Association between mortality and phone-line waiting time for non-urgent medical care: a Danish registry-based cohort study.

BACKGROUND AND IMPORTANCE: Telephone calls are often patients' first healthcare service contact, outcomes associated with waiting times are unknown. OBJECTIVES: Examine the association between waiting time to answer for a medical helpline and 1- and 30-day mortality. DESIGN, SETTING AND PARTICIPANTS: Registry-based cohort study using phone calls data (January 2014 to December 2018) to the Capital Region of Denmark's medical helpline. The service refers to hospital assessment/treatment, dispatches ambulances, or suggests self-care guidance. EXPOSURE: Waiting time was grouped into the following time intervals in accordance with political service targets for waiting time in the Capital Region: <30 s, 0:30-2:59, 3-9:59, and ≥10 min. OUTCOME MEASURES AND ANALYSIS: The association between time intervals and 1- and 30-day mortality per call was calculated using logistic regression with strata defined by age and sex. MAIN RESULTS: In total, 1 244 252 callers were included, phoning 3 956 243 times, and 78% of calls waited <10 min. Among callers, 30-day mortality was 1% (16 560 deaths). For calls by females aged 85-110 30-day mortality increased with longer waiting time, particularly within the first minute: 9.6% for waiting time <30 s, 10.8% between 30 s and 1 minute and 9.1% between 1 and 2 minutes. For calls by males aged 85-110 30-day mortality was 11.1%, 12.9% and 11.1%, respectively. Additionally, among calls with a Charlson score of 2 or higher, longer waiting times were likewise associated with increased mortality. For calls by females aged 85-110 30-day mortality was 11.6% for waiting time <30 s, 12.9% between 30 s and 1 minute and 11.2% between 1 and 2 minutes. For calls by males aged 85-110 30-day mortality was 12.7%, 14.1% and 12.6%, respectively. Fewer ambulances were dispatched with longer waiting times (4%/2%) with waiting times <30 s and >10 min. CONCLUSION: Longer waiting times for telephone contact to a medical helpline were associated with increased 1- and 30-day mortality within the first minute, especially among elderly or more comorbid callers.

Long-Term Quality of Life After Out-of-Hospital Cardiac Arrest.

Importance: Allocating resources to increase survival after cardiac arrest requires survivors to have a good quality of life, but long-term data are lacking. Objective: To determine the quality of life of survivors of out-of-hospital cardiac arrest from 2001 to 2019. Design, Setting, and Participants: This survey study used the EuroQol Health Questionnaire, 12-Item Short Form Health Survey (SF-12), and Hospital Anxiety and Depression Scale (HADS) to assess the health-related quality of life of all adult survivors of out-of-hospital cardiac arrest included in the Danish Cardiac Arrest Registry between June 1, 2001, and August 31, 2019, who were alive in October 2020 (follow-up periods, 0-1, >1-2, >2-4, >4-6, >6-8, >8-10, >10-15, and >15-20 years since arrest). The survey was conducted from October 1, 2020, through May 31, 2021. Exposure: All patients who experienced an out-of-hospital cardiac arrest. Main Outcome and Measures: Self-reported health was measured using the EuroQol Health Questionnaire index (EQ index) score and EQ visual analog scale. Physical and mental health were measured using the SF-12, and anxiety and depression were measured using the HADS. Descriptive statistics were used for the analysis. Results: Of 4545 survivors, 2552 (56.1%) completed the survey, with a median follow-up since their event of 5.5 years (IQR, 2.9-8.9 years). Age was comparable between responders and nonresponders (median [IQR], 67 [58-74] years vs 68 [56-78] years), and 2075 responders (81.3%) were men and 477 (18.7%) women (vs 1473 male [73.9%] and 520 female [26.1%] nonresponders). For the shortest follow-up (0-1 year) and longest follow-up (>15-20 years) groups, the median EQ index score was 0.9 (IQR, 0.7-1.0) and 0.9 (0.8-1.0), respectively. For all responders, the mean (SD) SF-12 physical health score was 43.3 (12.3) and SF-12 mental health score, 52.9 (8.3). All 3 scores were comparable to a general Danish reference population. Based on HADS scores, a low risk for anxiety was reported by 73.0% (54 of 74) of 0- to 1-year survivors vs 89.3% (100 of 112) of greater than 15- to 20-year survivors; for symptoms of depression, these proportions were 79.7% (n = 59) and 87.5% (n = 98), respectively. Health-related quality of life was similar in survivor groups across all follow-up periods. Conclusions and Relevance: Among this survey study's responders, who comprised more than 50% of survivors of out-of-hospital cardiac arrest in Denmark, long-term health-related quality of life up to 20 years after their event was consistently high and comparable to that of the general population. These findings support resource allocation and efforts targeted to increasing survival after out-of-hospital cardiac arrest.

