A Phase II study of pulse dose imatinib mesylate and weekly paclitaxel in patients aged 70 and over with advanced non-small cell lung cancer

BACKGROUND: In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR). METHODS: This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index (CCI) and Vulnerable Elder Survey-13 (VES-13) were correlated with outcomes. RESULTS: Thirty-four patients with median age 75 enrolled. Eleven of 29 (38%) were frail by VES-13 score. Overall RR was 11/34 (32%; 95% CI 17%-51%), meeting the primary endpoint. Median PFS and OS were 3.6 and 7.3 months, respectively. High tumoral PDGF-B expression predicted inferior PFS. Frail patients by VES-13 had significantly worse median PFS (3.2 vs. 4.5 months; p=0.02) and OS (4.8 vs. 12 months; p=0.02) than non-frail. CONCLUSIONS: The combination of imatinib and paclitaxel had encouraging activity as measured by the primary endpoint of RR. However, PFS and OS were typical for elderly patients treated with single agent chemotherapy and the regimen is not recommended for further study. Adjunct imatinib did not overcome the established association of tumoral PDGF-B expression with inferior PFS. VES-13 was a powerful predictor of poor survival outcomes. Frailty should be further studied as a predictor of non-benefit from chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01011075

Suicide Prevention in an Emergency Department Population: The ED-SAFE Study

Importance: Suicide is a leading cause of deaths in the United States. Although the emergency department (ED) is an opportune setting for initiating suicide prevention efforts, ED-initiated suicide prevention interventions remain underdeveloped. Objective: To determine whether an ED-initiated intervention reduces subsequent suicidal behavior. Design, Setting, and Participants: This multicenter study of 8 EDs in the United States enrolled adults with a recent suicide attempt or ideation and was composed of 3 sequential phases: (1) a treatment as usual (TAU) phase from August 2010 to December 2011, (2) a universal screening (screening) phase from September 2011 to December 2012, and (3) a universal screening plus intervention (intervention) phase from July 2012 to November 2013. Interventions: Screening consisted of universal suicide risk screening. The intervention phase consisted of universal screening plus an intervention, which included secondary suicide risk screening by the ED physician, discharge resources, and post-ED telephone calls focused on reducing suicide risk. Main Outcomes and Measures: The primary outcome was suicide attempts (nonfatal and fatal) over the 52-week follow-up period. The proportion and total number of attempts were analyzed. Results: A total of 1376 participants were recruited, including 769 females (55.9%) with a median (interquartile range) age of 37 (26-47) years. A total of 288 participants (20.9%) made at least 1 suicide attempt, and there were 548 total suicide attempts among participants. There were no significant differences in risk reduction between the TAU and screening phases (23% vs 22%, respectively). However, compared with the TAU phase, patients in the intervention phase showed a 5% absolute reduction in suicide attempt risk (23% vs 18%), with a relative risk reduction of 20%. Participants in the intervention phase had 30% fewer total suicide attempts than participants in the TAU phase. Negative binomial regression analysis indicated that the participants in the intervention phase had significantly fewer total suicide attempts than participants in the TAU phase (incidence rate ratio, 0.72; 95% CI, 0.52-1.00; P = .05) but no differences between the TAU and screening phases (incidence rate ratio, 1.00; 95% CI, 0.71-1.41; P = .99). Conclusions and Relevance: Among at-risk patients in the ED, a combination of brief interventions administered both during and after the ED visit decreased post-ED suicidal behavior

When is forgetting not forgetting? A discursive analysis of differences in forgetting talk between adults with cystic fibrosis with different levels of adherence to nebulizer treatments

