Residential Racial Segregation in Aortic Stenosis Diagnosis and Transcatheter Aortic Valve Implantation Among Medicare Patients.

Background: Transcatheter aortic valve implantation (TAVI) rates are lower among Black compared with White individuals. However, it is unclear whether racial residential segregation, which remains common in the United States, contributes to observed disparities in TAVI rates. Objectives: The purpose of this study was to evaluate the association between county-level racial segregation, and aortic stenosis (AS) diagnosis, management, and outcomes. Methods: We identified Black and White Medicare fee-for-service beneficiaries age ≥65 years living in metropolitan areas of the United States (2016-2019). Using the American Community Survey's Black-White residential segregation index, a measure of geographic racial distribution, we determined segregation in each beneficiary's county of residence. Using hierarchical modeling, we determined the association between racial segregation and rates of AS diagnosis, TAVI receipt, and 30-day clinical outcomes (mortality, readmission, stroke). Results: There were 29,264,075 beneficiaries, of whom 22% lived in a high-segregation county. Among Black beneficiaries, high-segregation county residence was associated with decreased rates of AS diagnosis (OR: 0.97; 95% CI: 0.96-0.98) and TAVI (OR: 0.89; 95% CI: 0.86-0.93) compared with low-segregation county residence. In contrast, among White beneficiaries, high-segregation county residence was associated with higher rates of AS diagnosis (OR: 1.02; 95% CI: 1.02-1.03) and no differences in TAVI (OR: 1.00; 95% CI: 0.99-1.00). Segregation and race were not independently associated with 30-day mortality. Conclusions: Among Black Medicare fee-for-service beneficiaries, living in a high-segregation county was independently associated with decreased rates of AS diagnosis and TAVI, an association not seen among White beneficiaries. Residential racial segregation may contribute to racial disparities seen in AS care.

Influence of the anatase/rutile ratio on the charge transport properties of TiO2-NTs arrays studied by dual wavelength opto-electrochemical impedance spectroscopy.

The modification of photo-generated charge transport properties in aligned titanium dioxide nanotubes (TiO2-NTs) regarding the anatase/rutile ratio was studied by photo-electrochemical methods. TiO2-NTs obtained by anodization were thermally treated under air flux at different temperatures to significantly modify the proportion of TiO2 anatase and rutile phases in the tubular structure. Material characterisation methods (XRD, SEM, UV-visible spectroscopy) were used to determine the characteristics of the different TiO2-NT electrodes in terms of dimensions, proportion of each phase and optical properties. The solar to chemical energy conversion efficiency of these electrodes during an oxidation process was investigated in basic aqueous solution, using methanol as a sacrificial agent, by cyclic voltametry and Incident Photon to Current conversion Efficiency (IPCE) measurements. TiO2-NTs with a high rutile content absorb photons of higher wavelengths, but despite this red shifted optical band gap, they exhibit the lowest photo-electrochemical conversion efficiency. To further investigate the transport properties in these photoelectrodes, Intensity-Modulated Photocurrent Spectroscopy (IMPS) was used with two different irradiation wavelengths to determine the transport and recombination properties of anatase and rutile separately. The results obtained by this set of experiments indicate that the presence of the rutile at the bottom of the nanotubes is the major factor limiting the photo-generated electron transfer.

Feasibility of sacrocolpopexy by outpatient laparoscopic surgery.

