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Introduction: Two vesicular monoamine transporter 2 (VMAT2) inhibitors are approved in the United States (US) for the treatment of tardive dyskinesia (TD). There is a paucity of information on the impact of VMAT2 inhibitor treatment on patient social and physical well-being. The study objective was to elucidate clinician-reported improvement in symptoms and any noticeable changes in social or physical well-being in patients receiving VMAT2 inhibitors. Methods: A web-based survey was offered to physicians, nurse practitioners, and physician assistants based in the US who prescribed valbenazine for TD within the past 24 months. Clinicians reported data from the charts of patients who met the inclusion criteria and were allowed to recall missing information. Results: Respondents included 163 clinicians who reviewed charts of 601 VMAT2-treated patients with TD: 47% had TD symptoms in ≥2 body regions, with the most common being in the head or face and upper extremities. Prior to treatment, 93% of patients showed impairment in ≥1 social domain, and 88% were impaired in ≥1 physical domain. Following treatment, among those with improvement in TD symptoms (n = 540), 80% to 95% showed improvement in social domains, 90% to 95% showed improvement in physical domains, and 73% showed improvement in their primary psychiatric condition. Discussion: In VMAT2-treated patients with TD symptom improvement, clinicians reported concomitant improvement in psychiatric disorder symptoms and in social and physical well-being. Regular assessment of TD impact on these types of domains should occur simultaneously with movement disorder ratings when evaluating the value of VMAT2 inhibitor therapy.

BACKGROUND: Vaccination during pregnancy reduces the incidence of infections and their associated adverse outcomes in both mothers and infants. The American College of Obstetricians and Gynecologists has recommended influenza and Tdap vaccination during pregnancy since 2004 and 2013, respectively. Several studies have examined disparities in vaccination rates during pregnancy by race/ethnicity. However, none have included American Indians/Alaska Natives as a specific racial/ethnic group on a national level. Current literature suggests that American Indian/Alaska Native infants experience increased morbidity and mortality from both influenza and pertussis infections compared with most other groups in the United States. OBJECTIVE: This study aimed to evaluate the uptake of influenza and Tdap vaccinations during pregnancy by race/ethnicity, with a specific focus on American Indian/Alaska Native people. STUDY DESIGN: This cross-sectional study used data from the Pregnancy Risk Assessment Monitoring System. Comparisons of vaccine uptake across racial/ethnic groups (American Indian/Alaska Native, Asian, non-Hispanic Black, non-Hispanic White, Hispanic, and “None of the above”) were evaluated using weighted logistic regression analyses to estimate prevalence odds ratios with 95% confidence intervals. Models were adjusted for maternal age, parity, maternal education, marital status, payment method at delivery, prenatal care in first trimester, maternal smoking status, Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) participation, and receipt of influenza vaccine reported by a health care provider. RESULTS: For both vaccines, Asian respondents had the highest uptake (influenza, 70.1%; Tdap, 68.2%), whereas Black respondents reported the lowest uptake (influenza, 44.4%; Tdap, 57.9%). For the influenza vaccine, American Indian/Alaska Native respondents demonstrated a higher uptake compared with White respondents, and the magnitude of difference increased markedly after adjusting for respondent characteristics (adjusted odds ratio, 1.74; 95% confidence interval, 1.58–1.90). In the unadjusted analyses, Black individuals reported influenza vaccination at approximately half the rate of their White counterparts during pregnancy. This effect was attenuated but remained lower after adjustment for respondent characteristics (adjusted odds ratio, 0.73; 95% confidence interval, 0.70–0.76). For the Tdap vaccine, American Indian/Alaska Native respondents reported lower uptake than White respondents; however, this difference disappeared when adjusted for respondent characteristics (adjusted odds ratio, 0.99; 95% confidence interval, 0.83–1.19). Asian and Hispanic respondents displayed a similar uptake compared with their White counterparts for both vaccines. CONCLUSION: Our findings indicate that there are racial/ethnic disparities in influenza and Tdap vaccination rates among pregnant individuals in the United States. Demonstration of increased uptake among American Indian/Alaska Native people in the crude analysis may reflect the success of various public health interventions through Tribal and Indian Health Service hospitals. Nonetheless, vaccination status during pregnancy remains seriously below national guideline recommendations. Greater measures must be taken to support preventative care in marginalized populations, with particular emphasis on community-driven solutions rooted in justice.

