tbuckley/cabot-search huggingface dataset:
Private finance initiative
Authors: F McGinty
Journal: BMJ (2000)

Editor—Smith voices concerns about the private finance initiative.1

The initiative is a procurement process. Many of his assumptions apply equally to traditional procurement. He did not highlight the advantages that can be realised from a new hospital. Through the private finance initiative, the public purse pays for this over several years in revenue payments, but traditional procurement would have increased capital charges and rates.

Smith claims that reducing bed numbers is one effect of an unaffordable system. Not so. We in Hereford are implementing a county-wide healthcare system, not just running a new hospital. Our strategy embraces recent changes in technology and management, including better use of community facilities, improved links with social services, and more home care within an NHS led by primary care. Consequently, fewer beds are needed.

However, we have not assumed we have got it right. We have planned flexibility by maintaining some beds in refurbished accommodation. We have quality new facilities and the flexibility to maintain services appropriately should other changes in health care occur.

Service delivery is not reducing in Hereford. Clinicians have fully participated in developing our project, and clinical functioning is paramount. We are satisfied with the result.

Smith discusses increasing private beds. We have no private beds. None are being planned to fund this project.

He also raises the issue of secrecy and the nature of the planning process using bed numbers “without thought for the knock-on for other parts of the NHS.” This may be found to be so elsewhere, but in Hereford the scheme is part of a county-wide strategy.

There was no closed decision making in Hereford. The full business case is in the public domain.

Smith may be right that one day there will be a scandal, as there have been with traditional procurements. With the private finance initiative these risks are reduced by transfer to the private sector, which is best able to deal with them.

Consider the advantages of the initiative. Our new hospital includes a new infrastructure for information technology and managed services for imaging and maintaining equipment. Our clinicians will work with the most modern imaging equipment throughout the lifetime of the contract.

Imperfections in the private finance initiative can be reduced by learning from the pilot schemes. The initiative is the government's chosen means of redeveloping public facilities. It should not be assumed that just because the private sector is involved in a partnership with the NHS it is wrong.
Abstract 13009: The Significance of ATP Therapy Failure During Appropriate ICD-Delivered Therapy in Patients With Ventricular Tachycardia
Authors: Dalia Giedrimiene, Craig Coleman, Danette Guertin, Jeffrey Kluger
Journal: Circulation (2014)

Prospective clinical trials have demonstrated that ICD-delivered therapy reduces mortality in patients at risk for sudden cardiac arrest due to ventricular tachycardia (VT). ICDs through anti-tachycardia pacing (ATP) modalities are able to terminate spontaneous VT. Although ATP is highly effective in terminating VT in ICD patients, 5 - 30% of these events ultimately need shocks. Unsuccessful ATP attempts, as well as shocks, prolong the duration of the episode and are associated with poor clinical outcomes. Methods: Our study focused on 1873 ICD-delivered therapies in pts who received ICD implants from 2008 to 2012 and completed one year follow up. Only patients who received ATP therapy for the first time for a ventricular tachycardia (VT) event were included. All therapy zones contained ATP therapy followed by shock therapy. Results: 806 pts with ICD implants for primary or secondary prevention were analyzed. Study population consisted of 636 (78.9%) males and 170 (21.1%) females with average age of 72.8±29.8y (range: 29 - 98y). 622 (77.2%) of these patients had successful termination of VT with ICD-delivered ATP therapy. In 184 (22.8%) patients with unsuccessful ATP, appropriate ICD shocks were delivered. Only 66.8% of patients with failed ATP had successful VT termination after 1st ICD shock. More than 33% of patients required 2 or more ICD-delivered shocks, of which 13% required four or more. No gender based difference was found regarding success for VT termination after first, second or multiple ICD delivered shocks. Conclusions: 1) ATP therapy is successful in the majority of patients. 2) After ATP failure only 66.8% of pts respond to first ICD shock. 33.2% require multiple ICD shocks that delay VT termination and may lead to worse clinical outcomes. 3) ATP failure for VT termination may identify patients who are at increased risk for failure to respond to ICD shocks. A careful observation and further clinical correlation is warranted in this group.
Abstract 4158: Novel PAK4-mediated regulation of endothelial CXCL1/CXCR2 signaling and angiogenesis in glioblastoma
Authors: Divya Kesanakurti, Jihong Xu, Alessandro Canella, Prabhakaran Nagarajan, Balveen Kaur, Vinay K. Puduvalli
Journal: Cancer Research (2015)