INTRODUCTION: Sacrocolpopexy (SP) is a common intervention that is most often performed by laparoscopy. This intervention usually involves standard hospitalization. Evaluation of whether this procedure can be safely carried out by outpatient hospitalization (OH) is of considerable relevance. The aim of our study was hence to evaluate the feasibility of SP by OH. PATIENTS AND METHODS: This was an observational multicenter study that included women who underwent SP by OH. The main assessment criteria were the success rate of OH and the rate of rehospitalisation in the month following the intervention. The secondary assessment criteria were the rate of complications in the month following the surgery, the level of patient satisfaction evaluated by a set of straightforward questions and two validated questionnaires (the Patient Global Impression of Improvement [PGI-I] and the Core questionnaire for the assessment of Patient Satisfaction with general Day care [COPS-D]). RESULTS: There were 55 women operated on by OH. The success rate for the OH was 49/55 (89.1% (80.7-97.3%)). Of the 31/55 women (56.4%) who answered the PGI-I questionnaire, 27/31 (87.1%) stated that the intervention improved their condition. Of the 30/55 women who answered the COPS-D questionnaire, 26/30 (86.7%) women were "satisfied" or "very satisfied" with the conditions for their discharge from the OH. CONCLUSION: The success rate for SP by OH was high in this study, with a very substantial level of patient satisfaction. These findings nonetheless ought to be confirmed with series involving higher numbers of women.

Beyond Bevacizumab: An Outlook to New Anti-Angiogenics for the Treatment of Ovarian Cancer.

In addition to the monoclonal vascular endothelial growth factor (VEGF) antibody bevacizumab, several alternative anti-angiogenic treatment strategies for ovarian cancer patients have been evaluated in clinical trials. Apart from targeting extracellular receptors by the antibody aflibercept or the peptibody trebananib, the multikinase inhibitors pazopanib, nintedanib, cediranib, sunitinib, and sorafenib were developed to interfere with VEGF receptors and multiple additional intracellular pathways. Nintedanib and pazopanib significantly improved progression-free survival in two positive phase III trials for first-line therapy. A reliable effect on overall survival could, however, not be observed for any anti-angiogenic first-line therapies so far. In terms of recurrent disease, two positive phase III trials revealed that trebananib and cediranib are effective anti-angiogenic agents for this indication. Patient selection and biomarker guided prediction of response seems to be a central aspect for future studies. Combining anti-angiogenics with other targeted therapies to possibly spare chemotherapy in certain constellations represents another very interesting future perspective for clinical trials. This short review gives an overview of current clinical trials for anti-angiogenic treatment strategies beyond bevacizumab. In this context, possible future perspectives combining anti-angiogenics with other targeted therapies and the need for specific biomarkers predicting response are elucidated.

Impact of climate change and population growth on a risk assessment for endocrine disruption in fish due to steroid estrogens in England and Wales.

In England and Wales, steroid estrogens: estrone, estradiol and ethinylestradiol have previously been identified as the main chemicals causing endocrine disruption in male fish. A national risk assessment is already available for intersex in fish arising from estrogens under current flow conditions. This study presents, to our knowledge, the first set of national catchment-based risk assessments for steroid estrogen under future scenarios. The river flows and temperatures were perturbed using three climate change scenarios (ranging from relatively dry to wet). The effects of demographic changes on estrogen consumption and human population served by sewage treatment works were also included. Compared to the current situation, the results indicated increased future risk:the percentage of high risk category sites, where endocrine disruption is more likely to occur, increased. These increases were mainly caused by changes in human population. This study provides regulators with valuable information to prepare for this potential increased risk.

Endovascular stent-graft repair of ascending aortic dissection with a commercially available thoracic endograft.

We describe the endovascular treatment of a type A thoracic aortic dissection (TAAD) in a patient deemed unfit for surgical repair with a commercially available thoracic endograft. A patient with a symptomatic acute TAAD, multiple medical comorbidities, and ascending thoracic aortic and arch dilation underwent successful endovascular repair with the use of a commercially available stent graft, resulting in complete resolution of his symptoms despite slight but persistent perigraft false lumen perfusion. Although surgical repair remains the gold standard, endografting has promise and may have a positive impact on the current treatment algorithm for TAAD. Advances must occur in graft manufacturing, and further data will be required before wider application is appropriate.

Exploiting monitoring data in environmental exposure modelling and risk assessment of pharmaceuticals.