Forgetting is often cited as a reason why people struggle to adhere to treatments for chronic conditions. Interventions have tried to improve forgetting behavior using reminders. We used a discursive psychological approach to explore differences in how high and low adherers constructed forgetting their nebulizer treatments for cystic fibrosis. Interviews were conducted with 18 adults from a cystic fibrosis center in the United Kingdom. High adherers constructed forgetting treatments as occasional lapses in automaticity and temporary lapses in memory that they found easy to repair. Low adherers utilized forgetting to normalize more consistent nonadherence to treatments. However, it is important to contextualize forgetting as a discursive resource that helped these participants to negotiate moral discourses around adherence to treatment that reminder interventions cannot address; we therefore recommend a more behavioral, patient-focused, theory-driven approach to intervention development

Large scale variation in Enterococcus faecalis illustrated by the genome analysis of strain OG1RF

A comparison of two strains of the hospital pathogen Enterococcus faecalis suggests that mediators of virulence differ between strains and that virulence does not depend on mobile gene element

Non-mental diseases associated with ADHD across the lifespan:Fidgety Philipp and Pippi Longstocking at risk of multimorbidity?

Several non-mental diseases seem to be associated with an increased risk of ADHD and ADHD seems to be associated with increased risk for non-mental diseases. The underlying trajectories leading to such brain-body co-occurrences are often unclear - are there direct causal relationships from one disorder to the other, or does the sharing of genetic and/or environmental risk factors lead to their occurring together more frequently or both? Our goal with this narrative review was to provide a conceptual synthesis of the associations between ADHD and non-mental disease across the lifespan. We discuss potential shared pathologic mechanisms, genetic background and treatments in co-occurring diseases. For those co-occurrences for which published studies with sufficient sample sizes exist, meta-analyses have been published by others and we discuss those in detail. We conclude that non-mental diseases are common in ADHD and vice versa and add to the disease burden of the patient across the lifespan. Insufficient attention to such co-occurring conditions may result in missed diagnoses and suboptimal treatment in the affected individuals

Predictors of Medication Adherence and Blood Pressure Control among Saudi Hypertensive Patients Attending Primary Care Clinics: A Cross-Sectional Study

Purpose To assess the level of medication adherence and to investigate predictors of medication adherence and blood pressure control among hypertensive patients attending primary healthcare clinics in Makkah, Saudi Arabia. Patients and methods Hypertensive patients meeting the eligibility criteria were recruited from eight primary care clinics between January and May 2016 for this study. The patients completed Arabic version of Morisky Medication Adherence Scale (MMAS-8), an eight-item validated, self-reported measure to assess medication adherence. A structured data collection form was used to record patients’ sociodemographic, medical and medication data. Results Two hundred and four patients, of which 71.6% were females, participated in the study. Patients’ mean age was 59.1 (SD 12.2). The mean number of medication used by patients was 4.4 (SD 1.89). More than half (110; 54%) of the patients were non-adherent to their medications (MMAS score 65 years (OR 2.0 [95% CI: 1.0–4.2; P = 0.04]), and being diabetic (OR 0.25 [95% CI: 0.1–0.6; P = 0.04]) were found to be independent predictors of medication adherence. Conclusion Medication adherence is alarmingly low among hypertensive patients attending primary care clinics in Saudi Arabia which may partly explain observed poor blood pressure control. There is a clear need to educate patients about the importance of medication adherence and its impact on improving clinical outcomes. Future research should identify barriers to medication adherence among Saudi hypertensive patients

Removing Systemic Barriers to Equity, Diversity, and Inclusion: Report of the 2019 Plant Science Research Network Workshop “Inclusivity in the Plant Sciences”

A future in which scientific discoveries are valued and trusted by the general public cannot be achieved without greater inclusion and participation of diverse communities. To envision a path towards this future, in January 2019 a diverse group of researchers, educators, students, and administrators gathered to hear and share personal perspectives on equity, diversity, and inclusion (EDI) in the plant sciences. From these broad perspectives, the group developed strategies and identified tactics to facilitate and support EDI within and beyond the plant science community. The workshop leveraged scenario planning and the richness of its participants to develop recommendations aimed at promoting systemic change at the institutional level through the actions of scientific societies, universities, and individuals and through new funding models to support research and training. While these initiatives were formulated specifically for the plant science community, they can also serve as a model to advance EDI in other disciplines. The proposed actions are thematically broad, integrating into discovery, applied and translational science, requiring and embracing multidisciplinarity, and giving voice to previously unheard perspectives. We offer a vision of barrier-free access to participation in science, and a plant science community that reflects the diversity of our rapidly changing nation, and supports and invests in the training and well-being of all its members. The relevance and robustness of our recommendations has been tested by dramatic and global events since the workshop. The time to act upon them is now

