Polymerase Chain Reaction on Respiratory Tract Specimens of Immunocompromised Patients to Diagnose Pneumocystis Pneumonia: A Systematic Review and Meta-analysis.

BACKGROUND: This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different respiratory tract samples, in both human immunodeficiency virus (HIV) and non-HIV populations. METHODS: A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group definition of proven PCP was examined. RESULTS: Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%-99.5%), adequate specificity of 89.3% (95% CI, 84.4%-92.7%), negative likelihood ratio (LR-) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%-99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%-88.3%), LR- of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%-96.5%), high specificity of 90.5% (95% CI, 80.9%-95.5%), LR- of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients. CONCLUSIONS: On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested.

Ecological and anthropogenic drivers of waterfowl productivity are synchronous across species, space, and time.

Knowledge of interspecific and spatiotemporal variation in demography-environment relationships is key for understanding the population dynamics of sympatric species and developing multispecies conservation strategies. We used hierarchical random-effects models to examine interspecific and spatial variation in annual productivity in six migratory ducks (i.e., American wigeon [Mareca americana], blue-winged teal [Spatula discors], gadwall [Mareca strepera], green-winged teal [Anas crecca], mallard [Anas platyrhynchos] and northern pintail [Anas acuta]) across six distinct ecostrata in the Prairie Pothole Region of North America. We tested whether breeding habitat conditions (seasonal pond counts, agricultural intensification, and grassland acreage) or cross-seasonal effects (indexed by flooded rice acreage in primary wintering areas) better explained variation in the proportion of juveniles captured during late summer banding. The proportion of juveniles (i.e., productivity) was highly variable within species and ecostrata throughout 1961-2019 and generally declined through time in blue-winged teal, gadwall, mallard, pintail, and wigeon, but there was no support for a trend in green-winged teal. Productivity in Canadian ecostrata declined with increasing agricultural intensification and increased with increasing pond counts. We also found a strong cross-seasonal effect, whereby more flooded rice hectares during winter resulted in higher subsequent productivity. Our results suggest highly consistent environmental and anthropogenic effects on waterfowl productivity across species and space. Our study advances our understanding of current year and cross-seasonal effects on duck productivity across a suite of species and at finer spatial scales, which could help managers better target working-lands conservation programs on both breeding and wintering areas. We encourage other researchers to evaluate environmental drivers of population dynamics among species in a single modeling framework for a deeper understanding of whether conservation plans should be generalized or customized given limited financial resources.

Flood-irrigated agriculture mediates climate-induced wetland scarcity for summering sandhill cranes in western North America.

Information about species distributions is lacking in many regions of the world, forcing resource managers to answer complex ecological questions with incomplete data. Information gaps are compounded by climate change, driving ecological bottlenecks that can act as new demographic constraints on fauna. Here, we construct greater sandhill crane (Antigone canadensis tabida) summering range in western North America using movement data from 120 GPS-tagged individuals to determine how landscape composition shaped their distributions. Landscape variables developed from remotely sensed data were combined with bird locations to model distribution probabilities. Additionally, land-use and ownership were summarized within summer range as a measure of general bird use. Wetland variables identified as important predictors of bird distributions were evaluated in a post hoc analysis to measure long-term (1984-2022) effects of climate-driven surface water drying. Wetlands and associated agricultural practices accounted for 1.2% of summer range but were key predictors of occurrence. Bird distributions were structured by riparian floodplains that concentrated wetlands, and flood-irrigated agriculture in otherwise arid and semi-arid landscapes. Findings highlighted the role of private lands in greater sandhill crane ecology as they accounted for 78% of predicted distributions. Wetland drying observed in portions of the range from 1984 to 2022 represented an emerging ecological bottleneck that could limit future greater sandhill crane summer range. Study outcomes provide novel insight into the significance of ecosystem services provided by flood-irrigated agriculture that supported nearly 60% of wetland resources used by birds. Findings suggest greater sandhill cranes function as a surrogate species for agroecology and climate change adaptation strategies seeking to reduce agricultural water use through improved efficiency while also maintaining distinct flood-irrigation practices supporting greater sandhill cranes and other wetland-dependent wildlife. We make our wetland and sandhill crane summering distributions available as interactive web-based mapping tools to inform conservation design.

