Alpelisib for treatment of patients with PIK3CA-related overgrowth spectrum (PROS).

PURPOSE: PIK3CA-related overgrowth spectrum (PROS) encompasses several rare conditions resulting from activating variants in PIK3CA. Alpelisib, a PI3Kα-selective inhibitor, targets the underlying etiology of PROS, offering a novel therapeutic approach to current management strategies. This study evaluated the safety and efficacy of alpelisib in pediatric and adult patients with PROS. METHODS: EPIK-P1 (NCT04285723) was a non-interventional, retrospective chart review of 57 patients with PROS (≥2 years) treated with alpelisib through compassionate use. Patients had severe/life-threatening PROS-related conditions and confirmed PIK3CA pathogenic variant. The primary end point assessed patient response to treatment at Week 24 (6 months). RESULTS: Twenty-four weeks (6 months) after treatment initiation, 12 of 32 (37.5%) patients with complete case records included in the analysis of the primary end point experienced a ≥20% reduction in target lesion(s) volume. Additional clinical benefit independent from lesion volume reduction was observed across the full study population. Adverse events (AEs) and treatment-related AEs were experienced by 82.5% (47/57) and 38.6% (22/57) of patients, respectively; the most common treatment-related AEs were hyperglycemia (12.3%) and aphthous ulcer (10.5%). No deaths occurred. CONCLUSION: EPIK-P1 provides real-world evidence of alpelisib effectiveness and safety in patients with PROS and confirms PI3Kα as a valid therapeutic target for PROS symptom management.

30 years on: A brave new world or an unfolding disaster?

In this short essay, the focus is on social and political aspects of forced migration. It is argued that policies designed to restrict access to developed countries have, rather like the American "prohibition", produced a thriving criminal market for smugglers, in this case of people. Making travel more difficult increases both their profits and the sophistication of their methods. Provision of targeted, properly controlled, support for refugees in countries neighbouring conflict zones might help to reduce the pressure on travel to Europe and could be both more successful and more hu-manitarian. For those who do reach devel-oped countries, there is scope to improve the legal decision-making process. Psychological input should include scientific investigation of legal assumptions, and the provision of rel-evant expert literature reviews, for example concerning modern knowledge of memory. Trust is the first casualty of repressive vio-lence, and mistrust among opposition groups is probably one of the key mechanisms of its success. We need to make sure that we do not provide further grounds for this sort of reaction. Although there is no brave or new world ahead, we must continue to confront ignorance and prejudice, as we seek to avoid more humanitarian disasters.It is now just over thirty years since we published a potential framework for under-standing how survivors of organised state vi-olence react to complex and severe trauma (Turner and Gorst-Unsworth, 1990). We argued that no single psychological process underpins the reactions to this experience, and therefore, there can be no unitary torture syndrome, but rather a series of understandable psychological pathways activated to varying degrees by dif-ferent experiences, leading to diversity of emo-tional response, with implications for recovery and treatment. We also asked family doctors about health needs of refugees (Ramsay and Turner, 1993), and it is wonderful to see how the evidence on treatment options has devel-oped since then, especially in recent years. In this paper, looking back over the last thirty years, in celebration of the anniversary of Torture journal, I will focus on political, legal and forensic aspects of forced migration.

Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment for Post Infarct Angina in Patients With Myocardial Infarction With Non-obstructive Coronary Arteries: A MINOCA-BAT Sub Study Rationale and Design.

Introduction: Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in ~10% of all patients with acute myocardial infarction (AMI), with an over-representation amongst women. Remarkably, it is estimated that as many as 1 in 4 patients with MINOCA experience ongoing angina at 12 months despite having no flow-restricting stenoses in their epicardial arteries. This manuscript presents the rationale behind Randomized Evaluation of Beta Blocker and Angiotensin-converting enzyme inhibitors/Angiotensin Receptor Blocker Treatment (ACEI/ARB) for Post Infarct Angina in MINOCA patients-The MINOCA BAT post infarct angina sub study. Methods: This trial is a registry-based, randomized, parallel, open-label, multicenter trial with 2 × 2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce post infarct angina in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 664 patients will be randomized into four groups; (i) ACEI/ARB with beta blocker, (ii) beta blocker only, (iii) ACEI/ARB only, or (iv) neither ACEI/ARB nor beta blocker and followed for 12 months. Results: The trial is currently recruiting in Australia and Sweden. Fifty six patients have been recruited thus far. Both sexes were equally distributed (52% women and 48% men) and the mean age was 56.3 ± 9.9 years. Conclusions: It remains unclear whether conventional secondary preventive therapies are beneficial to MINOCA patients in regard to post infarct angina. Existing registry-based literature suggest cardioprotective agents are less likely to be used in MINOCA patients. Thus, results from this trial will provide insights for future treatment strategies and guidelines specific to MINOCA patients.