Background. Female recipients of male donor kidneys are at increased risk for graft failure because of the HY antigen effect. However, whether prior transplant with a male donor impacts subsequent transplant outcomes is unknown. Therefore, the purpose of this study was to determine whether prior male-current male donor sex is associated with an increased risk of graft failure in female recipients. Methods. We performed a cohort study of adult female recipients undergoing a second kidney transplant (2000–2017), identified using the Scientific Registry of Transplant Recipients. Using multivariable Cox models, we analyzed the risk of death-censored graft loss (DCGL) if the second transplant was from a male versus female kidney donor, conditional on donor sex at the time of the first transplant. In a secondary analysis, we stratified results by recipient age (>50 or ≤50 y) at the time of retransplant. Results. Of 5594 repeat kidney transplants, 1397 (25.0%) developed DCGL. Overall, there was no association between first and second donor sex pairing and DCGL. A prior and current female donor (FD1FD2) posed a higher risk for DCGL in recipients aged >50 y at second transplant (hazard ratio,≤0.67, confidence interval 0.46-0.98, for all other donor combinations), but posed a lower risk if aged ≤50 y at retransplant (hazard ratio, ≥1.37, confidence interval 1.04-1.80, for all other donor combinations). Conclusions. Overall, past-current donor sex pairing was not associated with DCGL in female recipients undergoing second kidney transplant; however, the risk with a past and current female donor was increased in older, and decreased in younger, female recipients at retransplant.

Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2), by providing guidance on common and important clinical issues, such as: 1) How should HAE be diagnosed? 2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? 3) What are the goals of treatment? 4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast feeding women? 5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.

Pulmonary embolism is a life-threatening condition treated with anticoagulation and systemic thrombolysis when appropriate. In patients with contraindications to thrombolysis, catheter-directed thrombolysis may be considered. Here, we present a patient with massive pulmonary embolus and 3 contraindications to systemic thrombolysis who was successfully treated with pharmacomechanical thrombolysis using the Ekosonic Endovascular System.

Summary:. Field sterility is commonly used for skin and minor hand surgery performed in the ambulatory setting. Surgical site infection (SSI) rates are similar for these same procedures when performed in the main operating room (OR). In this paper, we aim to look at both current evidence and common sense logic supporting the use of some of the techniques and apparel designed to prevent SSI. This is a literature review of the evidence behind the ability of gloves, masks, gowns, drapes, head covers, footwear, and ventilation systems to prevent SSIs. We used MEDLINE, EMBASE, and PubMed and included literature from the inception of each database up to March 2019. We could not find substantial evidence to support the use of main OR sterility practices such as head covers, gowns, full patient draping, laminar airflow, and footwear to reduce SSIs in skin and minor hand surgery. Field sterility in ambulatory minor procedure rooms outside the main OR is appropriate for most skin and minor hand surgery procedures. SSIs in these procedures are easily treatable with minimal patient morbidity and do not justify the cost and waste associated with the use of main OR sterility.

Among younger men who have sex with men (MSM), the incidence of HIV is rising nationally. Of the 281 persons who entered into care at a large HIV clinic in the southeastern United States in 2010 to 2012, 78 (27.8%) were

ABSTRACT: Objective: Hyperinsulinemic hypoglycemia is an increasingly reported complication of Roux-en-Y gastric bypass surgery (RYGB), for which there is currently no acceptable treatment. We present a case of the reversal of severe hyperinsulinemic hypoglycemia through gastrostomy tube (GT) feeding to the remnant stomach and uniquely report the durable resolution of neuroglycopenic symptoms 3 years after GT placement.Methods: The case subject underwent standardized postprandial measurement of plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon concentrations after oral or GT administration of a standardized liquid meal.Results: Hypersecretion of insulin, GLP-1, and glucagon elicited by oral administration of the liquid meal were reversed with GT feeding. GIP was not secreted in excess of normal after the oral meal.Conclusion: This case of reversible hyperinsulinemic hypoglycemia through GT feeding illustrates the physiology of this disorder, pointing to an exaggerated GLP-1 response due to rapid nutrient transit to the distal bowel. The sustained resolution of the case subject's neuroglycopenic symptoms supports the use of GT as an effective and durable treatment for severe refractory hyperinsulinemic hypoglycemia after RYGB.Abbreviations: GIP glucose-dependent insulinotropic peptide GLP-1 glucagon-like peptide-1 GT gastrostomy tube RYGB Roux-en-Y gastric bypass