Abstract Increased endothelial cell proliferation and aberrant neovascularization are pathological hallmarks of glioblastoma that correlate with clinical outcome. Recent studies have also implicated ionizing radiation (IR)-induced angiogenesis as a potential cause for tumor recurrence and metastases in several malignancies. Its impact in gliomas has not been characterized. Factors that drive endothelial proliferation, angiogenesis and interaction of endothelial cells with tumor cells in the context of radiotherapy are potentially novel targets for glioma therapy. Our previous studies demonstrated high levels of expression of p21-activated kinase 4 (PAK4) in gliomas; analyses of tumor cell medium (CM) prepared from shRNA-mediated PAK4-knockdown cells using an angiogenesis antibody array showed a significant decrease in key angiogenic factors including CXCL1. Treatment of human brain microvascular endothelial cells (HBMECs) with CM from PAK4-knockdown cells (PAK4-kd CM) significantly inhibited proliferation, migration and microtubule formation compared with CM from control and scrambled vector-expressing glioma cells. PAK4-kd CM treatment also suppressed CXCR2 activation and decreased the expression levels of p-STAT3, VEGF, MMP-2 and cyclinD1 in HBMECs. Additionally, treatment with CM from ionizing radiation (IR, 8 Gy)-treated cells resulted in elevated CXCL1, MMP-2 and VEGF levels in HBMECs, and induced high levels of endothelial capillary network formation on matrigel, indicating an IR-induced angiogenesis in these cells. Conversely, PAK4-kd inhibited IR-induced angiogenesis and decreased p-STAT3, VEGF and MMP-2 levels in IR-treated HBMECS. Further, in vivo experiments with orthotopic intracranial tumors in nude mice showed growth suppression in PAK4-knockdown tumors compared to control tumors. Immunohistochemical analyses of brain tumor sections revealed a significant decrease in CXCL1, VEGF and MMP-2 in PAK4.sh tumors. In summary, our studies emphasize a novel regulation of angiogenic switch and endothelial CXCL1/CXCR2 signaling by PAK4 in tumor cells, thereby, suggests the role of PAK4 as a critical mediator of tumor-endothelial cell interactions in glioblastoma. Abrogation of key angiogenic signaling after IR treatment and inhibition of in vivo tumor growth by PAK4 suppression indicates its therapeutic potential in the treatment of glioma. Citation Format: Divya Kesanakurti, Jihong Xu, Alessandro Canella, Prabhakaran Nagarajan, Balveen Kaur, Vinay K. Puduvalli. Novel PAK4-mediated regulation of endothelial CXCL1/CXCR2 signaling and angiogenesis in glioblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4158. doi:10.1158/1538-7445.AM2015-4158
Ongoing Attention to Injurious Inpatient Falls and Pressure Ulcers—Reply
Authors: Teresa M. Waters, Michael J. Daniels, Gloria J. Bazzoli
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
The Effect of Telephone-Based Cognitive-Behavioral Therapy on Postnatal Depression: A Randomized Controlled Trial
Authors: Fei-Wan Ngai, Paul Wai-Ching Wong, Kwok-Yin Leung, Pui-Hing Chau, Ka-Fai Chung
Journal: Psychotherapy and Psychosomatics (2015)

Cognitive-behavioral therapy (CBT) is one of the most effective interventions for postnatal depression. However, few studies have evaluated the effect of CBT delivered via telephone for newborn mothers. The purpose of this study was to evaluate the efficacy of telephone-based CBT for postnatal depression at 6 weeks and 6 months postpartum.A multisite randomized controlled trial was conducted in the postnatal units at 3 regional hospitals in Hong Kong. A total of 397 women with an Edinburgh Postnatal Depression Scale (EPDS) score ≥10 on the second or third day postpartum were randomized to receive telephone-based CBT (n = 197) or standard care (n = 200). Primary outcome was the total EPDS score. A cutoff score of 9/10 on the EPDS was used to define women at risk of postnatal depression.Telephone-based CBT was associated with significantly lower depressive symptoms compared with standard care, when assessed at 6 weeks postpartum in the subgroups of mothers with minor depression (EPDS 10-12; difference = 1.90, 95% CI: 0.72-3.08; p = 0.002) and major depression (EPDS ≥13; difference = 5.00, 95% CI: 3.12-6.88; p < 0.001). The effect was sustained at 6 months postpartum in the subgroup with minor depression (difference = 1.20, 95% CI: 0.09-2.32; p = 0.034) but not significant in the subgroup with major depression (difference = 1.69, 95% CI: -0.10-3.47; p = 0.064). The proportion of women who satisfied our definition of postnatal depression was significantly lower in the intervention group at 6 weeks (difference = 23.3%, 95% CI: 13.7-33.0%; p < 0.001) and 6 months postpartum (difference = 11.4%, 95% CI: 1.9-20.8%; p = 0.019).Telephone-based CBT produced a significantly greater reduction in depressive symptoms than standard care during the postpartum period.
Effect of a Soy Isoflavone Supplement on Lung Function and Clinical Outcomes in Patients With Poorly Controlled Asthma
Authors: Lewis J. Smith, Ravi Kalhan, Robert A. Wise, Elizabeth A. Sugar, John J. Lima, Charles G. Irvin, Allen J. Dozor, Janet T. Holbrook
Journal: JAMA (2015)

Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control. To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult patients with poorly controlled disease. Multicenter, randomized, double-blind, placebo-controlled trial conducted between May 2010 and August 2012 at 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network. Three hundred eighty-six adults and children aged 12 years or older with symptomatic asthma while taking a controller medicine and low dietary soy intake were randomized, and 345 (89%) completed spirometry at week 24. Participants were randomly assigned to receive soy isoflavone supplement containing 100 mg of total isoflavones (n=193) or matching placebo (n=193) in 2 divided doses administered daily for 24 weeks. The primary outcome measure was change in forced expiratory volume in the first second (FEV1) at 24 weeks. Secondary outcome measures were symptoms, episodes of poor asthma control, Asthma Control Test score (range, 5-25; higher scores indicate better control), and systemic and airway biomarkers of inflammation. Mean changes in prebronchodilator FEV1 over 24 weeks were 0.03 L (95% CI, -0.01 to 0.08 L) in the placebo group and 0.01 L (95% CI, -0.07 to 0.07 L) in the soy isoflavone group, which were not significantly different (P = .36). Mean changes in symptom scores on the Asthma Control Test (placebo, 1.98 [95% CI, 1.42-2.54] vs soy isoflavones, 2.20 [95% CI, 1.53-2.87]; positive values indicate a reduction in symptoms), number of episodes of poor asthma control (placebo, 3.3 [95% CI, 2.7-4.1] vs soy isoflavones, 3.0 [95% CI, 2.4-3.7]), and changes in exhaled nitric oxide (placebo, -3.48 ppb [95% CI, -5.99 to -0.97 ppb] vs soy isoflavones, 1.39 ppb [95% CI, -1.73 to 4.51 ppb]) did not significantly improve more with the soy isoflavone supplement than with placebo. Mean plasma genistein level increased from 4.87 ng/mL to 37.67 ng/mL (P < .001) in participants receiving the supplement. Among adults and children aged 12 years or older with poorly controlled asthma while taking a controller medication, use of a soy isoflavone supplement, compared with placebo, did not result in improved lung function or clinical outcomes. These findings suggest that this supplement should not be used for patients with poorly controlled asthma. clinicaltrials.gov Identifier: NCT01052116.
Anthracycline-based preoperative chemotherapy plus lapatinib and trastuzumab or both in HER2-positive breast cancer: Preliminary cardiac safety report of the CHER LOB trial
Authors: V. Guarneri, A. Frassoldati, A. Bottini, K. Cagossi, L. Cavanna, A. Ravaioli, D. Amadori, G. Giardina, C. Oliva, P. Conte
Journal: Journal of Clinical Oncology (2009)

