bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life, depression and fatigue in mildly disabled patients with relapsing–remitting multiple sclerosis receiving subcutaneous interferon beta-1a: 3-year results from the COGIMUS (COGnitive Impairment in MUltiple Sclerosis) study
Authors: Patti F , Amato MP , Trojano M , Bastianello S , Tola MR , Picconi O , Cilia S , Cottone S , Centonze D , Gasperini C ,   the COGIMUS Study Group
Published: April 2011

Background: The precise relationships among quality of life, depression, fatigue and cognitive impairment in multiple sclerosis (MS) are complex and poorly understood.

Objective: To assess the effects of subcutaneous interferon beta-1a on quality of life, depression and fatigue over 3 years in the COGIMUS study, and to examine the relationship between these outcomes and baseline cognitive status.

Methods: COGIMUS was an observational 3-year trial assessing cognitive function in 459 patients with relapsing–remitting MS treated with subcutaneous interferon beta-1a.

Results: In total, 331 patients completed the study (168 received interferon beta-1a, 44 µg subcutaneously three times weekly, and 163 received interferon beta-1a, 22 µg subcutaneously three times weekly). Mean MS Quality of Life-54 (MSQoL-54) composite scores did not change over time. There were no significant differences between groups in MSQoL-54 composite scores when patients were grouped by treatment dose and baseline cognitive status. Mean (standard deviation) Hamilton Depression Rating Scale score decreased from 6.8 (4.9) at baseline to 5.8 (5.9) at year 3. Mean total Fatigue Impact Scale scores were low (<30) at all time points.

Conclusion: Quality of life, depression and fatigue remained largely stable over 3 years; no effects of treatment dose or baseline cognitive status were found.
The Ravello Profile: Development of a global standard neuropsychological assessment for young people with anorexia nervosa
Authors: Rose Mark , Davis Jennifer , Frampton Ian , Lask Bryan
Published: April 2011

Recent research suggests that neuropsychological factors may play an important role in the development and maintenance of anorexia nervosa. However, it has been difficult to draw firm conclusions because of the wide range of assessments and norms that have been used. The aim of the Ravello Profile is to define a common shared neuropsychological assessment battery that can be adopted by researchers and clinicians working with young people. We describe the background to the Ravello Profile and the process of developing it, before specifying the recommended tests. We present an illustrative case example and consider some of the potential clinical and research applications of the profile with young people suffering from anorexia nervosa.
Dismantling the welfare state from the left? Localization of global ideas in the case of Israel’s 1998 Public Housing Law
Authors: Asiskovitch Sharon
Published: April 2011

The article considers the contribution of actors not usually associated with globalization and liberalization to the institutionalization of neoliberalism. Neoliberal projects are considered to integrate global models with local values. Thus, the main battlegrounds are domestic arenas. Most analyses focus on powerful agents associated with neoliberalism. However, other actors may have a supportive role. In legislating Israel’s Public Housing Law in 1998, aimed at selling public dwellings to tenants, left-wing politicians, ‘social’ interest groups and tenants embraced the discourse and goals of privatization. To explain this anomaly, one must understand the weakness of social democracy among the Israeli left and the centrality of Jewish-Zionist nationalism: in effect, supporters of the law integrated neoliberal discourses of privatization with local discourses of republicanism to advance populist privatization. In this article, the author discusses this concept and elaborates on the perceptions, roles and contributions of actors not associated with neoliberalism to local neoliberal projects.
Characteristics of Frail Patients in a Geriatric-HIV Program: The Experience of an Urban Academic Center at One Year Follow-Up
Authors: Ruiz Marco , Cefalu Charles
Published: April 2011

Introduction: Frailty syndrome has not been explored in depth in elderly HIV-infected patients. Methods: As of December 2009, a total of 60 patients (out of 160 patients > 60 years) were screened and 20 patients were transferred to our newly created Geriatrics-HIV program. We divided this group of already ‘‘frail patients’’ in three different subgroups; the mildly, moderately and the very frail groups based on the number of domains failed during the initial geriatrics screening. Results: The percentages of mildly, moderately, and severely frail elderly patients in our cohort were 20% 50% and 30% respectively. The most common comorbidities found were HTN (60%), and history of AIDS-related opportunistic infections (40%). Smoking was highly prevalent in all groups. The average number of medications used per patient was 8.1 with 65% of patients being compliant with their regimens. Discussion: We found that cognitive impairment, presence of comorbidities, high number of medications used, and past history of any opportunistic infection are factors prevalent in severely frail patients infected with HIV in our cohort. The significance of these factors in development and progression of frailty syndrome in HIV-positive patients needs to be elucidated.
Early Results of Retrograde Expandable Nail Fixation of 29 Distal Femoral Fractures
Authors: Steinberg Ely Liviu , Elis Yacov , Shasha Nadav , Luger Elchanan
Published: April 2011