Effectiveness of Alpelisib + Fulvestrant Compared with Real-World Standard Treatment Among Patients with HR+, HER2-, PIK3CA-Mutated Breast Cancer.

BACKGROUND: The BYLieve trial (NCT03056755) confirmed efficacy and safety of alpelisib with fulvestrant for hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC), after cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with an aromatase inhibitor (AI) as immediate prior therapy. Further analyses were performed to compare efficacy from BYLieve with effectiveness of standard treatment in the real-world setting. MATERIALS AND METHODS: Patients who progressed on a CDK4/6i plus AI and were treated with alpelisib with fulvestrant in BYLieve were matched with a real-world patient cohort who received standard-of-care from a deidentified clinico-genomics database (CGDB). Primary and secondary endpoints were to compare progression-free survival (PFS), estimated by the Kaplan-Meier method, and the proportion of patients remaining progression-free at 6 months, respectively, between the two cohorts. RESULTS: A total of 855 patients with PIK3CA-mutant disease who had prior CDK4/6i plus hormone therapy were selected from the CGDB; further matching to 120 patients from BYLieve selected 95 patients without exposure to HER2-targeting agents, clinical study drug, or alpelisib. In unadjusted and postmatching results, primary and secondary endpoints favored treatment with alpelisib with fulvestrant in BYLieve more than standard treatments in the real-world cohort. Postadjustment, median PFS for patients treated with alpelisib in BYLieve was 7.3 versus 3.7 months in the real-world cohort, and 6-month PFS was 54.6% versus 40.1%, respectively. CONCLUSION: Matched/weighted analysis comparing BYLieve with the real-world setting further supports the clinical benefit of alpelisib with fulvestrant for treatment of HR+, HER2-, PIK3CA-mutant ABC after CDK4/6i treatment. IMPLICATIONS FOR PRACTICE: Approximately 40% of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC) have PIK3CA-mutated tumors, which have been associated with endocrine therapy resistance. Alpelisib, an α-selective phosphatidylinositol-3-kinase inhibitor, demonstrated significantly improved progression-free survival in SOLAR-1 and demonstrated clinical efficacy in BYLieve when combined with fulvestrant. Data are limited in comparing the efficacy of alpelisib combined with fulvestrant with effectiveness of standard therapy after CDK4/6i treatment. Using real-world data, this is the first analysis comparing alpelisib combined with fulvestrant with standard treatments for HR+, HER2-, PIK3CA-mutant ABC in the post-CDK4/6i setting.

Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study.

BACKGROUND: Alpelisib, a PI3Kα-selective inhibitor and degrader, plus fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in SOLAR-1; limited data are available in the post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess alpelisib plus endocrine therapy in this setting in three cohorts defined by immediate previous treatment; here, we report results from cohort A. METHODS: This ongoing, phase 2, multicentre, open-label, non-comparative study enrolled patients with hormone receptor-positive, HER2-negative, advanced breast cancer with tumour PIK3CA mutation, following progression on or after previous therapy, including CDK4/6 inhibitors, from 114 study locations (cancer centres, medical centres, university hospitals, and hospitals) in 18 countries worldwide. Participants aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 2 or less, with no more than two previous anticancer treatments and no more than one previous chemotherapy regimen, were enrolled in three cohorts. In cohort A, patients must have had progression on or after a CDK4/6 inhibitor plus an aromatase inhibitor as the immediate previous treatment. Patients received oral alpelisib 300 mg/day (continuously) plus fulvestrant 500 mg intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1. The primary endpoint was the proportion of patients alive without disease progression at 6 months per local assessment using Response Evaluation Criteria in Solid Tumors, version 1.1, in patients with a centrally confirmed PIK3CA mutation. This trial is registered with ClinicalTrials.gov, NCT03056755. FINDINGS: Between Aug 14, 2017, and Dec 17, 2019 (data cutoff), 127 patients with at least 6 months' follow-up were enrolled into cohort A. 121 patients had a centrally confirmed PIK3CA mutation. At data cutoff, median follow-up was 11·7 months (IQR 8·5-15·9). 61 (50·4%; 95% CI 41·2-59·6) of 121 patients were alive without disease progression at 6 months. The most frequent grade 3 or worse adverse events were hyperglycaemia (36 [28%] of 127 patients), rash (12 [9%]), and rash maculopapular (12 [9%]). Serious adverse events occurred in 33 (26%) of 127 patients. No treatment-related deaths were reported. INTERPRETATION: BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor. FUNDING: Novartis Pharmaceuticals.

