Inpatient and outpatient treatment patterns of cancer-associated thrombosis in the United States.

Low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are among the recommended treatment options for cancer-associated thrombosis (CAT) in the 2019 National Comprehensive Care Network guidelines. Little is known about the current utilization of DOACs in CAT patients, particularly on the inpatient to outpatient therapy transition. This study assessed real-world treatment patterns of CAT in hospital/ED in adult cancer patients (≥ 18 years) diagnosed with CAT during a hospital visit in IQVIA's Hospital Charge Data Master database between July 1, 2015 and April 30, 2018, and followed their outpatient medical and pharmacy claims to evaluate the initial inpatient/ED and outpatient anticoagulants received within 3 months post-discharge. Results showed that LMWH and unfractionated heparin (UFH) were the most common initial inpatient/ED CAT treatments (35.2% and 27.4%, respectively), followed by DOACs (9.6%); 20.8% of patients received no anticoagulants. Most DOAC patients remained on DOACs from inpatient/ED to outpatient settings (71.4%), while 24.1%, 43.5%, and 0.1% of patients treated with LMWH, warfarin, or UFH respectively, remained on the same therapy after discharge. In addition, DOACs were the most common initial post-discharge outpatient therapy. Outpatient treatment persistence and adherence appeared higher in patients using DOACs or warfarin versus LMWH or UFH. This study shows that DOACs are used as an inpatient/ED treatment option for CAT, and are associated with less post-discharge treatment switching and higher persistence and adherence. Further research generating real-world evidence on the role of DOACs to help inform the complex CAT clinical treatment decisions is warranted.

Recovery of horse fly populations in Louisiana marshes following the Deepwater Horizon oil spill.

The Deepwater Horizon oil spill in April 2010 had unprecedented impact on the Gulf of Mexico. We established the greenhead horse fly (Tabanus nigrovittatus Macquart) as a bioindicator of marsh health. This species is bound to coastal marshes, since its larvae develop as top invertebrate predators in the marsh soil. Immediately after the oil spill (2010-2011), populations of this horse fly declined in oiled areas of Louisiana marshes with significant impacts on genetic structure. In this follow-up study five years after the catastrophic event (2015-2016), we now report signs of recovery of populations in formerly oiled areas. Fly numbers increased compared to previous counts. Previously detected genetic bottlenecks in oiled populations have disappeared. Migration into oiled areas began to replenish formerly depleted horse fly populations in impacted regions with populations from non-oiled areas as an important source of migrants. Parameters of family structure that had been impacted by the oil spill (number of breeding parents, effective population size, number of family clusters) rebounded to levels similar to or exceeding those in non-oiled control areas.

Role of inward rectifier potassium channels in salivary gland function and sugar feeding of the fruit fly, Drosophila melanogaster.

The arthropod salivary gland is of critical importance for horizontal transmission of pathogens, yet a detailed understanding of the ion conductance pathways responsible for saliva production and excretion is lacking. A superfamily of potassium ion channels, known as inward rectifying potassium (Kir) channels, is overexpressed in the Drosophila salivary gland by 32-fold when compared to the whole body mRNA transcripts. Therefore, we aimed to test the hypothesis that pharmacological and genetic depletion of salivary gland specific Kir channels alters the efficiency of the gland and reduced feeding capabilities using the fruit fly Drosophila melanogaster as a model organism that could predict similar effects in arthropod disease vectors. Exposure to VU041, a selective Kir channel blocker, reduced the volume of sucrose consumption by up to 3.2-fold and was found to be concentration-dependent with an EC50 of 68µM. Importantly, the inactive analog, VU937, was shown to not influence feeding, suggesting the reduction in feeding observed with VU041 is due to Kir channel inhibition. Next, we performed a salivary gland specific knockdown of Kir1 to assess the role of these channels specifically in the salivary gland. The genetically depleted fruit flies had a reduction in total volume ingested and an increase in the time spent feeding, both suggestive of a reduction in salivary gland function. Furthermore, a compensatory mechanism appears to be present at day 1 of RNAi-treated fruit flies, and is likely to be the Na+-K+-2Cl- cotransporter and/or Na+-K+-ATPase pumps that serve to supplement the inward flow of K+ ions, which highlights the functional redundancy in control of ion flux in the salivary glands. These findings suggest that Kir channels likely provide, at least in part, a principal potassium conductance pathway in the Drosophila salivary gland that is required for sucrose feeding.