The authors retrospectively reviewed 27 consecutive patients with 29 fractures of the distal femur treated with the new retrograde expandable nail. One 10-mm diameter nail that expands to 16 mm was used with the possibility of locking in the condylar area only. Retrieved data included single versus multiple injuries, fracture type, operation time, reaming or nonreaming, hospitalization and healing times, and intra- and postoperative complications. The overall average operation time was 96 (range 40-320) minutes, but only 65 (range 40-120) minutes for isolated fractures. The overall mean hospitalization time was 16 (range 3-40) days, but only 7 (range 4-10) days for isolated fractures. Follow-up continued until fracture healing or for a minimum of 1 year (average 14 months, range 12-24 months). The average clinical union time was 83 (range 43-179) days, and the mean radiographic healing was 87 (range 43-179) days. One patient developed a nonunion that required exchange of the nail to the same device. Another patient underwent hardware removal during a procedure for a torn meniscus. These preliminary results demonstrate satisfactory healing and alignment for the treatment of distal femoral shaft fractures by means of this new device without jeopardizing the knee joint by nail protrusion.
Minimally Invasive Computer-Assisted Approach for Cochlear Implantation
Authors: Nguyen Yann , Miroir Mathieu , Vellin Jean-François , Mazalaigue Stéphane , Bensimon Jean-Loup , Bernardeschi Daniele , Ferrary Evelyne , Sterkers Olivier , Grayeli Alexis Bozorg
Published: April 2011

Computer-assisted navigation systems can now potentially guide the surgeon to the cochlea with a trajectory avoiding the facial nerve through a keyhole approach. Five temporal bone specimens, with 4 titanium screws placed in the mastoid cortex, were studied. Preoperative computed tomographic scan images were loaded on an electromagnetic computer-assisted surgery (CAS) system (Digipointeur, Collin, Bagneux, France). A drill was connected to the CAS to monitor its progression continuously. A conical approach passing through the facial recess and ending in the scala tympani was performed. A 0.5-mm wire was inserted into the cochlea. The keyhole approach was technically feasible in all cases. No facial nerve injury was observed on imaging and dissection control. The wire was positioned in the scala tympani and the position accuracy of the CAS was <0.76 mm on the target in all cases. The CAS system with fiducial markers yielded sufficient precision to allow a minimally invasive approach to the cochlea.
Change in cardiovascular risk factors in relation to diabetes status: the Tromsø Study
Authors: Joseph Josepha , Svartberg Johan , Njølstad Inger , Schirmer Henrik
Published: April 2011

Aims: To investigate changes in cardiovascular risk factors over 14 years in relation to diabetes status.

Methods: The study is based on 10,327 subjects who attended the Tromsø Study in 1994 and were screened again in 2007–8. At baseline there were 79 prevalent cases, and 397 incident cases of type 2 diabetes mellitus (DM2) were diagnosed between 1994 and 2008.

Results: Cases with DM2 had decreasing levels of high-density lipoprotein cholesterol (HDL-C), total cholesterol and blood pressure (BP) and increasing levels of triglycerides, body mass index (BMI), and anti-hypertensive treatment during 14 years of follow-up. Despite decreasing BP, more than 75% of the treated cases had BP above 135/80 at the end of follow-up. Similarly, less than 35% of incident cases using statins had low-density lipoprotein cholesterol (LDL-C) below the recommended threshold value of 2.6 mmol/l.

Conclusions: Despite greater relative reduction in cardiovascular risk factors among people with DM2 compared to those without, treatment targets were met in less than 50% of subjects with DM2. Thirteen percent reached the combined targets for glucose, BP and LDL-C control. This indicates a need for more effective strategies to control cardiovascular risk factors especially among individuals with DM2.
Revision of the Dutch clinical algorithm for assessing patient needs in cardiac rehabilitation based on identified implementation problems
Authors: van Engen-Verheul Mariëtte M , Kemps Hareld MC , de Keizer Nicolette F , Hellemans Irene M , Goud Rick , Kraaijenhagen Roderik A , Peek Niels
Published: April 2011

Background: Despite all available evidence of its effectiveness, cardiac rehabilitation and secondary prevention (CRSP) is still insufficiently implemented in current clinical practice. Based on an analysis of implementation problems, recently the Dutch clinical algorithm for the assessment of patient’s CRSP needs was revised. The purpose of this paper is to describe the revision process and its results to improve CRSP guideline implementation.

Methods: The National Institute for Health and Clinical Excellence (NICE) guidelines manual for conducting guideline revisions was followed. Information on the use of the algorithm in practice was collected from electronic medical records and by conducting semi-structured interviews. Next, an expert advisory group identified the problems for use in daily practice and defined the scope for the revision. A multidisciplinary guideline development group subsequently wrote the revised algorithm.

Results: A large variation in assessed patient needs was observed between CRSP clinics. Assessment based on clinical judgement was found to be a source of practice variation and is therefore avoided in the revised algorithm. It was decided to add assessment instruments for anxiety and depression, cardiovascular risk factors, stress, attitude of partner and lifestyle parameters.