In order to establish the environmental impact of an active pharmaceutical ingredient (API), good information on the level of exposure in surface waters is needed. Exposure concentrations are typically estimated using information on the usage of an API as well as removal rates in the patient, the wastewater system and in surface waters. These input data are often highly variable and difficult to obtain, so model estimates often do not agree with measurements made in the field. In this paper we present an approach which uses inverse modelling to estimate overall removal rates of pharmaceuticals at the catchment scale using a hydrological model as well as prescription and monitoring data for a few representative sites for a country or region. These overall removal rates are then used to model exposure across the broader landscape. Evaluation of this approach for APIs in surface waters across England and Wales showed good agreement between modelled exposure distributions and available monitoring data. The use of the approach, alongside estimates of predicted no-effect concentrations for the 12 study compounds, to assess risk of the APIs across the UK landscape, indicated that, for most of the compounds, risks to aquatic life were low. However, ibuprofen was predicted to pose an unacceptable risk in 49.5% of the river reaches studied. For diclofenac, predicted exposure concentrations were also compared to the Environmental Quality Standard previously proposed by the European Commission and 4.5% of river reaches were predicted to exceed this concentration. While the current study focused on pharmaceuticals, the approach could also be valuable in assessing the risks of other 'down the drain' chemicals and could help inform our understanding of the important dissipation processes for pharmaceuticals in the pathway from the patient to ecological receptors.

[Anaesthesia for patients with obstructive airway diseases].

Obstructive lung diseases like asthma or chronic obstructive lung diseases have a high prevalence and are one of the four most frequent causes of death. Obstructive lung diseases can be significantly influenced by the choice of anesthetic techniques and anesthetic agents. Basically, the severity of the COPD and the degree of bronchial hyperreactivity will determine the perioperative anesthetic risk. This risk has to be assessed by a thorough preoperative evaluation and will give the rationale on which to decide for the adequate anaesthetic technique. In particular, airway instrumentation can cause severe reflex bronchoconstriction. The use of regional anaesthesia alone or in combination with general anaesthesia can help to avoid airway irritation and leads to reduced postoperative complications. Prophylactic antiobstructive treatment, volatile anesthetics, propofol, opioids, and an adequate choice of muscle relaxants minimize the anesthetic risk, when general anesthesia is required In case, despite all precautions intra-operative bronchospasm occurs, deepening of anaesthesia, repeated administration of beta2-adrenergic agents and parasympatholytics, and a single systemic dose of corticosteroids represent the main treatment options.

Bosutinib: a novel second-generation tyrosine kinase inhibitor.

Bosutinib (SKI-606) is a 4-anilino-3-quinoline carbonitrile, which acts as a dual inhibitor of Src and ABL kinases. In addition, the BCR-ABL fusion gene product, a constitutively activated tyrosine kinase which is crucial for the development of chronic myeloid leukemia (CML), is highly sensitive to bosutinib. Interestingly, distinctly lower concentrations of bosutinib are required to ablate BCR-ABL phosphorylation when compared to the first-generation tyrosine kinase inhibitor imatinib (IM). Bosutinib is a potent inhibitor of CML cell proliferation in vitro and has demonstrated promising activity in CML patients resistant or intolerant to IM as well as in newly diagnosed patients with chronic phase CML (CML-CP). Remarkably, bosutinib has been found to be capable of overcoming the majority of IM-resistant BCR-ABL mutations. Bosutinib has the potency to induce deep and fast responses in second- and third-/fourth-line treatment, and as a consequence, the drug has recently been licensed for patients previously treated with one or more tyrosine kinase inhibitor(s) and for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options. Due to its potency and differing toxicity profile, it promises to be a good therapeutic option for a defined cohort of patients. The most common side effects are gastrointestinal with most of the patients suffering from nausea, vomiting, or diarrhea. For the most part, these gastrointestinal symptoms occur early after treatment initiation, are manageable, and often self-limiting. Continuous monitoring of liver enzymes upon treatment initiation is necessary during bosutinib treatment. In addition to CML treatment, bosutinib has shown some efficacy in selected patients suffering from advanced-stage solid tumors. In conclusion, bosutinib is a promising novel small molecule inhibitor approved now for targeted therapy of CML and in clinical development for other malignancies.