Systemic treatment of hormone receptor positive, human epidermal growth factor 2 negative metastatic breast cancer: retrospective analysis from Leeds Cancer Centre.

BACKGROUND: Study aimed to characterise treatment and outcomes for patients with hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2-) metastatic breast cancer (MBC) within a large regional cancer centre, as a benchmark for evaluating real-world impact of novel therapies. METHODS: Retrospective longitudinal cohort, using electronic patient records of adult females with a first diagnosis of HR+/HER2- MBC January 2012-March 2018. RESULTS: One hundred ninety-six women were identified with HR+/HER2- MBC. Median age was 67 years, 85.2% were post-menopausal and median time between primary diagnosis and metastasis was 5.4 years. Most (75.1%) patients received endocrine therapy as first line systemic treatment (1st LoT); use of 1st LoT chemotherapy halved between 2012 and 2017. Patients receiving 1st LoT chemotherapy were younger and more likely to have visceral metastasis (p < 0.01). Median OS was 29.5 months and significantly greater for patients with exclusively non-visceral metastasis (p < 0.01). The adjusted hazard ratio for death of patients with visceral (or CNS) metastasis was 1.91 relative to those with exclusively non-visceral metastasis. CONCLUSIONS: Diverse endocrine therapies predominate as 1st LoT for patients with HR+/HER2- MBC, chemotherapy being associated with more aggressive disease in younger patients, emphasising the importance of using effective and tolerable therapies early.

Atomic-scale viscoplasticity mechanisms revealed in high ductility metallic glass films.

The fundamental plasticity mechanisms in thin freestanding Zr65Ni35 metallic glass films are investigated in order to unravel the origin of an outstanding strength/ductility balance. The deformation process is homogenous until fracture with no evidence of catastrophic shear banding. The creep/relaxation behaviour of the films was characterized by on-chip tensile testing, revealing an activation volume in the range 100-200 Å3. Advanced high-resolution transmission electron microscopy imaging and spectroscopy exhibit a very fine glassy nanostructure with well-defined dense Ni-rich clusters embedded in Zr-rich clusters of lower atomic density and a ~2-3 nm characteristic length scale. Nanobeam electron diffraction analysis reveals that the accumulation of plastic deformation at room-temperature correlates with monotonously increasing disruption of the local atomic order. These results provide experimental evidences of the dynamics of shear transformation zones activation in metallic glasses. The impact of the nanoscale structural heterogeneities on the mechanical properties including the rate dependent behaviour is discussed, shedding new light on the governing plasticity mechanisms in metallic glasses with initially heterogeneous atomic arrangement.

Development, psychometric evaluation, and initial feasibility assessment of a symptom tracker for use by patients with heart failure (HFaST).

BACKGROUND: This study aimed to develop and provide a psychometric and feasibility pilot evaluation of the Heart Failure (HF) Symptom Tracker (HFaST), a new patient-reported tool designed to facilitate communication between patients and health care providers (HCPs) in routine clinical care. The HFaST enables patients to identify worsening HF symptoms, with a long-term goal of preventing hospitalizations or emergency room visits. METHODS: The HFaST was developed drawing on evidence from the literature, qualitatively with cognitive interviews (12 patient/caregiver and 8 HCPs), and evaluated quantitatively (psychometric, feasibility assessment). The HFaST was administered for 7 consecutive days to 100 individuals diagnosed with HF during a multisite, non-interventional US pilot study. Health care providers then completed a survey assessing the feasibility and importance of the HFaST in clinical practice. Qualitative development included a literature review and cognitive interviews with patients, caregivers, and HCPs. The psychometric properties of the HFaST were evaluated using classical test theory methods. Descriptive statistics provided insight into HCPs' perceptions of the feasibility of using the HFaST in clinical practice. RESULTS: A preliminary set of 40 items was developed for the symptom tracker and iteratively reduced to 10 items based on the qualitative phase. Test-retest reliability (weighted kappa 0.71-0.97), discriminating validity, and construct validity of the HFaST were acceptable. HCPs rated the HFaST as a good (70%) or excellent (30%) means of tracking HF symptoms. Six HFaST items were ultimately retained, covering concepts of fatigue, shortness of breath (3 items), swelling, and rapid weight gain. CONCLUSIONS: The 6-item HFaST is an easy-to-use tool designed to raise patients' awareness of HF symptoms and facilitate communication with HCPs. Future research should evaluate HFaST implementation in clinical practice and effectiveness as an intervention to potentially prevent hospitalizations and emergency room visits.