Background: Many surgeons add topical antibiotics to irrigation solutions assuming that this has a local effect and eliminates bacteria. However, prior studies have suggested that the addition of antibiotics to irrigation solution confers little benefit, adds cost, may potentiate anaphylactic reactions, and may contribute to antimicrobial resistance. We sought to compare the antimicrobial efficacy and cytotoxicity of an irrigation solution containing polymyxin-bacitracin with other commonly used irrigation solutions.Methods: Staphylococcus aureus and Escherichia coli were exposed to irrigation solutions containing topical antibiotics (500,000-U/L polymyxin and 50,000-U/L bacitracin; 1-g/L vancomycin; or 80-mg/L gentamicin), as well as commonly used irrigation solutions (saline solution 0.9%; povidone-iodine 0.3%; chlorhexidine 0.05%; Castile soap 0.45%; and sodium hypochlorite 0.125%). Following 1 and 3 minutes of exposure, surviving bacteria were manually counted. Failure to eradicate all bacteria in any of the 3 replicates was considered not effective for that respective solution. Cytotoxicity analysis in human fibroblasts, osteoblasts, and chondrocytes exposed to the irrigation solutions was performed by visualization of cell structure and was quantified by lactate dehydrogenase (LDH) activity. Efficacy and cytotoxicity were assessed in triplicate experiments, with generalized linear mixed models.Results: Polymyxin-bacitracin, saline solution, and Castile soap at both exposure times were not effective at eradicating S. aureus or E. coli. In contrast, povidone-iodine, chlorhexidine, and sodium hypochlorite irrigation were effective against both S. aureus and E. coli (p < 0.001). Vancomycin irrigation was effective against S. aureus but not against E. coli, whereas gentamicin irrigation showed partial efficacy against E. coli but none against S. aureus. Within fibroblasts, the greatest cytotoxicity was seen with chlorhexidine (mean [and standard error], 49.38% ± 0.80%; p < 0.0001), followed by Castile soap (33.57% ± 2.17%; p < 0.0001) and polymyxin-bacitracin (8.90% ± 1.40%). Povidone-iodine showed the least cytotoxicity of the efficacious solutions (5.00% ± 0.86%). Similar trends were seen at both exposure times and across fibroblasts, osteoblasts, and chondrocytes.Conclusions: Irrigation with polymyxin-bacitracin was ineffective at bacterial eradication, and statistically inferior to povidone-iodine. Chlorhexidine lavage conferred the greatest in vitro cytotoxicity.Clinical Relevance: These data suggest that the addition of polymyxin-bacitracin to saline solution irrigation has little value. Given the cost and antimicrobial resistance implications, our findings, combined with prior clinical literature, provide adequate reason to avoid widespread use of antibiotics in irrigation solutions. Povidone-iodine may be a more effective and safer option. [ABSTRACT FROM AUTHOR]

Background: Quadriceps weakness is a hallmark of total knee arthroplasty and is driven by reduced voluntary muscle activation following the surgical procedure. The mechanisms underlying postoperative activation deficits are not well established, although nociception has been implicated via both spinal reflex and supraspinal pathways. The purpose of this study was to assess the role of nociception in postoperative recovery of strength and activation.Methods: A total of 53 participants were assessed prior to total knee arthroplasty and at 6 weeks postoperatively. Quadriceps strength was measured by maximum voluntary isometric contraction, and activation was measured by the doublet interpolation technique. The pressure-pain threshold was used to measure local sensitization (at the knee joint) and systemic sensitization (at the forearm). Changes in outcomes (strength and activation) were regressed against pressure-pain threshold measurements. Mediation analyses were planned for significant associations to investigate whether deficits in voluntary activation were implicated on a causal pathway between pressure-pain threshold measures and postoperative strength loss.Results: Knee pressure-pain threshold measures were significantly associated with reduced voluntary quadriceps activation (beta = -0.04; p = 0.009) and diminished quadriceps strength after total knee arthroplasty (beta = -0.07; p = 0.001). There was also a mediation effect of voluntary activation on the relationship between the knee pressure-pain threshold and quadriceps strength. After correcting for multiple comparisons, relationships between the forearm pressure-pain threshold and strength and activation did not reach significance.Conclusions: The measures of local nociceptor sensitization were related to reduced strength and activation following total knee arthroplasty. This is consistent with a causal pathway linking increased firing of knee joint nociceptors to reduced activation and reduced strength. Future randomized studies should investigate whether peripherally directed pain therapies reduce pain while also promoting the recovery of quadriceps strength via an improved capacity for voluntary activation.Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Continuing professional development (CPD) can support delivery of high-quality care, but may not be optimized until we can understand cultural barriers and facilitators, especially as innovations emerge. Lifelong learning (LLL), linked with quality improvement, competence, and professionalism, is a core competency in medical education. The purpose of this study is to examine cultural factors (individual, organizational, and systemic) that influence CPD and specifically the use of clinical data to inform LLL and CPD activities. This mixed-method study will examine the perceptions of two learner groups (psychiatrists and general surgeons) in three phases: (1) a survey to understand the relationship between data-informed learning and orientation to LLL; (2) semistructured interviews using purposive and maximum variation sampling techniques to identify individual-, organizational-, and system-level barriers and facilitators to engaging in data-informed LLL to support practice change; and (3) a document analysis of legislation, policies, and procedures related to the access and the use of clinical data for performance improvement in CPD. We obtained research ethics approval from the University Health Network in Toronto, Ontario, Canada. By exploring two distinct learner groups, we will identify contextual features that may inform what educators should consider when conceptualizing and designing CPD activities and what initial actions need to be taken before CPD activities can be optimized. This study will lead to the development of a framework reflective of barriers and facilitators that can be implemented when planning to use data in CPD activities to support data adoption for LLL. [ABSTRACT FROM AUTHOR]