Conclusion: The Dutch clinical algorithm for assessing patient needs for CRSP was revised using a combination of patient data from routine practice, knowledge from academic experts and experience from field experts. The revised algorithm is a practical tool consisting of assessment instruments to improve CRSP guideline adherence in the Netherlands. This algorithm may also be useful for other Western countries to organize their CRSP needs assessment procedure.
Active mobilisation following single cross grasp four-strand flexor tenorrhaphy (Adelaide repair)
Authors: Sandow M. J. , McMahon M.
Published: April 2011

This paper presents our initial experience using a single cross grasp, four-strand repair with an active mobilization regimen in a general trauma hospital setting. Variably experienced members of the trauma service of a large general hospital used a four-strand single cross grasp tenorrhaphy technique for acute repair of 73 zone one and two flexor digitorum profundus tendon lacerations in 53 patients. Postoperatively, all patients commenced an active mobilization program within 12 hours of the surgical repair. With a minimum 3 months post-repair follow-up of 89% of the repaired flexor digitorum profundus tendons, 71% of fingers achieved a good or excellent outcome. There were three (4.6%) flexor digitorum profundus ruptures post surgery. A four-strand single cross grasp repair using 3-0 braided polyester suture and active post-repair mobilization can achieve satisfactory outcomes in the general trauma service setting; however, patient compliance remains a problem.
Iron Nutrition and the Female Athlete: Countermeasures for the Prevention of Poor Iron Status
Authors: Bass Laura J. , McClung James P.
Published: April 2011

Iron is a trace element found in the diet and is essential for cognition and energy metabolism. Poor iron status is a concern for female athletes, who might not consume adequate levels of dietary iron and could experience elevated iron loss from physiologic processes associated with physical activity. Physical performance and cognitive decrements have been demonstrated in female athletes with iron deficiency anemia; both improve with increased iron intake. Two approaches for increasing iron intake in female athletes are the consumption of iron supplements and increasing dietary intake of foods high in iron to include iron-fortified foods. Both of these approaches have advantages and disadvantages that should be considered when treating female athletes with poor iron status.
Adjuvant Androgen Deprivation for High-Risk Prostate Cancer After Radical Prostatectomy: SWOG S9921 Study
Authors: Dorff Tanya B. , Flaig Thomas W. , Tangen Catherine M. , Hussain Maha H.A. , Swanson Gregory P. , Wood David P. , Sakr Wael A. , Dawson Nancy A. , Haas Naomi B. , Crawford E. David , Vogelzang Nicholas J. , Thompson Ian M. , Glode L. Michael
Published: April 2011

Purpose

Men with high-risk features (extraprostatic extension or high Gleason grade) face a high risk of prostate cancer recurrence after radical prostatectomy. Clinical trials of adjuvant systemic therapy for such patients have been limited.

Patients and Methods

The SWOG (Southwest Oncology Group) S9921 study randomly assigned 983 men with high-risk features at prostatectomy to receive adjuvant therapy with androgen deprivation (ADT) alone or in combination with mitoxantrone chemotherapy. ADT consisted of goserelin and bicalutamide for 2 years.

Results

Although the final primary treatment comparison results are not ready for publication, this article reports results in the ADT-alone control arm with a median follow-up of 4.4 years. For these 481 men, the estimated 5-year biochemical failure-free survival is 92.5% (95% CI, 90 to 95), and 5-year overall survival is 95.9% (95% CI, 93.9 to 97.9).

Conclusion

The results of this trial, taken in context, make a compelling argument for counseling all high-risk patients with prostate cancer about adjuvant ADT. This article discusses the challenges in the design and implementation of clinical trials to take the next step forward in adjuvant therapy for prostate cancer because of the excellent survival achieved with currently available therapies and highlights the need for better molecular markers to personalize care.
Phase II Study of Carboplatin and Paclitaxel in Advanced Thymoma and Thymic Carcinoma
Authors: Lemma Girum L. , Lee Ju-Whei , Aisner Seena C. , Langer Corey J. , Tester William J. , Johnson David H. , Loehrer Patrick J.
Published: April 2011

Purpose

The purpose of this study was to evaluate the impact of carboplatin and paclitaxel in patients with advanced previously untreated thymoma and thymic carcinoma.

Patients and Methods

We conducted a prospective multicenter study in patients with unresectable thymoma (n = 21) or thymic carcinoma (n = 23). Patients were treated with carboplatin (area under the curve, 6) plus paclitaxel (225 mg/m2) every 3 weeks for a maximum of six cycles. The primary end point of this trial was to evaluate the objective response rate.

Results

From February 2001 through January 2008, 46 patients were enrolled. Thirteen patients had grade 4 or greater toxicity, mostly neutropenia. Using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria, three complete responses (CRs) and six partial responses (PRs; objective response rate [ORR], 42.9%; 90% CI, 24.5% to 62.8%) were observed in the thymoma cohort; 10 patients had stable disease. For patients with thymic carcinoma, no CRs and five PRs (ORR, 21.7%; 90% CI, 9.0% to 40.4%) were observed; 12 patients had stable disease. Progression-free survival (PFS) was 16.7 (95% CI, 7.2 to 19.8) and 5.0 (95% CI, 3.0 to 8.3) months for thymoma and thymic carcinoma cohorts, respectively. To date, only seven patients (33.3%) with thymoma have died, compared with 16 patients (69.6%) with thymic carcinoma. Median survival time was 20.0 months (95% CI, 5.0 to 43.6 months) for patients with thymic carcinoma, but it has not been reached for patients with thymoma.