Specificity of Myocardial Perfusion Imaging: Issues With Proposed MBS Item Review.

Myocardial perfusion scanning (MPS) is commonly used to assess patients with an intermediate to high risk of coronary artery disease. Concerns have been raised about the accuracy of this test. There is little recent data regarding the specificity of the MPS in the context of current medical therapy. The primary objective of this study is to determine the specificity of MPS in diagnosing obstructive coronary artery disease. A total of 184 patients fulfilled study criteria. The overall specificity of MPS for obstructive coronary artery disease was 54%.The only demographic variable that influenced specificity was gender: males with a specificity of 66% and females with a specificity of 29% (p-value=0.001). These results suggest that the real world specificity of MPS is lower than previously indicated, particularly in the female population. The limitations proposed by the Cardiac Services Committee Report are therefore unlikely to improve patient outcomes.

Characteristics of early sacubitril/valsartan patients and considerations for studies in electronic health record data.

AIM: We examined characteristics of early sacubitril/valsartan users in a large US electronic health records database. PATIENTS & METHODS: We identified three cohorts of patients with heart failure (HF): sacubitril/valsartan patients with a prior HF diagnosis; patients with HF with reduced ejection fraction; and patients with HF treated with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and a ß-blocker. RESULTS: Sacubitril/valsartan patients were younger than patients in the other cohorts; the mean age of sacubitril/valsartan patients increased by 2 years in the first 15 months of marketing. Most sacubitril/valsartan patients had prior use of HF treatment. CONCLUSION: Overall, sacubitril/valsartan patients resembled those in the HF with reduced ejection fraction cohort, and commonly used other drugs for HF.

Economic evaluation of micafungin versus liposomal amphotericin B (LAmB) for treating patients with candidaemia and invasive candidiasis (IC) in Turkey.

Micafungin was reported to be non-inferior to liposomal amphotericin B (LAmB) in treating patients with candidaemia and invasive candidiasis (IC). The current study aimed to evaluate the economic impact of using micafungin versus LAmB for treatment of candidaemia and IC in Turkey. A decision analytic model, which depicted economic consequences upon administration of micafungin or LAmB for treating patients with candidaemia and IC in the Turkish hospitals, was constructed. Patients were switched to an alternative antifungal agent if initial treatment failed due to mycological persistence. All patients were followed up until treatment success or death. Outcome probabilities were obtained from published literature and cost inputs were derived from the latest Turkish resources. Expert panels were used to estimate data that were not available in the literature. Cost per patient treated for each intervention was then calculated. Sensitivity analyses including Monte Carlo simulation were performed. For treatment of candidaemia and IC, micafungin (€4809) was associated with higher total cost than LAmB (€4467), with an additional cost of €341 per treated patient. Cost of initial antifungal treatment was the major cost driver for both comparators. The model outcome was robust over a wide variation in input variables except for drug acquisition cost and duration of initial antifungal treatment with micafungin or LAmB. LAmB is cost-saving relative to micafungin for the treatment of candidaemia and IC from the Turkish hospital perspective, with variation in drug acquisition cost of the critical factor affecting the model outcome.

Home-Time After Discharge Among Patients Hospitalized With Heart Failure.