"I just haven't experienced anything like this before": A qualitative exploration of callers' interpretation of experienced conditions in telephone consultations preceding a myocardial infarction.

OBJECTIVES: Callers with myocardial infarction presenting atypical symptoms in telephone consultations when calling out-of-hours medical services risk misrecognition. We investigated characteristics in callers' interpretation of experienced conditions through communication with call-takers. METHODS: Recording of calls resulting in not having an ambulance dispatched for 21 callers who contacted a non-emergency medical helpline, Copenhagen (Denmark), up to one week before they were diagnosed with myocardial infarction. Qualitative content analysis was applied. RESULTS: Awareness of illness, remedial actions and previous experiences contributed to callers' interpretation of the experienced condition. Unclear symptoms resulted in callers reacting to their interpretation by being unsure and worried. Negotiation of the interpretation was seen when callers tested the call-taker's interpretation of the condition and when either caller or call-taker suggested: "wait and see". CONCLUSION: Callers sought to interpret the experienced conditions but faced challenges when the conditions appeared unclear and did not correspond to the health system's understanding of symptoms associated with myocardial infarction. It affected the communicative interaction with the call-taker and influenced the call-taker's choice of response. PRACTICE IMPLICATIONS: Call-takers, as part of the decision-making process, could ask further questions about the caller's insecurity and worry. It might facilitate faster recognition of conditions warranting hospital referral.

Registered prodromal symptoms of out-of-hospital cardiac arrest among patients calling the medical helpline services.

Background Early identification of warning symptoms among out-of-hospital cardiac arrest (OHCA) patients remains challenging. Thus, we examined the registered prodromal symptoms of patients who called medical helpline services within 30-days before OHCA. Methods Patients unwitnessed by emergency medical services (EMS) aged ≥18 years during their OHCA were identified from the Danish Cardiac Arrest Registry (2014-2018) and linked to phone records from the 24-h emergency helpline (1-1-2) and out-of-hours medical helpline (1813-Medical Helpline) in Copenhagen before the arrest. The registered symptoms were categorized into chest pain; breathing problems; central nervous system (CNS)-related/unconsciousness; abdominal/back/urinary; psychiatric/addiction; infection/fever; trauma/exposure; and unspecified (diverse from the beforementioned categories). Analyses were divided by the time-period of calls (0-7 days/8-30 days preceding OHCA) and call type (1-1-2/1813-Medical Helpline). Results Of all OHCA patients, 18% (974/5442) called helpline services (males 56%, median age 76 years[Q1-Q3:65-84]). Among these, 816 had 1145 calls with registered symptoms. The most common symptom categories (except for unspecified, 33%) were breathing problems (17%), trauma/exposure (17%), CNS/unconsciousness (15%), abdominal/back/urinary (12%), and chest pain (9%). Most patients (61%) called 1813-Medical Helpline, especially for abdominal/back/urinary (17%). Patients calling 1-1-2 had breathing problems (24%) and CNS/unconsciousness (23%). Nearly half of the patients called within 7 days before their OHCA, and CNS/unconsciousness (19%) was the most registered. The unspecified category remained the most common during both time periods (32%;33%) and call type (24%;39%). Conclusions Among patients who called medical helplines services up to 30-days before their OHCA, besides symptoms being highly varied (unspecified (33%)), breathing problems (17%) were the most registered symptom-specific category.

Symptoms reported in calls to emergency medical services within 24 hours prior to out-of-hospital cardiac arrest.