Clinical management of epithelial ovarian cancer during pregnancy.

UNLABELLED: Epithelial ovarian cancer (EOC) in pregnancy is a rare situation. Due to its low incidence with a consecutive lack of clinical trials many questions regarding indication of different treatment approaches are unanswered. This article discusses the current literature to elaborate recommendations for the management of EOC during pregnancy. A literature search of diagnostic approaches and treatment strategies for EOC complicated by pregnancy was performed. We reviewed the available information with emphasis on surgery as well as chemotherapeutical treatment options. EOC in pregnancy is often diagnosed at early stage and no data support that concurrent pregnancy influences the growth rate or propensity for spread of EOC. Radical cytoreduction of all visible tumour followed by subsequent systemic chemotherapy is the standard treatment of EOC in most non-pregnant women. In pregnant women, however, chemotherapy as well as radical surgery should be avoided in the first trimester because of teratogenesis and high abortion rates. Besides induced abortion followed by classic management of EOC, pregnancy preserving surgery, followed by chemotherapy in the second or third trimester, timely delivery as well as neo-adjuvant chemotherapy with subsequent completing surgery appear to be viable treatment options. CONCLUSIONS: Since there is only very limited information regarding the optimal therapeutic approach to EOC during pregnancy, each case needs to be addressed individually. Treatment in specialised centres should be intended especially in this rare and challenging situation.

Novel aspects of therapy with the dual Src and Abl kinase inhibitor bosutinib in chronic myeloid leukemia.

The dual Src/Abl kinase inhibitor bosutinib (SKI-606) targets the tyrosine kinase brc-abl, the key enzyme in the development of chronic myeloid leukemia (CML). In clinical trials, bosutinib yielded promising results with regard to efficacy, tolerability and toxicity in first-, second- and third-line therapy of CML patients. Remarkably, bosutinib is able to overcome most imatinib-resistant BCR-ABL1-1 mutations except V299L and T315I. Mostly, low-to-moderate grade gastrointestinal toxicitis are the most common treatment-emergent adverse events observed under bosutinib. Unlike other tyrosine kinase inhibitors approved for CML treatment to date, bosutinib shows only minimal inhibitory activity against c-KIT and the PDGF receptor. This may be causative for its favorable hematologic toxicity profile. In this review, the authors give an overview on the mechanism of action and currently available preclinical and clinical data for bosutinib in CML.

Estimating surface water concentrations of "down-the-drain" chemicals in China using a global model.

Predictions of surface water exposure to "down-the-drain" chemicals are presented which employ grid-based spatially-referenced data on average monthly runoff, population density, country-specific per capita domestic water and substance use rates and sewage treatment provision. Water and chemical load are routed through the landscape using flow directions derived from digital elevation data, accounting for in-stream chemical losses using simple first order kinetics. Although the spatial and temporal resolution of the model are relatively coarse, the model still has advantages over spatially inexplicit "unit-world" approaches, which apply arbitrary dilution factors, in terms of predicting the location of exposure hotspots and the statistical distribution of concentrations. The latter can be employed in probabilistic risk assessments. Here the model was applied to predict surface water exposure to "down-the-drain" chemicals in China for different levels of sewage treatment provision. Predicted spatial patterns of concentration were consistent with observed water quality classes for China.

Interactive video dance games for healthy older adults.

