Rapid Responder Research Articles

The Israeli health system’s rapid responses during the COVID-19 pandemic

BackgroundThe COVID-19 pandemic posed numerous challenges to health systems around the world. In addressing many of those challenges, Israel responded quite rapidly. While quick action is not an end in it itself, it can be important in responding to disease outbreaks. Some of Israel's rapid responses to the pandemic contributed significantly to population health and provided important learning opportunities for other countries.Main bodySome of the most prominent Israeli rapid responses were related to vaccination. Israel led the world in the pace of its initial vaccine rollout, and it was also the first country to approve and administer booster vaccines to broad segments of the population. In addition, Israeli scholars published a series of timely reports analyzing vaccination impact, which informed policy in Israel and other countries. Israel was a rapid responder in additional areas of public health. These include the partial closure of its borders, the adoption of physical distancing measures, the use of digital surveillance technology for contact tracing, the use of wastewater surveillance to monitor viral spread, and the use of vaccine certificates ("green passes") to facilitate a return to routine in the face of the ongoing pandemic. Many factors contributed to Israel's capacity to repeatedly respond rapidly to a broad array of COVID-19 challenges. These include a national health insurance system that promotes public–private coordination, a system of universal electronic health records, a high level of emergency preparedness, a culture of focusing on goal attainment, a culture of innovation, and the presence of a strong scientific community which is highly connected internationally. In addition, some of the rapid responses (e.g., the rapid initial vaccination rollout) facilitated rapid responses in related areas (e.g., the analysis of vaccination impact, the administration of boosters, and the adoption of green passes). While rapid response can contribute to population health and economic resilience, it can also entail costs, risks, and limitations. These include making decisions and acting before all the relevant information is available; deciding without sufficient consideration of the full range of possible effects, costs, and benefits; not providing enough opportunities for the involvement of relevant groups in the decision-making process; and depleting non-renewable resources.ConclusionsBased on our findings, we encourage leaders in the Israeli government to ensure that its emergency response system will continue to have the capacity to respond rapidly to large-scale challenges, whether of a military or civilian nature. At the same time, the emergency response systems should develop mechanisms to include more stakeholders in the fast-paced decision-making process and should improve communication with the public. In addition, they should put into place mechanisms for timely reconsideration, adjustment, and—when warranted—reversal of decisions which, while reasonable when reached, turn out to have been ill-advised in the light of subsequent developments and evidence. These mechanisms could potentially involve any or all branches of government, as well as the public, the press, and professional organizations. Our findings also have implications for health system leaders in other countries. The Israeli experience can help them identify key capacities to develop during non-emergency periods, thus positioning themselves to respond more rapidly in an emergency. Finally, health system leaders in other countries could monitor Israel's rapid responses to future global health emergencies and adopt selected actions in their own countries.

Integrating Phenotypic and Chemoproteomic Approaches to Identify Covalent Targets of Dietary Electrophiles in Platelets.

A large variety of dietary phytochemicals has been shown to improve thrombosis and stroke outcomes in preclinical studies. Many of these compounds feature electrophilic functionalities that potentially undergo covalent addition to the sulfhydryl side chain of cysteine residues within proteins. However, the impact of such covalent modifications on the platelet activity and function remains unclear. This study explores the irreversible engagement of 23 electrophilic phytochemicals with platelets, unveiling the unique antiplatelet selectivity of sulforaphane (SFN). SFN impairs platelet responses to adenosine diphosphate (ADP) and a thromboxane A2 receptor agonist while not affecting thrombin and collagen-related peptide activation. It also substantially reduces platelet thrombus formation under arterial flow conditions. Using an alkyne-integrated probe, protein disulfide isomerase A6 (PDIA6) was identified as a rapid kinetic responder to SFN. Mechanistic profiling studies revealed SFN's nuanced modulation of PDIA6 activity and substrate specificity. In an electrolytic injury model of thrombosis, SFN enhanced the thrombolytic activity of recombinant tissue plasminogen activator (rtPA) without increasing blood loss. Our results serve as a catalyst for further investigations into the preventive and therapeutic mechanisms of dietary antiplatelets, aiming to enhance the clot-busting power of rtPA, currently the only approved therapeutic for stroke recanalization that has significant limitations.