Introduction: Fellows of the Royal College of Physicians and Surgeons of Canada are required to participate in assessment activities for all new 5-year cycles beginning on or after January 2014 to meet the maintenance of certification program requirements. This study examined the assessment activities which psychiatrists reported in their maintenance of certification e-portfolios to determine the types and frequency of activities reported; the resultant learning, planned learning, and/or changes to the practice they planned or implemented; and the interrelationship between the types of assessment activities, learning that was affirmed or planned, and changes planned or implemented. Methods: A total of 5000 entries from 2195 psychiatrists were examined. A thematic analysis drawing on the framework analysis was undertaken of the 2016 entries. Results: There were 3841 entries for analysis; 1159 entries did not meet the criteria for assessment. The most commonly reported activities were self-assessment programs, feedback on teaching, regular performance reviews, and chart reviews. Less frequent were direct observation, peer supervision, and reviews by provincial medical regulatory authorities. In response to the data, psychiatrists affirmed that their practices were appropriate, identified gaps they intended to address, planned future learning, and/or planned or implemented changes. The assessment activities were internally or externally initiated and resulted in no or small changes (accommodations and adjustments) or redirections. Discussion: Psychiatrists reported participating in a variety of assessment activities that resulted in variable impact on learning and change. The study underscores the need to ensure that assessments being undertaken are purposeful, relevant, and designed to enable identification of outcomes that impact practice. [ABSTRACT FROM AUTHOR]

Effective fluid handling by wound dressings is crucial in the management of exuding wounds through maintaining a clean, moist environment, facilitating healing by removing excess exudate and promoting tissue regeneration. In this context, the availability of reliable and clinically relevant standardised testing methods for wound dressings are critical for informed decision making by clinicians, healthcare administrators, regulatory/reimbursement bodies and product developers. The widely used standard EN 13726 specifies the use of Solution A, an aqueous protein-free salt solution, for determining fluid-handling capacity (FHC). However, a simulated wound fluid (SWF) with a more complex composition, resembling the protein, salt, and buffer concentrations found in real-world clinical exudate, would provide a more clinically relevant dressing performance assessment. This study compared selected physicochemical parameters of Solution A, an alternative, novel simulated wound fluid (SWF A), and a benchmark reference serum-containing solution (SCS) simulating chronic wound exudate. Additionally, FHC values for eight advanced bordered and non-bordered foam dressings were determined for all three test fluids, following EN 13726. Our findings demonstrate a close resemblance between SWF A and SCS. This study highlights the critical importance of selecting a physiochemically appropriate test fluid for accurate FHC testing resulting in clinically meaningful evaluation of dressing performance., (© 2024 Mölnlycke Health Care AB. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Objective: To evaluate whether the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a responsive instrument in psoriatic arthritis (PsA) and whether it differentiates between axial and peripheral disease activity in PsA., Methods: Individuals with PsA initiating therapy in a longitudinal cohort study based in the United States were included. Axial PsA (axPsA), most often also associated with peripheral disease, was defined as fulfillment of the Assessment of Spondyloarthritis international Society axial spondyloarthritis classification criteria or presence of axial disease imaging features. Baseline BASDAI, individual BASDAI items, patient global assessment, patient pain, and Routine Assessment of Patient Index Data 3, and score changes following therapy initiation were descriptively reported. Standardized response means (SRMs) were calculated as the mean change divided by the SD of the change., Results: The mean (SD) baseline BASDAI score at the time of therapy initiation was 5.0 (2.2) among those with axPsA (n = 40) and 4.8 (2.0) among those with peripheral-only disease (n = 79). There was no significant difference in patient-reported outcome scores between the groups. The mean change for BASDAI was similar among axial vs peripheral disease (-0.75 vs -0.83). SRMs were similar across axial vs peripheral disease for BASDAI (-0.37 vs -0.44) and the individual BASDAI items., Conclusion: BASDAI has reasonable responsiveness in PsA but does not differentiate between axPsA and peripheral PsA. (ClinicalTrials.gov: NCT03378336)., (Copyright © 2024 by the Journal of Rheumatology.)