AIM: There is limited evidence regarding prodromal symptoms of out-of-hospital cardiac arrest (OHCA). We aimed to describe patient characteristics, prodromal symptoms, and prognosis of patients contacting emergency medical services (EMS) within 24 hours before OHCA. METHODS: We identified all OHCA treated by Copenhagen EMS from 2016 through 2018 using the Danish Cardiac Arrest Registry and linked them to emergency calls. We included all pre-arrest calls by patients or bystanders if they were performed 1) within 24 hours before the OHCA call or 2) during the OHCA event for EMS-witnessed OHCA. Calls were reviewed by healthcare professionals using a survey guide. RESULTS: Among 4,071 patients, 481 patients (12 %) had 539 calls within 24 hours prior to OHCA (60 % male, median age 74 years of age). The patient spoke on the phone in 25 % of calls. The most common symptoms were breathing problems (59 %), confusion (23 %), unconsciousness (20 %), chest pain (20 %), and paleness (19 %). Patients with breathing problems compared to chest pain were more likely to be ≤ 75 years of age (55 % versus 35 %), less likely to be male (52 % versus 73 %), have shockable rhythm (10 % versus 38 %), receive bystander defibrillation (6 % versus 19 %) or EMS defibrillation (15 % versus 65 %), achieve return of spontaneous circulation (37 % versus 68 %) and survive 30 days following OHCA (10 % versus 50 %). CONCLUSION: More than 10% of patients with OHCA had a call to EMS within 24 hours before OHCA. The most common symptom was breathing problems which compared to chest pain had lower 30-day survival.

"Like a rainy weather inside of me": Qualitative content analysis of telephone consultations concerning back pain preceding out-of-hospital cardiac arrest.

INTRODUCTION: Cardiac arrest patients presenting with back pain are at risk of not receiving the appropriate help when calling emergency medical services. In telephone consultations regarding patients with back pain preceding an out-of-hospital cardiac arrest, we investigated how communication between caller and call-taker influenced the call-taker's interpretation of back pain descriptions and decision-making about choice of response. METHOD: The study was conducted using 20 recorded phone calls from 17 patients who contacted the Copenhagen Emergency Medical Services (Denmark) reporting back pain up to 24 hours before an out-of-hospital cardiac arrest. Qualitative content analysis was applied. RESULTS: Two main categories emerged: (1) reasons, including subcategories: reported conditions, descriptions of conditions, patient's interpretation of condition and patient's own remedial actions; and (2) considerations, including subcategories: assessment of the severity, call-taker's interpretation of the condition, arguments for chosen response and conditions not facilitating further communication by the call-taker. CONCLUSION: In telephone consultations regarding patients with back pain preceding an out-of-hospital cardiac arrest the communication was influenced by the communicative preconditions of the call-taker. Communication in consultations where ambulances were not dispatched was characterized by complex descriptions of symptoms not easily fitting into the health system's interpretations of conditions warranting an urgent response.

Community established best practice recommendations for tephra studies-from collection through analysis.

Tephra is a unique volcanic product with an unparalleled role in understanding past eruptions, long-term behavior of volcanoes, and the effects of volcanism on climate and the environment. Tephra deposits also provide spatially widespread, high-resolution time-stratigraphic markers across a range of sedimentary settings and thus are used in numerous disciplines (e.g., volcanology, climate science, archaeology). Nonetheless, the study of tephra deposits is challenged by a lack of standardization that inhibits data integration across geographic regions and disciplines. We present comprehensive recommendations for tephra data gathering and reporting that were developed by the tephra science community to guide future investigators and to ensure that sufficient data are gathered for interoperability. Recommendations include standardized field and laboratory data collection, reporting and correlation guidance. These are organized as tabulated lists of key metadata with their definition and purpose. They are system independent and usable for template, tool, and database development. This standardized framework promotes consistent documentation and archiving, fosters interdisciplinary communication, and improves effectiveness of data sharing among diverse communities of researchers.

Contacts With the Health Care System Before Out-of-Hospital Cardiac Arrest.

Background It remains challenging to identify patients at risk of out-of-hospital cardiac arrest (OHCA). We aimed to examine health care contacts in patients before OHCA compared with the general population that did not experience an OHCA. Methods and Results Patients with OHCA with a presumed cardiac cause were identified from the Danish Cardiac Arrest Registry (2001-2014) and their health care contacts (general practitioner [GP]/hospital) were examined up to 1 year before OHCA. In a case-control study (1:9), OHCA contacts were compared with an age- and sex-matched background population. Separately, patients with OHCA were examined by the contact type (GP/hospital/both/no contact) within 2 weeks before OHCA. We included 28 955 patients with OHCA. The weekly percentages of patient contacts with GP the year before OHCA were constant (25%) until 1 week before OHCA when they markedly increased (42%). Weekly percentages of patient contacts with hospitals the year before OHCA gradually increased during the last 6 months (3.5%-6.6%), peaking at the second week (6.8%) before OHCA; mostly attributable to cardiovascular diseases (21%). In comparison, there were fewer weekly contacts among controls with 13% for GP and 2% for hospital contacts (P<0.001). Within 2 weeks before OHCA, 57.8% of patients with OHCA had a health care contact, and these patients had more contacts with GP (odds ratio [OR], 3.17; 95% CI, 3.09-3.26) and hospital (OR, 2.32; 95% CI, 2.21-2.43) compared with controls. Conclusions The health care contacts of patients with OHCA nearly doubled leading up to the OHCA event, with more than half of patients having health care contacts within 2 weeks before arrest. This could have implications for future preventive strategies.