Helicopter Rescue for Flood Disaster: Scheduling, Simulation, and Evaluation

Frequent severe floods have caused great losses to urban safety and the economy, which raises high requirements for the efficiency and effectiveness of emergency rescue. Due to the flood characteristics, flood rescue requires a more rapid responder and decision-making compared with other kinds of disaster rescue. In recent years, aviation emergency rescue (AER) has attracted much attention for flood applications. In order to evaluate the effectiveness of AER for flood disasters, the present study proposes a conceptual model of helicopter AER scheduling and develops a simulation system of helicopter AER scheduling using multiple agents. Seven elements are considered in the conceptual model: helicopters, the command-and-control center, temporary take-off/landing points, mission demand points, resettlement points, loading points, and unloading points. Furthermore, process-oriented and object-oriented scheduling rules are developed as the general guide for scheduling. In order to efficiently simulate and evaluate an AER mission (assisting the decision maker), the simulation system is designed with multiple agents and a user interface, which can quickly load mission settings, run the simulation, and collect data for further evaluation. A standardized mission makespan is adopted as the evaluation index. Based on that, the minimum integrated index can be derived to finally assess the different rescue schemes and choose the best. In the case study, the comparison results indicate that the rescue efficiency of large helicopters (Mi-26 in the case) could be limited by the capabilities of loading points and unloading points. This problem is solved by scheduling small/medium-size helicopters to transfer the personnel. Alternately, two types of helicopters can be used: one for passenger transfer and the other for goods/material transfer. Anyway, the analyses in the case study illustrate the correlation between effectiveness and scheduling, which demonstrates the significance of decision-making. By using the proposed scheduling and modeling methods, the simulation system can be served as a convenient decision-making support tool for practical rescue applications.

Estimation of Person Ability under Rapid and Effortful Responding.

The goal of the present study was to extend earlier work on the estimation of person theta using maximum likelihood estimation in R by accounting for rapid guessing. This paper provides a modified R function that accommodates person thetas using the Rasch or 2PL models and implements corrections for the presence of rapid guessing or informed guessing behaviors. Initially, a sample of 200 participants was generated using Mplus in order to demonstrate the use of the function with the full sample and a single participant in particular. Subsequently, the function was applied to data from the General Aptitude Test (GAT) and the measurement of cognitive ability. Using a sample of 8500 participants, the present R function was demonstrated. An illustrative example of a single participant, assumed to be either a rapid responder or a successful guesser, is provided using MLE and BME. It was concluded that the present function can contribute to a more valid estimation of person ability.

Clinical efficacy of thyroid-stimulating immunoglobulin detection for diagnosing Graves’ disease and predictors of responsiveness to methimazole

BackgroundAs thyroid-stimulating immunoglobulins (TSI) are a sign of Graves' disease (GD), measuring TSI titers is becoming increasingly important for GD diagnosis. This study evaluated the diagnostic accuracy of a new fully automated TSI immunoassay (Immulite™ TSI assay) in GD patients and compared it to the third generation thyroid-stimulating hormone receptor antibody (TRAb) electrochemiluminescence assay (Elecsys Anti-TSHR assay). Additionally, clinical characteristics associated with responsiveness to methimazole in patients with newly diagnosed GD were preliminarily explored. MethodsThis study involved 324 subjects, comprising patients with untreated GD (GD-UT), Graves’ ophthalmopathy (GO) patients, GD patients who had been treated for > 12 months (GD-T), autoimmune thyroiditis (AIT) patients, and healthy subjects (HS). The Immulite™ TSI and Elecsys Anti-TSHR assay were performed on all samples. According to their responsiveness to methimazole, the GD-UT patients were divided into rapid and slow responder groups, and their clinical characteristics were compared. ResultsA receiver operating characteristic (ROC) curve analysis of GD-UT patients showed that the optimal TSI cut-off value was 0.57 IU/L. Logistic regression revealed that age and initial FT4 and TSI levels in the middle-dose methimazole group were related to a rapid response, while the initial FT4 level, but not TSI, in the high-dose group was also associated with a rapid response. ConclusionsThe clinical diagnostic performance of the Immulite™ TSI assay for diagnosing GD was comparable to that of the Elecsys Anti-TSHR assay. The initial FT4 and TSI levels can be used as predictors of the responsiveness to methimazole in patients with newly diagnosed GD.