Conclusion

Carboplatin plus paclitaxel has moderate clinical activity for patients with thymic malignancies, but this seems less than expected with anthracycline-based therapy. Patients with thymic carcinoma have poorer PFS and overall survival than patients with thymoma.
Cetuximab Plus Irinotecan, Fluorouracil, and Leucovorin As First-Line Treatment for Metastatic Colorectal Cancer: Updated Analysis of Overall Survival According to Tumor KRAS and BRAF Mutation Status
Authors: Van Cutsem Eric , Köhne Claus-Henning , Láng István , Folprecht Gunnar , Nowacki Marek P. , Cascinu Stefano , Shchepotin Igor , Maurel Joan , Cunningham David , Tejpar Sabine , Schlichting Michael , Zubel Angela , Celik Ilhan , Rougier Philippe , Ciardiello Fortunato
Published: April 2011

Purpose

The addition of cetuximab to irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated survival analysis, including additional patients analyzed for tumor mutation status, was undertaken.

Patients and Methods

Patients were randomly assigned to receive FOLFIRI with or without cetuximab. DNA was extracted from additional slide-mounted tumor samples previously used to assess epidermal growth factor receptor expression. Clinical outcome according to the tumor mutation status of KRAS and BRAF was assessed in the expanded patient series.

Results

The ascertainment rate of patients analyzed for tumor KRAS status was increased from 45% to 89%, with mutations detected in 37% of tumors. The addition of cetuximab to FOLFIRI in patients with KRAS wild-type disease resulted in significant improvements in overall survival (median, 23.5 v 20.0 months; hazard ratio [HR], 0.796; P = .0093), progression-free survival (median, 9.9 v 8.4 months; HR, 0.696; P = .0012), and response (rate 57.3% v 39.7%; odds ratio, 2.069; P < .001) compared with FOLFIRI alone. Significant interactions between KRAS status and treatment effect were noted for all key efficacy end points. KRAS mutation status was confirmed as a powerful predictive biomarker for the efficacy of cetuximab plus FOLFIRI. BRAF tumor mutation was a strong indicator of poor prognosis.

Conclusion

The addition of cetuximab to FOLFIRI as first-line therapy improves survival in patients with KRAS wild-type mCRC. BRAF tumor mutation is an indicator of poor prognosis.
The Effect of Market Structure on Cellular Technology Adoption and Pricing
Authors: Seim Katja , Viard V. Brian
Published: April 2011

We examine how structural changes in the mobile telecommunications industry between 1996, when local markets were duopolies, and 1998, when varying degrees of regulated entry had occurred, affected firms' product offerings and nonlinear pricing strategies. We relate firms' digital technology adoption and the characteristics of their calling plan menus to the amount of entry in local markets. We find that entry induces firms to offer larger menus with more evenly spread plans, both directly and by accelerating the introduction of digital menus with such features. Prices decline with entry, in particular for high-valuation consumers who benefit from steeper quantity discounts. (JEL L11, L13, L96, L98, O33)
Zeros, Quality, and Space: Trade Theory and Trade Evidence
Authors: Baldwin Richard , Harrigan James
Published: April 2011

Bilateral, product-level data exhibit a number of strong patterns that can be used to evaluate international trade theories, notably the spatial incidence of “export zeros” (correlated with distance and importer size), and of export unit values (positively related to distance). We show that leading theoretical trade models fail to explain at least some of these facts, and propose a variant of the Melitz model that can account for all the facts. In our model, high quality firms are the most competitive, with heterogeneous quality increasing with firms' heterogeneous cost. (JEL F11, F14, F40)
Molecular mimicry between virus and host and its implications for dengue disease pathogenesis
Authors: Lin Yee-Shin , Yeh Trai-Ming , Lin Chiou-Feng , Wan Shu-Wen , Chuang Yung-Chun , Hsu Tan-Kuei , Liu Hsiao-Sheng , Liu Ching-Chuan , Anderson Robert , Lei Huan-Yao
Published: April 2011

Numerous infectious agents may trigger autoimmunity or even result in autoimmune diseases. Several mechanisms have been proposed for pathogen-triggered autoimmunity including molecular mimicry, cryptic antigens, epitope spreading, bystander activation and polyclonal activation. In the case of dengue virus infection which causes serious public health problems, the mechanisms regarding the pathogenesis of dengue hemorrhagic syndrome are not fully resolved. Our previous studies suggest a mechanism of molecular mimicry in which antibodies directed against dengue virus non-structural protein 1 (NS1) cross-react with human platelets and endothelial cells and cause their damage and dysfunction, which may be related to the clinical features of dengue disease. Several cell surface proteins recognized by patient serum samples and anti-NS1 antibodies have been identified. Based on proteomic studies and sequence analysis, the C-terminal region of dengue virus NS1 shows sequence homology with target proteins. In addition, different regions of dengue virus proteins including core, prM, E and NS1 proteins show sequence homology with different coagulatory molecules. As an example, the amino acid sequence 101–106 of E protein (WGNGCG) shows sequence homology with factors XI, X, IX, VII, II (thrombin), plasminogen and tissue plasminogen activator. Furthermore, single chain variable region against NS1 can interfere with fibrin formation, which leads to prolonged thrombin time. We hypothesize that molecular mimicry between dengue virus proteins and coagulatory molecules may induce cross-reactive autoantibodies that can interfere with coagulation activation. A molecular mimicry pathogenesis for dengue disease which involves cross-reactivity of dengue virus with human endothelial cells, platelets and coagulatory molecules is proposed.
Effect of Cement Kiln Dust and Rock Dust as Mineral Fillers on Bulk Specific Gravity of Fine Aggregates
Authors: Gupta Ashish , Zaman Musharraf , Laguros Joakim , Ghabchi Rouzbeh
Published: April 2011