Symptom presentation of SARS-CoV-2-positive and negative patients: a nested case-control study among patients calling the emergency medical service and medical helpline.

OBJECTIVE: Currently effective symptom-based screening of patients suspected of COVID-19 is limited. We aimed to investigate age-related differences in symptom presentations of patients tested positive and negative for SARS-CoV-2. DESIGN: SETTING: Calls to the medical helpline (1-8-1-3) and emergency number (1-1-2) in Copenhagen, Denmark. At both medical services all calls are recorded. PARTICIPANTS: We included calls for patients who called for help/guidance at the medical helpline or emergency number prior to receiving a test for SARS-CoV-2 between April 1st and 20th 2020 (8423 patients). Among these calls, we randomly sampled recorded calls from 350 patients who later tested positive and 250 patients tested negative and registered symptoms described in the call. OUTCOME: RESULTS: After exclusions, 544 calls (312 SARS-CoV-2 positive and 232 negative) were included in the analysis. Fever and cough remained the two most common of COVID-19 symptoms across all age groups and approximately 42% of SARS-CoV-2 positive and 20% of negative presented with both fever and cough. Symptoms including nasal congestion, irritation/pain in throat, muscle/joint pain, loss of taste and smell, and headache were common symptoms of COVID-19 for patients younger than 60 years; whereas loss of appetite and feeling unwell were more commonly seen among patients over 60 years. Headache and loss of taste and smell were rare symptoms of COVID-19 among patients over 60 years. CONCLUSION: Our study identified age-related differences in symptom presentations of SARS-CoV-2-positive patients calling for help or medical advice. The specific symptoms of loss of smell or taste almost exclusively reported by patients younger than 60 years. Differences in symptom presentation across age groups must be considered when screening for COVID-19.

Impact of myocardial infarction symptom presentation on emergency response and survival.

AIMS: We examined associations between symptom presentation and chance of receiving an emergency dispatch and 30-day mortality among patients with acute myocardial infarction (MI). METHODS AND RESULTS: Copenhagen, Denmark has a 24-h non-emergency medical helpline and an emergency number 1-1-2 (equivalent to 9-1-1). Both services register symptoms/purpose of calls. Among patients with MI as either hospital diagnosis or cause of death within 72 h after a call, the primary symptom was categorized as chest pain, atypical symptoms (breathing problems, unclear problem, central nervous system symptoms, abdominal/back/urinary, other cardiac symptoms, and other atypical symptoms), unconsciousness, non-informative symptoms, and no recorded symptoms. We identified 4880 emergency and 3456 non-emergency calls from patients with MI. The most common symptom was chest pain (N = 5219) followed by breathing problems (N = 556). Among patients with chest pain, 95% (3337/3508) of emergency calls and 76% (1306/1711) of non-emergency calls received emergency dispatch. Mortality was 5% (163/3508) and 3% (49/1711) for emergency/non-emergency calls, respectively. For atypical symptoms 62% (554/900) and 17% (137/813) of emergency/non-emergency calls received emergency dispatch and mortality was 23% (206/900) and 15% (125/813). Among unconscious, patients 99%/100% received emergency dispatch and mortality was 71%/75% for emergency/non-emergency calls. Standardized 30-day mortality was 4.3% for chest pain and 15.6% for atypical symptoms, and associations between symptoms and emergency dispatch remained in subgroups of age and sex. CONCLUSION: Myocardial infarction patients presenting with atypical symptoms when calling for help have a reduced chance of receiving an emergency dispatch and increased 30-day mortality compared to MI patients with chest pain.

Rapid dispatch for out-of-hospital cardiac arrest is associated with improved survival.