High resistance to intestinal nematode infection is associated with a strong bias for TFH cell responses, rapid IgG1 class switch and limited Th2 effector cell expansion

Abstract Gastrointestinal nematode infections are highly prevalent in nature, lead to considerable morbidity in infected humans and cause high economical loss in animal husbandry. While it is clear that type 2 responses orchestrated by CD4+GATA-3+ Th2 cells are pivotal for the control of GI nematodes, the basis for differential susceptibility of distinct host genetic backgrounds is less well understood. The high resistance of ‘rapid responder’ SJL mice to infections with the small intestinal nematode H. polygyrus is evident in low parasite egg production and the termination of infection within a few weeks. Comparing the SJL line to slow responder C57BL/6 mice, we found that SJL mice generated relatively few Th2 effector cells, many follicular T helper cells and strong antibody responses in spleen and gut draining lymph nodes. These Th2 effector cells of SJL mice expressed high levels of the gut/mucosal homing markers CCR9/a4b7, resulting in the rapid accumulation of Th2 cells in the infected small intestine. Surprisingly, resistance was further associated with exceptionally high proportions of Treg in the spleen of SJL mice at steady state and the vigorous expansion of Treg in mLN after infection. This coincided with a bias for follicular T helper cells expansion in both mLN and spleen and, consequently, more extensive IgG1 class switching by GL7+ germinal center B cells in both organs. Infection-derived B cells transfer provides protection in SJL mice, not in B6 mice. In conclusion, resistance versus susceptibility to primary H. polygyrus infection appears to be less dependent on the overall magnitude of Th2 responses, but rather seems to depend on rapid Th2 effector homing, follicular T helper cells and the rapid instruction of antibody responses.

Emergency Response Preparation in a New Outpatient Proton Center

Patient acuity is increasing in the ambulatory setting. New treatments and techniques assist patients in living longer, in turn allowing additional comorbidities to develop. Many of these comorbidities may require urgent treatment. Emergency response preparation can have a positive impact on readiness and timed responses to prevent and respond to emergencies. A new 80,000 square-foot ambulatory proton center was built within an academically-aligned community hospital. As part of its opening, protocols for emergency response preparation were developed and enacted. The aim of this Quality Improvement project was to develop a plan for emergency response as it pertains to declining patients and medical codes in a newly-opened ambulatory radiation oncology setting. Emergency response plans were developed in collaboration with the Armstrong Institute using the Systems Engineering Initiative for Patient Safety model (SEIPS) model to guide practice. The SEIPS model provides guidance when analyzing factors that affect patient safety. The focus of the plan was to identify potential risks and mitigate them in order to minimize adverse safety events for patients. Additionally, the plan was designed to allow for process improvement to improve quality and patient outcomes. The response plan was tested with three simulated scenarios: rapid response to a patient fall, pediatric cardiac arrest, and a medical emergency during an MRI procedure. Due to the scope of the exercise, only the pediatric cardiac arrest was trialed more than once. For the patient fall scenario, a hospital wide alert was dispatched in 25 seconds for the response team. The first rapid responder arrived within 85 seconds and the stretcher was brought to the scene in an additional 90 seconds. During the MRI scenario, staff were able to reduce the time to move the patient from 64 to 42 seconds. In the pediatric cardiac arrest scenario, there were decreases in time for staff arrival, arrival of an emergency cart, defibrillation, stretcher arrival, and transport to an appropriate level of care. Overall practice gaps identified include issues with the automated communications, and the need for ergonomic techniques for moving heavy equipment, an MRI stretcher, lighting in stairwells, and badge access. This quality improvement project utilized scenarios to facilitate identification of gaps in practice. Common themes amongst the scenarios were identified, and team members from various disciplines were able to work together to identify solutions to close the gaps. When opening a new outpatient clinical site, it is important to identify and test emergency response plans in order to promote patient safety.