The bulk specific gravity (Gsb) of aggregates is a critical parameter in the design of asphalt mixes. In the Superpave volumetric mix design, Gsb is used to determine the amount of asphalt binder absorbed by aggregates and the percentage of voids in the mineral aggregate. Problems with the current test methods of measuring the Gsb of fine aggregates, i.e., AASHTO T84 or ASTM C128, have been reported in some previous studies as well as in the current study. These standard test methods remain questionable under certain conditions: (1) When rough and angular as well as small and varying particle size distributions of fine aggregates are present and (2) when water reactive mineral fillers (passing No. 200 sieve) are added to fine aggregates. This study examined the addition of two selected mineral fillers, namely, Cement Kiln Dust (CKD) and rock dust, on the overall Gsb of fine aggregates by employing the AASHTO T84 and the CoreLok-Aggplus test procedures. When using the AASHTO T84 test method, the overall Gsb values reduce for both the additives. When using a newly developed CoreLok method, the Gsb values increased for rock dust up to 10 %, beyond which a reduction is observed. With CKD, the Gsb values show an increase for up to 6 % addition of it and then a decrease is observed. The data suggest that the AASHTO T84 test method may not be applicable in the presence of CKD due to the chemical reactions in the presence of water and the formation of cementitious products. A possibility of chemical reaction due to the presence of limestone in the rock dust and its fine gradation influence the results of the AASHTO T84 test method. Thus, use of the CoreLok method appears more appropriate in the presence of such reactive materials. To further analyze the problem, the specific surface area of fine aggregates and mineral fillers was measured using water vapor and nitrogen adsorption methods. This study also reveals that angular fine aggregates with a high angularity and rough surface texture pose significant difficulty in measuring Gsb by the AASHTO T84 test method.
Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients
Authors: Battezzati A , Mari A , Zazzeron L , Alicandro G , Claut L , Battezzati P M , Colombo C
Published: April 2011

Background

Cystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance.

Aim

To evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population.

Methods

A total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas β-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration.

Results

Fifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. β-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6 pmol/min per m2 per mM, P<0.001) and decreased significantly with age by −2.7 pmol/min per m2 per mM per year (confidence interval (CI) −4.5 to −0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower β-cell function and higher insulin sensitivity.

Conclusion

The major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining β-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.
PPARα agonists regulate lipid metabolism and nitric oxide production and prevent placental overgrowth in term placentas from diabetic rats
Authors: Martínez Nora , Kurtz Melisa , Capobianco Evangelina , Higa Romina , White Verónica , Jawerbaum Alicia
Published: April 2011

Maternal diabetes impairs fetoplacental metabolism and growth. Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor capable of regulating lipid metabolism and inflammatory pathways. In this study, we analyzed whether placental and fetal PPARα activation regulates lipid metabolism and nitric oxide (NO) production in term placentas from diabetic rats. Diabetes was induced by neonatal streptozotocin administration. On day 21 of pregnancy, placentas from control and diabetic rats were cultured in the presence of PPARα agonists (clofibrate and leukotriene B4 (LTB4)) for further evaluation of levels, synthesis, and peroxidation of lipids as well as NO production. Besides, on days 19, 20, and 21 of gestation, fetuses were injected with LTB4, and the placentas were explanted on day 21 of gestation for evaluation of placental weight and concentrations of placental lipids, lipoperoxides, and NO metabolites. We found that placentas from diabetic rats showed reduced PPARα concentrations. They presented no lipid overaccumulation but reduced lipid synthesis, parameters negatively regulated by PPARα activators. Lipid peroxidation and NO production, increased in placentas from diabetic rats, were negatively regulated by PPARα activators. Fetal PPARα activation in diabetic rats does not change placental lipid concentrations but reduced placental weight and NO production. In conclusion, PPARα activators regulate lipid metabolism and NO production in term placentas from diabetic rats, an activation that regulates placental growth and can partly be exerted by the developing fetus.
Parents' Attitudes Toward Pediatric Genetic Testing for Common Disease Risk
Authors: Tercyak Kenneth P. , Hensley Alford Sharon , Emmons Karen M. , Lipkus Isaac M. , Wilfond Benjamin S. , McBride Colleen M.
Published: April 2011

OBJECTIVE:

To describe parents' attitudes toward pediatric genetic testing for common, adult-onset health conditions and to identify factors underlying these attitudes.

PARTICIPANTS AND METHODS:

Parents (n = 219) enrolled in a large, group-practice health plan were offered a “multiplex” genetic test for susceptibility to 8 common, adult-onset health conditions and completed an online survey assessing attitudes and beliefs about the risks and benefits of the test for their child, their willingness to consider having their child tested, and other psychosocial variables.

