approach to mentorship and interpersonal dynamics, (2) allyship and management of power imbalance, (3) academic sponsorship, and (4) institutional barriers impacting navigation of academia. These themes, along with identified mentorship needs by developmental stage, provide insights mentors can use to better support the success of their mentees with diverse intersectional identities. As highlighted in our discussion, a mentor's awareness of systemic barriers along with active allyship are foundational for their role.

The association between mode of transport and out-of-hospital cardiac arrest outcomes in Singapore.

OBJECTIVE: We aimed to examine the survival outcomes of out-of-hospital cardiac arrest (OHCA) patients, stratified by the transportation modes to the Emergency Department (ED). METHODS: This was a retrospective analysis of Singapore's Pan-Asian Resuscitation Outcomes Study registry from Apr 2010-Dec 2017. The primary outcome was survival to discharge or 30 days post-arrest. Secondary outcomes were the return of spontaneous circulation (ROSC) rate and neurological outcomes. A subgroup analysis was performed for OHCA cases who collapsed enroute. RESULTS: A total of 15,376 cases were analysed. 15,129 (98.4%) were conveyed by Emergency Medical Services (EMS), 111 (0.72%) by private ambulance, 106 (0.69%) by own transport and 30 (0.2%) by public transport. 80% of patients brought by public transport arrested enroute, compared to 48.1% by own transport, 25.2% by private ambulance and 2.5% in the EMS group. 33/120 (27.5%) of paediatric OHCA cases were brought in by non-EMS transport to paediatric hospitals. The EMS group had the lowest survival rate at 4.5%, compared to 13.3% for public transport, 11.3% for own transport and 14.4% for private ambulance. ROSC rate was statistically significant but not for neurological outcomes. For the subgroup analysis, there was no statistical difference for primary and secondary outcomes across the groups. CONCLUSION: In Singapore, most OHCA patients are conveyed by EMS to the hospital, but some OHCA patients still arrive via alternative transport without prehospital interventions like bystander CPR. More can be done to educate the public to recognise an impending cardiac arrest and to activate EMS early for such cases.

Early Coronary Angiography Is Associated with Improved 30-Day Outcomes among Patients with Out-of-Hospital Cardiac Arrest.

We evaluated the association between early coronary angiography (CAG) and outcomes in resuscitated out-of-hospital cardiac arrest (OHCA) patients, by linking data from the Singapore Pan-Asian Resuscitation Outcomes Study, with a national registry of cardiac procedures. The 30-day survival and neurological outcome were compared between patients undergoing early CAG (within 1-calender day), versus patients not undergoing early CAG. Inverse probability weighted estimates (IPWE) adjusted for non-randomized CAG. Of 976 resuscitated OHCA patients of cardiac etiology between 2011-2015 (mean(SD) age 64(13) years, 73.7% males), 337 (34.5%) underwent early CAG, of whom, 230 (68.2%) underwent PCI. Those who underwent early CAG were significantly younger (60(12) vs. 66(14) years old), healthier (42% vs. 59% with heart disease; 29% vs. 44% with diabetes), more likely males (86% vs. 67%), and presented with shockable rhythms (69% vs. 36%), compared with those who did not. Early CAG with PCI was associated with better survival and neurological outcome (adjusted odds ratio 1.91 and 1.82 respectively), findings robust to IPWE adjustment. The rates of bleeding and stroke were similar. CAG with PCI within 24 h was associated with improved clinical outcomes after OHCA, without increasing complications. Further studies are required to identify the characteristics of patients who would benefit most from this invasive strategy.

Vaccine-induced thrombosis and thrombocytopenia (VITT) in Ireland: A review of cases and current practices.

Since the beginning of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) virus pandemic, several highly effective and safe vaccines have been produced at remarkable speed. Following global implementation of vaccination programmes, cases of thrombosis with thrombocytopenia following administration of adenoviral vector-based vaccines started being reported. In this review we discuss the known pathogenesis and epidemiology of so-called vaccine induced thrombocytopenia and thrombosis (VITT). We consider the available guidelines, diagnostic laboratory tests and management options for these patients. Finally, we discuss important unanswered questions and areas for future research in this novel pathoclinical entity.

The RASSF1A Tumor Suppressor Binds the RasGAP DAB2IP and Modulates RAS Activation in Lung Cancer.