Shining light on the response to repair intermediates in DNA of living cells

Fluorescently-tagged repair proteins have been widely used to probe recruitment to micro-irradiation-induced nuclear DNA damage in living cells. Here, we quantify APE1 dynamics after micro-irradiation. Markers of DNA damage are characterized and UV-A laser micro-irradiation energy conditions are selected for formation of oxidatively-induced DNA base damage and single strand breaks, but without detectable double strand breaks. Increased energy of laser micro-irradiation, compared with that used previously in our work, enables study of APE1 dynamics at the lesion site. APE1 shows rapid transient kinetics, with recruitment half-time of less than 1 s and dissociation half-time of less than 15 s. In cells co-transfected with APE1 and PARP1, the recruitment half-time of PARP1 was slower than that of APE1, indicating APE1 is a rapid responder to the damage site. While recruitment of APE1 is unchanged in the presence of co-transfected PARP1, APE1 dissociation is 3-fold slower, revealing PARP1 involvement in APE1 dynamics. Further, we find that APE1 dissociation kinetics are strongly modified in the absence of DNA polymerase β (pol β). After unchanged recruitment to the damage site, dissociation of APE1 became undetectable. This indicates a necessary role for pol β in APE1 release after its recruitment to the damage site. These observations represent an advance in our understanding of in vivo dynamics of base excision repair factors APE1, PARP1 and pol β.

Staff's Perception of the Intensive Care Outreach Nurse Role: A Multisite Cross-sectional Study.

Rapid Response Systems are emerging internationally to provide a patient-focused approach to prevent potentially avoidable deaths and serious adverse events. This study focused on ward nurses in the United Arab Emirates (UAE) government hospitals who were perceived to lack the confidence and knowledge to detect and/or respond to deteriorating patients. A cross-sectional study design was used to evaluate the Intensive Care Outreach Nurse (ICON) role from the perspectives of the ICONs, their managers/educators, and ward-based physicians and nurses. ICONs are intensive care experienced nurses with additional education in the role of rapid responder to the deteriorating patient. An ICON role was implemented across 4 hospitals to respond to and support clinicians in the recognition and management of the deteriorating patient on general inpatient wards. ICON skills perceived as most beneficial by respondents included staff education, respiratory therapy, medication administration, and intravenous access. The ICON role is able to support recognition and management of the deteriorating patients.

The Mass Casualty Incident in Turin, 2017: A Case Study of Disaster Responders' Mental Health in an Italian Level I Hospital.

To assess the psychological impact of a mass casualty incident (MCI) in a subset of personnel in a level I hospital. Emergency department staff responded to an MCI in June 2017 in Turin, Italy by an unexpected sudden surge of casualties following a stampede (mass escape). Participants completed the Psychological Simple Triage and Rapid Treatment Responder Self-Triage System (PsySTART-R), which classified the potential risk of psychological distress in "no risk" versus "at risk" categorization and identified a range of impacts aggregated for the population of medical responders. Participants were administered a questionnaire on the perceived effectiveness of management of the MCI. Two months later, the participants were evaluated using the Hospital Anxiety and Depression Scale (HADS), the Kessler Psychological Distress Scale (K6), and the Posttraumatic Stress Disorder Checklist (PCL-5). The majority of the responders were classified as "no risk" by the PsySTART-R; no significant differences on HADS, K6, and PCL-5 were found in the participants grouped by the PsySTART-R categories. The personnel acquainted to work in emergency contexts (emergency department and intensive care unit) scored significantly lower in the HADS than the personnel usually working in other wards. The number of positive PsySTART-R criteria correlated with the HADS depression score. Most of the adverse psychological implications of the MCI were well handled and averted by the responders. A possible explanation could be related to factors such as the clinical condition of the victims (most were not severely injured, no fatalities), the small number of casualties (87) brought to the hospital, the event not being considered life-threatening, and its brief duration, among others. Responders had mainly to cope with a sudden surge in casualties and with organizational issues.

Early Blood Profile of C57BL/6 Mice Exposed to Chronic Unpredictable Stress.

Physiological responses to psychological stressors are protective in acute fight or flight situations; however, there is increasing evidence suggesting the detrimental impact of chronic psychological stress on disease. Chronic stress has been associated with inflammation, poor prognosis, increased morbidity, and poor outcome in many diseases including atherosclerosis, cancer, and pulmonary disease. Given the systemic impact of stress, and the role of the hematopoietic system as a rapid responder to homeostatic insults, we hypothesized that early blood profile changes and biochemical alterations could be detected in a model of chronic stress. To test this hypothesis, a variation of the chronic unpredictable stress (CUS) model was employed. Following 10 days of CUS, C57BL/6 mice exhibited a chronic-stress-associated corticosterone profile. Complete blood count (CBC) revealed mild normochromic, normocytic anemia, and reduced monocyte and lymphocyte count. Serum analysis demonstrated hypoferremia with unchanged total iron binding capacity and serum ferritin levels. These findings are consistent with clinical diagnostic parameters for anemia of chronic disease and indicate that CUS results in significant changes in blood and serum biochemical profile in C57BL/6 mice. These studies identify early changes in blood parameters in response to CUS and identify hematopoietic and biochemical alterations that are often associated with increased morbidity in patients experiencing chronic-stress-associated mental health disease.