RESULTS:

Parents viewed the benefits of pediatric testing to outweigh its risks (positive decisional balance) and were moderately interested in pediatric testing. Variables associated with positive decisional balance included greater interest in knowing about gene-health associations in their child, anticipation of less difficulty understanding their child's genetic health risks, and more positive emotional reactions to learning about their child's decreased health risks (adjusted R2 = 0.33, P < .0001). Similarly, variables associated with greater parental willingness to test were being a mother (versus being a father), greater perceived risk of diseases in their child, greater interest in knowing about gene-health relationships in their child, anticipating less difficulty learning about their child's genetic health risks, anticipating more positive emotional reactions to learning about their child's decreased health risks, and positive decisional balance (adjusted R2 = 0.57, P < .0001).

CONCLUSIONS:

As genetic susceptibility testing for common, adult-onset health conditions proliferates, pediatricians should anticipate parents' interest in testing children and be prepared to facilitate informed decision making about such testing.
Ethics of Resuscitation at Different Stages of Life: A Survey of Perinatal Physicians
Authors: Laventhal Naomi , Spelke M. Bridget , Andrews Bree , Larkin L. Knoll , Meadow William , Janvier Annie
Published: April 2011

OBJECTIVE:

We surveyed US neonatologists and high-risk obstetricians about preferences for resuscitation in ethically difficult situations to determine whether (1) their responses adhered to traditional ethical principles of best interests and patient autonomy and (2) physician specialty seemed to influence the response.

METHODS:

In an electronic survey, we presented 8 vignettes with varying prognoses for survival and long-term outcome. Respondents were provided outcome data for mortality and morbidity in each vignette. We asked whether resuscitation was in the patient's best interest and whether the physician would accede to requests for nonresuscitation.

RESULTS:

We analyzed surveys for 587 neonatologists and 108 high-risk obstetricians (15% overall response rate, 75% of web site visitors). There were no statistically significant differences in responses between the 2 physician subspecialty groups. As expected, in most cases there were inverse relationships between valuation of best interest and deferred resuscitation at the family's request. For example, for the oldest patient (an 80-year-old), 9.9% found resuscitation to be in the patient's best interest and 94.3% would allow nonresuscitation; for a 2-month-old, 93.9% found resuscitation to be in the patient's best interest and 24.5% would allow nonresuscitation. However, this pattern was not observed in the 2 newborn cases, in which resuscitation and nonresuscitation were both acceptable. In the triage scenario, the 7-year-old with cerebral palsy and acute trauma was consistently resuscitated first despite others having equivalent or better short- and long-term prognoses.

CONCLUSIONS:

On the basis of our results, physicians' decisions to resuscitate seem to be context-specific, rather than based on prognosis or consistent application of best-interest or autonomy principles. Despite their different professional perspectives, neonatologists and high-risk obstetricians seemed to converge on these judgments.
Ensuring the Optimal Safety of Licensed Vaccines: A Perspective of the Vaccine Research, Development, and Manufacturing Companies
Authors: Kanesa-thasan Niranjan , Shaw Alan , Stoddard Jeffrey J. , Vernon Thomas M.
Published: April 2011

Vaccine safety is increasingly a focus for the general public, health care providers, and vaccine manufacturers, because the efficacy of licensed vaccines is accepted as a given. Commitment to ensuring safety of all vaccines, including childhood vaccines, is addressed by the federal government, academia, and industry. Safety activities conducted by the vaccine research, development, and manufacturing companies occur at all stages of product development, from selection and formulation of candidate vaccines through postlicensure studies and surveillance of adverse-event reports. The contributions of multiple interacting functional groups are required to execute these tasks through the life cycle of a product. We describe here the safeguards used by vaccine manufacturers, including specific examples drawn from recent experience, and highlight some of the current challenges. Vaccine-risk communication becomes a critical area for partnership of vaccine companies with government, professional associations, and nonprofit advocacy groups to provide information on both benefits and risks of vaccines. The crucial role of the vaccine companies in ensuring the optimal vaccine-safety profile, often overlooked, will continue to grow with this dynamic arena.
Statistical, Epidemiological, and Risk-Assessment Approaches to Evaluating Safety of Vaccines Throughout the Life Cycle at the Food and Drug Administration
Authors: Ball Robert , Horne Dale , Izurieta Hector , Sutherland Andrea , Walderhaug Mark , Hsu Henry
Published: April 2011

The public health community faces increasing demands for improving vaccine safety while simultaneously increasing the number of vaccines available to prevent infectious diseases. The passage of the US Food and Drug Administration (FDA) Amendment Act of 2007 formalized the concept of life-cycle management of the risks and benefits of vaccines, from early clinical development through many years of use in large numbers of people. Harnessing scientific and technologic advances is necessary to improve vaccine-safety evaluation. The Office of Biostatistics and Epidemiology in the Center for Biologics Evaluation and Research is working to improve the FDA's ability to monitor vaccine safety by improving statistical, epidemiologic, and risk-assessment methods, gaining access to new sources of data, and exploring the use of genomics data. In this article we describe the current approaches, new resources, and future directions that the FDA is taking to improve the evaluation of vaccine safety.
Internet-Based Reporting to the Vaccine Adverse Event Reporting System: A More Timely and Complete Way for Providers to Support Vaccine Safety
Authors: Haber Penina , Iskander John , Walton Kimp , Campbell Scott R. , Kohl Katrin S.
Published: April 2011

BACKGROUND:

On March 22, 2002, Internet-based reports (IBRs) were added to the Vaccine Adverse Event Reporting System (VAERS) to allow rapid, expedited reporting of adverse events (AEs) in anticipation of wider use of counter-bioterrorism vaccines such as those against smallpox and anthrax.