Remote delivery of a weight management intervention for adults with intellectual disabilities: Results from a randomized non-inferiority trial.

BACKGROUND: Remote delivery of multi-component weight management interventions results in clinically meaningful weight loss in adults without intellectual disabilities (ID), but the effectiveness of remotely delivered weight management interventions in adults with ID has not previously been evaluated. OBJECTIVE: To determine if a weight management intervention delivered remotely could achieve weight loss (kg) at 6 months that is non-inferior to in-person visits in adults with ID and overweight or obesity (BMI ≥25 kg/m2). METHODS: Participants were randomized to a 24-mo. trial (6 mos weight loss,12 mos weight maintenance, 6 mos. no-contact follow up) to compare weight loss achieved with the same multicomponent intervention delivered to individual participants in their home either remotely (RD) or during face-to-face home visits (FTF). RESULTS: One hundred twenty adults with ID (∼32 years of age, 53 % females) were randomized to the RD (n = 60) or the FTF arm (n = 60). Six-month weight loss in the RD arm (-4.9 ± 7.8 kg) was superior to 6-month weight loss achieved in the FTF arm (-2.1 ± 6.7 kg, p = 0.047). However, this may be partially attributed to the COVID-19 pandemic, since weight loss in the FTF arm was greater in participants who completed the intervention entirely pre-COVID (n = 33,-3.2 %) compared to post-COVID (n = 22, -0.61 %). Weight loss across did not differ significantly between intervention arms at 18 (p = 0.33) or 24 months (p = 0.34). CONCLUSION: Our results suggest that remote delivery is a viable option for achieving clinically relevant weight loss and maintenance in adults with ID. NCT REGISTRATION: NCT03291509.

An Overview of Systematic Reviews of Polymerase Chain Reaction (PCR) for the Diagnosis of Invasive Aspergillosis in Immunocompromised People: A Report of the Fungal PCR Initiative (FPCRI)-An ISHAM Working Group.

This overview of reviews (i.e., an umbrella review) is designed to reappraise the validity of systematic reviews (SRs) and meta-analyses related to the performance of Aspergillus PCR tests for the diagnosis of invasive aspergillosis in immunocompromised patients. The methodological quality of the SRs was assessed using the AMSTAR-2 checklist; the quality of the evidence (QOE) within each SR was appraised following the GRADE approach. Eight out of 12 SRs were evaluated for qualitative and quantitative assessment. Five SRs evaluated Aspergillus PCR on bronchoalveolar lavage fluid (BAL) and three on blood specimens. The eight SRs included 167 overlapping reports (59 evaluating PCR in blood specimens, and 108 in BAL), based on 107 individual primary studies (98 trials with a cohort design, and 19 with a case-control design). In BAL specimens, the mean sensitivity and specificity ranged from 0.57 to 0.91, and from 0.92 to 0.97, respectively (QOE: very low to low). In blood specimens (whole blood or serum), the mean sensitivity ranged from 0.57 to 0.84, and the mean specificity from 0.58 to 0.95 (QOE: low to moderate). Across studies, only a low proportion of AMSTAR-2 critical domains were unmet (1.8%), demonstrating a high quality of methodological assessment. Conclusions. Based on the overall methodological assessment of the reviews included, on average we can have high confidence in the quality of results generated by the SRs.

Repurposing antifungals: population pharmacokinetics of itraconazole and hydroxy-itraconazole following administration of a nanocrystal formulation.