BACKGROUND: Physical activity promotes health in older adults but participation rates are low. Interactive video dance games can increase activity in young persons but have not been designed for use with older adults. The purpose of this research was to evaluate healthy older adults' interest and participation in a dance game adapted for an older user. METHODS: Healthy older adults were recruited from 3 senior living settings and offered three months of training and supervision using a video dance game designed for older people. Before and after the program, data was collected on vital signs, physical function and self reported quality of life. Feedback was obtained during and after training. RESULTS: Of 36 persons who entered (mean age 80.1 + 5.4 years, 83 % female), 25 completed the study. Completers were healthier than noncompleters. Completers showed gains in narrow walk time, self-reported balance confidence and mental health. While there were no serious adverse events, 4 of 11 noncompleters withdrew due to musculoskeletal complaints. CONCLUSIONS: Adapted Interactive video dance is feasible for some healthy older adults and may help achieve physical activity goals.

[Urinalysis: what a primary care physician needs to know]. / Analyse d'urines: l'ABC du praticien.

Dipstick urinalysis is a very useful diagnostic tool in primary care when used in a specific context (urinary complaints, follow-up of systemic diseases, or pregnancy), but not as a screening instrument. Urine collection in appropriate conditions, together with a correct interpretation of dipstick results, reduces the use of microscopic urinalysis and urine culture. Leucocyturia and positive nitrits indicate the presence of a urinary tract infection and do not generally require additional tests. Persistent haematuria or proteinuria need to be further explored (microscopic urinalysis and 24h urine collection). Presence of crystals in the microscopic urinalysis reflects the precipitation of the substance eliminated in the urinary tract, but does not systematically indicate a disease.

Targeted renal therapy and contrast-induced nephropathy during endovascular abdominal aortic aneurysm repair: results of a feasibility pilot trial.

PURPOSE: To evaluate the feasibility of targeted renal therapy (TRT) to decrease the rate of contrast-induced nephropathy (CIN) during endovascular aortic aneurysm repair (EVAR) in patients at risk for CIN. METHODS: A prospective nonrandomized analysis of TRT was performed in 10 high-risk patients (8 men; median age 66.5 years, range 56-80) with pre-existing renal insufficiency. TRT involved high-dose intrarenal artery infusions of fenoldopam (FEN), a short acting selective dopamine-1 agonist and renal arteriolar vasodilator, delivered percutaneously via a left brachial access using the 5-F Benephit PV Infusion System during EVAR. RESULTS: There were no device-related complications. TRT infusion duration ranged from 3.5 to 6.0 hours (median 4.5). Median contrast dosage was 120 mL (range 50-200). At 24 and 72 hours after EVAR, creatinine clearance (CrCl) had improved in 7 (70%) patients, remained unchanged in 2 (20%), and declined >25% in 1 (10%); the latter returned to baseline on day 5. At 30 days, 7 (70%) patients had improved CrCl and 3 (30%) remained unchanged. CONCLUSION: TRT is feasible during EVAR in high-risk patients. Further investigation is warranted to determine the safety and efficacy of TRT in preserving renal function during EVAR.

A new generic approach for estimating the concentrations of down-the-drain chemicals at catchment and national scale.

A new generic approach for estimating chemical concentrations in rivers at catchment and national scales is presented. Domestic chemical loads in waste water are estimated using gridded population data. River flows are estimated by combining predicted runoff with topographically derived flow direction. Regional scale exposure is characterised by two summary statistics: PEC(works), the average concentration immediately downstream of emission points, and, PEC(area), the catchment-average chemical concentration. The method was applied to boron at national (England and Wales) and catchment (Aire-Calder) scales. Predicted concentrations were within 50% of measured mean values in the Aire-Calder catchment and in agreement with results from the GREAT-ER model. The concentration grids generated provide a picture of the spatial distribution of expected chemical concentrations at various scales, and can be used to identify areas of potentially high risk.

A practical demonstration in modelling diclofenac and propranolol river water concentrations using a GIS hydrology model in a rural UK catchment.