Use of non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients: insights from a specialist atrial fibrillation clinic.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are broadly preferable to vitamin K antagonists (VKAs) for stroke prevention in non-valvular atrial fibrillation (AF) given their overall net clinical benefit. We report an audit of the profile of OAC usage and adverse events in patients attending a specialist AF clinic. METHODS: Patients attending our specialist AF clinic who were commenced on NOACs for SPAF between January 2013 and August 2014 were included and electronic medical records were retrospectively reviewed between August 2014 and November 2014, to collect demographic, clinical and outcome data. Outcomes included cerebrovascular and bleeding events, death, switching between NOACs or to VKA, dose changes, cessation of NOACs and the reasons for these. To provide perspective, descriptive comparisons were made with a historical cohort of warfarin users attending the specialist AF clinic prior to the introduction of NOACs. RESULTS: We report data on 813 patients as follows: (i) 233 consecutive patients (mean (standard deviation) age 74 (10) years, 45.1% female) initiated on NOACs, with median (interquartile range) CHA2 DS2 -VASc score 3 (2-5) and HAS-BLED score 1 (1-2); and (ii) a historical cohort of 580 patients on warfarin (mean (SD) age 75 (10) years, 42.1% female) with broadly similar demographics. Overall, 54.5% (127/233) were started on rivaroxaban, 22.7% (53/233) on dabigatran and 22.7% on apixaban. Two patients experienced a transient ischaemic attack; 31 patients (13%) contributed to 37 documented bleeding events of which five bleeds (in four patients, 1.7%) were classified as major. There were seven deaths; cause of death was not available for three and the others were not related to NOACs. Eighteen (7.7%) patients switched NOACs, 2 (0.9%) patients switched to warfarin and 8 (3.4%) had their NOACs stopped. There were no ischaemic strokes in the NOAC cohort, compared with nine in the warfarin cohort, with a similar rate of major bleeding (1.7% for NOACs and 1.6% for warfarin). There were more gastrointestinal haemorrhages in the NOAC cohort (3.4% vs. 0.7% with warfarin). CONCLUSION: In this specialist AF clinic, patients prescribed NOACs had a favourable adverse event profile with good efficacy for stroke prevention, with a low rate of cessation or switch to warfarin.

Multivitamin and mineral use and breast cancer mortality in older women with invasive breast cancer in the women's health initiative.

Multivitamin use is common in the United States. It is not known whether multivitamins with minerals supplements (MVM) used by women already diagnosed with invasive breast cancer would affect their breast cancer mortality risk. To determine prospectively the effects of MVM use on breast cancer mortality in postmenopausal women diagnosed with invasive breast cancer, a prospective cohort study was conducted of 7,728 women aged 50-79 at enrollment in the women's health initiative (WHI) in 40 clinical sites across the United States diagnosed with incident invasive breast cancer during WHI and followed for a mean of 7.1 years after breast cancer diagnosis. Use of MVM supplements was assessed at WHI baseline visit and at visit closest to breast cancer diagnosis, obtained from vitamin pill bottles brought to clinic visit. Outcome was breast cancer mortality. Hazard ratios and 95 % confidence intervals (CIs) for breast cancer mortality comparing MVM users to non-users were estimated using Cox proportional hazard regression models. Analyses using propensity to take MVM were done to adjust for potential differences in characteristics of MVM users versus non-users. At baseline, 37.8 % of women reported MVM use. After mean post-diagnosis follow-up of 7.1 ± 4.1 (SD) years, there were 518 (6.7 %) deaths from breast cancer. In adjusted analyses, breast cancer mortality was 30 % lower in MVM users as compared to non-users (HR = 0.70; 95 % CI 0.55, 0.91). This association was highly robust and persisted after multiple adjustments for potential confounding variables and in propensity score matched analysis (HR = 0.76; 95 % CI 0.60-0.96). Postmenopausal women with invasive breast cancer using MVM had lower breast cancer mortality than non-users. The results suggest a possible role for daily MVM use in attenuating breast cancer mortality in women with invasive breast cancer but the findings require confirmation.

Neurokinin-1 receptors in cholinergic neurons of the rat ventral pallidum have a predominantly dendritic distribution that is affected by apomorphine when combined with startle-evoking auditory stimulation.