BACKGROUND: Surveys of patients with cardiovascular disease have suggested that "home-time"-being alive and out of any health care institution-is a prioritized outcome. This novel measure has not been studied among patients with heart failure (HF). OBJECTIVES: This study sought to characterize home-time following hospitalization for HF and assess its relationship with patient characteristics and traditionally reported clinical outcomes. METHODS: Using GWTG-HF (Get With The Guidelines-Heart Failure) registry data, patients discharged alive from an HF hospitalization between 2011 and 2014 and ≥65 years of age were identified. Using Medicare claims, post-discharge home-time over 30-day and 1-year follow-up was calculated for each patient as the number of days alive and spent outside of a hospital, skilled nursing facility (SNF), or rehabilitation facility. RESULTS: Among 59,736 patients, 57,992 (97.1%) and 42,153 (70.6%) had complete follow-up for home-time calculation through 30 days and 1 year, respectively. The mean home-time was 21.6 ± 11.7 days at 30 days and 243.9 ± 137.6 days at 1 year. Contributions to reduced home-time varied by follow-up period, with days spent in SNF being the largest contributor though 30 days and death being the largest contributor through 1 year. Over 1 year, 2,044 (4.8%) patients had no home-time following index hospitalization discharge, whereas 8,194 (19.4%) had 365 days of home-time. In regression models, several conditions were associated with substantially reduced home-time, including chronic obstructive pulmonary disease, renal insufficiency, and dementia. Through 1 year, home-time was highly correlated with time-to-event endpoints of death (tau = 0.72) and the composite of death or HF readmission (tau = 0.59). CONCLUSIONS: Home-time, which can be readily calculated from administrative claims data, is substantially reduced for many patients following hospitalization for HF and is highly correlated with traditional time-to-event mortality and hospitalization outcomes. Home-time represents a novel, easily measured, patient-centered endpoint that may reflect effectiveness of interventions in future HF studies.

Nanodiamonds as "artificial proteins": Regulation of a cell signalling system using low nanomolar solutions of inorganic nanocrystals.

The blocking of specific protein-protein interactions using nanoparticles is an emerging alternative to small molecule-based therapeutic interventions. However, the nanoparticles designed as "artificial proteins" generally require modification of their surface with (bio)organic molecules and/or polymers to ensure their selectivity and specificity of action. Here, we show that nanosized diamond crystals (nanodiamonds, NDs) without any synthetically installed (bio)organic interface enable the specific and efficient targeting of the family of extracellular signalling molecules known as fibroblast growth factors (FGFs). We found that low nanomolar solutions of detonation NDs with positive ζ-potential strongly associate with multiple FGF ligands present at sub-nanomolar concentrations and effectively neutralize the effects of FGF signalling in cells without interfering with other growth factor systems and serum proteins unrelated to FGFs. We identified an evolutionarily conserved FGF recognition motif, ∼17 amino acids long, that contributes to the selectivity of the ND-FGF interaction. In addition, we inserted this motif into a de novo constructed chimeric protein, which significantly improved its interaction with NDs. We demonstrated that the interaction of NDs, as purely inorganic nanoparticles, with proteins can mitigate pathological FGF signalling and promote the restoration of cartilage growth in a mouse limb explant model. Based on our observations, we foresee that NDs may potentially be applied as nanotherapeutics to neutralize disease-related activities of FGFs in vivo.

Signs, symptoms, and treatment patterns across serial ambulatory cardiology visits in patients with heart failure: insights from the NCDR PINNACLE® registry.

BACKGROUND: Due to a relative lack of outpatient heart failure (HF) clinical registries, we aimed to describe symptoms, signs, and medication treatment among ambulatory patients with heart failure (HF) over time. METHODS: Using health records from 234 PINNACLE (Practice Innovation and Clinical Excellence) U.S. cardiology practices (2008-2014), serial visits for patients with HF were characterized. Symptoms, signs, and HF medications (angiotensin-converting enzyme inhibitors [ACEI], angiotensin receptor blockers [ARB], beta blockers [BB], and diuretics) were compared between visits. RESULTS: Among 763,331 patients with HF, 550,581 had ≥2 clinic visits < 1 year apart, with 2,998,444 visit pairs. In the 12 months following an index visit, patients had a mean of 2.5 ± 2.3 additional visits. Recorded index visit symptoms ranged from dyspnea (53.6%) to orthopnea (23.1%); signs ranged from peripheral edema (52.2%) to hepatomegaly (0.6%). Of those with ejection fraction < 40%, ACEI was prescribed in 58.6%, ARB in 18.5%, BB in 85.2%, and diuretics in 70.0%. Between-visit recorded changes were infrequent: dyspnea appeared in 3.8%, resolved in 2.7%; NYHA class increased in 2.9%, decreased in 2.9%; number of signs increased in 6.0%, decreased in 5.1%; ACEI/ARB or BB added in 6.4%, removed in 6.2%; diuretic added in 3.7%, removed in 3.8%. Changes in recorded symptoms were rarely associated with initiation or discontinuation in HF medication classes. CONCLUSIONS: Ambulatory HF care in U.S. cardiology practices seldom recorded changes in symptoms, signs, and medication class. Although templated medical records and absence of medication dosing likely underestimated the degree to which clinical changes occur over serial visits for HF, these PINNACLE data suggest opportunities for greater symptom-based and therapy-focused visits.

