Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

Increase in the proportion of patients hospitalized with acute myocardial infarction with do-not-resuscitate orders already in place between 2001 and 2007: a nonconcurrent prospective study

BACKGROUND AND OBJECTIVE: Shared decision making and advance planning in end-of-life decisions have become increasingly important aspects of the management of seriously ill patients. Here, we describe the use and timing of do-not-resuscitate (DNR) orders in patients hospitalized with acute myocardial infarction (AMI). STUDY DESIGN AND SETTING: The nonconcurrent prospective study population consisted of 4182 patients hospitalized with AMI in central Massachusetts in four annual periods between 2001 and 2007. RESULTS: One-quarter (25%) of patients had a DNR order written either prior to or during hospitalization. The frequency of DNR orders remained constant (24% in 2001; 26% in 2007). Among patients with DNR orders, there was a significant increase in orders written prior to hospitalization (2001: 9%; 2007: 55%). Older patients and those with a medical history of heart failure or myocardial infarction were more likely to have prior DNR orders than respective comparison groups. Patients with prior DNR orders were less likely to die 1 month after hospitalization than patients whose DNRs were written during hospitalization. CONCLUSION: Although the use of DNR orders in patients hospitalized with AMI was stable during the period under study, in more recent years, patients are increasingly being hospitalized with DNR orders already in place

Investigating the acceptability of non-mesh, long-lasting insecticidal nets amongst nomadic communities in Garissa County, Kenya using a prospective, longitudinal study design and cross-sectional household surveys.

BACKGROUND: North East Kenya is an area of semi-arid terrain, prone to malaria epidemics. The distribution of long-lasting insecticidal nets (LLINs) has long been a key malaria intervention, however, for nomadic populations who live and sleep outside, in harsh climates and areas with increasing reports of exophagic behaviour of mosquitoes, traditional LLINs are often inadequate. This study investigates the acceptability of non-mesh LLINs, specifically designed to suit nomadic, outdoor sleeping communities. METHODS: In September 2011, 13,922 non-mesh LLINs were distributed to 8,511 nomadic households in Garissa County, North East Province, Kenya. A prospective, longitudinal study design was used to assess the acceptability of this novel type of LLIN. Cross-sectional household surveys, focus group discussions (FGDs), and key informant interviews (KIs) were used to collect data on attitudes and practices regarding the Dumuria nets. RESULTS: A very high level of acceptability was reported with 95.3% of respondents stating they liked the nets. Of the factors reportedly determining net use the most frequently mentioned was "vulnerability". Of those with concerns about the nets, the colour (white) was the most frequently reported. CONCLUSION: The tailoring of LLINs to specific communities and contexts leads to increased levels of acceptability. Large-scale, blanket net distribution campaigns, which are currently the standard practice, do not cater for the specific and nuanced needs of the differing communities they often serve. This non-mesh LLIN offers a highly effective and desirable malaria prevention option to a typically hard to reach and underserved nomadic population at increased risk of malaria infection

Investigating a Non-Mesh Mosquito Net Among Outdoor Sleeping Nomadic Communities in Kenya.

Rising reports of exophagic malaria vectors make even more pressing the need for alternatives to traditional, mesh, long-lasting insecticidal nets (LLINs) designed for indoor sleeping and often inadequate in the protection of outdoor-sleeping populations. This study tests and evaluates the retention, utilization, and durability of novel, non-mesh nets designed for outdoor use. Longitudinal, cross-sectional surveys were conducted, the physical condition of nets was assessed, and bio-efficacy and insecticide content were tested. At 22 months, retention was 98.0%; 97.1% of nets fell within the World Health Organization (WHO) category of being in "good" condition; none were in the "torn" category. At 18 months post-distribution, 100% of nets had at least WHO Pesticide Evaluation Scheme (WHOPES)-acceptable levels of insecticide, this proportion was 66.7% at 22 months. This novel mosquito net has the potential to provide a durable and context-specific tool to prevent malaria among traditionally hard-to-protect and highly vulnerable populations

Race and place differences in patients hospitalized with an acute coronary syndrome: Is there double jeopardy? Findings from TRACE-CORE