The pattern of symptom change during prolonged exposure therapy and present-centered therapy for PTSD in active duty military personnel.

Few studies have investigated the patterns of posttraumatic stress disorder (PTSD) symptom change in prolonged exposure (PE) therapy. In this study, we aimed to understand the patterns of PTSD symptom change in both PE and present-centered therapy (PCT). Participants were active duty military personnel (N = 326, 89.3% male, 61.2% white, 32.5 years old) randomized to spaced-PE (S-PE; 10 sessions over 8 weeks), PCT (10 sessions over 8 weeks), or massed-PE (M-PE; 10 sessions over 2 weeks). Using latent profile analysis, we determined the optimal number of PTSD symptom change classes over time and analyzed whether baseline and follow-up variables were associated with class membership. Five classes, namely rapid responder (7-17%), steep linear responder (14-22%), gradual responder (30-34%), non-responder (27-33%), and symptom exacerbation (7-13%) classes, characterized each treatment. No baseline clinical characteristics predicted class membership for S-PE and M-PE; in PCT, more negative baseline trauma cognitions predicted membership in the non-responder v. gradual responder class. Class membership was robustly associated with PTSD, trauma cognitions, and depression up to 6 months after treatment for both S-PE and M-PE but not for PCT. Distinct profiles of treatment response emerged that were similar across interventions. By and large, no baseline variables predicted responder class. Responder status was a strong predictor of future symptom severity for PE, whereas response to PCT was not as strongly associated with future symptoms.

Safety of on-scene medical care by EMS nurses in non-transported patients: a prospective, observational study

BackgroundAfter on-scene examination and /or treatment, emergency medical services (EMS) nurses must decide whether the patient requires further assessment or treatment, most frequently in a hospital. The primary objective of this study was to assess the reliability of the current EMS protocol by determining whether the decision not to transport the patient to a care provider was correct or not.MethodsAdults receiving on-scene medical care by an EMS rapid responder or full team without transport to the hospital were included in this prospective observational study. The primary outcome measure was secondary consultation within 24 h after an on-scene EMS evaluation without transport for the same or a closely related complaint. The secondary outcome measures were patient satisfaction, type of secondarily consulted health care provider, provisional and definitive diagnosis, and correctness of the EMS members’ decision to provide on-scene medical care without transport.ResultsOf the 1095 participating patients, 271 (24.7%) patients requested secondary medical attention for the same complaint. This percentage was significantly larger in incidents attended by an ambulance team than by a rapid responder (N = 248 (26.5%) vs. N = 23 (14.4%); p < 0.05). In eleven (1.0%) cases an urgent medical diagnosis requiring admission was missed. A total of 873 (79.7%) patients were satisfied with the decision not to be transported. In 44 (4.0%) cases the EMS nurse’s decision was rated incorrect since the patient needed help contradictory to the EMS nurse’s recommendation.ConclusionsThe data show that EMS nurses can effectively examine patients, but a low threshold of referral for consultation should be considered because one in four patients requested secondary medical attention for the same complaint(s) again. However, due to a low response rate (11.3%) more research is needed to further determine the safety of the current EMS protocol.Trial registrationNot applicable.

Free Thyroxine, Anti-Thyroid Stimulating Hormone Receptor Antibody Titers, and Absence of Goiter Were Associated with Responsiveness to Methimazole in Patients with New Onset Graves' Disease.