Translocation science has made considerable progress over the last two decades; however, reptile translocations still frequently fail around the world. Major knowledge gaps surround the basic ecology of reptile species, including basic factors such as habitat preference, which have a critical influence on translocation success. The western spiny-tailed skink ( Egernia stokesii badia ) is used here as a case study to exemplify how empirical research can directly inform on-ground management and future translocation planning. A combination of studies, including LiDAR scanning of microhabitat structures, camera trapping, plasticine replica model experiments and unbounded point count surveys to assess predation risk, and visual and DNA analysis of dietary requirements, were all used to better understand the ecological requirements of E. s. badia . We found that the skinks have specific log pile requirements, both native and non-native predator management requirements, and a largely herbivorous, broad diet, which all influence translocation site selection and management planning. The use of E. s. badia as an Australian case study provides a clear strategic framework for the targeted research of meaningful ecological factors that influence translocation decision-making. Similar approaches applied to other reptile species are likely to fundamentally increase the capacity for effective management, and the likelihood of future successful translocations.

B-cell acute lymphoblastic leukemia (ALL) is derived from an accumulation of malignant, immature B cells in the bone marrow and blood. Relapse due, in part, to the emergence of tumor cells that are resistant to front line standard chemotherapy is associated with poor patient outcomes. This challenge highlights the need for new treatment strategies to eliminate residual chemoresistant tumor cells. Based on the use of pitavastatin in acute myeloid leukemia (AML), we evaluated its efficacy in an REH ALL cell line derived to be resistant to vincristine. We found that pitavastatin inhibited the proliferation of both parental and vincristine-resistant REH tumor cells at an IC 50 of 449 nM and 217 nM, respectively. Mitochondrial bioenergetic assays demonstrated that neither vincristine resistance nor pitavastatin treatment affected cellular oxidative phosphorylation, beta-oxidation, or glycolytic metabolism in ALL cells. In a co-culture model of ALL cells with bone marrow stromal cells, pitavastatin significantly decreased cell viability more robustly in the vincristine-resistant ALL cells compared with their parental controls. Subsequently, NSG mice were used to develop an in vivo model of B-cell ALL using both parental and vincristine-resistant ALL cells. Pitavastatin (10 mg/kg i.p.) significantly reduced the number of human CD45+ REH ALL cells in the bone marrow of mice after 4 weeks of treatment. Mechanistic studies showed that pitavastatin treatment in the vincristine-resistant cells led to apoptosis, with increased levels of cleaved PARP and protein-signaling changes for AMP-activated protein kinase/FoxO3a/Puma. Our data suggest the possible repurposing of pitavastatin as a chemotherapeutic agent in a model of vincristine-resistant B-cell ALL.

The lack of complete therapeutic success in the treatment of B-cell acute lymphoblastic leukemia (ALL) has been attributed, in part, to a subset of cells within the bone marrow microenvironment that are drug resistant. Recently, the cholesterol synthesis inhibitor, pitavastatin (PIT), was shown to be active in acute myeloid leukemia, prompting us to evaluate it in our in vitro co-culture model, which supports a chemo-resistant ALL population. We used phospho-protein profiling to evaluate the use of lipid metabolic active compounds in these chemo-resistant cells, due to the up-regulation of multiple active survival signals. In a co-culture with stromal cells, a shift towards anabolic processes occurred, which was further confirmed by assays showing increased lipid content. The treatment of REH leukemia cells with pitavastatin in the co-culture model resulted in significantly higher leukemic cell death than exposure to the standard-of-care chemotherapeutic agent, cytarabine (Ara-C). Our data demonstrates the use of pitavastatin as a possible alternative treatment strategy to improve patient outcomes in chemo-resistant, relapsed ALL.