The objectives of this longitudinal study were to examine differences between whites and blacks, and across two geographical regions, in the socio-demographic, clinical, and psychosocial characteristics, hospital treatment practices, and post-discharge mortality for hospital survivors of an acute coronary syndrome (ACS). In this prospective cohort study, we performed in-person interviews and medical record abstractions for patients discharged from the hospital after an ACS at participating sites in Central Massachusetts and Central Georgia during 2011-2013. Among the 1143 whites in Central Massachusetts, 514 whites in Central Georgia, and 277 blacks in Central Georgia, we observed a gradient of socioeconomic position with whites in Central Massachusetts being the most privileged, followed by whites and then blacks from Central Georgia; similar gradients pertained to psychosocial vulnerability (e.g., 10.7%, 25.1%, and 49.1% had cognitive impairment, respectively) and to the hospital receipt of all 4 evidence-based cardiac medications (35.5%, 18.1%, and 14.4%, respectively) used in the acute management of patients hospitalized with an ACS. Multivariable adjusted odds ratios (95% confidence intervals) for the receipt of a percutaneous coronary intervention for whites and blacks in Georgia vs. whites in Massachusetts were 0.57 (0.46-0.71) and 0.40(0.30-0.52), respectively. Thirty-day and one-year mortality risks exhibited a similar gradient. The results of this contemporary clinical/epidemiologic study in a diverse patient cohort suggest that racial and geographic disparities continue to exist for patients hospitalized with an ACS

Combined Inflammatory and Metabolic Defects Reflected by Reduced Serum Protein Levels in Patients with Buruli Ulcer Disease

Buruli ulcer is a skin disease caused by Mycobacterium ulcerans that is spreading in tropical countries, with major public health and economic implications in West Africa. Multi-analyte profiling of serum proteins in patients and endemic controls revealed that Buruli ulcer disease down-regulates the circulating levels of a large array of inflammatory mediators, without impacting on the leukocyte composition of peripheral blood. Notably, several proteins contributing to acute phase reaction, lipid metabolism, coagulation and tissue remodelling were also impacted. Their down-regulation was selective and persisted after the elimination of bacteria with antibiotic therapy. It involved proteins with various functions and origins, suggesting that M. ulcerans infection causes global and chronic defects in the host’s protein metabolism. Accordingly, patients had reduced levels of total serum proteins and blood urea, in the absence of signs of malnutrition, or functional failure of liver or kidney. Interestingly, slow healers had deeper metabolic and coagulation defects at the start of antibiotic therapy. In addition to providing novel insight into Buruli ulcer pathogenesis, our study therefore identifies a unique proteomic signature for this disease

Preoperative spinal tumor embolization: an institutional experience with Onyx.

BACKGROUND: Preoperative embolization has the potential to decrease intraoperative blood loss and facilitate spinal cord decompression and tumor resection. OBJECTIVE: We report our institutional experience with the embolization of hypervascular extradural spinal tumors with Onyx as well as earlier embolic agents in a series of 28 patients. METHODS: A retrospective case review was conducted on patients undergoing preoperative transarterial embolization of a spinal tumor between 1995 and 2012 at our institution. RESULTS: Twenty-eight patients met the inclusion criteria, with a mean age of 60.6 years. Twenty-eight patients had metastatic tumors. In 14 (50%) patients the metastases were from renal cell carcinomas. Fifty-four vessels were embolized using PVA, NBCA, Onyx, coils, or embospheres. Sixteen patients were treated with Onyx, 6 patients with PVA, 3 patients with embospheres, 2 patients with NBCA, and 3 patients with a combination of embolic agents. The average decrease in tumor blush was 97.8% with Onyx versus 92.7% with the rest of the embolic agents (p=0.08). The estimated blood loss was 1616ml (range 350-5000ml). Blood loss was 750cm(3) on average with Onyx versus 1844 with the rest of the embolic agents (p=0.14). The mean length of stay was 16 days. The mortality rate was zero. Pre- and post-operative modified Rankin Score (mRS) did not differ significantly in the series (3.12 versus 3.10, respectively, p=0.9). CONCLUSION: In our experience, the use of transarterial tumor embolization as an adjunct for spinal surgery is a safe and feasible option

The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators

An Energy-Water Corridor Along the US/Mexico Border: Changing the \u27Conversation\u27

Over the last decade, migration has become a divisive issue around the world. A large number of countries have erected barriers along their borders to prevent migration, leading to geopolitical tension. Climate change effects will likely exacerbate migration tensions, which will require bold and creative solutions to this difficult social predicament. Here we detail a plan to construct an energy-water corridor along a border that has been the focus of much attention recently: The U.S.-Mexico border. Our proposed solution helps to alleviate some of the negative effects of climate change, while providing energy and economic stimulus to an area that begs for sustainable development. The energy-water corridor will take advantage of the unique renewable energy resources along the border states and will use state-of-the-art water desalination and treatment systems to provide the resources for economic development in the region