OBJECTIVES:

To evaluate the impact of IBRs on the timeliness and completeness of vaccine AE reporting.

METHODS:

To evaluate timeliness and completeness, we compared the proportions of IBRs with non–Internet-based reports (NIBRs). Report interval was analyzed for timeliness and age at vaccination, birth date, and onset date for report completeness. To evaluate the impact of the smallpox vaccination program, we compared smallpox vaccine reports separately. Because influenza vaccine is the most widely used vaccine in adults each year, we compared influenza vaccine reports separately.

RESULTS:

During the study period, VAERS received 54 364 NIBRs (85.8%) and 9008 IBRs (14.2%). Sixteen percent (1455) of IBRs followed smallpox vaccination. Overall, for all vaccines and for smallpox vaccine alone, IBRs had a greater proportion of completeness and a shorter report interval. The proportion of most frequently reported AEs did not differ between IBRs and NIBRs. A higher proportion of adults (18–64 years old) who received influenza vaccine chose to complete an IBR (62% vs 48%).

CONCLUSIONS:

The improved timeliness and completeness of IBRs allow VAERS to more rapidly detect new or rare vaccine AEs. This important advantage is critical in times of increased public concern about vaccine safety. Clinical vaccine providers should be aware of VAERS and use IBRs whenever feasible to report vaccine AEs.
Immunization Safety in US Print Media, 1995–2005
Authors: Hussain Hamidah , Omer Saad B. , Manganello Jennifer A. , Kromm Elizabeth Edsall , Carter Terrell C. , Kan Lilly , Stokley Shannon , Halsey Neal A. , Salmon Daniel A.
Published: April 2011

OBJECTIVE:

To identify and describe vaccine safety in US newspaper articles.

METHODS:

Articles (1147) from 44 states and Washington, DC, between January 1, 1995, and July 15, 2005, were identified by using the search terms “immunize or vaccine” and “adverse events or safety or exemption or danger or risk or damage or injury or side effect” and were coded by using a standardized data-collection instrument.

RESULTS:

The mean number of vaccine-safety articles per state was 26. Six (not mutually exclusive) topics were identified: vaccine-safety concerns (46%); vaccine policy (44%); vaccines are safe (20%); immunizations are required (10%); immunizations are not required (8%); and state/school exemption (8%). Three spikes in the number of newspaper articles about vaccine-safety issues were observed: in 1999 regarding rotavirus vaccine and in 2002 and 2003 regarding smallpox vaccine. Excluding articles that referred to rotavirus and smallpox vaccines, 37% of the articles had a negative take-home message.

CONCLUSION:

Ongoing monitoring of news on vaccine safety may help the content and framing of vaccine-safety messages.
Sources and Perceived Credibility of Vaccine-Safety Information for Parents
Authors: Freed Gary L. , Clark Sarah J. , Butchart Amy T. , Singer Dianne C. , Davis Matthew M.
Published: April 2011

CONTEXT:

The source of health information can have an impact on the manner and frequency of its use. In the arena of vaccine safety, a variety of sources promulgate information from very different perspectives. The spectrum runs from traditional sources such as public health officials and physicians to nontraditional sources, such as celebrities.

OBJECTIVE:

To assess what proportion of parents trust vaccine information from different sources and whether different groups of parents vary in their trust of such information.

METHODS:

In January 2009, as part of a larger study of parents and nonparents, 2521 online surveys were fielded to a nationally representative sample of parents of children aged ≤17 years. The main outcome measure was the source credibility of vaccine-safety information used by parents.

RESULTS:

The response rate was 62%. Parents reported trusting their children's doctor for vaccine-safety information most often (76% endorsed a lot of trust), followed by other health care providers (26%), government vaccine experts/officials (23%), and family and friends (15%). In contrast, celebrities were trusted a lot by 2% of the respondents and not at all by 76% of the respondents. Levels of trust in specific sources of vaccine-safety information varied significantly by gender (women > men) and race/ethnicity (Hispanics > other groups).

CONCLUSIONS:

Although most parents place a lot of trust in their child(ren)'s physician, parents' trust in non–health professional sources for such information should not be discounted. Those who design public health efforts to provide evidence-based information must recognize that different strategies may be required to reach some groups of parents who use other information sources.
Familial Aggregation of Autoimmune Disease in Juvenile Dermatomyositis
Authors: Niewold Timothy B. , Wu Stephanie C. , Smith Molly , Morgan Gabrielle A. , Pachman Lauren M.
Published: April 2011

OBJECTIVE:

Familial aggregation of autoimmune diseases likely reflects shared pathogenic factors between different diseases. Familial aggregation of autoimmunity has not been examined in juvenile dermatomyositis. Interferon-α is thought to be a pathogenic factor in both systemic lupus erythematosus and juvenile dermatomyositis, and we have previously demonstrated familial aggregation of serum interferon-α.