Removal of arsenic and mercury species from water by covalent triazine framework encapsulated γ-Fe2O3 nanoparticles.

The covalent triazine framework, CTF-1, served as host material for the in situ synthesis of Fe2O3 nanoparticles. The composite material consisted of 20 ±â€¯2 m% iron, mainly in γ-Fe2O3 phase. The resulting γ-Fe2O3@CTF-1 was examined for the adsorption of AsIII, AsV and HgII from synthetic solutions and real surface-, ground- and wastewater. The material shows excellent removal efficiencies, independent from the presence of Ca2+, Mg2+ or natural organic matter and only limited dependency on the presence of phosphate ions. Its adsorption capacity towards arsenite (198.0 mg g-1), arsenate (102.3 mg g-1) and divalent mercury (165.8 mg g-1) belongs amongst the best-known adsorbents, including many other iron-based materials. Regeneration of the adsorbent can be achieved for use over multiple cycles without a decrease in performance by elution at 70 °C with 0.1 M NaOH, followed by a stirring step in a 5 m% H2O2 solution for As or 0.1 M thiourea and 0.001 M HCl for Hg. In highly contaminated water (100 µg L-1), the adsorbent polishes the water quality to well below the current WHO limits.

Thiol-ethylene bridged PMO: A high capacity regenerable mercury adsorbent via intrapore mercury thiolate crystal formation.

Highly ordered thiol-ethylene bridged Periodic Mesoporous Organosilicas were synthesized directly from a homemade thiol-functionalized bis-silane precursor. These high surface area materials contain up to 4.3mmol/g sulfur functions in the walls and can adsorb up to 1183mg/g mercury ions. Raman spectroscopy reveals the existence of thiol and disulfide moieties. These groups have been evaluated by a combination of Raman spectroscopy, Ellman's reagent and elemental analysis. The adsorption of mercury ions was evidenced by different techniques, including Raman, XPS and porosimetry, which indicate that thiol groups are highly accessible to mercury. Scanning transmission electron microscopy combined with EDX showed an even homogenous distribution of the sulfur atoms throughout the structure, and have revealed for the first time that a fraction of the adsorbed mercury is forming thiolate nanocrystals in the pores. The adsorbent is highly selective for mercury and can be regenerated and reused multiple times, maintaining its structure and functionalities and showing only a marginal loss of adsorption capacity after several runs.

Cost-effectiveness analysis of anidulafungin vs fluconazole for the treatment of invasive candidiasis (IC) in Turkey.

Anidulafungin has been shown to be non-inferior to, and possibly more efficacious, than fluconazole in treating patients with invasive candidiasis (IC). This study aimed to determine the cost-effectiveness of anidulafungin vs fluconazole for treatment of IC in the Turkish setting. A decision analytic model was constructed to depict downstream economic consequences of using anidulafungin or fluconazole for treatment of IC in the Turkish hospitals. Transition probabilities (ie treatment success, observed or indeterminate treatment failures) were obtained from a published randomised clinical trial. Cost inputs were from the latest Turkish resources. Data not available in the literature were estimated by expert panels. Sensitivity analyses were performed to assess the robustness of the model outcome. While anidulafungin [TL 17 171 (USD 4589)] incurred a higher total cost than fluconazole [TL 8233 (USD 2200) per treated patient, treatment with anidulafungin was estimated to save an additional 0.58 life-years, with an incremental cost-effectiveness ratio of TL 15 410 (USD 4118) per life-years saved. Drug acquisition cost and hospitalisation were the main cost drivers for anidulafungin and fluconazole arms respectively. The model findings were robust over a wide range of input variables except for anidulafungin drug cost. Anidulafungin appears to be a cost-effective therapy in treating IC from the Turkish hospital perspective.