AIM: As proxy for initiation of the first link in the Chain of Survival by the dispatcher, we aimed to investigate the effect of time to first dispatch on 30-day survival among patients with OHCA ultimately receiving the highest-level emergency medical response. METHODS: We linked data on all OHCA unwitnessed by emergency medical services (EMS) treated by Copenhagen EMS from 2016 through 2018 to corresponding emergency call records. Among patients receiving highest priority emergency response, we calculated time to dispatch as time from start of call to time of first dispatch. RESULTS: We included 3548 patients with OHCA. Of these, 94.1% received the highest priority response (median time to dispatch 0.84 min, 25th-75th percentile 0.58-1.24 min). Patients with time to dispatch within one minute compared to three or more minutes were more likely to receive bystander cardiopulmonary resuscitation (77.3 vs 54.2%), bystander defibrillation (11.5 vs 6.5%) and defibrillation by emergency medical services (24.1 vs 7.5%) and were 2.6-fold more likely to survive 30 days after the OHCA (P = 0.004). Results from multivariate logistic regression were similar: odds ratio (OR) of survival 0.83 per minute increase (95% confidence interval 0.70-1.00, P = 0.04). However, survival was similar between those who received highest priority response and those who did not: OR of survival 0.88 (95% confidence interval 0.53-1.46, P = 0.61). CONCLUSION: Rapid time to dispatch among patients with highest priority response was significantly associated with a higher probability of 30-day survival following OHCA.

National all-cause mortality during the COVID-19 pandemic: a Danish registry-based study.

Denmark implemented early widespread social distancing to reduce pressure on the healthcare system from the coronavirus disease 2019 (COVID-19) pandemic, with the aims to reduce mortality. Unintended consequences might be delays in treatment for other diseases and subsequent mortality. We examined national all-cause mortality comparing weeks 1-27 in 2020 and 2015-2019. This registry-based study used Danish national registry data until 5 July 2020. We examined all-cause mortality rates among all deaths recorded from 2015 to 2020 and among chronic conditions (cardiovascular (cardiac & circulatory), chronic pulmonary, chronic kidney disease, cancer, and diabetes), comparing each week in 2020 to weeks in 2015-2019. In 2020, there were 28,363 deaths in weeks 1-27 (30 December 2019-5 July 2020), the mean deaths in 2015-2019 were 28,630 deaths (standard deviation 784). Compared to previous years, the mortality rate in weeks 3-10 of 2020 was low, peaking in week 14 (17.6 per 100,000 persons in week 9, 19.9 per 100,000 in week 14). Comorbidity prevalence among deceased individuals was similar in 2020 and 2015-2019: 71.1% of all deceased had a prior cardiovascular diagnosis, 30.0% of all deceased had a prior cardiac diagnosis. There were 493 deaths with COVID-19 in weeks 11-27, (59.8% male), and 75.1% had a prior cardiovascular diagnosis. Weekly mortality rates for pre-existing chronic conditions peaked in week 14, and then declined. During the COVID-19 pandemic, due to timely lockdown measures, the mortality rate in Denmark has not increased compared to the mortality rates in the same period during 2015-2019.

Decomposer diversity increases biomass production and shifts aboveground-belowground biomass allocation of common wheat.

Biodiversity is well known to enhance many ecosystem functions, but empirical evidence for the role of soil biodiversity for plant biomass production and allocation is scarce. Here we studied the effects of animal decomposer diversity (1, 2, and 4 species as well as a control without any decomposers) on the biomass production and aboveground-belowground biomass allocation of common wheat using two earthworm and two Collembola species using an additive design in two soil management types (organic and mineral fertilizer treatments) in a microcosm experiment. Shoot (+11%), spike (+7%), and root biomass (+56%), increased significantly with increasing decomposer diversity, and these effects were consistent across the two soil management types. Notably, decomposer diversity effects were stronger on root than on shoot biomass, significantly decreasing the shoot-to-root ratio (-27%). Increased plant biomass production was positively correlated with a decomposer richness-induced increase in soil water nitrate concentrations five weeks after the start of the experiment. However, elevated soil nitrate concentrations did not cause significantly higher plant tissue nitrogen concentrations and nitrogen amounts, suggesting that additional mechanisms might be at play. Consistent decomposer diversity effects across soil management types indicate that maintaining soil biodiversity is a robust and sustainable strategy to enhance crop yield.

Fossil and genomic evidence constrains the timing of bison arrival in North America.