A central principle of threatened species management is the requirement for detailed understanding of species habitat requirements. Difficult terrain or cryptic behaviour can, however, make the study of habitat or microhabitat requirements difficult, calling for innovative data collection techniques. We used high-resolution terrestrial LiDAR imaging to develop three-dimensional models of log piles, quantifying the structural characteristics linked with occupancy of an endangered cryptic reptile, the western spiny-tailed skink (Egernia stokesii badia). Inhabited log piles were generally taller with smaller entrance hollows and a wider main log, had more high-hanging branches, fewer low-hanging branches, more mid- and understorey cover, and lower maximum canopy height. Significant characteristics linked with occupancy were longer log piles, an average of three logs, less canopy cover, and the presence of overhanging vegetation, likely relating to colony segregation, thermoregulatory requirements, and foraging opportunities. In addition to optimising translocation site selection, understanding microhabitat specificity of E. s. badia will help inform a range of management objectives, such as targeted monitoring and invasive predator control. There are also diverse opportunities for the application of this technology to a wide variety of future ecological studies and wildlife management initiatives pertaining to a range of cryptic, understudied taxa., (© 2022. The Author(s).)

Mitigation translocation is a subgroup of conservation translocation, categorized by a crisis-responsive time frame and the immediate goal of relocating individuals threatened with death. However, the relative successes of conservation translocations with longer time frames and broader metapopulation- and ecosystem-level considerations have been used to justify the continued implementation of mitigation translocations without adequate post hoc monitoring to confirm their effectiveness as a conservation tool. Mitigation translocations now outnumber other conservation translocations, and understanding the effectiveness of mitigation translocations is critical given limited global conservation funding especially if the mitigation translocations undermine biodiversity conservation by failing to save individuals. We assessed the effectiveness of mitigation translocations by conducting a quantitative review of the global literature. A total of 59 mitigation translocations were reviewed for their adherence to the adaptive scientific approach expected of other conservation translocations and for the testing of management options to continue improving techniques for the future. We found that mitigation translocations have not achieved their potential as an effective applied science. Most translocations focused predominantly on population establishment- and persistence-level questions, as is often seen in translocations more broadly, and less on metapopulation and ecosystem outcomes. Questions regarding the long-term impacts to the recipient ecosystem (12% of articles) and the carrying capacity of translocation sites (24% of articles) were addressed least often, despite these factors being more likely to influence ultimate success. Less than half (47%) of studies included comparison of different management techniques to facilitate practitioners selecting the most effective management actions for the future. To align mitigation translocations with the relative success of other conservation translocations, it is critical that future mitigation translocations conform to an established experimental approach to improve their effectiveness. Effective mitigation translocations will require significantly greater investment of time, expertise, and resources in the future., (© 2020 Society for Conservation Biology.)