OBJECTIVES: To describe itraconazole and hydroxy-itraconazole pharmacokinetics following intravenous (IV) administration of a previously developed nanocrystal formulation (NCF) in haematopoietic cell transplant (HCT) recipients for prophylaxis of invasive fungal disease. METHODS: In a prospective Phase II study, 10 HCT recipients received itraconazole NCF administered in 2-hour infusions of 200 mg twice daily for 2 days, followed by 200 mg once daily until Day 14. Full pharmacokinetic curves were obtained on Days 7 and 14. Additional samples were collected pre- and post-infusion until Day 6, pre-infusion on Days 10 and 12, and during washout on Days 16, 17, 18, 19 and 28. Itraconazole and hydroxy-itraconazole pharmacokinetics were analysed by non-linear mixed-effects population pharmacokinetic modelling. RESULTS: Four-hundred and seventy-one itraconazole and 471 paired hydroxy-itraconazole concentrations from 10 patients were included for analysis. Data were best described by a semi-mechanistic model with central and peripheral itraconazole compartments and a hydroxy-itraconazole compartment with dissolution of itraconazole drug particles from nanocrystals and first-order distribution and elimination. The final model included interindividual variability on itraconazole clearance and hydroxy-itraconazole clearance. CONCLUSIONS: This study provides information on the pharmacokinetic properties of the itraconazole NCF useful for development of this formulation. Our results suggest that itraconazole NCF is a suitable formulation and may warrant renewal in the setting of repurposing. Our findings may be useful for the reformulation of other highly lipophilic compounds as well.

Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer.

BACKGROUND: Empiric antifungal therapy is considered the standard of care for high-risk neutropenic patients with persistent fever. The impact of a preemptive, diagnostic-driven approach based on galactomannan screening and chest computed tomography scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. METHODS: Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (arm A) or preemptively (arm B), while receiving fluconazole 400 mg daily prophylactically. The primary end point of this noninferiority study was overall survival (OS) 42 days after randomization. RESULTS: Of 556 patients recruited, 549 were eligible: 275 in arm A and 274 in arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy, and 93% of them were in the first induction phase. At day 42, the OS was not inferior in arm B (96.7%; 95% confidence interval [CI], 93.8%-98.3%) when compared with arm A (93.1%; 95% CI, 89.3%-95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95% CI, 4.5%-10.8%) in arm B vs 6.6% (95% CI, 3.6%-9.5%) in arm A. The rate of patients who received caspofungin was significantly lower in arm B (27%) than in arm A (63%; P < .001). CONCLUSIONS: The preemptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs. Clinical Trials Registration. NCT01288378; EudraCT 2010-020814-27.

Multi-institutional and multi-disciplinary care: A successfully managed aortic dissection in the third trimester of pregnancy.

Multi-disciplinary collaborative care for pregnant women with complex and emergent conditions is essential. Logistical planning, clear communication and human factor awareness are all non-clinical skills which need to be utilised in order to maximise outcomes. We describe the case of a proximal aortic dissection in the late third trimester of pregnancy diagnosed in a peripheral hospital that was transferred to a cardiothoracic centre for successful operative management 160 km away. This required the time-sensitive mobilisation and liaison of a receiving cardiothoracic, anaesthesiology and perfusionist team in conjunction with obstetric and midwifery support from an affiliated maternity hospital, as well as the national neonatal transport team. We emphasise the importance of multidisciplinary team management in complex cases and how imperative good inter-disciplinary communication is to ensure safe inter-hospital transfer.

Fetoscopic Laser Ablation for Twin-to-Twin Transfusion Syndrome: A 15-year Review of Perinatal Survival.

Objective Twin to twin transfusion syndrome (TTTS) complicates 5-15% of monochorionic twin pregnancies and untreated is associated with a 90% mortality rate. The aim was to present the perinatal survival of patients with TTTS treated with laser ablation, by a national fetal medicine team. Methods This was a review of all cases of TTTS treated with fetoscopic laser ablation performed from March 2006 through to December 2020. All patients treated with fetoscopic laser were identified from the hospital database. The perinatal outcomes for the overall cohort and the individual Quintero stages were determined. Results A total of 155 cases of TTTS underwent fetoscopic laser ablation during the study period. The median gestational age at diagnosis was 19+1 weeks, with a mean growth discordance of 23.6%. The Quintero stage at diagnosis was: Stage 1 6.5% (10/155), Stage 2 49% (76/155), Stage 3 38.7% (60/155), Stage 4 5.8% (9/155). There was at least one survivor in 83.2% (129/155) of pregnancies, with dual survival in 52.9% (82/155). An increase in the rate of any survivor was observed from 75% (2006-2014) to 94% (2014-2020) (p<0.05). Dual survival decreased with increasing Quintero Stage (p<0.05). 80.6% (125/155) of pregnancies delivered prior to 34+6 weeks gestation. Conclusion Fetoscopic laser ablation is the recommended first line treatment for severe TTTS. We observed a survival rate of at least one twin in 83.2% pregnancies which is comparable to internationally published data on single-centre outcomes.