The arrival of bison in North America marks one of the most successful large-mammal dispersals from Asia within the last million years, yet the timing and nature of this event remain poorly determined. Here, we used a combined paleontological and paleogenomic approach to provide a robust timeline for the entry and subsequent evolution of bison within North America. We characterized two fossil-rich localities in Canada's Yukon and identified the oldest well-constrained bison fossil in North America, a 130,000-y-old steppe bison, Bison cf. priscus We extracted and sequenced mitochondrial genomes from both this bison and from the remains of a recently discovered, ∼120,000-y-old giant long-horned bison, Bison latifrons, from Snowmass, Colorado. We analyzed these and 44 other bison mitogenomes with ages that span the Late Pleistocene, and identified two waves of bison dispersal into North America from Asia, the earliest of which occurred ∼195-135 thousand y ago and preceded the morphological diversification of North American bison, and the second of which occurred during the Late Pleistocene, ∼45-21 thousand y ago. This chronological arc establishes that bison first entered North America during the sea level lowstand accompanying marine isotope stage 6, rejecting earlier records of bison in North America. After their invasion, bison rapidly colonized North America during the last interglaciation, spreading from Alaska through continental North America; they have been continuously resident since then.

Convergence of soil microbial properties after plant colonization of an experimental plant diversity gradient.

BACKGROUND: Several studies have examined the effects of plant colonization on aboveground communities and processes. However, the effects of plant colonization on soil microbial communities are less known. We addressed this gap by studying effects of plant colonization within an experimental plant diversity gradient in subplots that had not been weeded for 2 and 5 years. This study was part of a long-term grassland biodiversity experiment (Jena Experiment) with a gradient in plant species richness (1, 2, 4, 8, 16, and 60 sown species per plot). We measured plant species richness and productivity (aboveground cover and biomass) as well as soil microbial basal respiration and biomass in non-weeded subplots and compared the results with those of weeded subplots of the same plots. RESULTS: After 2 and 5 years of plant colonization, the number of colonizing plant species decreased with increasing plant diversity, i.e., low-diversity plant communities were most vulnerable to colonization. Plant colonization offset the significant relationship between sown plant diversity and plant biomass production. In line with plant community responses, soil basal respiration and microbial biomass increased with increasing sown plant diversity in weeded subplots, but soil microbial properties converged in non-weeded subplots and were not significantly affected by the initial plant species richness gradient. CONCLUSION: Colonizing plant species change the quantity and quality of inputs to the soil, thereby altering soil microbial properties. Thus, plant community convergence is likely to be rapidly followed by the convergence of microbial properties in the soil.

How do earthworms, soil texture and plant composition affect infiltration along an experimental plant diversity gradient in grassland?

BACKGROUND: Infiltration is a key process in determining the water balance, but so far effects of earthworms, soil texture, plant species diversity and their interaction on infiltration capacity have not been studied. METHODOLOGY/PRINCIPAL FINDINGS: We measured infiltration capacity in subplots with ambient and reduced earthworm density nested in plots of different plant species (1, 4, and 16 species) and plant functional group richness and composition (1 to 4 groups; legumes, grasses, small herbs, tall herbs). In summer, earthworm presence significantly increased infiltration, whereas in fall effects of grasses and legumes on infiltration were due to plant-mediated changes in earthworm biomass. Effects of grasses and legumes on infiltration even reversed effects of texture. We propose two pathways: (i) direct, probably by modifying the pore spectrum and (ii) indirect, by enhancing or suppressing earthworm biomass, which in turn influenced infiltration capacity due to change in burrowing activity of earthworms. CONCLUSIONS/SIGNIFICANCE: Overall, the results suggest that spatial and temporal variations in soil hydraulic properties can be explained by biotic processes, especially the presence of certain plant functional groups affecting earthworm biomass, while soil texture had no significant effect. Therefore biotic parameters should be taken into account in hydrological applications.

Children's interpretation of disjunction in the scope of 'before': a comparison of English and Mandarin.

This study investigates three- to five-year-old children's interpretation of disjunction in sentences like 'The dog reached the finish line before the turtle or the bunny'. English disjunction has a conjunctive interpretation in such sentences ('The dog reached the finish line before the turtle and before the bunny'). This interpretation conforms with classical logic. Mandarin disjunction ('huozhe') can take scope over 'before' ('zai … zhiqian'), so the same sentence can mean 'The dog reached the finish line before the turtle or before the bunny (I don't know which)'. If children are guided by adult input in the acquisition of sentence meanings, English- and Mandarin-speaking children should assign different interpretations to such sentences. If children are guided by logical principles, then children acquiring either language should initially assign the conjunctive interpretation of disjunction. A truth-value judgment task was used to test this prediction and English- and Mandarin-speaking children were found to behave similarly.