Change the management of patients with heart failure: Rationale and design of the CHAMP-HF registry.

Heart failure (HF) with reduced ejection fraction (HFrEF) is a common and costly condition that diminishes patients' health status and confers a poor prognosis. Despite the availability of multiple guideline-recommended pharmacologic and cardiac device therapies for patients with chronic HFrEF, outcomes remain suboptimal. Currently, there is limited insight into the rationale underlying clinical decisions by health care providers and patient factors that guide the use and intensity of outpatient HF treatments. A better understanding of current practice patterns has the potential to improve patients' outcomes. The CHAnge the Management of Patients with Heart Failure (CHAMP-HF) registry will evaluate the care and outcomes of patients with chronic HFrEF by assessing real-world treatment patterns, as well as the reasons for and barriers to medication treatment changes. CHAMP-HF will enroll approximately 5,000 patients with chronic HFrEF (left ventricular ejection fraction ≤40%) at approximately 150 US sites, and patients will be followed for a maximum duration of 24 months. Participating sites will collect data from both providers (HF history, examination findings, results of diagnostic studies, pharmacotherapy treatment patterns, decision-making factors, and clinical outcomes) and patients (medication adherence and patient-reported outcomes). The CHAMP-HF registry will provide a unique opportunity to study practice patterns and the adoption of new HF therapies across a diverse mix of health care providers and outpatient practices in the United States that care for HFrEF patients.

Early Adoption of Sacubitril/Valsartan for Patients With Heart Failure With Reduced Ejection Fraction: Insights From Get With the Guidelines-Heart Failure (GWTG-HF).

OBJECTIVES: The aim of this study was to assess the prevalence and variation in angiotensin receptor/neprilysin inhibitor (ARNI) prescription among a real-world population with heart failure with reduced ejection fraction (HFrEF). BACKGROUND: The U.S. Food and Drug Administration approved sacubitril/valsartan for patients with HFrEF in July 2015. Little is known about the early patterns of use of this novel therapy. METHODS: The study included patients discharged alive from hospitals in Get With the Guidelines-Heart Failure (GWTG-HF), a registry of hospitalized patients with heart failure, between July 2015 and June 2016 who had documentation of whether ARNIs were prescribed at discharge. Patient and hospital characteristics were compared among patients with HFrEF (ejection fraction ≤40%) with and without ARNI prescription at discharge, excluding those with documented contraindications to ARNIs. To evaluate hospital variation, hospitals with at least 10 eligible hospitalizations during the study period were assessed. RESULTS: Of 21,078 patients hospitalized with HFrEF during the study period, 495 (2.3%) were prescribed ARNIs at discharge. Patients prescribed ARNIs were younger (median age 65 years vs. 70 years; p < 0.001), had lower ejection fractions (median 23% vs. 25%; p < 0.001), and had higher use of aldosterone antagonists (45% vs. 31%; p < 0.001) at discharge. At the 241 participating hospitals with 10 or more eligible admissions, 125 (52%) reported no discharge prescriptions of ARNIs. CONCLUSIONS: Approximately 2.3% of patients hospitalized for HFrEF in a national registry were prescribed ARNI therapy in the first 12 months following Food and Drug Administration approval. Further study is needed to identify and overcome barriers to implementing new evidence into practice, such as ARNI use among eligible patients with HFrEF.

Synthesis of single-crystal-like nanoporous carbon membranes and their application in overall water splitting.

Nanoporous graphitic carbon membranes with defined chemical composition and pore architecture are novel nanomaterials that are actively pursued. Compared with easy-to-make porous carbon powders that dominate the porous carbon research and applications in energy generation/conversion and environmental remediation, porous carbon membranes are synthetically more challenging though rather appealing from an application perspective due to their structural integrity, interconnectivity and purity. Here we report a simple bottom-up approach to fabricate large-size, freestanding and porous carbon membranes that feature an unusual single-crystal-like graphitic order and hierarchical pore architecture plus favourable nitrogen doping. When loaded with cobalt nanoparticles, such carbon membranes serve as high-performance carbon-based non-noble metal electrocatalyst for overall water splitting.