Cholinergic neurons of the basal forebrain are implicated in startle reflex inhibition by a prior weak stimulus often referred to as prepulse inhibition (PPI) and used as an index of sensorimotor gating deficits in schizophrenia. Gating deficits can be produced in rodent models by acute systemic administration of apomorphine, a non-selective dopamine D1 and D2 receptor agonist that also affects trafficking of neurokinin-1 (NK(1)) receptors induced by startle evoking auditory stimulation (AS) in midbrain neurons. We used electron microscopic immunolabeling of NK(1) receptors and the vesicular acetylcholine transporter (VAchT) to test the hypothesis that the subcellular distributions of these receptors in cholinergic neurons of the rat ventral pallidum are subject to a similar regulation. In vehicle controls, NK(1) immunogold was often seen near cytoplasmic endomembranes in somata and large dendrites, but was more equally distributed in cytoplasmic and plasmalemmal compartments of medium dendrites, and principally located on the plasma membrane of small dendrites. These labeling patterns appeared to be largely independent of whether the NK(1) receptor was co-expressed with VAchT, however only the medium and small VAchT-labeled dendrites showed significant treatment-specific differences in NK(1) immunogold distributions. The NK(1) receptor immunogold particle density on the plasma membrane of medium cholinergic dendrites was significantly enhanced by combined apomorphine and AS, while neither alone affected either the plasmalemmal density or the equality of the plasmalemmal and cytoplasmic distributions of NK(1) receptors in these dendrites. Small cholinergic dendrites showed a significant AS-induced increase in both the plasmalemmal and cytoplasmic density of NK(1) gold particles, and an apomorphine-induced disruption of the preferential plasmalemmal targeting of the NK(1) receptors. These results provide ultrastructural evidence that NK(1) receptors in cholinergic neurons of the ventral pallidum have subcellular locations and plasticity conducive to active involvement in dopamine-dependent sensorimotor processing.

Cultural differences in music chosen for pain relief.

Nurses use music therapeutically but often assume that all patients will equally appreciate the same type of music. Cultural differences in music preferences are compared across five pain studies. Music preferences for pain relief are described as the most frequently chosen type of music for each culture. Findings indicate that in four studies, musical choices were related to cultural background (p = .002 to .049). Although the majority in each group chose among the other types of music, Caucasians most frequently chose orchestra music, African Americans chose jazz, and Taiwanese chose harp music. For culturally congruent care, nurses should become aware of cultural differences in music preference and provide culturally specific selections among other music expected to have a therapeutic effect.

Simulation applied to health services: opportunities for applying the system dynamics approach.

The aim of this essay is to raise awareness and broaden understanding within the health services community of the system dynamics (SD) simulation approach to policy analysis. The application of simulation in health services is reviewed. A comparison is made between the SD and traditional simulation approaches and is illustrated by considering reductions in waiting times for coronary heart disease treatment. Traditionally, simulation studies have tended to focus on the analysis of localized decisions and therefore on problems orientated towards individual patients. Although these methods are extremely powerful and effective, there is scope for an alternative modelling approach which is based on a more holistic perspective; SD is one such approach. It can assist in the design of robust policies by supporting debate on how the underlying structure might influence the evolutionary behaviour of a system. Using this method we can consider the time variation both of tangibles, such as waiting times and health care costs, and intangibles, such as patient anxiety and the effects of various pressures on purchasing decisions. We propose that SD holds great potential in assisting policy formation in health care.

Iron pre-load for major joint replacement.

Patients undergoing total hip or knee replacement frequently receive blood transfusion. Homologous blood transfusion carries appreciable risks and should therefore be reduced to a minimum. We have investigated the use of preoperative oral iron supplements to optimize haemoglobin concentration and iron stores prior to surgery. All patients attending a preadmission clinic 4 weeks prior to primary hip or knee replacement had a haemoglobin measurement. If the haemoglobin concentration (Hb) was less than 12 g dL-1 they were given a four week course of ferrous sulphate. If it was greater than or equal to 12 g dL-1 they were randomized to a control group or given a supplementation course of ferrous sulphate. One hundred patients were seen. Of these 18 (18%) had haemoglobin less than 12 g dL-1 and 16 were treated with iron. The mean Hb was 10.8 g dL-1 and mean cell volume (MCV) 86. These patients increased their Hb by a mean 1.1 g dL-1 prior to admission (P = 0.008). MCV was the best predictor of response (r = -0.63, P < 0.02). This group dropped their haemoglobin by a mean 1.4 g dL-1 in the first post-operative week. In the study groups there was no significant preoperative rise in Hb. However, the control group dropped their Hb by a mean 1.3 g dL-1 in the week following surgery compared with 0.4 g dL-1 in the group which had received iron supplements (P < 0.001). We conclude that at least 18% of patients attending for hip or knee replacement in this region are frankly anaemic and benefit significantly from preoperative iron supplements over 4 weeks. Iron supplementation in patients without obvious anaemia protects against a fall in Hb during the immediate post-operative period, suggesting a widespread underlying depletion of iron stores in this group despite a normal Hb. Preoperative iron supplements may reduce transfusion requirements as part of a co-ordinated strategy in this group of patients.