Lung cancer is the leading cause of cancer-related death worldwide. Lung cancer is commonly driven by mutations in the RAS oncogenes, the most frequently activated oncogene family in human disease. RAS-induced tumorigenesis is inhibited by the tumor suppressor RASSF1A, which induces apoptosis in response to hyperactivation of RAS. RASSF1A expression is suppressed in cancer at high rates, primarily owing to promoter hypermethylation. Recent reports have shown that loss of RASSF1A expression uncouples RAS from apoptotic signaling in vivo, thereby enhancing tumor aggressiveness. Moreover, a concomitant upregulation of RAS mitogenic signaling upon RASSF1A loss has been observed, suggesting RASSF1A may directly regulate RAS activation. Here, we present the first mechanistic evidence for control of RAS activation by RASSF1A. We present a novel interaction between RASSF1A and the Ras GTPase Activating Protein (RasGAP) DAB2IP, an important negative regulator of RAS. Using shRNA-mediated knockdown and stable overexpression approaches, we demonstrate that RASSF1A upregulates DAB2IP protein levels in NSCLC cells. Suppression of RASSF1A and subsequent downregulation of DAB2IP enhances GTP loading onto RAS, thus increasing RAS mitogenic signaling in both mutant- and wildtype-RAS cells. Moreover, co-suppression of RASSF1A and DAB2IP significantly enhances in vitro and in vivo growth of wildtype-RAS cells. Tumors expressing wildtype RAS, therefore, may still suffer from hyperactive RAS signaling when RASSF1A is downregulated. This may render them susceptible to the targeted RAS inhibitors currently in development.

Nation-Wide Observational Study of Cardiac Arrests Occurring in Nursing Homes and Nursing Facilities in Singapore.

INTRODUCTION: Nursing home (NH) residents with out-of-hospital cardiac arrests (OHCA) have unique resuscitation priorities. This study aimed to describe OHCA characteristics in NH residents and identify independent predictors of survival. MATERIALS AND METHODS: OHCA cases between 2010-16 in the Pan-Asian Resuscitation Outcomes Study were retrospectively analysed. Patients aged <18 years old and non-emergency cases were excluded. Primary outcome was survival at discharge or 30 days. Good neurological outcome was defined as a cerebral performance score between 1-2. RESULTS: A total of 12,112 cases were included. Of these, 449 (3.7%) were NH residents who were older (median age 79 years, range 69-87 years) and more likely to have a history of stroke, heart and respiratory diseases. Fewer NH OHCA had presumed cardiac aetiology (62% vs 70%, P <0.01) and initial shockable rhythm (8.9% vs 18%, P <0.01), but had higher incidence of bystander cardiopulmonary resuscitation (74% vs 43%, P <0.01) and defibrillator use (8.5% vs 2.8%, P <0.01). Non-NH (2.8%) residents had better neurological outcomes than NH (0.9%) residents (P <0.05). Factors associated with survival for cardiac aetiology included age <65 years old, witnessed arrest, bystander defibrillator use and initial shockable rhythm; for non-cardiac aetiology, these included witnessed arrest (adjusted odds ratio [AOR] 3.8, P <0.001) and initial shockable rhythm (AOR 5.7, P <0.001). CONCLUSION: Neurological outcomes were poorer in NH survivors of OHCA. These findings should inform health policies on termination of resuscitation, advance care directives and do-not-resuscitate orders in this population.

Pumping the brakes on RAS - negative regulators and death effectors of RAS.

Mutations that activate the RAS oncoproteins are common in cancer. However, aberrant upregulation of RAS activity often occurs in the absence of activating mutations in the RAS genes due to defects in RAS regulators. It is now clear that loss of function of Ras GTPase-activating proteins (RasGAPs) is common in tumors, and germline mutations in certain RasGAP genes are responsible for some clinical syndromes. Although regulation of RAS is central to their activity, RasGAPs exhibit great diversity in their binding partners and therefore affect signaling by multiple mechanisms that are independent of RAS. The RASSF family of tumor suppressors are essential to RAS-induced apoptosis and senescence, and constitute a barrier to RAS-mediated transformation. Suppression of RASSF protein expression can also promote the development of excessive RAS signaling by uncoupling RAS from growth inhibitory pathways. Here, we will examine how these effectors of RAS contribute to tumor suppression, through both RAS-dependent and RAS-independent mechanisms.