BackgroundAnti-thyroid drug therapy is considered a treatment of choice for Graves' disease; however, treatment response varies among individuals. Although several studies have reported risk factors for relapse after initial treatment, few have assessed responsiveness during the early treatment period. Our study aimed to identify the clinical characteristics for responsiveness to methimazole.MethodsWe included 99 patients diagnosed with Graves' disease for the first time. Drug responsiveness was defined as the correlation coefficients between decreasing rates of free thyroxine level per month and methimazole exposure dose. According to their responsiveness to treatment, the patients were classified into rapid or slow responder groups, and age, sex, free thyroxine level, and thyrotropin binding inhibiting immunoglobulin (TBII) titers were compared between groups.ResultsThe mean patient age was 44.0±13.5 years and 40 patients were male (40%). The mean TBII titer was 36.6±74.4 IU/L, and the mean free thyroxine concentration was 48.9±21.9 pmol/L. The rapid responder group showed higher TBII titer and free thyroxine level at diagnosis, while age, sex, smoking, and presence of goiter did not differ between the two groups. Logistic regression analyses revealed that high level of serum thyroxine, high titer of TBII, and absence of goiter were significantly associated with a rapid response, while age, sex, and smoking were not significant factors for the prediction of responsiveness.ConclusionIn patients with new onset Graves' disease, high level of free thyroxine, high titer of TBII, and absence of goiter were associated with rapid responsiveness to methimazole treatment.

Compliance tables for an EMS system with two types of medical response units

In this paper, we consider an Emergency Medical Services (EMS) system with two types of medical response units: Rapid Responder Ambulances (RRAs) and Regular Transport Ambulances (RTAs). The key difference between both is that RRAs are faster, but they lack the ability to transport a patient to the hospital. To maintain the ability to respond to emergency requests timely when ambulances get busy, we consider compliance tables, which indicate the desired locations of the available ambulances. Our system brings forth additional complexity to the problem of computing optimal compliance tables, as we have two kinds of ambulances. We propose an Integer Linear Program (ILP) computing compliance tables for such a system, which uses outcomes of a Hypercube model as input parameters. Moreover, we include nestedness constraints and we set bounds on the relocation times in the ILP. To obtain more credible results, we simulate the computed compliance tables for different input parameters. Results show that bounding the time a relocation may last is beneficial in certain settings. Besides, including the nestedness constraints ensures that the number of relocations and the relocation time is reduced, while the performance stays unaffected.

Innate lymphoid cells in type 2 immune responses.

In recent years, several distinct innate lymphoid cell populations (ILC) have been characterized in mice and humans. Group 2 ILC function as a rapid responder population in type 2 immune responses. Thus, a wealth of data has implicated an important role for ILC2 in immunity to parasitic infection and in immune pathology in inflammatory and allergic responses. In this review, we describe recent progress in our understanding of the development and ontogeny of ILC2 populations and the mechanisms by which these cells function in a variety of infection and disease settings. Finally, we emphasize recent findings indicating functional interactions between these innate cells and their adaptive CD4(+) Th2 cell counterparts.

Validating the Rapid Responder Construct Within a Practice Research Network

The present study was a replication and extension of prior work (Stulz, Lutz, Leach, Lucock, & Barkham, ) that identified multiple groups of clients in treatment with high-symptom severity and markedly different recovery trajectories (rapid/early response vs. little or no response). Using data collected through repeated administrations of the Depression subscale of the Treatment Outcome Package (n = 147), growth mixture modeling was employed to determine whether clients fell into discrete groups of response trajectories during 15 sessions of psychotherapy. Additionally, logistic regressions were conducted to assess possible predictors of group membership. Three separate groups of treatment responders were identified: 2 high-symptom groups-rapid responders and nonresponders-and 1 low-symptom group of nonresponders. Elevated social conflict and suicidality predicted increased likelihood of membership in the high-symptom nonresponder group. Increased feelings of interpersonal hostility and better sexual functioning predicted increased likelihood of membership in the rapid responder group. Replication of earlier results provides further evidence for the usefulness of modeling change during psychotherapy using multiple trajectories. Predictors of group membership indicate the influence of functional impairment on recovery, and support the importance of multidimensional measurement of client problems.