Case report: localization of lipiodol-radioiodine in hepatic metastases from renal cell carcinoma.

Lipiodol, an iodinated derivative of poppyseed oil, is selectively retained in hepatocellular carcinoma and has been used as a vehicle to deliver localized doses of chemotherapeutic and radioactive agents to such tumours, thereby reducing the problems of external beam irradiation and the systemic toxicity of chemotherapy. We describe the first reported case where Lipiodol-targeted radiotherapy has been administered to a patient with secondary renal cell carcinoma in the liver. Localization was good and there were no complications. This case suggests that in future such patients may benefit from this therapy for unresectable lesions.

Mutations of p53 and ras genes in radon-associated lung cancer from uranium miners.

Radon increases the risk of lung cancer in smoking and non-smoking underground miners. To investigate the mutational spectrum associated with exposure to high levels of radon, we sequenced exons 5-9 of the p53 tumour suppressor gene and codons 12-13 of the Ki-ras protooncogene in 19 lung cancers from uranium miners exposed to radon and tobacco smoke. Mutations were not found in Ki-ras, but 9 p53 mutations, including 2 deletions, were found in 7 patients by direct DNA sequencing after polymerase chain reaction amplification of DNA from formalin-fixed, paraffin-embedded tissue. In tumours from 5 patients, the mutation produced an aminoacid change and an increased nuclear content of p53 protein. The tumours with either a stop codon or frame-shift deletion in the p53 gene were negative by immunohistochemistry. None of the mutations were G:C to T:A transversions in the coding strand of the p53 gene, which are the most frequent base substitutions associated with tobacco smoking, and none were found at the hotspot codons described in lung cancer. The observed differences from the usual lung cancer mutational spectrum may reflect the genotoxic effects of radon.

Auditory attention switching in hyperactive children.

The ability to rapidly reorient attention in the auditory modality was studied in hyperactive children. Hyperactive and nonhyperactive subjects matched on age, sex, and IQ listened to dichotically presented lists for prespecified targets. Reorientation was studied by comparing performance on trials requiring subjects to reorient their attention during a list to performance on trials requiring no switching of attention. The results indicate that although nonhyperactive children were temporarily disrupted by the switch, they eventually reoriented to the cued ear. In contrast, once hyperactive children were disrupted by the switch, they did not reorient to the cued ear. As the pattern in performance comparing hyperactive and nonhyperactive subjects resembles the pattern previously found in comparing younger and older subjects, these results are consistent with the hypothesis that the auditory reorientation skills of hyperactive children are developmentally immature.

The elderly on dialysis: some considerations in compliance.

Compliance with scheduled treatments, dietary and fluid restrictions, and multiple medications is an important component in the care and well-being of end-stage renal disease (ESRD) patients. Given the rigorus and complex demands of dialysis, it is important to examine the issue of compliance, focusing on a large and ever-increasing segment of our patient population, the elderly. The ESRD literature reflects efforts to define and measure levels of compliance, identify factors that influence and predict compliance, and develop intervention strategies to improve adherence to treatment regimens. While limited attention has been focused specifically on the elderly, there are studies suggesting that age may be a factor associated with improved adherence and that social support may be a significant contributor to compliance in this patient group. In an effort to examine the current status and needs of the dialysis elderly, research is in progress at Chromalloy American Kidney Center, Washington University, which replicates a study of 5 years ago. Eighty-four patients age 60 and over, on dialysis for a minimum of 6 months, were identified. Sociodemographic, treatment, compliance, and functional capacity data were collected; additional mental and psychological testing was completed on patients willing and able to participate. Preliminary data suggest the current elderly population is larger and significantly older than that of 5 years ago. Other sociodemographic data indicate the population is increasingly female, black, and more socioeconomically disadvantaged. In regard to compliance, the vast majority of elderly demonstrate good compliance as measured by serum potassium, fair to good compliance with phosphorus, and fair to poor compliance with fluid restrictions.(ABSTRACT TRUNCATED AT 250 WORDS)