Nation-Wide Observational Study of Cardiac Arrests Occurring in Nursing Homes and Nursing Facilities in Singapore

INTRODUCTION@#Nursing home (NH) residents with out-of-hospital cardiac arrests (OHCA) have unique resuscitation priorities. This study aimed to describe OHCA characteristics in NH residents and identify independent predictors of survival.@*MATERIALS AND METHODS@#OHCA cases between 2010-16 in the Pan-Asian Resuscitation Outcomes Study were retrospectively analysed. Patients aged <18 years old and non-emergency cases were excluded. Primary outcome was survival at discharge or 30 days. Good neurological outcome was defined as a cerebral performance score between 1-2.@*RESULTS@#A total of 12,112 cases were included. Of these, 449 (3.7%) were NH residents who were older (median age 79 years, range 69-87 years) and more likely to have a history of stroke, heart and respiratory diseases. Fewer NH OHCA had presumed cardiac aetiology (62% vs 70%, <0.01) and initial shockable rhythm (8.9% vs 18%, <0.01), but had higher incidence of bystander cardiopulmonary resuscitation (74% vs 43%, <0.01) and defibrillator use (8.5% vs 2.8%, <0.01). Non-NH (2.8%) residents had better neurological outcomes than NH (0.9%) residents ( <0.05). Factors associated with survival for cardiac aetiology included age <65 years old, witnessed arrest, bystander defibrillator use and initial shockable rhythm; for non-cardiac aetiology, these included witnessed arrest (adjusted odds ratio [AOR] 3.8, <0.001) and initial shockable rhythm (AOR 5.7, <0.001).@*CONCLUSION@#Neurological outcomes were poorer in NH survivors of OHCA. These findings should inform health policies on termination of resuscitation, advance care directives and do-not-resuscitate orders in this population.

Comparison of Outcomes and Characteristics of Emergency Medical Services (EMS)-Witnessed, Bystander-Witnessed, and Unwitnessed Out-of-Hospital Cardiac Arrests in Singapore.

Objectives: The objective was to compare the survival outcomes of emergency medical services (EMS)-witnessed to bystander-witnessed, and unwitnessed out-of-hospital cardiac arrests (OHCA) in Singapore. Secondary aims are to describe the 5-year trend in survival rates of EMS-witnessed arrests. Methods: This was a retrospective analysis of the Singapore's OHCA registry data from 2011 to 2015. Excluded from the analysis were patients younger than 18 years old, arrests of traumatic etiology, resuscitation not attempted, and cases not conveyed by EMS. The primary outcome was survival to hospital discharge or 30 days post-arrest. Secondary outcomes were return of spontaneous circulation (ROSC) and survival to hospital admission. Results: 8,394 cases were analyzed, with 650 (7.7%) EMS-witnessed arrests, 4480 (53.4%) bystander-witnessed arrests, and 3264 (38.9%) unwitnessed arrests. Among EMS-witnessed arrests, the majority were presumed to be of cardiac etiology (62.8%) and the most common presenting rhythm was pulseless electrical activity (PEA; 57.2%). Survival to discharge or 30th day post-arrest was higher in EMS-witnessed arrests compared to bystander-witnessed and unwitnessed arrests (11.2% vs. 5.3% and 1.3%, p < 0.001). Survival to discharge for EMS-witnessed cases increased from 2011 (13.2%) to 2015 (18.9%). Conclusions: EMS-witnessed OHCAs were more likely to have favorable outcomes compared to bystander-witnessed and unwitnessed OHCAs. High PEA rates in EMS-witnessed arrests were associated with older patients with underlying preexisting medical conditions. Increasing public awareness on recognition of prodromal symptoms and early activation of EMS could improve post-arrest survival and neurological outcomes of OHCA.

Psychological Comfort of Paramedics with Field Death Pronouncement: A National Asian Study to Prepare Paramedics for Field Termination of Resuscitation.

OBJECTIVES: Paramedics' decision to terminate field resuscitation without a physician present may depend on personal and external factors. This study investigates factors associated with paramedic psychological comfort with termination of resuscitation (TOR) to inform future training. METHODS: We administered an anonymous survey to all practicing paramedics in a large urban Asian Emergency Medical Services system where formal TOR training had not yet been conducted and field TOR was not routinely applied. The survey assessed psychological comfort using the validated Psychological Comfort Total (PCT) scale (summed score of 28 items, with higher scores representing greater comfort). We examined scores associated with four personal (prior resolution of personal loss, knowledge of survival probability, religious affiliation and experience with death pronouncements) and two external (location of patient and perceived trust of family) factors. Data were entered into Excel and analyzed by t-tests and ANOVA. RESULTS: Response rate was 73.6% (254/345). Respondents were 30.3 years (mean, SD 7.1) with 7.2 years (mean, SD 5.54) of practice experience. Over 60% had been involved in 6 or more field death pronouncements in the prior 12 months. Higher PCT scores were associated with prior resolution of personal loss and knowledge of survival probability. Lower PCT scores were associated with patient location in a public place and perceived family lack of trust. PCT scores were not associated with paramedic religious affiliation or number of prior death pronouncements. CONCLUSIONS: Paramedic psychological comfort with field death pronouncement is associated with personal and external factors. Since paramedic comfort is important for protocol adoption, TOR education should target not only knowledge, but also public arena management, communication skills for engaging with families, and help paramedics resolve prior personal loss.