Purpose: Despite the achievement of complete remission with chemotherapy in patients with acute myeloid leukemia (AML), relapse is common and the majority of patients will die of their disease. Patients who achieve a remission after refractory or relapsed disease as well as elderly patients have a very high rate of relapse even if they achieve a complete remission. A phase 3 randomized ECOG-ACRIN-led intergroup study was conducted to determine whether post-remission therapy with the farnesyl transferase inhibitor, tipifarnib (R115777), improved the disease-free survival (DFS) of adult patients with AML in complete remission (CR), at high risk for relapse., Patients and Methods: Adult patients with AML in remission after salvage therapy and/or over age 60 in first remission were enrolled in this study. They were randomly assigned to treatment with tipifarnib or observation (control). The primary objective was to compare the disease-free survival (DFS) between the two arms based on intention to treat, which includes all randomized patients., Results: One hundred and forty-four patients were enrolled on the study. Median DFS was 8.9 vs 5.3 months, for tipifarnib vs observation (one-sided p = 0.026) and did not cross the pre-specified boundary to call the study positive. For the 134 eligible patients, median DFS was 10.8 vs 5.3 months for those randomized to tipifarnib vs observation (one-sided p = 0.008). Moreover in an ad hoc evaluation of all women (n = 71) median DFS was 12.1 vs 3.9 months for tipifarnib vs observation (one-sided p = 0.0004) while median OS was 26.5 vs 8.4 months respectively (one-sided p = 0.001)., Conclusion: This study was not able to demonstrate a benefit to tipifarnib as maintenance therapy in patients with AML in remission. While subsets of patients may indeed benefit, additional studies would be needed to elucidate that benefit which is unlikely given that other seemingly better options have since become available., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Significant portions of the world's forests have been impacted by severe and large-scale tree declines characterised by gradual but widespread loss of vigour and subsequent death of either single or several tree species. Tree deaths represent a threat for fauna that are dependent on forest habitats for their survival. Although tree declines have received considerable scientific attention, surprisingly, little is known about their impacts on fauna. In total, we calculated 631 effect sizes across 59 studies that quantified the impact of tree declines on animal abundance. Data representing 186 bird species indicated an overall increase in bird abundance in response to tree declines (meta-analysis mean ± estimation g = 0.172 ± 0.053 [CI 0.069 to 0.275], P = 0.001); however, there was substantial variability in responses (significant heterogeneity P < 0.001) with a strong influence of diet as well as nesting guild on bird responses. Granivores (especially ground-foraging species, e.g. Passerellidae species), bark-foraging insectivores (e.g. woodpeckers), as well as ground- and cavity-nesting species apparently benefitted from tree declines, while nectarivorous birds [and, although not significant, aerially foraging insectivores (e.g. flycatchers) and leaf-gleaning insectivores (canopy-feeding)] were less common in the presence of tree declines. Data representing 33 mammal species indicate a tendency for detrimental effects of tree declines on mammals that use trees as refuges, while aerial foragers (i.e. bats) may benefit from opening up the canopy. Overall the average effect for mammals was neutral (meta-analysis mean estimation g = -0.150 ± 0.145 [-0.433 to 0.134], P = 0.302). Data representing 20 reptile species showed an insufficient range of responses to determine any diet or foraging effect on their responses. Data for 28 arthropod taxa should be considered with caution, as we could not adequately separate taxa according to their specialisations and reliance on key habitat. The data broadly suggest a detrimental effect of tree declines (meta-analysis mean estimation g = -0.171 ± 0.072 [-0.311 to -0.031], P = 0.017) with ground-foraging arthropods (e.g. detritivores and predators such as spiders and centipedes) more likely to be detrimentally impacted by tree declines. The range of responses to tree declines signifies substantially altered animal communities. In many instances, altered ecosystem function due to loss of key animal services will represent a significant threat to forest health., (© 2021 Cambridge Philosophical Society.)

Introduced mammalian predators can have devastating impacts on recipient ecosystems and disrupt native predator-prey relationships. Feral cats (Felis catus) have been implicated in the decline and extinction of many Australian native species and developing effective and affordable methods to control them is a national priority. While there has been considerable progress in the lethal control of feral cats, effective management at landscape scales has proved challenging. Justification of the allocation of resources to feral cat control programs requires demonstration of the conservation benefit baiting provides to native species susceptible to cat predation. Here, we examined the effectiveness of a landscape-scale Eradicat® baiting program to protect threatened northern quolls (Dasyurus hallucatus) from feral cat predation in a heterogeneous rocky landscape in the Pilbara region of Western Australia. We used camera traps and GPS collars fitted to feral cats to monitor changes in activity patterns of feral cats and northern quolls at a baited treatment site and unbaited reference site over four years. Feral cat populations appeared to be naturally sparse in our study area, and camera trap monitoring showed no significant effect of baiting on cat detections. However, mortality rates of collared feral cats ranged from 18-33% after baiting, indicating that the program was reducing cat numbers. Our study demonstrated that feral cat baiting had a positive effect on northern quoll populations, with evidence of range expansion at the treatment site. We suggest that the rugged rocky habitat preferred by northern quolls in the Pilbara buffered them to some extent from feral cat predation, and baiting was sufficient to demonstrate a positive effect in this relatively short-term project. A more strategic approach to feral cat management is likely to be required in the longer-term to maximise the efficacy of control programs and thereby improve the conservation outlook for susceptible threatened fauna., Competing Interests: Rio Tinto provided funding for this study under a Threatened Species Offset Plan and a Memorandum of Understanding with the Western Australian Department of Biodiversity, Conservation and Attractions (DBCA). This commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials. The Eradicat® bait used in this study is manufactured and supplied by DBCA’s Bait Factory. The registration of Eradicat® in Western Australia restricts its use to fauna conservation programs on lands managed by or in agreement with DBCA. Any use in other Australian states is subject to a minor use research permit from the Australian Pesticides and Veterinary Medicines Authority. Proposals for the use of Eradicat® are assessed by DBCA’s Feral Cat Technical Committee, of which, L. Gibson is a member. All remaining authors have no competing interests to declare.