Mycobacterial infections in adults with haematological malignancies and haematopoietic stem cell transplants: guidelines from the 8th European Conference on Infections in Leukaemia.

Mycobacterial infections, both tuberculosis and nontuberculous, are more common in patients with haematological malignancies and haematopoietic stem cell transplant recipients than in the general population-although these infections remain rare. Mycobacterial infections pose both diagnostic and therapeutic challenges. The management of mycobacterial infections is particularly complicated for patients in haematology because of the many drug-drug interactions between antimycobacterial drugs and haematological and immunosuppressive treatments. The management of mycobacterial infections must also consider the effect of delaying haematological management. We surveyed the management practices for latent tuberculosis infection (LTBI) in haematology centres in Europe. We then conducted a meticulous review of the literature on the epidemiology, diagnosis, and management of LTBI, tuberculosis, and nontuberculous mycobacterial infections among patients in haematology, and we formulated clinical guidelines according to standardised European Conference on Infections in Leukaemia (ECIL) methods. In this Review, we summarise the available literature and the recommendations of ECIL 8 for managing mycobacterial infections in patients with haematological malignancies.

Climate change and lithium mining influence flamingo abundance in the Lithium Triangle.

The development of technologies to slow climate change has been identified as a global imperative. Nonetheless, such 'green' technologies can potentially have negative impacts on biodiversity. We explored how climate change and the mining of lithium for green technologies influence surface water availability, primary productivity and the abundance of three threatened and economically important flamingo species in the 'Lithium Triangle' of the Chilean Andes. We combined climate and primary productivity data with remotely sensed measures of surface water levels and a 30-year dataset on flamingo abundance using structural equation modelling. We found that, regionally, flamingo abundance fluctuated dramatically from year-to-year in response to variation in surface water levels and primary productivity but did not exhibit any temporal trends. Locally, in the Salar de Atacama-where lithium mining is focused-we found that mining was negatively correlated with the abundance of two of the three flamingo species. These results suggest continued increases in lithium mining and declines in surface water could soon have dramatic effects on flamingo abundance across their range. Efforts to slow the expansion of mining and the impacts of climate change are, therefore, urgently needed to benefit local biodiversity and the local human economy that depends on it.

An overview of using fungal DNA for the diagnosis of invasive mycoses.

INTRODUCTION: Fungal PCR has undergone considerable standardization and, together with the availability of commercial assays, external quality assessment schemes, and extensive performance validation data, is ready for widespread use for the screening and diagnosis of invasive fungal disease (IFD). AREAS COVERED: Drawing on the experience and knowledge of the leads of the various working parties of the Fungal PCR initiative, this review will address general considerations concerning the use of molecular tests for the diagnosis of IFD, before focusing specifically on the technical and clinical aspects of molecular testing for the main causes of IFD and recent technological developments. EXPERT OPINION: For infections caused by Aspergillus, Candida, and Pneumocystis jirovecii, PCR testing is recommended, and combination with serological testing will likely enhance the diagnosis. For other IFD (e.g. mucormycosis), molecular diagnostics represent the only non-classical mycological approach toward diagnoses, and continued performance validation and standardization have improved confidence in such testing. The emergence of antifungal resistance can be diagnosed, in part, through molecular testing. Next-generation sequencing has the potential to significantly improve our understanding of fungal phylogeny, epidemiology, pathogenesis, mycobiome/microbiome, and interactions with the host, while identifying novel and existing mechanisms of antifungal resistance and novel diagnostic/therapeutic targets.

Intrapersonal, interpersonal and environmental correlates of moderate to vigorous physical activity and sedentary time in adolescents with intellectual and developmental disabilities.