Phase II study of a 3-day schedule with topotecan and cisplatin in patients with previously untreated small cell lung cancer and extensive disease.

INTRODUCTION: Treatment with a topoisomerase I inhibitor in combination with a platinum results in superior or equal survival compared with etoposide-based treatment in extensive disease small cell lung cancer (SCLC). Five-day topotecan is inconvenient and therefore shorter schedules of topotecan and cisplatin are needed. The aim of this phase II study was to establish the response rate and response duration in chemo-naive patients with SCLC receiving a 3-day topotecan and cisplatin schedule. METHODS: Simons optimal two-stage design was used. Patients with previously untreated extensive disease SCLC, adequate organ functions and performance status less than 3 were eligible. Topotecan (2.0 mg/m, intravenously) was administered on days 1 to 3 with cisplatin (50 mg/m, intravenously) on day 3 every 3 weeks for a total of six cycles. RESULTS: Forty-three patients received 219 cycles of chemotherapy. Median age was 59 (range 44-74), 79% had performance status 0 or 1. Thirty-one patients completed all six cycles. Grade 3/4 anemia, neutrocytopenia, and thrombocytopenia were recorded in 9.5%, 66.7%, and 21.4% of patients, respectively. Fourteen percent of patients experienced neutropenic fever. No episodes of fatal sepsis occurred. Non-hematologic toxicity was mild and manageable. Overall and complete response rates were 72.1% and 9.3%, respectively. The median overall survival and response duration were 10.3 months (95% confidence interval: 8.6-12.0) and 7.0 months (95% confidence interval: 6.3-7.7), respectively. CONCLUSION: Three-day topotecan with cisplatin on day 3 is active and safe in extensive disease SCLC. An ongoing phase III randomized trial compares this combination to standard treatment.

Topotecan and cisplatin in combination with concurrent twice-daily chemoradiation in limited disease small cell lung cancer-a Danish Oncological Lung Cancer Group (DOLG) phase II trial.

INTRODUCTION: The longest survival time reported in randomised trials of limited disease (LD) SCLC has been achieved with early twice-daily concurrent chemoradiation. Topotecan is active in recurrent SCLC and in extensive disease as first line treatment. AIM: To incorporate and assess the effect of topotecan with concurrent twice-daily radiochemotherapy in LD SCLC. PATIENT AND METHODS: Multicentre phase II study of three cycles of regimen A (topotecan i.v., 1.5mg/m(2), day 1-5; cisplatin 50mg/m(2), day 1) and three cycles of regimen B (etoposide i.v., 120mg/m(2), day 1-3; carboplatin, AUC=5, day 1; vincristine, 1.3mg/m(2), day 1) given in the following sequence: A-B-B-A-B-A every 21 days. Twice-daily radiotherapy (1.5Gyx30, 10fr/wk, 45Gy) was delivered concurrently with the first cycle B. Prophylactic cranial irradiation was offered to patients (pts) in complete remission. Eligible were pts with LD SCLC with no prior treatment for SCLC, adequate organ functions, and WHO performance status (PS) < or =2. Pts older than 64 years with PS=2 and LDH>two times the upper limit were excluded. RESULT: Fourty-five pts were included in four centres. Five patients did not meet the inclusion criteria. The median age of the eligible pts was 60 years, range 43-75. PS was < or =1 in 90% of pts. Non-haematological toxicity was mild except grade 3 esophagitis, which was observed in 26.5% of pts. One pt developed an esophageal stricture. Grade 3/4 leucopenia and thrombocytopenia were observed in 82.5% and 75.0 of pts, respectively. One patient died due to neutropenic sepsis. The overall response rate was 77.5% with 30.0% achieving a complete response. Median progression-free survival was 11.8 months (95% CI: 1.3-22.2). Median overall survival was 22.9 months (95% CI: 13.4-31.5) and 5-year survival was 21%. CONCLUSION: The combination of topotecan and cisplatin with concurrent twice-daily chemoradiation results in long-term survivors. As expected the incidence of severe esophagitis is high.