Thermal Remote Sensing for Global Volcano Monitoring: Experiences From the MIROVA System

Volcanic activity is always accompanied by the transfer of heat from the Earth’s crust to the atmosphere. This heat can be measured from space and its measurement is a very useful tool for detecting volcanic activity on a global scale. MIROVA (Middle Infrared Observation of Volcanic Activity) is an automatic volcano hot spot detection system, based on the analysis of MODIS data (Moderate Resolution Imaging Spectroradiometer). The system is able to detect, locate and quantify thermal anomalies in near real-time, by providing, on a dedicated website (www.mirovaweb.it), infrared images and thermal flux time-series on over 200 volcanoes worldwide. Thanks to its simple interface and intuitive representation of the data, MIROVA is currently used by several volcano observatories for daily monitoring activities and reporting. In this paper, we present the architecture of the system and we provide a state of the art on satellite thermal data usage for operational volcano monitoring and research. In particular, we describe the contribution that the thermal data have provided in order to detect volcanic unrest, to forecast eruptions and to depict trends and patterns during eruptive crisis. The current limits and requirements to improve the quality of the data, their distribution and interpretation are also discussed, in the light of the experience gained in recent years within the volcanological community. The results presented clearly demonstrate how the open access of satellite thermal data and the sharing of derived products allow a better understanding of ongoing volcanic phenomena, and therefore constitute an essential requirement for the assessment of volcanic hazards

Protocol for the immediate delivery versus expectant care of women with preterm prelabour rupture of the membranes close to term (PPROMT) Trial [ISRCTN44485060]

BACKGROUND: Preterm prelabour rupture of membranes (PPROM) complicates up to 2% of all pregnancies and is the cause of 40% of all preterm births. The optimal management of women with PPROM prior to 37 weeks, is not known. Furthermore, diversity in current clinical practice suggests uncertainty about the appropriate clinical management. There are two options for managing PPROM, expectant management (a wait and see approach) or early planned birth. Infection is the main risk for women in which management is expectant. This risk need to be balanced against the risk of iatrogenic prematurity if early delivery is planned. The different treatment options may also have different health care costs. Expectant management results in prolonged antenatal hospitalisation while planned early delivery may necessitate intensive care of the neonate for problems associated with prematurity. METHODS/DESIGN: We aim to evaluate the effectiveness of early planned birth compared with expectant management for women with PPROM between 34 weeks and 36(6 )weeks gestation, in a randomised controlled trial. A secondary aim is a cost analysis to establish the economic impact of the two treatment options and establish the treatment preferences of women with PPROM close to term. The early planned birth group will be delivered within 24 hours according to local management protocols. In the expectant management group birth will occur after spontaneous labour, at term or when the attending clinician feels that birth is indicated according to usual care. Approximately 1812 women with PPROM at 34–36(6 )weeks gestation will be recruited for the trial. The primary outcome of the study is neonatal sepsis. Secondary infant outcomes include respiratory distress, perinatal mortality, neonatal intensive care unit admission, assisted ventilation and early infant development. Secondary maternal outcomes include chorioamnionitis, postpartum infection treated with antibiotics, antepartum haemorrhage, induction of labour, mode of delivery, maternal satisfaction with care, duration of hospitalisation, and maternal wellbeing at four months postpartum. DISCUSSION: This trial will provide evidence on the optimal care for women with PPROM close to term (34–37 weeks gestation). Consideration of both the clinical and economic sequelae of the management of PPROM will enable informed decision making and guideline development