Building trust in science and evidence-based decision-making depends heavily on the credibility of studies and their findings. Researchers employ many different study designs that vary in their risk of bias to evaluate the true effect of interventions or impacts. Here, we empirically quantify, on a large scale, the prevalence of different study designs and the magnitude of bias in their estimates. Randomised designs and controlled observational designs with pre-intervention sampling were used by just 23% of intervention studies in biodiversity conservation, and 36% of intervention studies in social science. We demonstrate, through pairwise within-study comparisons across 49 environmental datasets, that these types of designs usually give less biased estimates than simpler observational designs. We propose a model-based approach to combine study estimates that may suffer from different levels of study design bias, discuss the implications for evidence synthesis, and how to facilitate the use of more credible study designs.

Background: Midostaurin, a multikinase inhibitor, is approved for treatment of FLT3-mutant acute myeloid leukemia (AML). A phase I study established that midostaurin 75 mg orally twice daily for 14 days with standard dose azacitidine was safe and tolerable in elderly patients with AML. Herein, we report the phase II expansion cohort of previously untreated elderly or unfit patients with AML., Patients and Methods: Primary objectives were to further describe the toxicity profile and determine the response rate in untreated patients with AML. Patients received midostaurin 75 mg orally twice daily on days 8 to 21 in combination with intravenous azacitidine at 75 mg/m 2 on days 1 to 7. Plasma inhibitory activity assay for FLT3 was performed pretreatment and on day 8 and day 15 of each cycle., Results: Twenty-six patients (median age, 74 years; range, 59-85 years) with FLT3 wild-type AML were accrued. Patients received a median of 2 cycles of therapy (range, 1-10 cycles). Seven (29%) of 24 evaluable patients achieved a clinical response (4 complete response; 1 complete response with incomplete count recovery; and 2 partial response). The median overall survival was 244 days (95% confidence interval, 203-467 days). Hematologic, infectious, and gastrointestinal toxicities were comparable to similar studies. Peripheral blood FLT3 wild-type phosphorylation declined to 8% to 55% of pretreatment by day 15 of cycle 1 (7 patients) and declined with subsequent cycles (< 10% baseline) in 2 patients who were analyzed after cycle 3., Conclusion: Multiple cycles of azacitidine and midostaurin were not well-tolerated, but persistent inhibition of FLT3 wild-type phosphorylation suggest intermittent dosing of midostaurin should be considered in future low-intensity regimens for FLT3-mutant AML., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Outcomes for patients with peripheral T-cell lymphoma (PTCL) who fail to achieve complete response (CR) or relapse after front-line therapy are poor with lack of prospective outcomes data., Objectives: COMPLETE is a prospective registry of 499 patients enrolled at academic and community sites in the United States detailing patient demographics, treatment and outcomes for patients with aggressive T cell lymphomas. We report results for patients with primary refractory and relapsed disease., Methods: Primary refractory disease was defined as an evaluable best response to initial treatment (induction ± maintenance or consolidation/transplant) other than CR, and included a partial response, progressive disease, or no response/stable disease. Relapsed disease was defined as an evaluable best response to initial treatment of CR, followed by disease progression at a later date, irrespective of time to progression. Patients were included in the analysis if initial treatment began within 30 days of enrollment and treatment duration was ≥4 days., Results: Of 420 evaluable patients, 97 met the definition for primary refractory and 58 with relapsed disease. In the second-line setting, relapsed patients received single-agent therapies more often than refractory patients (52 vs. 28%; p = 0.01) and were more likely to receive single-agent regimens (74 vs. 53%; p = 0.03). The objective response rate to second-line therapy was higher in relapsed patients (61 vs. 40%; p = 0.04) as was the proportion achieving a CR (41 vs. 14%; p = 0.002). Further, relapsed patients had longer overall survival (OS) compared to refractory patients, with a median OS of 29.1 versus 12.3 months., Conclusions: Despite the availability of newer active single agents, refractory patients were less likely to receive these therapies and continue to have inferior outcomes compared to those with relapsed disease. PTCL in the real world remains an unmet medical need, and improvements in front-line therapies are needed., (© 2019 S. Karger AG, Basel.)