An existing GIS hydrology water quality model, LF2000-WQX, was applied to predict the concentrations of the pharmaceuticals diclofenac and propranalol in catchments. As a practical exercise the predominantly rural Tamar (UK) catchment was chosen. Consumption, excretion, and fate data were used to estimate the pharmaceutical input load for the model. The predicted concentrations throughout most of the catchment were 1 ng/L or less under low flow (90th percentile) conditions. However, at a few locations, downstream of small sewage treatment plants, concentrations above 25 ng/L were predicted. This exercise shows that it is relatively straightforward to predict the concentrations of new and emerging organic microcontaminants in real catchments using existing GIS hydrology water quality models. Further testing will be required to establish their accuracy.

A review of the early experience with Targeted Renal Therapy for renal function preservation during endovascular and surgical treatments for cardiovascular disease.

Multiple reports describe the high clinical morbidity and mortality associated with contrast-induced nephropathy (CIN). Similarly, reports have described the glomerular filtration rate (GFR) and worsening renal function as predictors of adverse short and long-term outcomes in several large cardiovascular patient populations including acute myocardial infarction, congestive heart failure, coronary artery bypass surgery (CABG), and endovascular aneurysm repair (EVAR). Targeted renal therapy (TRT) is a novel emerging treatment where high-dose fenoldopam (FEN), a selective renal dopamine-1 receptor agonist and renal arteriolar vasodilator, is infused into both renal arteries via the US FDA-approved 5 Fr bifurcated Benephit PV Catheter Infusion System. TRT has been shown to significantly increase the GFR by 25% vs. placebo and IV-FEN (p < 0.001), which may have important clinical implications in CIN prophylaxis and during surgical procedures including CABG. The aim of this report is to review the early clinical experience and pilot trials with TRT in several clinical scenarios at high-risk for CIN or worsening renal function including percutaneous peripheral vascular interventions (PPI), percutaneous coronary interventions (PCI), CABG and EVAR.

Estimating population served by sewage treatment works from readily available GIS data.

Environmental risk assessment of household chemicals at the catchment scale requires an estimate of the load at individual Sewage Treatment Works (STWs). This can be achieved based upon population served and market consumption data. Although the population served is difficult to obtain, this paper shows that reasonable estimates can be made using readily available spatially referenced data. A new method is developed using STW data from the Exe and the Aire and Calder catchments and validated using 193 STWs within the Environment Agency's Anglian region. The estimated populations served were compared with available estimates of Population Equivalents (PEs). The population estimates were broadly similar to PEs for small works but agreement was lower for larger plants. The discrepancy for larger works is consistent with trade influent inclusion in the PE. The method is suitable for application to both rural areas and large urbanised areas, although the interpretation of corroborating data becomes increasingly difficult in very large urban areas serving more than one STW.

Risk assessment of "down-the-drain" chemicals: search for a suitable model.

Legal and regulatory authorities around the world generally require that risk assessments are undertaken for the licensing of new and existing substances that present high risk to the environment or the human health. This applies to 'down-the-drain' chemicals that are usually found in household products, such as detergents, that are mainly discharged into rivers via sewer systems. However, the data available for these chemicals is often limited due to cost constraints: in particular, concentration time series for works effluent are generally unavailable, even load data for specific works is often scarce. Although a wide range of models are available, there is a general lack of knowledge on their suitability to model the fate of down-the-drain chemicals at the catchment scale. Several models are presented in this review. The models selected are: the Mackay models, EUSES, Mike 11, QUAL2E, TOMCAT and GREAT-ER. Various applications of these models were investigated to investigate their strength and weaknesses. It appears that, where the availability of data is limited, multimedia fate models such as the Mackay models and EUSES may best be applied to estimate the global risk within each media. However, for site-specific risk assessment the GREAT-ER in-stream water quality model was considered to be more appropriate for modelling down-the-drain chemicals, because it accounts for both spatial and temporal variability, while its data requirements are lower than for models such as Mike 11 and QUAL2E.