573 Background: The combination of anthracyclines and anti-HER-2 agents is highly active in HER-2 positive breast cancer, but its use is limited by an enhanced risk of cardiac toxicity. We are running a randomized phase II trial of combined preoperative chemotherapy (CT) with anthracycline plus trastuzumab, lapatinib, or both in HER-2 positive stage II-IIIA breast cancer patients. Aims of the study are the percentage of pathological complete response (pCR = breast + axillary nodes) and cardiac safety. We report the updated cardiac safety and activity data following the IDMC recommendation to continue study accrual. Methods: CT consists of sequential paclitaxel (P) 80 mg/m 2 weekly for 12 weeks followed by 4 courses of FE 75 C administered every 3 weeks. Arm A is CT + trastuzumab 2 mg/kg weekly; arm B is CT + lapatinib 1500 mg po daily; arm C is CT + trastuzumab 2 mg/kg weekly + lapatinib 1,000 mg po daily. Both trastuzumab and lapatinib are started concomitantly with the first P administration, and are administered throughout the duration of CT. Left ventricular ejection fraction (LVEF) is evaluated at baseline, before the start of FE 75 C, and at the completion of treatment. The planned sample size is 120 patients, and has been calculated according to the two steps Simon's design. Results: 53 out of the 120 planned patients have been randomized: 16 in arm A, 17 in arm B, and 20 in arm C. Median age is 48 years (range 27–66). The mean LVEF was 63% (range 54–77%) at baseline, 61% (50–78%) at the completion of weekly P + trastuzumab, lapatinib, or trastuzumab + lapatinib, and 60.3% (54–74%) at the completion of the whole treatment plan. Thirty patients underwent surgery: 19 patients (63%) received breast conserving surgery; 13 patients (43%) achieved a pCR. Conclusions Following the updated interim analysis, the combination of T, L or both with an anthracycline-containing regimen is feasible, with very interesting level of activity. The next planned analysis will be performed when 60 patients will be evaluable and will be presented at the Meeting. [Table: see text]
FATAL FUNGUS INFECTION IN SARCOIDOSIS: REPORT OF TWO CASES TREATED WITH ANTIBIOTICS AND CORTISONE
Authors: I STEINBERG
Journal: Annals of Internal Medicine (1958)

ExcerptReports of fatal fungus infection following antibiotic and hormonal (ACTH and cortisone) therapy are continuing to appear in the literature. This is due in part to improved cultural and animal inoculation and histopathologic technics, increasing interest in fungi, and to the greater incidence and virulence of the fungi because of extensive antibiotic and hormonal therapy.1-5 Zimmerman1 has emphasized also the tendency of certain disseminated fungus infections to become associated with such primary disease as aplastic anemia, the lymphomata, leukemia, diabetes, tuberculosis and cancer.In 1952 the first instance was reported of fungus infection causing lung abscesses in a patient with...
Abstract 5213: RUNX2 modulates the angiogenic potential of human neuroblastoma cells
Authors: Manu Gnanamony, Indra Mohanam, Sanjeeva Mohanam
Journal: Cancer Research (2015)

Abstract Neuroblastoma is the most common extracranial pediatric solid tumor with an undifferentiated status and characterized by heterogeneous clinical courses ranging from spontaneous regression to a very aggressive malignant progression. The RUNX gene family comprises RUNX1, RUNX2, and RUNX3 transcription factors and plays pivotal roles in development, differentiation and tumorigenesis. Hypoxia is known to be a significant physiological stress in the tumor microenvironment and is associated with tumor malignant phenotype. In this study, we examined the effects of hypoxia on the Runx2 expression in human neuroblastoma cells and the role of RUNX2 on angiogenic potential of neuroblastoma cells. Runx2 has two isoforms, Runx2-I and Runx2-II. Isoform I is controlled by the P2 proximal promoter whereas isoform II is transcribed from the P1 distal promoter. Increased expression of mRNAs of isoform I and II as well as intact isoform of RUNX2 was observed in NB1691 cells exposed to hypoxia. Furthermore, hypoxia enhanced the activity of a luciferase reporter containing Runx2 P1 promoter in NB1691 cells. Hypoxic exposure caused an increase in protein levels of RUNX2 as well as survivin, a RUNX2 downstream target gene in NB1691 cells. Hypoxia also stabilized RUNX2 protein levels in NB1691 cells without altering the stability of RUNX2 mRNA. Hypoxia enhanced angiogenic potential of NB1691 cells. Knockdown of Runx2 significantly decreased VEGF mRNA and protein in NB1691 cells exposed to hypoxia. A decrease in angiogenesis was observed in chorioallantoic membrane assay performed using conditioned medium collected from RUNX2 siRNA treated hypoxic NB1691 cells compared with control. Further, transcript levels were measured by PCR array of human angiogenesis pathway and the analysis showed down regulation of EDN1, FIGF, TEK and VEGF A mRNAs in hypoxic NB1691 cells treated with RUNX2 siRNA. In conclusion, our study suggests that hypoxia upregulates RUNX2 expression in NB1691 cells and knockdown of RUNX2 decreases the angiogenic potential of hypoxic NB1691 cells. Citation Format: Manu Gnanamony, Indra Mohanam, Sanjeeva Mohanam. RUNX2 modulates the angiogenic potential of human neuroblastoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5213. doi:10.1158/1538-7445.AM2015-5213
Bone Cancer: Selenite-Releasing Bone Mineral Nanoparticles Retard Bone Tumor Growth and Improve Healthy Tissue Functions In Vivo (Adv. Healthcare Mater. 12/2015)
Authors: Yanhua Wang, Hang Hao, Haoming Liu, Yifan Wang, Yan Li, Gaojie Yang, Jun Ma, Chuanbin Mao, Shengmin Zhang
Journal: Advanced Healthcare Materials (2015)

On page 1813 Chuanbin Mao, Shengmin Zhang, and co-workers show that selenite-doped bone mineral nanoparticles can retard the growth of osteosarcoma, inhibit tumor metastasis and improve the functions of liver, kidney and heart in a nude mice model, which is achieved through sustained release of selenite ions from the nanoparticles via a degradation-mediated fashion.
Il28B C/c Genotype Is Predictive of >= 1 Log10 Iu/ml Reduction in Plasma Hcv Rna After 4 Weeks of Peginterferon (Pegifn) and Ribavirin (Rbv) Therapy: Implications for the Use of the Lead-In Strategy for Direct-Acting Antiviral-Based Treatment Regimens
Authors: Alexander J. Thompson, Paul J. Clark, Hans L. Tillmann, Keyur Patel, Susanna Naggie, F. Fred Poordad, Eric Lawitz, Bruce R. Bacon, John M. Vierling, Stephanie Noviello, Clifford A. Brass, Janice K. Albrecht, David B. Goldstein, John G. McHutchison, Mark S. Sulkowski, Andrew J. Muir
Journal: Hepatology (2011)
Creativity as cognitive selection: The blind-variation and selective-retention model
Authors: Dean Keith Simonton
Journal: Behavioral and Brain Sciences (2001)

Campbell (1960) proposed a “blind-variation and selective retention” model of creative cognition. Subsequent researchers have developed this BVSR model into a comprehensive theory of human creativity, one that recognizes that human creativity operates by more than one cognitive process. The question is then raised of how the BVSR model can be accommodated within the Hull et al. selectionist system.
Mixed Bacterial Toxins in the Treatment of Tumors
Authors: H. Francis Havas, Andrew J. Donnelly, Stanley I. Levine
Journal: Cancer Research (1958)

Toxins obtained from several strains of Streptococcus pyogenes and of Serratia marcescens were tested singly and in combination for their effect in causing regression of Sarcoma 37 in Swiss mice. It was found that the mode of growth, as well as the bacterial strain, plays a determinant role in the ensuing oncolytic potency. From the regression rates it is apparent that some of the mixed preparations are less toxic than, and superior in oncolytic effect to, those from Serratia marcescens alone or its purified polysaccharide.

Possible mechanisms responsible for tumor destruction by the bacterial toxins are discussed.
Abstract 13046: Colesevelam in Combination with Metformin Significantly Reduces Low-Density Lipoprotein Particle Concentration in Patients with Early Type 2 Diabetes
Authors: Ronald B Goldberg, W. Timothy Garvey, Vivian A Fonseca, Yehuda Handelsman, Eric Hernandez-Triana, Michael R Jones, Stacey L Abby, Xiaoping Jin, Soamnauth Misir, Sukumar Nagendran, Julio Rosenstock
Journal: Circulation (2010)

Elevated low-density lipoprotein (LDL) cholesterol (LDL-C) is a risk factor for cardiovascular (CV) events in patients (pts) with type 2 diabetes mellitus (T2DM). However, residual CV risk remains high even in pts with well-controlled LDL-C. Studies suggest that LDL particle (LDL-P) concentration may explain this risk. A 16-week, randomized, double-blind, placebo (PBO)-controlled, multicenter study was conducted to evaluate the glucose- and lipid-lowering effect of initial combination therapy with metformin (MET) + colesevelam (COL) in pts with early T2DM. In total, 286 antidiabetes-drug-naive adults with T2DM (A1C 6.5%−10.0%), LDL-C ≥100 mg/dL, and triglycerides (TG) <500 mg/dL were randomized 1:1 to open-label MET (initiated at 850 mg/d; uptitrated to 1700 mg/d) + double-blind COL 3.75 g/d (n=145) or PBO (n=141). Lipoprotein particle concentrations and sizes were determined by nuclear magnetic resonance spectroscopy. At baseline, 11 pts (8% [MET+COL]) and 9 pts (6% [MET+PBO]) were on statin therapy. In ...