BACKGROUND: Although correlates of physical activity (PA) have been extensively examined in both children and adolescents who are typically developing, little is known about correlates of moderate to vigorous physical activity (MVPA) and sedentary time in adolescents with intellectual and developmental disabilities (IDD). Therefore, we examined intrapersonal, interpersonal and environmental factors and their association with device-based MVPA and sedentary time in adolescents with IDD. METHODS: MVPA and sedentary time was assessed using a hip-worn ActiGraph model wGT3x-BT tri-axial accelerometer across a 7-day period in adolescents with IDD and one of their parents. Pearson and point-biserial correlations were calculated to inspect the associations of PA (MVPA, sedentary time) with intrapersonal factors (demographic characteristic, BMI, waist circumference, motor ability, muscle strength, grip strength, cardiovascular fitness and self-efficacy for PA), interpersonal factors (parent demographics, parent BMI, parent MVPA and sedentary time, family social support for PA, parent barriers and support for PA, parent's beliefs/attitudes towards PA and number of siblings), and environmental factors (meteorologic season and COVID-19). Ordinary least squares regression was used to estimate the unique contributions of key factors to PA after controlling for participants' age, sex, race, waist circumference and total wear time. RESULTS: Ninety-two adolescents (15.5 ± 3.0 years old, 21.7% non-White, 6.5% Hispanic, 56.5% female) provided valid accelerometer data. Average sedentary time was 494.6 ± 136.4 min/day and average MVPA was 19.8 ± 24.2 min/day. Age (r = 0.27, P = 0.01), diagnosis of congenital heart disease (r = -0.26, P = 0.01) and parent sedentary time (r = 0.30, P = 0.01) were correlated with sedentary time. BMI (r = -0.24, P = 0.03), waist circumference (r = -0.28, P = 0.01), identifying as White (r = -0.23, P = 0.03) and parent MVPA (r = 0.56, P < 0.001) were correlated with MVPA. After adjusting for the adolescent's age, sex, race, waist circumference, and total wear time, the association between parent and adolescent MVPA remained significant (b = 0.55, P < 0.01, partial η2  = 0.11). CONCLUSION: The results of this study provide evidence that race, waist circumference and parental MVPA may influence the amount of MVPA in adolescents with IDD. The limited available information and the potential health benefits of increased MVPA highlight the need to evaluate the effectiveness of multi-component interventions targeting both intrapersonal and interpersonal levels to promote increased PA in adolescents with IDD.

Changes in physical activity across a 6-month weight loss intervention in adolescents with intellectual and developmental disabilities.

BACKGROUND: Adolescents and young adults with intellectual and developmental disabilities (IDD) have high rates of obesity and low levels of physical activity. This analysis examined changes in light, moderate-to-vigorous physical activity (MVPA) and sedentary time, and the association between changes in MVPA and weight loss in adolescents and young adults with IDD and overweight and obesity participating in a 6-month multi-component weight loss intervention. METHODS: Adolescents and young adults with IDD and overweight or obesity (body mass index ≥ 85 percentile, n = 110, age ~16 years, 52.7% female) and a parent were randomised to one of three intervention groups: face-to-face delivery/conventional reduced energy diet (n = 36), remote delivery (RD)/conventional reduced energy diet (n = 39), or RD/reduced energy enhanced stop light diet (eSLD) (n = 35.) Participants were asked to engage in 60 min/day of MVPA on 5 or more days/wk. Participants and a parent attended twice monthly education/behavioural counselling sessions with a health educator to assist participants in complying with dietary and MVPA recommendations. Education/counselling in the RD arms was delivered remotely using video conferencing, and self-monitoring of MVPA and daily steps was completed using a wireless activity tracker. Education/counselling in the face-to-face arm was delivered during home-visits and self-monitoring of MVPA and daily steps was completed by self-report using paper tracking forms designed for individuals with IDD. MVPA, light activity, and sedentary time were assessed over 7 days at baseline and 6 months using a portable accelerometer (ActiGraph wGT3x-BT). RESULTS: Mixed modelling analysis completed using participants with valid accelerometer data (i.e. ≥4-10 h days) at baseline (n = 68) and 6 months (n = 30) revealed no significant changes in light, moderate- MVPA, or sedentary time across the 6-month intervention (all P > 0.05). Participants obtained 15.2 ± 21.5 min/day of MVPA at baseline and 19.7 ± 19.7 min/day at 6 months (P = 0.119). Mixed modelling indicated no significant effects of group (P = 0.79), time (P = 0.10), or group-by-time interaction (P = 0.21) on changes in MVPA from baseline to 6 months. Correlational analysis conducted on participants with valid accelerometer data at both baseline and 6 months (n = 24) revealed no significant associations between baseline sedentary time (r = 0.10, P = 0.40) and baseline MVPA (r = -0.22, P = 0.30) and change in MVPA across the 6-month intervention. Additionally, attendance at education/counselling sessions (r = 0.26, P = 0.22) and frequency of self-monitoring of MVPA were not significantly associated with change in MVPA from baseline to 6 months (r = 0.26, P = 0.44). Baseline MVPA (r = 0.02, P = 0.92) and change in MVPA from baseline to 6 months (r = 0.13, P = 0.30) were not associated with changes in body weight across the 6-month intervention. CONCLUSION: We observed a non-significant increase in MVPA (30%), which was not associated with the magnitude of weight loss in a sample of adolescents and young adults with IDD who participated in a 6-month multi-component weight loss intervention. Additional strategies to increase MVPA in adolescents and young adults with IDD participating in weight loss interventions need to be developed and evaluated.