Population pharmacokinetics of teicoplanin and attainment of pharmacokinetic/pharmacodynamic targets in adult patients with haematological malignancy.

OBJECTIVES: To describe the population pharmacokinetics of teicoplanin in adult patients with haematological malignancies receiving higher than standard doses, and to perform Monte Carlo simulations to determine dosing regimens associated with optimal teicoplanin concentrations. METHODS: This was a hospital-based clinical trial (EudraCT 2013-004535-72). Nine blood samples were collected on Day 3, plus single trough samples on Days 7 and 10, and 24 and 48 hours after the last dose. Teicoplanin minimum inhibitory concentrations were determined for Gram-positive isolates from study patients. Population pharmacokinetic analyses and Monte Carlo dosing simulations were undertaken using Pmetrics. RESULTS: Thirty adult haematological malignancy patients were recruited with a mean (SD) loading dose, age, total body weight, and creatinine clearance of 9.5 (1.9) mg/kg, 63 (12) years, 69.1 (15.8) kg, and 72 (41) mL/min, respectively. A three-compartment linear pharmacokinetic model best described the teicoplanin concentration data. Covariates supported for inclusion in the final model were creatinine clearance for clearance and total body weight for volume of the central compartment. The median (IQR) area under the concentration-time curve from 48 to 72 hours (AUC48-72h) was 679 (319) mg.h/L. There was a strong correlation between the AUC48-72h and trough concentration at 72 hours (Pearson correlation coefficient 0.957, p <0.001). Dosing simulations showed that administration of five loading doses at 12-hourly intervals, stratified by total body weight and creatinine clearance, increased the probability of achieving target concentrations within 72 hours. CONCLUSIONS: To increase the number of patients achieving optimal teicoplanin concentrations an individualized dosing approach, based on body weight and creatinine clearance, is recommended.

Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome.

BACKGROUND: With the exception of the presence of the FIP1L1-PDGFRA fusion gene, little is known about predictors of imatinib response in clinically-defined hypereosinophilic syndrome (HES). METHODS: Subjects with FIP1L1-PDGFRA-myeloid neoplasm (FP; n =12), PDGFRA-negative HES with ≥4 criteria suggestive of a myeloid neoplasm (MHES; n =10), or steroid-refractory PDGFRA-negative HES with <4 myeloid criteria (SR; n = 5) were enrolled in a prospective study of imatinib therapy (NCT00044304: registered at clinicaltrials.gov). The primary outcome was an eosinophil count <1.5 × 109/L at one month and improvement of clinical symptoms. Clinical, molecular, and bone marrow responses to imatinib were assessed. A retrospective cohort of 18 subjects with clinically-defined HES who received imatinib (300-400 mg daily ≥ 1 month) were classified according to the criteria used in the prospective study. RESULTS: Overall, imatinib response rates were 100% in the FP group (n = 16), 54% in the MHES group (n = 13) and 0% in the SR group (n = 16). The presence of ≥ 4 myeloid features was the sole predictor of response. After ≥ 18 months in complete remission, imatinib was tapered and discontinued in 8 FP and 1 MHES subjects. Seven subjects (6 FP, 1 MHES) remain in remission off therapy for a median of 29 months (range 14-36). CONCLUSIONS: Clinical features of MHES predict imatinib response in PDGFRA-negative HES.

Barriers to continuing education and continuing professional development among occupational health nurses in Japan.

As Japan's industries pursue technical innovations, the responsibilities of occupational health nurses are becoming increasingly complex. With such change, continuing professional development (CPD) and continuing education (CE) are crucial to the provision of appropriate care for workers. This study examined current practices of occupational health nurses and identified barriers to conducting occupational CPD and CE activities. A survey questionnaire was sent to 2,077 occupational health nurses late in 2010, asking about factors affecting attendance at and participation in CPD and CE activities, including challenges for occupational health nurses in practice. Findings demonstrated that many occupational health nurses do not work for companies that support CPD and CE. A significant finding was that occupational health nurses in Japan desire CPD activities and recognize the importance of attending CE activities. Continuing education is viewed by occupational health nurses as essential for their professional development and advancement with broader practice responsibilities and authority. Findings from this study are useful in crafting recommendations to increase occupational health nurse participation in both CPD and CE, leading to improvement in overall workplace health and safety in Japan.