Lymphotropic hepatitis C virus has an interferon‐resistant phenotype

Hepatitis C virus (HCV) infects and associates with B cells, leading to abnormal B-cell activation and development of lymphoproliferative and autoimmune disorders. This immune perturbation may in turn be associated with the resistance of HCV against the host immune system. The objective of this study was to analyse the effects of HCV infection of B cells on the efficacy of interferon (IFN)-based therapy. The study enrolled 102 patients with chronic hepatitis C who were treated with pegylated IFN plus ribavirin. HCV RNA titres in B cells were compared in patients with rapid viral responder (RVR) vs non-RVR, sustained viral responder (SVR) vs non-SVR and null viral responder (NVR) vs VR. The levels of HCV RNA in B cells were significantly higher in non-RVR, non-SVR and NVR groups. Association between the therapy outcome and the positive B-cell HCV RNA was also investigated in relation to other known viral and host factors. Multivariable analyses showed that the positive B-cell HCV RNA and the minor single-nucleotide polymorphism near the IL28B gene (rs8099917) were independent factors associated with NVR in patients infected with HCV genotype 1. When these two factors were combined, the sensitivity, specificity, positive and negative predictive values for NVR were 92.3%, 98.2%, 92.3% and 98.2%, respectively. Genotype 1 and the presence of one or no mutations in the IFN-sensitivity determining region were associated with higher levels of B-cell HCV RNA. B-cell-tropic HCV appears to have an IFN-resistant phenotype. B-cell HCV RNA positivity is a predictive factor for resistance to IFN-based therapy.

Rapid Neurological Recovery after Intravenous Tissue Plasminogen Activator in Stroke: Prognostic Factors and Outcome

Background: Treatment with tissue plasminogen activator (tPA) is associated with improved outcome in acute ischemic stroke. Of note, a proportion of patients demonstrate rapid and significant neurological recovery within 24 h. This has previously not been systematically studied. We aimed to examine its incidence, predictive factors and correlation with clinical outcomes. Methods: We included 161 patients with acute ischemic stroke who received intravenous tPA within 4.5 h. Patient demographics and clinical data were collected. Rapid neurological recovery was defined as an improvement of at least 50% within 24 h as measured by the National Institute of Health Stroke Scale (NIHSS) score, and long-term outcomes were assessed by 3-month modified Rankin Scale. The incidence of rapid neurological recovery and its correlation with outcomes were studied. The predictors of the phenomenon were examined by univariate analysis. Results: Rapid neurological recovery was present in 44 of the 161 patients (27.3%). This correlated with favorable outcomes at 3 months (p < 0.0005). Lower baseline NIHSS score (p = 0.006), mild (NIHSS score <12) versus severe stroke (NIHSS score ≧12; p = 0.002), normal serum glucose levels on admission (3.3–7.7 mmol/l; p = 0.009) and younger age (p = 0.043) predicted rapid neurological recovery. However, there was no association with time to treatment (p = 0.3). Conclusion: Rapid neurological recovery defines a rapid responder population and was demonstrated in a quarter of patients treated with intravenous tPA. It strongly predicts a good clinical outcome.

Young Adults With Acute Lymphoblastic Leukemia Have an Excellent Outcome With Chemotherapy Alone and Benefit From Intensive Postinduction Treatment: A Report From the Children's Oncology Group

Patients 16 to 21 years of age with acute lymphoblastic leukemia (ALL) have an inferior outcome compared with younger children, leading some medical oncologists to advocate allogeneic stem-cell transplantation in first remission for these patients. We examined outcome for young adults with ALL enrolled onto the Children's Cancer Group (CCG) 1961 study between 1996 and 2002. CCG 1961 entered patients with ALL 1 to 21 years of age with initial WBC count > or = 50,000/microL and/or age > or = 10 years. Randomly assigned therapies evaluated the impact of postinduction treatment intensification on outcome. We examined outcome and prognostic factors for 262 young adults with ALL. Five-year event-free and overall survival rates for young adult patients are 71.5% (SE, 3.6%) and 77.5% (SE, 3.3%), respectively. Rapid responder patients (< 25% bone marrow blasts on day 7) randomly assigned to augmented therapy had 5-year event-free survival of 81.8% (SE, 7%), as compared with 66.8% (SE, 6.7%) for patients receiving standard therapy (P = .07). One versus two interim maintenance and delayed intensification courses had no significant impact on event-free survival. WBC count more than 50,000/microL was an adverse prognostic factor. Young adult patients with ALL showing a rapid response to induction chemotherapy benefit from early intensive postinduction therapy but do not benefit from a second interim maintenance and delayed intensification phase. Given the excellent outcome with this chemotherapy, there seems to be no role for the routine use of allogeneic stem-cell transplantation in first remission for young adults with ALL.