Migration stopover ecology of Cinnamon Teal in western North America.

Identifying migration routes and fall stopover sites of Cinnamon Teal (Spatula cyanoptera septentrionalium) can provide a spatial guide to management and conservation efforts, and address vulnerabilities in wetland networks that support migratory waterbirds. Using high spatiotemporal resolution GPS-GSM transmitters, we analyzed 61 fall migration tracks across western North America during our three-year study (2017-2019). We marked Cinnamon Teal primarily during spring/summer in important breeding and molting regions across seven states (California, Oregon, Washington, Idaho, Utah, Colorado, and Nevada). We assessed fall migration routes and timing, detected 186 fall stopover sites, and identified specific North American ecoregions where sites were located. We classified underlying land cover for each stopover site and measured habitat selection for 12 land cover types within each ecoregion. Cinnamon Teal selected a variety of flooded habitats including natural, riparian, tidal, and managed wetlands; wet agriculture (including irrigation ditches, flooded fields, and stock ponds); wastewater sites; and golf and urban ponds. Wet agriculture was the most used habitat type (29.8% of stopover locations), and over 72% of stopover locations were on private land. Relatively scarce habitats such as wastewater ponds, tidal marsh, and golf and urban ponds were highly selected in specific ecoregions. In contrast, dry non-habitat across all ecoregions, and dry agriculture in the Cold Deserts and Mediterranean California ecoregions, was consistently avoided. Resources used by Cinnamon Teal often reflected wetland availability across the west and emphasize their adaptability to dynamic resource conditions in arid landscapes. Our results provide much needed information on spatial and temporal resource use by Cinnamon Teal during migration and indicate important wetland habitats for migrating waterfowl in the western United States.

When to change treatment of acute invasive aspergillosis: an expert viewpoint.

Invasive aspergillosis (IA) is an acute infection affecting patients who are immunocompromised, as a result of receiving chemotherapy for malignancy, or immunosuppressant agents for transplantation or autoimmune disease. Whilst criteria exist to define the probability of infection for clinical trials, there is little evidence in the literature or clinical guidelines on when to change antifungal treatment in patients who are receiving prophylaxis or treatment for IA. To try and address this significant gap, an advisory board of experts was convened to develop criteria for the management of IA for use in designing clinical trials, which could also be used in clinical practice. For primary treatment failure, a change in antifungal therapy should be made: (i) when mycological susceptibility testing identifies an organism from a confirmed site of infection, which is resistant to the antifungal given for primary therapy, or a resistance mutation is identified by molecular testing; (ii) at, or after, 8 days of primary antifungal treatment if there is increasing serum galactomannan, or galactomannan positivity in serum, or bronchoalveolar lavage fluid when the antigen was previously undetectable, or there is sudden clinical deterioration, or a new clearly distinct site of infection is detected; and (iii) at, or after, 15 days of primary antifungal treatment if the patient is clinically stable but with ≥2 serum galactomannan measurements persistently elevated compared with baseline or increasing, or if the original lesions on CT or other imaging, show progression by >25% in size in the context of no apparent change in immune status.