METHODS:

Family histories were obtained from 304 families of children with juvenile dermatomyositis via 3-generation structured interviews performed by the same person. Rates of autoimmune disease in families of children with juvenile dermatomyositis were compared with published population rates. Serum interferon-α, tumor necrosis factor-α, and neopterin were measured using standard techniques.

RESULTS:

A total of 51% of families of children with juvenile dermatomyositis reported at least 1 additional member affected by an autoimmune disease. In particular, both type 1 diabetes and systemic lupus erythematosus were significantly more common than would be expected (odds ratio >5, P ≤ 1 × 10−7 for both). Pedigree analysis showed particularly strong familial clustering of systemic lupus erythematosus with little decrease in incidence across generations, suggesting the possibility of rare causal genes with large effect. Untreated subjects with juvenile dermatomyositis with a family history of systemic lupus erythematosus had higher serum interferon-α than those who did not (P = .047).

CONCLUSIONS:

We find strong familial aggregation of specific autoimmune diseases in families of children with juvenile dermatomyositis, suggesting that these conditions share pathogenic factors. Higher serum interferon-α in juvenile dermatomyositis patients with a family history of systemic lupus erythematosus suggesting that interferon-α is one such shared factor.
Computerized Physician Order Entry With Decision Support Decreases Blood Transfusions in Children
Authors: Adams Eloa S. , Longhurst Christopher A. , Pageler Natalie , Widen Eric , Franzon Deborah , Cornfield David N.
Published: April 2011

OBJECTIVE:

Timely provision of evidence-based recommendations through computerized physician order entry with clinical decision support may improve use of red blood cell transfusions (RBCTs).

METHODS:

We performed a cohort study with historical controls including inpatients admitted between February 1, 2008, and January 31, 2010. A clinical decision-support alert for RBCTs was constructed by using current evidence. RBCT orders resulted in assessment of the patient's medical record with prescriber notification if parameters were not within recommended ranges. Primary end points included the average pretransfusion hemoglobin level and the rate of RBCTs per patient-day.

RESULTS:

In total, 3293 control discharges and 3492 study discharges were evaluated. The mean (SD) control pretransfusion hemoglobin level in the PICU was 9.83 (2.63) g/dL (95% confidence interval [CI]: 9.65–10.01) compared with the study value of 8.75 (2.05) g/dL (95% CI: 8.59–8.90) (P < .0001). The wards' control value was 7.56 (0.93) g/dL (95% CI: 7.47–7.65), the study value was 7.14 (1.01) g/dL (95% CI: 6.99–7.28) (P < .0001). The control PICU rate of RBCTs per patient-day was 0.20 (0.11) (95% CI: 0.13–0.27), the study rate was 0.14 (0.04) (95% CI: 0.11–0.17) (P = .12). The PICU's control rate was 0.033 (0.01) (95% CI: 0.02–0.04), and the study rate was 0.017 (0.007) (95% CI: 0.01–0.02) (P < .0001). There was no difference in mortality rates across all cohorts.

CONCLUSIONS:

Implementation of clinical decision-support alerts was associated with a decrease in RBCTs, which suggests improved adoption of evidence-based recommendations. This strategy might be widely applied to promote timely adoption of scientific evidence.
Negative Effects of Alcohol Intake and Estrogen Deficiency Combination on Osseointegration in a Rat Model
Authors: de Deco Camila Porto , da Silva Marchini Adriana Mathias Pereira , Bárbara Mary Anne Moreira , de Vasconcellos Luana Marotta Reis , da Rocha Rosilene Fernandes , Marchini Leonardo
Published: April 2011

Alcohol intake and estrogen deficiency can both affect bone physiology and have shown to have an adverse effect on dental implant therapy. However, the combination of both factors on osseointegration is unknown. The aim of this study was to evaluate osseointegration in rats fed with alcohol and presenting induced estrogen deficiency. Ninety-six female rats were divided according to diet and hormonal condition into 6 groups as follows: group Sh-W: sham (simulated ovariectomy) control, food and water ad libitum; group Sh-Et: sham, food and 20% ethanol solution ad libitum; group Sh-Su: sham, food and sucrose solution controlled to ensure an isocaloric diet in relation to Sh-Et; group Ov-W: ovariectomy, food and water ad libitum; group Ov-Et: ovariectomy, food and 20% ethanol solution ad libitum; and group Ov-Su: ovariectomy, food and sucrose solution controlled to ensure an isocaloric diet as Ov-Et. The groups were subdivided according to time of euthanasia: 30 and 45 days after placement of implants. Implant surgery was performed 1 month after ovariectomy or sham. After euthanasia, the femurs were removed and evaluated by histomorphometry. Groups Ov-Et and Ov-Su showed the lowest percentage of bone-to-implant contact. The combination of alcohol intake and estrogen deficiency, and the combination of estrogen deficiency and reduced ingestion of food can negatively affect osseointegration in rats.