bluuebunny/crossref_metadata_2025 huggingface dataset:
Health care utilization in the elderly Mexican population: Expenditures and determinants
Authors: González-González César , Sánchez-García Sergio , Juárez-Cedillo Teresa , Rosas-Carrasco Oscar , Gutiérrez-Robledo Luis M , García-Peña Carmen
Published: April 2011

Background

Worldwide population aging has been considered one of the most important demographic phenomena, and is frequently referred as a determinant of health costs and expenditures. These costs are an effect either of the aging process itself (social) or because of the increase that comes with older age (individual).

Objective

To analyze health expenditures and its determinants in a sample of Mexican population, for three dimensions acute morbidity, ambulatory care and hospitalization focusing on different age groups, particularly the elderly.

Methods

A secondary analysis of the Mexican National Health and Nutrition Survey (ENSANUT), 2006 was conducted. A descriptive analysis was performed to establish a health profile by socio-demographic characteristics. Logistic regression models were estimated to determine the relation between acute morbidity, ambulatory care, hospitalization and age group; to establish the determinants of hospitalization among the population 60 years and older; and to determine hospitalization expenditures by age.

Results

Higher proportion of elderly reporting health problems was found. Average expenditures of hospitalization in households were $240.6 am dlls, whereas in households exclusively with elderly the expenditure was $308.9 am dlls, the highest among the considered age groups. The multivariate analysis showed higher probability of being hospitalized among the elderly, but not for risks for acute morbidity and ambulatory care. Among the elderly, older age, being male or living in a city or in a metro area implied a higher probability of hospitalization during the last year, with chronic diseases playing a key role in hospitalization.

Conclusions

The conditions associated with age, such as chronic diseases, have higher weight than age itself; therefore, they are responsible for the higher expenditures reported. Conclusions point towards a differentiated use and intensity of health services depending on age. The projected increase in hospitalization and health care needs for this group requires immediate attention.
Plasmodium berghei ANKA infection increases Foxp3, IL-10 and IL-2 in CXCL-10 deficient C57BL/6 mice
Authors: Sarfo Bismark Y , Wilson Nana O , Bond Vincent C , Stiles Jonathan K
Published: April 2011

Background

Cerebral malaria (CM) is a major cause of malaria mortality. Sequestration of infected red blood cells and leukocytes in brain vessels coupled with the production of pro-inflammatory factors contribute to CM. CXCL-10 a chemokine that is chemotactic to T cells has been linked to fatal CM. Mice deficient for CXCL-10 gene are resistant to murine CM, while antibody ablation of CXCL-10 enhanced the production of regulatory T cells (CD4+Cd25+Foxp3+) and IL-10 which regulate the immune system. Interleukin-2 (IL-2), a pro-inflammatory cytokine implicated in malaria pathogenesis has also been shown to be a key regulator of Foxp3. However the role of Foxp3 in resistant murine CM is not well understood.

Methods

The hypothesis that resistance of CXCL-10-/- mice to murine CM may be due to enhanced expression of Foxp3 in concert with IL-10 and IL-2 was tested. CXCL-10-/- and WT C57BL/6 mice were infected withPlasmodium bergheiANKA and evaluated for CM symptoms. Brain, peripheral blood mononuclear cells (PBMCs) and plasma were harvested from infected and uninfected mice at days 2, 4 and 8. Regulatory T cells (CD4+CD25+) and non-T regs (CD4+CD25-) were isolated from PBMCs and cultured withP. bergheiantigens in vitro with dendritic cells as antigen presenting cells. Regulatory T cell transcription and specific factor Foxp3, was evaluated in mouse brain and PBMCs by realtime-PCR and Western blots while IL-10, and IL-2 were evaluated in plasma and cultured supernatants by ELISA.

Results

Wild type mice exhibited severe murine CM symptoms compared with CXCL-10-/- mice. Foxp3 mRNA and protein in brain and PBMC's of CXCL-10-/- mice was significantly up-regulated (p < 0.05) by day 4 post-infection (p.i) compared with WT. Plasma levels of IL-10 and IL-2 in infected CXCL-10-/- were higher than in WT mice (p < 0.05) at days 2 and 4 p.i. Ex-vivo CD4+CD25+ T cells from CXCL-10-/- re-stimulated withP. bergheiantigens produced more IL-10 than WT CD4+CD25+ T cells.

Conclusion

The results indicate that in the absence of CXCL-10, the resulting up-regulation of Foxp3, IL-10 and IL-2 may be involved in attenuating fatal murine CM.
Solitary fibrous tumor of the liver: a case report
Authors: Sun Ke , Lu Jian-Ju , Teng Xiao-Dong , Ying Li-Xiong , Wei Jian-Feng
Published: April 2011

Hepatic solitary fibrous tumor (SFT) is a rare tumor originating from the mesenchyme. Here we report a new case of SFT in the liver and review the clinical presentation, radiological and operative findings, diagnosis, treatment, and outcome. The patient was a 59-year-old man who presented with progressive fatigue for 3 months and an abdominal mass for 3 days. On laboratory tests, no abnormality was detected except that abdominal ultrasonography revealed a 9.0 × 6.2 cm hypoechogenic mass in the left lobe of the liver. A computed tomographic scan confirmed a hypodense lesion in the left lobe of the liver. The patient underwent left hepatectomy. SFT was diagnosed on the basis of histopathological findings. The patient was free from all symptoms and had no signs of local recurrence after 24 months' follow up.
Quantum interference effect in electron tunneling through a quantum-dot-ring spin valve
Authors: Ma Jing-Min , Zhao Jia , Zhang Kai-Cheng , Peng Ya-Jing , Chi Feng
Published: April 2011

Spin-dependent transport through a quantum-dot (QD) ring coupled to ferromagnetic leads with noncollinear magnetizations is studied theoretically. Tunneling current, current spin polarization and tunnel magnetoresistance (TMR) as functions of the bias voltage and the direct coupling strength between the two leads are analyzed by the nonequilibrium Green's function technique. It is shown that the magnitudes of these quantities are sensitive to the relative angle between the leads' magnetic moments and the quantum interference effect originated from the inter-lead coupling. We pay particular attention on the Coulomb blockade regime and find the relative current magnitudes of different magnetization angles can be reversed by tuning the inter-lead coupling strength, resulting in sign change of the TMR. For large enough inter-lead coupling strength, the current spin polarizations for parallel and antiparallel magnetic configurations will approach to unit and zero, respectively.

PACS numbers:
Monodisperse upconversion GdF3:Yb, Er rhombi by microwave-assisted synthesis
Authors: Wang Haiqiao , Nann Thomas
Published: April 2011

We have synthesized a variety of monodisperse colloidal GdF3:Yb, Er upconversion nanocrystals with different shape, size, and dopants by microwave-assisted synthesis. Typical upconversion emission from Er3+ was observed. In addition to highly monodisperse spherical particles, we were able to prepare monodispersed rhombic-shaped slices that showed a tendency for self-assembly into stacks.
Nanomechanical properties of α-synuclein amyloid fibrils: a comparative study by nanoindentation, harmonic force microscopy, and Peakforce QNM
Authors: Sweers Kim , van der Werf Kees , Bennink Martin , Subramaniam Vinod
Published: April 2011

We report on the use of three different atomic force spectroscopy modalities to determine the nanomechanical properties of amyloid fibrils of the human α-synuclein protein. α-Synuclein forms fibrillar nanostructures of approximately 10 nm diameter and lengths ranging from 100 nm to several microns, which have been associated with Parkinson's disease. Atomic force microscopy (AFM) has been used to image the morphology of these protein fibrils deposited on a flat surface. For nanomechanical measurements, we used single-point nanoindentation, in which the AFM tip as the indenter is moved vertically to the fibril surface and back while the force is being recorded. We also used two recently developed AFM surface property mapping techniques: Harmonic force microscopy (HarmoniX) and Peakforce QNM. These modalities allow extraction of mechanical parameters of the surface with a lateral resolution and speed comparable to tapping-mode AFM imaging. Based on this phenomenological study, the elastic moduli of the α-synuclein fibrils determined using these three different modalities are within the range 1.3-2.1 GPa. We discuss the relative merits of these three methods for the determination of the elastic properties of protein fibrils, particularly considering the differences and difficulties of each method.
Long-Term Potentiation in Spinal Nociceptive Pathways as a Novel Target for Pain Therapy
Authors: Ruscheweyh Ruth , Wilder-Smith Oliver , Drdla Ruth , Liu Xian-Guo , Sandkühler Jürgen
Published: April 2011

Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.
5-Hydroxyindolacetic Acid (5-HIAA), a Main Metabolite of Serotonin, is Responsible for Complete Freund's Adjuvant-Induced Thermal Hyperalgesia in Mice
Authors: Chen Yong , Palm Florian , Lesch Klaus-Peter , Gerlach Manfred , Moessner Rainald , Sommer Claudia
Published: April 2011

Background:

The role of serotonin (5-hydroxytrptamine, 5-HT) in the modulation of pain has been widely studied. Previous work led to the hypothesis that 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, might by itself influence pain thresholds.

Results:

In the present study, we investigated the role of 5-HIAA in inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) into the hind paw of mice. Wild-type mice were compared to mice deficient of the 5-HT transporter (5-HTT−/− mice) using behavioral tests for hyperalgesia and high-performance liquid chromatography (HPLC) to determine tissue levels of 5-HIAA. Wild-type mice reproducibly developed thermal hyperalgesia and paw edema for 5 days after CFA injection. 5-HTT−/− mice treated with CFA had reduced thermal hyperalgesia on day 1 after CFA injection and normal responses to heat thereafter. The 5-HIAA levels in spinal cord and sciatic nerve as measured with HPLC were lower in 5-HTT−/− mice than in wild-type mice after CFA injection. Pretreatment of wild-type mice with intraperitoneal injection of para-chlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, resulted in depletion of the 5-HIAA content in spinal cord and sciatic nerve and decrease in thermal hyperalgesia in CFA injected mice. The application of exogenous 5-HIAA resulted in potentiation of thermal hyperalgesia induced by CFA in 5-HTT−/− mice and in wild-type mice pretreated with p-CPA, but not in wild-type mice without p-CPA pretreatment. Further, methysergide, a broad-spectrum serotonin receptor antagonist, had no effect on 5-HIAA-induced potentiation of thermal hyperalgesia in CFA-treated wild-type mice.

Conclusion:

Taken together, the present results suggest that 5-HIAA plays an important role in modulating peripheral thermal hyperalgesia in CFA induced inflammation, probably via a non-serotonin receptor mechanism.
Exploration of plant genomes in the FLAGdb++ environment
Authors: Dèrozier Sandra , Samson Franck , Tamby Jean-Philippe , Guichard Cécile , Brunaud Véronique , Grevet Philippe , Gagnot Séverine , Label Philippe , Leplé Jean-Charles , Lecharny Alain , Aubourg Sébastien
Published: April 2011

Background

In the contexts of genomics, post-genomics and systems biology approaches, data integration presents a major concern. Databases provide crucial solutions: they store, organize and allow information to be queried, they enhance the visibility of newly produced data by comparing them with previously published results, and facilitate the exploration and development of both existing hypotheses and new ideas.

Results

The FLAGdb++ information system was developed with the aim of using whole plant genomes as physical references in order to gather and merge available genomic data from in silico or experimental approaches. Available through a JAVA application, original interfaces and tools assist the functional study of plant genes by considering them in their specific context: chromosome, gene family, orthology group, co-expression cluster and functional network. FLAGdb++ is mainly dedicated to the exploration of large gene groups in order to decipher functional connections, to highlight shared or specific structural or functional features, and to facilitate translational tasks between plant species (Arabidopsis thaliana, Oryza sativa, Populus trichocarpa and Vitis vinifera).

Conclusion

Combining original data with the output of experts and graphical displays that differ from classical plant genome browsers, FLAGdb++ presents a powerful complementary tool for exploring plant genomes and exploiting structural and functional resources, without the need for computer programming knowledge. First launched in 2002, a 15th version of FLAGdb++ is now available and comprises four model plant genomes and over eight million genomic features.
Differential effects of Radix Paeoniae Rubra (Chishao) on cytokine and chemokine expression inducible by mycobacteria
Authors: Wang Liangjie , Yang Cindy Lai Hung , Or Terry Cho Tsun , Chen Gang , Zhou Jian , Li James Chun Tsun , Lau Allan Sik Yin
Published: April 2011

Background

Upon initial infection with mycobacteria, macrophages secrete multiple cytokines and chemokines, including interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α), to mediate host immune responses against the pathogen. Mycobacteria also induce the production of IL-10viaPKR activation in primary human monocytes and macrophages. As an anti-inflammatory cytokine, over-expression of IL-10 may contribute to mycobacterial evasion of the host immunity.Radix Paeoniae Rubra(RPR,Chishao), a Chinese medicinal herb with potentials of anti-inflammatory, hepatoprotective and neuroprotective effects, is used to treat tuberculosis. This study investigates the immunoregulatory effects of RPR on primary human blood macrophages (PBMac) during mycobacterial infection.

Methods

The interaction of Bacillus Calmette-Guerin (BCG) with PBMac was used as an experimental model. A series of procedures involving solvent extraction and fractionation were used to isolate bioactive constituents in RPR. RPR-EA-S1, a fraction with potent immunoregulatory effects was obtained with a bioactivity guided fractionation scheme. PBMac were treated with crude RPR extracts or RPR-EA-S1 before BCG stimulation. The expression levels of IL-6, IL-8, IL-10 and TNF-α were measured by qPCR and ELISA. Western blotting was used to determine the effects of RPR-EA-S1 on signaling kinases and transcriptional factors in the BCG-activated PBMac.

Results

In BCG-stimulated macrophages, crude RPR extracts and fraction RPR-EA-S1 specifically inhibited IL-10 production while enhanced IL-8 expression at both mRNA and protein levels without affecting the expressions of IL-6 and TNF-α. Inhibition of BCG-induced IL-10 expression by RPR-EA-S1 occurred in a dose- and time-dependent manner. RPR-EA-S1 did not affect the phosphorylation of cellular protein kinases including MAPK, Akt and GSK3β. Instead, it suppressed the degradation of IκBα in the cytoplasm and inhibited the translocation of transcription factor NF-κB1 p50 to the nucleus.

Conclusion

RPR crude extracts and its fraction RPR-EA-S1 inhibited anti-inflammatory cytokine IL-10 and enhanced pro-inflammatory chemokine IL-8 expression in BCG-activated PBMac. The inhibitory effects of RPR-EA-S1 on IL-10 expression in BCG-activated PBMac may be due to the reduced nuclear translocation of NF-κB1 p50.
Generation and Characterization of a genetic zebrafish model of SMA carrying the human SMN2gene
Authors: Hao Le T , Burghes Arthur HM , Beattie Christine E
Published: April 2011

Background

Animal models of human diseases are essential as they allow analysis of the disease process at the cellular level and can advance therapeutics by serving as a tool for drug screening and target validation. Here we report the development of a complete genetic model of spinal muscular atrophy (SMA) in the vertebrate zebrafish to complement existing zebrafish, mouse, and invertebrate models and show its utility for testing compounds that alter SMN2 splicing.

Results

The human motoneuron disease SMA is caused by low levels, as opposed to a complete absence, of the survival motor neuron protein (SMN). To generate a true model of SMA in zebrafish, we have generated a transgenic zebrafish expressing the human SMN2 gene (hSMN2), which produces only a low amount of full-length SMN, and crossed this onto the smn
-/- background. We show that human SMN2 is spliced in zebrafish as it is in humans and makes low levels of SMN protein. Moreover, we show that an antisense oligonucleotide that enhances correct hSMN2 splicing increases full-length hSMN RNA in this model. When we placed this transgene on the smn mutant background it rescued the neuromuscular presynaptic SV2 defect that occurs in smn mutants and increased their survival.

Conclusions

We have generated a transgenic fish carrying the human hSMN2 gene. This gene is spliced in fish as it is in humans and mice suggesting a conserved splicing mechanism in these vertebrates. Moreover, antisense targeting of an intronic splicing silencer site increased the amount of full length SMN generated from this transgene. Having this transgene on the smn mutant fish rescued the presynaptic defect and increased survival. This model of zebrafish SMA has all of the components of human SMA and can thus be used to understand motoneuron dysfunction in SMA, can be used as an vivo test for drugs or antisense approaches that increase full-length SMN, and can be developed for drug screening.
Cecal obstruction due to primary intestinal tuberculosis: a case series
Authors: Michalopoulos Antonis , Papadopoulos Vassilis N , Panidis Stavros , Papavramidis Theodossis S , Chiotis Anastasios , Basdanis George
Published: April 2011

Introduction

Primary intestinal tuberculosis is a rare variant of tuberculosis. The preferred treatment is usually pharmaceutical, but surgery may be required for complicated cases.

Case presentation

We report two cases of primary intestinal tuberculosis where the initial diagnosis was wrong, with colonic cancer suggested in the first case and a Crohn's disease complication in the second. Both of our patients were Caucasians of Greek nationality. In the first case (a 60-year-old man), a right hemicolectomy was performed. In the second case (a 26-year-old man), excision was impossible due to the local conditions and peritoneal implantations. Histopathology revealed an inflammatory mass of tuberculous origin in the first case. In the second, cell culture and polymerase chain reaction tests revealed Mycobacterium tuberculosis. Both patients were given anti-tuberculosis therapy and their post-operative follow-up was uneventful.

Conclusions

Gastrointestinal tuberculosis still appears sporadically and should be considered in the differential diagnosis along with other conditions of the bowel. The use of immunosuppressants and new pharmaceutical agents can change the prevalence of tuberculosis.
Dynamics of distribution and efficacy of different spot-on permethrin formulations in dogs artificially infested with Dermacentor reticulatus
Authors: Lüssenhop Johanna , Bäumer Wolfgang , Kietzmann Manfred , Schnieder Thomas , Wolken Sonja
Published: April 2011

Background

Varying reports concerning the duration and reliability of different permethrin preparations' efficacy can be found in the literature. The aim of this study was to investigate the dynamics of the distribution and efficacy of four different spot-on formulations with permethrin as the active ingredient formulated with different solvents. To examine the influence of these solvents on the speed of distribution and the acaricidal activity of permethrin in the coat, an in vivo study under laboratory conditions was performed. Six dogs per test period were treated with the recommended dose and 1, 14 and 28 days after treatment dogs were infested with Dermacentor reticulatus ticks: a) on the back, near the application site, and b) on the hind leg, the greatest possible distance from the application site. Efficacies were determined 6 hours after tick infestation to examine the repellent effect and the speed of kill of the products which plays an important role in the context of tick transmitted diseases.

Results

After six hours of exposure, a significant acaricidal efficacy (p < 0.001) could be observed in all treated groups over the whole duration of the study, regardless of which product was used. While the arithmetic mean of attached ticks was < 3 on Day 1, numbers increased over the course of the study to a mean of > 9 on Day 28. However, most of these ticks were dead even 28 days after treatment, as the mean of live attached ticks was still < 2. Significant differences could neither be found between the different permethrin spot-on formulations, nor between the two parts of the body (p > 0.05).

Conclusions

All products were able to kill ticks within six hours following infestation from Day 1 to Day 28 after treatment. Additionally, no significant difference between the tick numbers on the back and the hind leg could be found at any time, which implies a homogenous distribution of permethrin over the body. The efficacy of all four products was comparable during the whole study period, showing that the different solvents do not significantly affect the dynamics of distribution.
Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer
Authors: Oermann Eric K , Suy Simeng , Hanscom Heather N , Kim Joy S , Lei Sue , Yu Xia , Zhang Guowei , Ennis Brook , Rohan JoyAnn P , Piel Nathaniel , Sherer Benjamin A , Borum Devin , Chen Viola J , Batipps Gerald P , Constantinople Nicholas L , Dejter Stephen W , Bandi Gaurav , Pahira John , McGeagh Kevin G , Adams-Campbell Lucile , Jha Reena , Dawson Nancy A , Collins Brian T , Dritschilo Anatoly , Lynch John H , Collins Sean P
Published: April 2011

Background

The CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism.

Methods

Twenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires.

Results

All 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (p < 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment.

Conclusions

Hypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment.
Driving a decade of change: HIV/AIDS, patents and access to medicines for all
Authors: Hoen Ellen 't , Berger Jonathan , Calmy Alexandra , Moon Suerie
Published: April 2011

Since 2000, access to antiretroviral drugs to treat HIV infection has dramatically increased to reach more than five million people in developing countries. Essential to this achievement was the dramatic reduction in antiretroviral prices, a result of global political mobilization that cleared the way for competitive production of generic versions of widely patented medicines.

Global trade rules agreed upon in 1994 required many developing countries to begin offering patents on medicines for the first time. Government and civil society reaction to expected increases in drug prices precipitated a series of events challenging these rules, culminating in the 2001 World Trade Organization's Doha Declaration on the Agreement on Trade‐Related Aspects of Intellectual Property Rights and Public Health. The Declaration affirmed that patent rules should be interpreted and implemented to protect public health and to promote access to medicines for all. Since Doha, more than 60 low‐ and middle‐income countries have procured generic versions of patented medicines on a large scale.

Despite these changes, however, a “treatment timebomb” awaits. First, increasing numbers of people need access to newer antiretrovirals, but treatment costs are rising since new ARVs are likely to be more widely patented in developing countries. Second, policy space to produce or import generic versions of patented medicines is shrinking in some developing countries. Third, funding for medicines is falling far short of needs. Expanded use of the existing flexibilities in patent law and new models to address the second wave of the access to medicines crisis are required.

One promising new mechanism is the UNITAID‐supported Medicines Patent Pool, which seeks to facilitate access to patents to enable competitive generic medicines production and the development of improved products. Such innovative approaches are possible today due to the previous decade of AIDS activism. However, the Pool is just one of a broad set of policies needed to ensure access to medicines for all; other key measures include sufficient and reliable financing, research and development of new products targeted for use in resource‐poor settings, and use of patent law flexibilities. Governments must live up to their obligations to protect access to medicines as a fundamental component of the human right to health.
The prognostic value of markers of right ventricular dysfunction in pulmonary embolism: a meta-analysis
Authors: Coutance Guillaume , Cauderlier Emmanuelle , Ehtisham Javed , Hamon Michèle , Hamon Martial
Published: April 2011

Introduction

In pulmonary embolism (PE) without hemodynamic compromise, the prognostic value of right ventricular (RV) dysfunction as measured by echocardiography, computed tomography (CT) or biological (natriuretic peptides) markers has only been assessed in small studies.

Methods

Databases were searched using the combined medical subject headings for right ventricular dysfunction or right ventricular dilatation with the exploded term acute pulmonary embolism. This retrieved 8 echocardiographic marker based studies (n = 1249), three CT marker based studies (n = 503) and 7 natriuretic peptide based studies (n = 582). A meta-analysis of these data was performed with the primary endpoint of mortality within three months after pulmonary embolism, and a secondary endpoint of overall mortality and morbidity by pulmonary embolism.

Results

Patients with PE without hemodynamic compromise on admission and the presence of RV dysfunction determined by echocardiography and biological markers were associated with increased short-term mortality (odds ratio (OR) ECHO = 2.36; 95% confidence interval (CI): 1.3-43; OR BNP = 7.7; 95% CI: 2.9-20) while CT was not (ORCT = 1.54-95% CI: 0.7-3.4). However, corresponding pooled negative and positive likelihood ratios independent of death rates were unsatisfactory for clinical usefulness in risk stratification.

Conclusions

The presence of echocardiographic RV dysfunction or elevated natriuretic peptides is associated with short-term mortality in patients with pulmonary embolism without hemodynamic compromise. In contrast, the prognostic value of RV dilation on CT has yet to be validated in this population. As indicated both by positive and negative likelihood ratios the current prognostic value in clinical practice remains very limited.
Randomized, Placebo-Controlled, Phase III Study of First-Line Oxaliplatin-Based Chemotherapy Plus PTK787/ZK 222584, an Oral Vascular Endothelial Growth Factor Receptor Inhibitor, in Patients With Metastatic Colorectal Adenocarcinoma
Authors: Hecht J. Randolph , Trarbach Tanja , Hainsworth John D. , Major Pierre , Jäger Elke , Wolff Robert A. , Lloyd-Salvant Katherine , Bodoky György , Pendergrass Kelly , Berg William , Chen Bee-Lian , Jalava Tarja , Meinhardt Gerold , Laurent Dirk , Lebwohl David , Kerr David
Published: April 2011

Purpose

PTK787/ZK 222584 (PTK/ZK; vatalanib), an orally active, multitargeted angiogenesis inhibitor, has shown tolerability and promising activity in early-phase studies, which led to a phase III trial in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4).

Patients and Methods

Patients (N = 1,168) with previously untreated metastatic colorectal cancer were randomly assigned 1:1 to receive FOLFOX4 plus PTK/ZK or placebo (ClinicalTrials.gov identifier: NCT00056459). Stratification factors included WHO performance status (0 v 1 or 2) and serum lactate dehydrogenase (LDH; ≤ v > 1.5× the upper limit of normal). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and overall response rate (ORR).

Results

PFS, OS, and ORR were not statistically improved with PTK/ZK (P > .05). Median PFS by central review was 7.7 months with PTK/ZK versus 7.6 months with placebo (hazard ratio [HR], 0.88; 95% CI, 0.74 to 1.03; P = .118); median OS was 21.4 months with PTK/ZK versus 20.5 months with placebo (HR, 1.08; 95% CI, 0.94 to 1.24; P = .260). In an exploratory post hoc analysis of PFS in patients (n = 158 per arm) with high serum LDH, a potential marker of hypoxia, PFS was longer with PTK/ZK versus placebo (7.7 v 5.8 months, respectively; HR, 0.67; 95% CI, 0.49 to 0.91; P = .009).

Conclusion

Although the efficacy objectives of this study were not met, a subgroup of patients who may potentially benefit from small-molecule vascular endothelial growth factor receptor inhibitor therapy has been identified and further research is warranted.
Phase I Dose-Escalation Study of Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer
Authors: Boike Thomas P. , Lotan Yair , Cho L. Chinsoo , Brindle Jeffrey , DeRose Paul , Xie Xian-Jin , Yan Jingsheng , Foster Ryan , Pistenmaa David , Perkins Alida , Cooley Susan , Timmerman Robert
Published: April 2011

Purpose

To evaluate the tolerability of escalating doses of stereotactic body radiation therapy in the treatment of localized prostate cancer.

Patients and Methods

Eligible patients included those with Gleason score 2 to 6 with prostate-specific antigen (PSA) ≤ 20, Gleason score 7 with PSA ≤ 15, ≤ T2b, prostate size ≤ 60 cm3, and American Urological Association (AUA) score ≤ 15. Pretreatment preparation required an enema and placement of a rectal balloon. Dose-limiting toxicity (DLT) was defined as grade 3 or worse GI/genitourinary (GU) toxicity by Common Terminology Criteria of Adverse Events (version 3). Patients completed quality-of-life questionnaires at defined intervals.

Results

Groups of 15 patients received 45 Gy, 47.5 Gy, and 50 Gy in five fractions (45 total patients). The median follow-up is 30 months (range, 3 to 36 months), 18 months (range, 0 to 30 months), and 12 months (range, 3 to 18 months) for the 45 Gy, 47.5 Gy, and 50 Gy groups, respectively. For all patients, GI grade ≥ 2 and grade ≥ 3 toxicity occurred in 18% and 2%, respectively, and GU grade ≥ 2 and grade ≥ 3 toxicity occurred in 31% and 4%, respectively. Mean AUA scores increased significantly from baseline in the 47.5-Gy dose level (P = .002) as compared with the other dose levels, where mean values returned to baseline. Rectal quality-of-life scores (Expanded Prostate Cancer Index Composite) fell from baseline up to 12 months but trended back at 18 months. In all patients, PSA control is 100% by the nadir + 2 ng/mL failure definition.

Conclusion

Dose escalation to 50 Gy has been completed without DLT. A multicenter phase II trial is underway treating patients to 50 Gy in five fractions to further evaluate this experimental therapy.
Duration of Chemotherapy for Metastatic Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Gennari Alessandra , Stockler Martin , Puntoni Matteo , Sormani Mariapia , Nanni Oriana , Amadori Dino , Wilcken Nicholas , D'Amico Mauro , DeCensi Andrea , Bruzzi Paolo
Published: April 2011

Purpose

To evaluate the effect of different first-line chemotherapy durations in patients with metastatic breast cancer (MBC) on overall survival (OS) and progression-free survival (PFS).

Methods

We searched literature databases to identify randomized controlled trials that compared different chemotherapy durations in the first-line treatment of MBC. Only trials with unconfounded comparisons of additional cycles of chemotherapy were included. The main outcome measures for this analysis were OS and PFS. Published data from retrieved studies were analyzed according to standard meta-analytic techniques.

Results

We found 11 randomized clinical trials including 2,269 patients. Longer first-line chemotherapy duration resulted into a significantly improved OS (hazard ratio [HR], 0.91; 95% CI, 0.84 to 0.99; P = .046) and PFS (HR, 0.64; 95% CI, 0.55 to 0.76; P < .001). There were no differences in effects on either OS or PFS between subgroups defined by time of random assignment, study design, number of chemotherapy cycles in the control arm or concomitant endocrine therapy.

Conclusion

Longer first-line chemotherapy duration is associated with marginally longer OS and a substantially longer PFS.
Active Surveillance Program for Prostate Cancer: An Update of the Johns Hopkins Experience
Authors: Tosoian Jeffrey J. , Trock Bruce J. , Landis Patricia , Feng Zhaoyong , Epstein Jonathan I. , Partin Alan W. , Walsh Patrick C. , Carter H. Ballentine
Published: April 2011

Purpose

We assessed outcomes of men with prostate cancer enrolled in active surveillance.

Patients and Methods

Since 1995, a total of 769 men diagnosed with prostate cancer have been followed prospectively (median follow-up, 2.7 years; range, 0.01 to 15.0 years) on active surveillance. Enrollment criteria were for very-low-risk cancers, defined by clinical stage (T1c), prostate-specific antigen density < 0.15 ng/mL, and prostate biopsy findings (Gleason score ≤ 6, two or fewer cores with cancer, and ≤ 50% cancer involvement of any core). Curative intervention was recommended on disease reclassification on the basis of biopsy criteria. The primary outcome was survival free of intervention, and secondary outcomes were rates of disease reclassification and exit from the program. Outcomes were compared between men who did and did not meet very-low-risk criteria.

Results

The median survival free of intervention was 6.5 years (range, 0.0 to 15.0 years) after diagnosis, and the proportions of men remaining free of intervention after 2, 5, and 10 years of follow-up were 81%, 59%, and 41%, respectively. Overall, 255 men (33.2%) underwent intervention at a median of 2.2 years (range, 0.6 to 10.2 years) after diagnosis; 188 men (73.7%) underwent intervention on the basis of disease reclassification on biopsy. The proportions of men who underwent curative intervention (P = .026) or had biopsy reclassification (P < .001) were significantly lower in men who met enrollment criteria than in those who did not. There were no prostate cancer deaths.

Conclusion

For carefully selected men, active surveillance with curative intent appears to be a safe alternative to immediate intervention. Limiting surveillance to very-low-risk patients may reduce the frequency of adverse outcomes.
The impact of patient choice of provider on equity: Analysis of a patient survey
Authors: Robertson Ruth , Burge1 Peter
Published: April 2011

Objectives

To understand the impact on equity of giving patients a choice of provider.

Methods

A postal survey of 5997 patients in four areas of England about choice at their recent referral and, using a discrete choice experiment, how they would choose in hypothetical situations. Binary logistic regression and a series of multinomial and nested logit models were used to analyse the data to discover whether patients with particular characteristics were more likely to: think choice is important; be offered a choice; and, choose a non-local provider.

Results

The response rate was 36%. Choice was more important to older patients aged 51-80 years, patients from non-white backgrounds, women, those with no qualifications and those with a bad past experience of their local hospital. There were no significant differences in who was offered a choice in terms of education, age group or ethnicity. In both real and hypothetical situations patients with no formal qualifications and those living in urban centres were more likely to choose their local hospital, and patients with a bad or mixed past experience at the local hospital were more likely to choose an alternative. In hypothetical choices those who do not normally travel by car and without Internet access were more likely to choose their local hospital irrespective of that hospital's characteristics.

Conclusions

More educated, affluent patients were no more likely to be offered a choice than other population groups, but there does appear to be a social gradient in who chose to travel beyond the local area for treatment. If these results were replicated across England, there is at least the potential risk that when local hospitals are failing, patient choice could result in inequitable access to high quality care, rather than enhancing equity as the policy's architects had hoped.
Pattern of homicide coroner's autopsies at University College Hospital, Ibadan, Nigeria: 1997–2006
Authors: Eze U O , Akang E E U , Odesanmi W O
Published: April 2011

There is relatively little information regarding the pattern of homicides in developing countries such as Nigeria. This study is aimed at determining the pattern and demographic factors associated with homicide cases seen in a Nigerian Teaching Hospital. It is a descriptive autopsy study of homicide cases seen at the University College Hospital (UCH), Ibadan over a 10-year period from January 1997 to December 2006. All the coroner's autopsies for the period, of homicides or suspected homicides, were reviewed with emphasis on the following: gender, age, occupation, circumstances surrounding event, likely motive, type of weapon used, site(s) of injury and mechanism of death. Homicides accounted for 153 (3.1%) of the 4928 coroner's cases at the UCH within the study period. One hundred and thirty-seven of the 152 cases were men, and the overall age range was 4–83 years. The mechanism of death was haemorrhagic shock in 91 cases (59.9%); severe raised intracranial pressure in 58 cases (38.2%); septicaemic shock in two cases (1.3%); and asphyxia in one case (0.7%). Gunshot injuries accounted for 64.5% of the fatalities, sharp objects 21.1% and blunt force 14.5%. Most were victims of armed robbery attacks. The head, abdomen, chest and lower limbs were single sites of injuries in descending order of frequency and most of the cases sustained multiple injuries involving two or more of these sites. Gunshot deaths were the commonest form of homicides in the period under review. Young males and victims of armed robbery attacks were most susceptible.
Medication misuse and abuse: duties and responsibilities of dispensing pharmacists
Authors: Berland-Benhaïm C , Giocanti D , Bartoli C , Sastre C , Leonetti G , Pelissier-Alicot Al
Published: April 2011

Misuse of medications can have major consequences for the consumer or patient's health. In the case of a drug delivered only on medical prescription, the misuse usually results from an error or negligence on the part of the prescribing doctor and/or the pharmacist dispensing the medication. But whereas, under French Law, doctors are regularly prosecuted for their irresponsibility, pharmacists frequently avoid any legal charges. This is even more surprising in view of the fact that French Legislation controls the practice of pharmacy very strictly. The authors discuss four cases that illustrate this issue and present a study of comparative pharmaceutical law requirements.
Incentives and Problem Uncertainty in Innovation Contests: An Empirical Analysis
Authors: Boudreau Kevin J. , Lacetera Nicola , Lakhani Karim R.
Published: April 2011

Contests are a historically important and increasingly popular mechanism for encouraging innovation. A central concern in designing innovation contests is how many competitors to admit. Using a unique data set of 9,661 software contests, we provide evidence of two coexisting and opposing forces that operate when the number of competitors increases. Greater rivalry reduces the incentives of all competitors in a contest to exert effort and make investments. At the same time, adding competitors increases the likelihood that at least one competitor will find an extreme-value solution. We show that the effort-reducing effect of greater rivalry dominates for less uncertain problems, whereas the effect on the extreme value prevails for more uncertain problems. Adding competitors thus systematically increases overall contest performance for high-uncertainty problems. We also find that higher uncertainty reduces the negative effect of added competitors on incentives. Thus, uncertainty and the nature of the problem should be explicitly considered in the design of innovation tournaments. We explore the implications of our findings for the theory and practice of innovation contests.

This paper was accepted by Christian Terwiesch, operations management.
Retail Channel Structure Impact on Strategic Engineering Product Design
Authors: Williams Nathan , Kannan P. K. , Azarm Shapour
Published: April 2011

We examine, in a strategic setting, the broad issue of how retail channel structures—retail monopoly versus retail duopoly—impact a manufacturer's optimal new product design, both in terms of engineering design specifications as well as manufacturer and retailer profits. Our strategic framework enables manufacturers in specific contexts to anticipate the reactions of the retailers and competitive manufacturers to new designs in terms of the retail and wholesale pricing and to understand how different channel structures and channel strategies (such as an exclusive channel strategy) impact the engineering design of the new product, conditional on consumer preference distributions and competitor product attributes. Based on a simple numerical and a power tool design example, we illustrate how the insight from the framework translates to design guidelines; specifically, understanding which designs are optimal under differing channel structure conditions, and which design variables need precise targeting given their profit sensitivity.

This paper was accepted by Christoph Loch, R&D and product development.
Can Losing Lead to Winning?
Authors: Berger Jonah , Pope Devin
Published: April 2011

Individuals, groups, and teams who are behind their opponents in competition tend to be more likely to lose. In contrast, we show that through increasing motivation, being slightly behind can actually increase success. Analysis of more than 18,000 professional basketball games illustrates that being slightly behind at halftime leads to a discontinuous increase in winning percentage. Teams behind by a point at halftime, for example, actually win more often than teams ahead by one, or approximately six percentage points more often than expected. This psychological effect is roughly half the size of the proverbial home-team advantage. Analysis of more than 45,000 collegiate basketball games finds consistent, though smaller, results. Experiments corroborate the field data and generalize their findings, providing direct causal evidence that being slightly behind increases effort and casting doubt on alternative explanations for the results. Taken together, these findings illustrate that losing can sometimes lead to winning.

This paper was accepted by Peter Wakker, decision analysis.
Rituximab: Primary Immune Thrombocytopenia (Idiopathic Thrombocytopenic Purpura)
Authors: Generali Joyce A. , Cada Dennis J.
Published: April 2011

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a quarterly publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@kumc.edu .