Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia

Background: Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. Methods: We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran’s Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. Results: Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27–0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36–1.87) or overall mortality (RR 0.95, 95% CI 0.46–1.99). The pre-emptive strategy cost $324 less (95$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. Conclusions: Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals

Effect of freshwater discharge from Namgang Dam on ichthyoplankton assemblage structure in Jinju Bay, Korea

The movement of fish eggs and larvae in bay and estuarine systems is affected by freshwater discharge. In this study, the assemblage structures of ichthyoplankton eggs and larvae were assessed for the first time in Jinju Bay, South Korea, to identify the spawning and nursery functions of the bay. Fish eggs and larvae and several environmental parameters were sampled monthly from April 2015 to March 2016 inside and outside of the bay. Within the bay we collected eggs and larvae from 25 and 35 species, respectively, indicating greater diversity than outside the bay, where we collected eggs and larvae of 20 and 28 species, respectively. Fluctuations in water temperature and salinity were larger inside than outside of the bay, and chlorophyll-a concentration was higher within the bay, likely due to discharge from the Namgang Dam, which causes water to flow from the inside to the outside of the bay. This process influences fish larva abundance, such that more larvae are found outside than inside the bay. We also found that 28 fish species use Jinju Bay as a spawning ground. For some species, the timing of egg and larva appearance differed inside and outside of the bay, suggesting that the timing of spawning may differ between the two environments

Global Rice Atlas: Disaggregated seasonal crop calendar and production

Purpose: Rice is an important staple crop cultivated in more than 163 million ha globally. Although information on the distribution of global rice production is available by country and, at times, at subnational level, information on its distribution within a year is often lacking in different rice growing regions. Knowing when and where rice is planted and harvested and the associated production is crucial to policy and decision making on food security. To examine seasonal and geographic variations in food supply, we developed a detailed rice crop calendar and linked it with disaggregated production data. Approach and methods used: We compiled from various sources detailed data on rice production, and planting and harvesting dates by growing season. To standardize the production data to the same period, we adjusted the production values so that the totals for each country will be the same as those of FAO for 2010-2012. We then linked data on rice production with the corresponding crop calendar information to estimate production at harvest time by month then we calculated totals for each country and region. Key results: The bulk of global annual harvests of rice is from September to November, corresponding with the harvest of the wet season rice in Asia and Africa. Total rough rice production during those peak months exceed 381 million tons, which account for about half of annual global rice output. Production is lowest in January with only 11 million tons in total. Regional production is lowest in Asia in January, Americas in December, Africa in July and rest of the world in May. Synthesis and Applications: A globally complete and spatially detailed rice crop calendar is important to crop growth simulation modelling and assessment of vulnerability of rice areas to biotic and abiotic stresses. Linked to production estimates, it can be used in analyzing spatial and seasonal production trends to better assess and predict price fluctuations , and to mitigate potential significant shortfalls in food production at certain times of the year

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Review of Community Pharmacy Staff Educational Needs for Supporting Mental Health Consumers and Carers

Development of a mental health education package for community pharmacy staff should be informed by mental health consumers/carers’ needs, expectations and experiences, and staff knowledge, skills and attitudes. This review (1) explored research on community pharmacy practice and service provision for mental health consumers/carers, and (2) identified validated methods for assessing staff knowledge, skills and attitudes about mental illness to inform the development of a training questionnaire. A literature scan using key words knowledge, skills, attitudes, and beliefs combined with community pharmacy, pharmacist, and pharmacy support staff, and mental illness, depression, anxiety was conducted. A small number of studies were found that used reliable methods to assess pharmacists’ training needs regarding mental illness and treatment options. There was little published specifically in relation to depression and anxiety in community pharmacy practice. No studies assessed the training needs of pharmacy support staff. A systematic analysis of pharmacy staff learning needs is warranted

The TOP-SCOPE Survey of Planck Galactic Cold Clumps : Survey Overview and Results of an Exemplar Source, PGCC G26.53+0.17

The low dust temperatures (<14 K) of Planck Galactic cold clumps (PGCCs) make them ideal targets to probe the initial conditions and very early phase of star formation. "TOP-SCOPE" is a joint survey program targeting similar to 2000 PGCCs in J = 1-0 transitions of CO isotopologues and similar to 1000 PGCCs in 850 mu m continuum emission. The objective of the "TOP-SCOPE" survey and the joint surveys (SMT 10 m, KVN 21 m, and NRO 45 m) is to statistically study the initial conditions occurring during star formation and the evolution of molecular clouds, across a wide range of environments. The observations, data analysis, and example science cases for these surveys are introduced with an exemplar source, PGCC G26.53+0.17 (G26), which is a filamentary infrared dark cloud (IRDC). The total mass, length, and mean line mass (M/L) of the G26 filament are similar to 6200 M-circle dot, similar to 12 pc, and similar to 500 M-circle dot pc(-1), respectively. Ten massive clumps, including eight starless ones, are found along the filament. The most massive clump as a whole may still be in global collapse, while its denser part seems to be undergoing expansion owing to outflow feedback. The fragmentation in the G26 filament from cloud scale to clump scale is in agreement with gravitational fragmentation of an isothermal, nonmagnetized, and turbulent supported cylinder. A bimodal behavior in dust emissivity spectral index (beta) distribution is found in G26, suggesting grain growth along the filament. The G26 filament may be formed owing to large-scale compression flows evidenced by the temperature and velocity gradients across its natal cloud.Peer reviewe

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension