bluuebunny/crossref_metadata_2025 huggingface dataset:
Increase of body mass index in a tight controlled methotrexate‐based strategy with prednisone in early rheumatoid arthritis: Side effect of the prednisone or better control of disease activity?
Authors: Jurgens Maud S. , Jacobs Johannes W. G. , Geenen Rinie , Bossema Ercolie R. , Bakker Marije F. , Bijlsma Johannes W. J. , van Albada‐Kuipers Iet A. , Ehrlich Johan C. , Lafeber Floris P. J. G. , Welsing Paco M. J. ,   on behalf of The Utrecht Arthritis Cohort Study Group
Published: November 2012

Objective

To clarify whether increase of body weight in patients with early rheumatoid arthritis (RA) upon administration of prednisone is a side effect of prednisone or a result of better control of disease activity, we examined the association of prednisone and disease activity with a subsequent change in body mass index (BMI).

Methods

In the Computer Assisted Management in Early Rheumatoid Arthritis Trial‐II, patients ages ≥18 years with early RA (disease duration <1 year and no prior use of disease‐modifying antirheumatic drugs) had been randomized to a methotrexate (MTX)–based tight control strategy with either 10 mg of prednisone (MTX + prednisone) or placebo (MTX + placebo). The MTX + prednisone group had lower disease activity, but gained more weight than the MTX + placebo group (mean ± SD 2.9 ± 4.2 kg versus 1.3 ± 5.3 kg; P = 0.03). Data from patients with monthly measurements of disease activity (Disease Activity Score in 28 joints [DAS28]) and BMI were analyzed with a longitudinal regression (mixed model) analysis with BMI as the dependent variable and treatment strategy and DAS28 as the independent variables, correcting for baseline BMI and possible confounders (sex, age, and rheumatoid factor status).

Results

There was no independent association of glucocorticoid therapy with a change in BMI, but a lower DAS28 was associated with an increased BMI 6 months later. The association of the DAS28 with BMI was most strongly present in postmenopausal women. Clinical cutoff points showed a clear association between DAS28 level and the change in BMI 6 months later.

Conclusion

Weight gain during treatment with prednisone seems attributable to a reduction of disease activity and is probably, at least partly, regained weight.
Adalimumab treatment in patients with rheumatoid arthritis with renal insufficiency
Authors: Sumida Keiichi , Ubara Yoshifumi , Suwabe Tatsuya , Hayami Noriko , Hiramatsu Rikako , Hasegawa Eiko , Yamanouchi Masayuki , Hoshino Junichi , Sawa Naoki , Takaichi Kenmei
Published: November 2012

Objective

To elucidate the safety of adalimumab for rheumatoid arthritis (RA) patients with renal insufficiency, including those with end‐stage renal disease undergoing hemodialysis.

Methods

Sixty‐five RA patients, including 2 patients undergoing hemodialysis, treated with adalimumab in our hospital from December 1, 2008 to June 30, 2011 were retrospectively analyzed. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) calculated from the Cockcroft‐Gault formula at the start and end of followup after adalimumab treatment. The proportion of the patients who discontinued or switched adalimumab treatment and the change of the eGFR were compared between patients with (n = 39) and without (n = 26) renal insufficiency, defined as an eGFR <60 ml/minute/1.73 m2.

Results

There was no significant difference between the 2 groups in the proportion of the patients who discontinued or switched adalimumab treatment (51.3% versus 50.0%; P = 0.53). The mean ± SD changes of eGFR were from 41.6 ± 13.3 to 43.4 ± 17.9 ml/minute/1.73 m2 in patients with renal insufficiency and from 83.6 ± 17.5 to 83.0 ± 16.8 ml/minute/1.73 m2 in patients without renal insufficiency, and the differences in each group were not statistically significant (P = 0.92 and P = 0.78, respectively). No severe infections or other severe adverse events were observed in either group during adalimumab treatment.

Conclusion

Our data indicate that adalimumab does not worsen renal function and has no serious adverse events even for RA patients with renal insufficiency, including those undergoing hemodialysis, and suggest that it could be a potential therapeutic option for them.
Racial and ethnic differences in physical activity guidelines attainment among people at high risk of or having knee osteoarthritis
Authors: Song Jing , Hochberg Marc C. , Chang Rowland W. , Hootman Jennifer M. , Manheim Larry M. , Lee Jungwha , Semanik Pamela A. , Sharma Leena , Dunlop Dorothy D. ,   for the Osteoarthritis Initiative Investigators
Published: November 2012

Objective

This cross‐sectional study examined racial/ethnic differences in meeting the 2008 United States Department of Health and Human Services Physical Activity Guidelines aerobic component (≥150 moderate‐to‐vigorous minutes/week in bouts of ≥10 minutes) among persons with or at risk of radiographic knee osteoarthritis (RKOA).

Methods

We evaluated African American versus white differences in guideline attainment using multiple logistic regression, adjusting for sociodemographic (age, sex, site, income, and education) and health factors (comorbidity, depressive symptoms, overweight/obesity, and knee pain). Our analyses included adults ages 49–84 years who participated in accelerometer monitoring at the Osteoarthritis Initiative 48‐month visit (n = 1,142 with RKOA and n = 747 at risk of RKOA).

Results

Two percent of African Americans and 13.0% of whites met the guidelines. For adults with and at risk of RKOA, significantly lower rates of guidelines attainment among African Americans compared to whites were partially attenuated by health factor differences, particularly overweight/obesity and knee pain (with RKOA: adjusted odds ratio [OR] 0.24, 95% confidence interval [95% CI] 0.08–0.72; at risk of RKOA: OR 0.28, 95% CI 0.07–1.05).

Conclusion

Despite known benefits from physical activity, attainment of the physical activity guidelines among persons with and at risk of RKOA was low. African Americans were 72–76% less likely than whites to meet the guidelines. Culturally relevant interventions and environmental strategies in the African American community targeting overweight/obesity and knee pain may reduce future racial/ethnic differences in physical activity and improve health outcomes.
Assessment of SpondyloArthritis International Society criteria for axial spondyloarthritis in chronic back pain patients with a high prevalence of HLA–B27
Authors: Bakland Gunnstein , Alsing Rikke , Singh Kulbir , Nossent Johannes C.
Published: November 2012

Objective

The Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (SpA) allow SpA classification of HLA–B27–positive patients if ≥2 specific clinical SpA features are present. We investigated the performance of these clinical ASAS criteria in a population with a high prevalence of HLA–B27.

Methods

A total of 807 persons reporting chronic back pain (CBP) lasting for >4 weeks during a population survey underwent a clinical, laboratory, and radiologic evaluation. The ASAS criteria for axial SpA were then used to determine classification status.

Results

Only 332 patients (41% of all CBP patients) fulfilled the prerequisite ASAS definitions for CBP (duration of ≥3 months and onset at age <45 years). In this ASAS‐defined CBP cohort (51% women, CBP onset at age 27.2 years, 17% HLA–B27 positive), ASAS classification criteria for axial SpA were met by 8.4% of patients. Radiographic SpA by the modified New York criteria was present in 2.4%, while 6% fulfilled the clinical arm of the ASAS SpA criteria only. One‐fifth of patients with clinical SpA developed radiographic evidence of SpA after a median of 8 years.

Conclusion

Application of the clinical ASAS classification criteria in an area with a high prevalence of HLA–B27 leads to significant increases in the prevalence of axial SpA compared to radiologic SpA among CBP patients. This increase in the prevalence of disease is likely to have significant ramifications for patient management and health care systems.
Excess body weight and four‐year function outcomes: Comparison of African Americans and whites in a prospective study of osteoarthritis
Authors: Colbert Carmelita J. , Almagor Orit , Chmiel Joan S. , Song Jing , Dunlop Dorothy , Hayes Karen W. , Sharma Leena
Published: November 2012

Objective

We evaluated whether African Americans in the Osteoarthritis Initiative (OAI) have a greater risk (versus whites) of poor 4‐year function outcome within strata defined by sex, body mass index (BMI), and waist circumference.

Methods

Using Western Ontario and McMaster Universities Osteoarthritis Index function, 20‐meter walk, and chair stand performance, poor outcome was defined as moving into a worse function group or remaining in the 2 worst groups over 4 years. Logistic regression was used to evaluate the relationship between racial group and outcome within each stratum, adjusting for age, education, and income, and then further adjusting for BMI, comorbidity, depressive symptoms, physical activity, knee pain, and osteoarthritis (OA) severity.

Results

In 3,695 persons with or at higher risk for knee OA, higher BMI and large waist circumference were each associated with poor outcome. Among women with high BMI and among women with large waist circumference, African Americans were at greater risk for poor outcome by every measure, adjusting for age, education, and income. From fully adjusted models, potential explanatory factors included income, comorbidity, depressive symptoms, pain, and disease severity. Findings were less consistent for men, emerging only for the 20‐meter walk or chair stand outcomes, and potentially explained by age and knee pain.

Conclusion

Among OAI women with excess body weight, African Americans are at greater risk than whites for poor 4‐year outcome. Modifiable factors that may help to explain these findings in the OAI include comorbidity, depressive symptoms, and knee pain. Targeting such factors, while supporting weight loss, may help to lessen the outcome disparity between African American and white women.
Elderly‐ versus younger‐onset rheumatoid arthritis: Higher levels of ultrasound‐detected inflammation despite comparable clinical disease activity
Authors: Dejaco Christian , Duftner Christina , Wipfler‐Freissmuth Edith , Weiss Helmut , Schneider Thomas , Schirmer Michael
Published: November 2012

Objective

To compare ultrasound‐verified joint inflammation between elderly‐onset rheumatoid arthritis (EORA) and younger‐onset rheumatoid arthritis (YORA) patients.

Methods

We conducted a retrospective analysis of 145 consecutive rheumatoid arthritis patients routinely assessed by sonography of wrists, metacarpophalangeal joints, and proximal interphalangeal joints, including semiquantitative scoring of synovial hypertrophy/effusion (SH/E) and power Doppler (PD) signals. Global ultrasound (GU) scores were calculated adding SH/E and PD results. EORA was defined by disease onset at age ≥60 years. Number of tender joints and swollen joints, global assessment of disease activity by physician or patient, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI) scores were recorded. Respective values for disease activity were accounted for in group comparisons using SPSS statistical software (version 18.0).

Results

Seventy patients were diagnosed with EORA (mean ± SD age 71.0 ± 7.3 years, 81.4% women) and 75 patients with YORA (mean ± SD age 46.8 ± 10.2 years, 86.7% women). EORA patients had higher GU scores (median 18.5 [interquartile range (IQR) 17.0] versus 12.0 [IQR 15.0], P = 0.009) and SH/E scores (median 12.0 [IQR 10.0] versus median 9.0 [IQR 9.0], P = 0.004) than patients with YORA. Patients with EORA were more likely to show PD signals in at least 1 joint than YORA patients (85% versus 72%; odds ratio 3.9 [95% confidence interval 1.3–11.5], P = 0.015). DAS28, CDAI, and SDAI scores did not differ between the groups. The sonographic pattern of joint involvement was similar in both groups, with active inflammation most commonly presenting at the wrists.

Conclusion

Ultrasound examination indicated higher inflammatory burden in EORA patients than in YORA patients despite similar clinical disease activity.
Impact of obesity and hypertriglyceridemia on gout development with or without hyperuricemia: A prospective study
Authors: Chen Jiunn‐Horng , Pan Wen‐Harn , Hsu Chih‐Cheng , Yeh Wen‐Ting , Chuang Shao‐Yuan , Chen Pin‐Yu , Chen Hui‐Chen , Chang Chwen‐Tzuei , Huang Wei‐Lun
Published: November 2012

Objective

Hyperuricemia is the most important risk factor for the development of gout; however, not all patients with hyperuricemia develop gout, and patients experiencing a gout attack are not necessarily found to have hyperuricemia. We hypothesized that the interactions between serum uric acid (sUA) and other potential metabolic comorbidities increase the risk of gout development.

Methods

A prospective study was conducted to link baseline metabolic profiles from the MJ Health Screening Center to gout outcomes extracted from the Taiwan National Health Insurance database. A Cox proportional hazards model was used to assess the metabolic risks for incident gout stratified by hyperuricemia status (sUA level >7 mg/dl or not).

Results

During a mean followup period of 6.45 years (261,500 person‐years), 1,189 patients with clinical gout (899 men, 202 women ages >50 years, and 88 women ages ≤50 years) were identified among the 40,513 examinees. The multivariate adjusted hazard ratios (HRs) of hyperuricemia for gouty arthritis were 5.80 (95% confidence interval [95% CI] 4.93–6.81) in men and 4.37 (95% CI 3.38–5.66) in women. Hypertriglyceridemia (triglyceride level >150 mg/dl) was found as an independent risk factor, with HRs of 1.38 (95% CI 1.18–1.60) in men with hyperuricemia and 1.40 (95% CI 1.02–1.92) in men without hyperuricemia. General obesity (body mass index >27 kg/m2) was independently associated with gout in older women, with HRs of 1.72 (95% CI 1.15–2.56) in women with hyperuricemia and 2.19 (95% CI 1.47–3.26) in women without hyperuricemia.

Conclusion

General obesity in women and hypertriglyceridemia in men may potentiate an sUA effect for gout development. Further investigation is needed.
Self‐oscillation loop design and measurement for an MEMS resonant accelerometer
Authors: Heng Liu , Li Meng Rui
Published: November 2012

This paper provides detailed information about the dynamic model and closed‐loop control theory of resonant accelerometer based on electrostatic stiffness. After the resonant accelerometer principle based on electrostatic stiffness has been analyzed, a dynamic model was built. According to the requirement of constant stable vibration amplitude for a different applied acceleration, control equations based on self‐sustained oscillation loop technology were also developed for the whole system. By applying the averaging method, the system behaviors were analyzed, and equilibria for the vibration amplitude were achieved. Theoretical analysis and simulation showed that the vibration amplitude became stable and attractive only when the stable criterion was satisfied. Using a PI controller, constant level vibrating amplitude can be achieved when the input acceleration changes. A resonant accelerometer was fabricated using bulk‐silicon dissolved process. Under the aforementioned conditions, the accelerometer was driven and tested using a self‐sustained oscillation loop. When the sensing voltage was 5 V, the sensitivity was 58 Hz/g, and the resolution was 3.5 mg for a single vibrating beam. Copyright © 2012 John Wiley & Sons, Ltd.
High‐Performance n‐Channel Thin‐Film Field‐Effect Transistors Based on a Nanowire‐Forming Polymer
Authors: Hahm Suk Gyu , Rho Yecheol , Jung Jungwoon , Kim Se Hyun , Sajoto Tissa , Kim Felix S. , Barlow Stephen , Park Chan Eon , Jenekhe Samson A. , Marder Seth R. , Ree Moonhor
Published: November 2012

A new electrontransport polymer, poly{[N,N′‐dioctylperylene‐3,4,9,10‐bis(dicarboximide)‐1,7(6)‐diyl]‐alt‐[(2,5‐bis(2‐ethyl‐hexyl)‐1,4‐phenylene)bis(ethyn‐2,1‐diyl]} (PDIC8‐EB), is synthesized. In chloroform, the polymer undergoes self‐assembly, forming a nanowire suspension. The nanowire's optical and electrochemical properties, morphological structure, and field‐effect transistor (FET) characteristics are investigated. Thin films fabricated from a PDIC8‐EB nanowire suspension are composed of ordered nanowires and ordered and amorphous non‐nanowire phases, whereas films prepared from a homogeneous PDIC8‐EB solution consist of only the ordered and amorphous non‐nanowire phases. X‐ray scattering experiments suggest that in both nanowires and ordered phases, the PDIC8 units are laterally stacked in an edge‐on manner with respect to the film plane, with full interdigitation of the octyl chains, and with the polymer backbones preferentially oriented within the film plane. The ordering and orientations are significantly enhanced through thermal annealing at 200 °C under inert conditions. The polymer film with high degree of structural ordering and strong orientation yields a high electron mobility (0.10 ± 0.05 cm2V−1s−1), with a high on/off ratio (3.7 × 106), a low threshold voltage (8 V), and negligible hysteresis (0.5 V). This study demonstrates that the polymer in the nanowire suspension provides a suitable material for fabricating the active layers of high‐performance n‐channel FET devices via a solution coating process.
A Spatiotemporal Analysis of Agricultural Prices: An Application to Colombian Data
Authors: Iregui Ana María , Otero Jesús
Published: November 2012

This study focusses on whether the geographical separation of markets constitutes a factor that helps explain the dynamics of agricultural prices. To do this, the authors employ a highly disaggregated dataset for Colombia that consists of weekly observations on wholesale prices for 18 agricultural products traded in markets scattered around the country. The sample period spans almost a decade. According to their results, which are based on generalized impulse response functions, distance (and thus transportation costs) is a factor that helps explain the speed at which prices adjust to shocks in other locations, thus confirming that price adjustments take longer for markets farther apart.
Seizure characteristics in Pallister–Killian syndrome
Authors: Candee Meghan S. , Carey John C. , Krantz Ian D. , Filloux Francis M.
Published: November 2012

Pallister–Killian syndrome (PKS) is a congenital disorder attributed to supernumerary isochromosome 12p mosaicism. Craniofacial dysmorphism, learning impairment and seizures are considered cardinal features. However, little is known regarding the seizure and epilepsy patterns in PKS. To better define the prevalence and spectrum of seizures in PKS, we studied 51 patients (39 male, 12 female; median age 4 years and 9 months; age range 7 months to 31 years) with confirmed 12p tetrasomy. Using a parent‐based structured questionnaire, we collected data regarding seizure onset, frequency, timing, semiology, and medication therapy. Patients were recruited through our practice, at PKS Kids family events, and via the PKS Kids website. Epilepsy occurred in 27 (53%) with 23 (85%) of those with seizures having seizure onset prior to 3.5 years of age. Mean age at seizure onset was 2 years and 4 months. The most common seizure types were myoclonic (15/27, 56%), generalized convulsions (13/27, 48%), and clustered tonic spasms (similar to infantile spasms; 8/27, 30%). Thirteen of 27 patients with seizures (48%) had more than one seizure type with 26 out of 27 (96%) ever having taken antiepileptic medications. Nineteen of 27 (70%) continued to have seizures and 17/27 (63%) remained on antiepileptic medication. The most commonly used medications were: levetiracetam (10/27, 37%), valproic acid (10/27, 37%), and topiramate (9/27, 33%) with levetiracetam felt to be “most helpful” by parents (6/27, 22%). Further exploration of seizure timing, in‐depth analysis of EEG recordings, and collection of MRI data to rule out confounding factors is warranted. © 2012 Wiley Periodicals, Inc.
Epilepsy due to 20q13.33 subtelomere deletion masquerading as pyridoxine‐dependent epilepsy
Authors: Mefford Heather C. , Cook Joseph , Gospe Sidney M.
Published: November 2012

A cause of antiepileptic medication resistant seizures presenting in neonates and young infants is pyridoxine‐dependent epilepsy (PDE), an organic aciduria, which is due to recessive mutations in the ALDH7A1 gene, resulting in deficiency of antiquitin. Since the discovery of molecular basis of this disorder, a few patients have been reported with a similar clinical phenotype but without evidence of antiqutin dysfunction. We report on a patient who had carried a clinical diagnosis of PDE for 7 years, but who was than shown to have normal ALDH7A1 sequencing and the absence of biomarkers characteristic of this familial epilepsy. Array comparative genomic hybridization (CGH) demonstrated a 1.5‐Mb terminal deletion of the long arm of chromosome 20, which included deletion of the KCNQ2 and CHRNA4 genes, both of which have been associated with specific epilepsy syndromes. We suggest that this boy's neonatal epilepsy and neurodevelopmental disabilities are secondary to this deletion and that his clinical response to pyridoxine was coincidental. This patient's history emphasizes the utility of array CGH in the evaluation of children with epilepsy of unknown etiology. © 2012 Wiley Periodicals, Inc.
Clinical geneticists' views of VACTERL/VATER association
Authors: Solomon Benjamin D. , Bear Kelly A. , Kimonis Virginia , de Klein Annelies , Scott Daryl A. , Shaw‐Smith Charles , Tibboel Dick , Reutter Heiko , Giampietro Philip F.
Published: November 2012

VACTERL association (sometimes termed “VATER association” depending on which component features are included) is typically defined by the presence of at least three of the following congenital malformations, which tend to statistically co‐occur in affected individuals: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo‐Esophageal fistula, Renal anomalies, and Limb abnormalities. Although the clinical criteria for VACTERL association may appear to be straightforward, there is wide variability in the way clinical geneticists define the disorder and the genetic testing strategy they use when confronted with an affected patient. In order to describe this variability and determine the most commonly used definitions and testing modalities, we present the results of survey responses by 121 clinical geneticists. We discuss the results of the survey responses, provide a literature review and commentary from a group of physicians who are currently involved in clinical and laboratory‐based research on VACTERL association, and offer an algorithm for genetic testing in patients with this association. © 2012 Wiley Periodicals, Inc.
Clinical and radiological features of Japanese patients with a severe phenotype due to CASK mutations
Authors: Takanashi Jun‐ichi , Okamoto Nobuhiko , Yamamoto Yuto , Hayashi Shin , Arai Hiroshi , Takahashi Yukitoshi , Maruyama Koichi , Mizuno Seiji , Shimakawa Shuichi , Ono Hiroaki , Oyanagi Reiki , Kubo Satomi , Barkovich A. James , Inazawa Johji
Published: November 2012

Heterozygous loss of function mutations of CASK at Xp11.4 in females cause severe intellectual disability (ID) and microcephaly with pontine and cerebellar hypoplasia (MICPCH). However, the longitudinal clinical and radiological course of affected patients, including patterns of postnatal growth, has not been described. Neurodevelopmental and imaging information was retrospectively accrued for 16 Japanese (15 female and 1 male) patients with ID and MICPCH associated with CASK mutations. All records were analyzed; patient age ranged from 2 to 16 years at the time of the most recent examinations. The growth pattern, neurological development, neurological signs/symptoms, and facial features were similar in the 15 female patients. Their head circumference at birth was within the normal range in about half, and their height and weight were frequently normal. This was followed by early development of severe microcephaly and postnatal growth retardation. The patients acquired head control almost normally between 3 and 6 months, followed by motor delay. More than half of the female patients had epilepsy. Their MRIs showed microcephaly, brainstem, and cerebellar hypoplasia in early infancy, and a normal or large appearing corpus callosum. The male patient showed a more severe clinical phenotype. These uniform clinical and radiological features should facilitate an early diagnosis and be useful for medical care of females with ID and MICPCH associated with CASK mutations. © 2012 Wiley Periodicals, Inc.
Developmental and behavioral characteristics of individuals with Pallister–Killian syndrome
Authors: Kostanecka Anna , Close Lindsey B. , Izumi Kosuke , Krantz Ian D. , Pipan Mary
Published: November 2012

Pallister–Killian syndrome is a sporadic disorder caused by the presence of mosaic tetrasomy of the short arms of chromosome 12. Case reports of children with Pallister–Killian syndrome have described a range of developmental and behavioral outcomes, but no systematic studies of these outcomes exist. The objective of this study was to describe developmental and behavioral characteristics of individuals with Pallister–Killian syndrome participating in a national meeting of families and their affected children. Sixteen individuals with Pallister–Killian syndrome, ages 16 months to 19 years, were studied using questionnaires and direct interview. Among the 16 patients enrolled in the study, 3 probands were between 16 and 19 months, and had severe developmental delay. Among the rest of the 13 probands older than 24 months, 11 children had a developmental level of less than 8 months age equivalent. They were non‐ambulatory, non‐verbal, and passive, requiring extensive assistance in daily living. There were two higher functioning children who were ambulatory, and verbal. One of these children met criteria for Autism on the Autism Diagnostic Interview‐Revised. Thus, although most individuals with Pallister–Killian syndrome studied showed profound intellectual disability and sensory impairments, individuals with Pallister–Killian syndrome can have mild to moderate intellectual disability. Therefore, in individuals with physical examination findings of Pallister–Killian syndrome, formal diagnostic testing should be considered, even in individuals with mild to moderate intellectual disability. Further studies will be needed to determine if these higher functioning children with Pallister–Killian syndrome are at increased risk for autism. © 2012 Wiley Periodicals, Inc.
Head‐to‐head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: Findings of a phase IIIb, multinational, prospective, randomized study
Authors: Weinblatt Michael E. , Schiff Michael , Valente Robert , van der Heijde Désirée , Citera Gustavo , Zhao Cathy , Maldonado Michael , Fleischmann Roy
Published: November 2012

Objective

There is a need for comparative studies to provide evidence‐based treatment guidance for biologic agents in rheumatoid arthritis (RA). Therefore, this study was undertaken as the first head‐to‐head comparison of subcutaneous (SC) abatacept and SC adalimumab, both administered along with background methotrexate (MTX), for the treatment of RA.

Methods

Patients with active RA who were naive to treatment with biologic agents and had an inadequate response to MTX were randomly assigned to receive 125 mg SC abatacept weekly or 40 mg SC adalimumab biweekly, both given in combination with MTX, in a 2‐year study. The primary end point was treatment noninferiority, assessed according to the American College of Rheumatology 20% improvement response (ACR20) at 1 year.

Results

Of the 646 patients who were randomized and treated, 86.2% receiving SC abatacept and 82% receiving SC adalimumab completed 12 months of treatment. At 1 year, 64.8% of patients in the SC abatacept group and 63.4% in the SC adalimumab group demonstrated an ACR20 response; the estimated difference between groups was 1.8% (95% confidence interval −5.6%, 9.2%), thus demonstrating the noninferiority of abatacept compared to adalimumab. All efficacy measures showed similar results and kinetics of response between treatments. The rate of radiographic nonprogression (defined as a total modified Sharp/van der Heijde score [SHS] less than or equal to the smallest detectable change) was 84.8% for SC abatacept–treated patients and 88.6% for SC adalimumab–treated patients, while the mean change from baseline in the total SHS was 0.58 and 0.38, respectively. In the SC abatacept and SC adalimumab groups, the incidence of serious adverse events (SAEs) was 10.1% and 9.1%, respectively, and the rate of serious infections was 2.2% and 2.7%, respectively. In patients treated with SC abatacept, the frequency of discontinuations due to AEs was 3.5% and discontinuations due to SAEs was 1.3%, while in patients treated with SC adalimumab, the frequencies were 6.1% and 3%, respectively. Injection site reactions occurred in 3.8% of patients receiving SC abatacept compared to 9.1% of patients receiving SC adalimumab (P = 0.006).

Conclusion

The results demonstrate that SC abatacept and SC adalimumab have comparable efficacy in patients with RA, as shown by similar kinetics of response and comparable inhibition of radiographic progression over 1 year of treatment. The safety was generally similar, other than the occurrence of significantly more local injection site reactions in patients treated with SC adalimumab.
Sentiment analysis of twitter audiences: Measuring the positive or negative influence of popular twitterers
Authors: Bae Younggue , Lee Hongchul
Published: November 2012

Twitter is a popular microblogging service that is used to read and write millions of short messages on any topic within a 140‐character limit. Popular or influential users tweet their status and are retweeted, mentioned, or replied to by their audience. Sentiment analysis of the tweets by popular users and their audience reveals whether the audience is favorable to popular users. We analyzed over 3,000,000 tweets mentioning or replying to the 13 most influential users to determine audience sentiment. Twitter messages reflect the landscape of sentiment toward its most popular users. We used the sentiment analysis technique as a valid popularity indicator or measure. First, we distinguished between the positive and negative audiences of popular users. Second, we found that the sentiments expressed in the tweets by popular users influenced the sentiment of their audience. Third, from the above two findings we developed a positive‐negative measure for this influence. Finally, using a Granger causality analysis, we found that the time‐series‐based positive‐negative sentiment change of the audience was related to the real‐world sentiment landscape of popular users. We believe that the positive‐negative influence measure between popular users and their audience provides new insights into the influence of a user and is related to the real world.
The Behavioral Phenotype in MECP2 Duplication Syndrome: A Comparison With Idiopathic Autism
Authors: Peters Sarika U. , Hundley Rachel J. , Wilson Amy K. , Warren Zachary , Vehorn Alison , Carvalho Claudia M.B. , Lupski James R. , Ramocki Melissa B.
Published: November 2012

Alterations in the X‐linked gene MECP2 encoding the methyl‐CpG‐binding protein 2 have been linked to autism spectrum disorders (ASDs). Most recently, data suggest that overexpression of MECP2 may be related to ASD. To better characterize the relevance of MECP2 overexpression to ASD‐related behaviors, we compared the core symptoms of ASD in MECP2 duplication syndrome to nonverbal mental age‐matched boys with idiopathic ASD. Within the MECP2 duplication group, we further delineated aspects of the behavioral phenotype and also examined how duplication size and gene content corresponded to clinical severity. We compared ten males with MECP2 duplication syndrome (ages 3–10) with a chronological and mental age‐matched sample of nine nonverbal males with idiopathic ASD. Our results indicate that boys with MECP2 duplication syndrome share the core behavioral features of ASD (e.g. social affect, restricted/repetitive behaviors). Direct comparisons of ASD profiles revealed that a majority of boys with MECP2 duplication syndrome are similar to idiopathic ASD; they have impairments in social affect (albeit to a lesser degree than idiopathic ASD) and similar severity in restricted/repetitive behaviors. Nonverbal mental age did not correlate with severity of social impairment or repetitive behaviors. Within the MECP2 duplication group, breakpoint size does not predict differences in clinical severity. In addition to social withdrawal and stereotyped behaviors, we also found that hyposensitivity to pain/temperature are part of the behavioral phenotype of MECP2 duplication syndrome. Our results illustrate that overexpression/increased dosage of MECP2 is related to core features of ASD. Autism Res 2012, ●●: ●●–●●. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.
A COMPARISON OF DISCRETE TRIAL TEACHING IMPLEMENTED IN A ONE‐TO‐ONE INSTRUCTIONAL FORMAT AND IN A GROUP INSTRUCTIONAL FORMAT
Authors: Leaf Justin B. , Tsuji Kathleen H. , Lentell Amy E. , Dale Stephanie E. , Kassardjian Alyne , Taubman Mitchell , McEachin John , Leaf Ronald , Oppenheim‐Leaf Misty L.
Published: November 2012

Discrete trial teaching (DTT) is a systematic form of intervention commonly implemented with children and adolescents diagnosed with autism spectrum disorder. Experimenters and clinicians have implemented DTT in both one‐to‐one instructional formats and group instructional formats to teach a wide variety of skills to children and adolescents diagnosed with autism spectrum disorder. The purpose of this study was to compare DTT implemented in a one‐to‐one instructional format with DTT implemented in a group instructional format in order to determine which format was more effective, efficient, resulted in higher observational learning, and resulted in better maintenance when teaching a variety of expressive skills. The experimenters utilized a parallel treatment design, and the results indicated that both instructional formats were equally effective, there were mixed results in terms of maintenance and efficiency, and group instruction resulted in observational learning. Copyright © 2012 John Wiley & Sons, Ltd.
Contemporary perioperative care strategies
Authors: Adamina M , Gié O , Demartines N , Ris F
Published: November 2012

Background

Historically, the preoperative and postoperative care of patients with gastrointestinal cancer was provided by surgeons. Contemporary perioperative care is a truly multidisciplinary endeavour with implications for cancer-specific outcomes.

Methods

A literature review was performed querying PubMed and the Cochrane Library for articles published between 1966 to 2012 on specific perioperative interventions with the potential to improve the outcomes of surgical oncology patients. Keywords used were: fast-track, enhanced recovery, accelerated rehabilitation, multimodal and perioperative care. Specific interventions included normothermia, hyperoxygenation, surgical-site infection, skin preparation, transfusion, non-steroidal anti-inflammatory drugs, thromboembolism and antibiotic prophylaxis, laparoscopy, radiotherapy, perioperative steroids and monoclonal antibodies. Included articles had to be randomized controlled trials, prospective or nationwide series, or systematic reviews/meta-analyses, published in English, French or German.

Results

Important elements of modern perioperative care that improve recovery of patients and outcomes in surgical oncology include accelerated recovery pathways, thromboembolism and antibiotic prophylaxis, hyperoxygenation, maintenance of normothermia, avoidance of blood transfusion and cautious use of non-steroidal anti-inflammatory drugs, promotion of laparoscopic surgery, chlorhexidine–alcohol skin preparation and multidisciplinary meetings to determine multimodal therapy.

Conclusion

Multidisciplinary management of perioperative patient care has improved outcomes.
Improving outcomes in gastrointestinal cancer
Authors: Alderson D , Winter D C
Published: November 2012

Plenty of challenges for the GI surgeon
Liquid chromatography tandem mass spectrometry method for the simultaneous stereoselective determination of venlafaxine and its major metabolite, O‐desmethylvenlafaxine, in human plasma
Authors: Dutta Lalit , Ahmad Syed Imran , Mukherjee Subhra Kanti , Mishra Sanjeev , Khuroo Arshad , Monif Tausif
Published: November 2012

A sensitive, accurate and highly stereoselective assay for the simultaneous determination of venlafaxine (VEN) and its equipotent metabolite, O‐desmethyl venlafaxine (ODV), in human plasma was developed and validated. Analytes were simultaneously extracted from plasma using solid‐phase extraction and detected by tandem mass spectrometry in positive ion mode with a turbo ion spray interface. Deuterium‐labeled VEN and ODV were used as internal standards. Chromatographic separation was performed on a Chiral AGP column, using a time programmed gradient flow with a total run time of 16 min. The method has a lower limit of quantitation of 0.60 ng/mL. The assay was linear over a range 0.60–300.00 ng/mL for both the enantiomers of VEN and ODV, respectively, with coefficient of correlation > 0.99. The extraction recoveries were >77.0% on an average for all the four analytes. The analytes were found stable in plasma through three freeze (−15 °C) and thaw cycles and under storage at room temperature for 8 h, and also in mobile phase at 10 °C for 54 h. The method has shown good reproducibility, with intra‐ and inter‐day variation coefficients < 9%, for all the analytes, and has proved to be very reliable for analysis of VEN and its metabolite in clinical study samples. Copyright © 2012 John Wiley & Sons, Ltd.
Advances in analytical methods to study cholesterol metabolism: the determination of serum noncholesterol sterols
Authors: Andrade Isabel , Santos Lèlita , Ramos Fernando
Published: November 2012

Cholesterol biosynthesis precursors and plant sterols are noncholesterol sterols currently used as relative surrogate markers of cholesterol synthesis and absorption, respectively. Its determination in serum samples is a way of diagnosing inherited disorders and also a tool for health evaluation during lipid‐lowering lifestyle/drug therapy monitoring. This approach is the only one that can be used for large‐scale clinical trials or population based studies, but, nevertheless, there is no reference method for the quantification of noncholesterol sterols in human serum samples and only analysis by GC‐FID and GC‐MS has been reported to be completely validated. Although there has been a wider use of noncholesterol sterols for the measurement and characterization of cholesterol metabolism, there is a lack of harmonization of measurements and of standardization of the methodology, which is essential for routine measurements of diagnostic utility. New recent advances in analytical methods for the determination of serum noncholesterol sterols are highlighted, focusing on the sample preparation, separation and detection techniques, which will enhance the range of applications in clinical practice. Copyright © 2012 John Wiley & Sons, Ltd.
Programming in Situ Immunofluorescence Intensities through Interchangeable Reactions of Dynamic DNA Complexes
Authors: Zimak Jan , Schweller Ryan M. , Duose Dzifa Y. , Hittelman Walter N. , Diehl Michael R.
Published: November 2012

The regulation of antibody reporting intensities is critical to various in situ fluorescence‐imaging analyses. Although such control is often necessary to visualize sparse molecular targets, the ability to tune marker intensities is also essential for highly multiplexed imaging strategies in which marker reporting levels must be tuned both to optimize dynamic detection ranges and to minimize crosstalk between different signals. Existing chemical amplification approaches generally lack such control. Here, we demonstrate that linear and branched DNA complexes can be designed to function as interchangeable building blocks that can be assembled into organized, fluorescence‐reporting complexes. We show that the ability to program DNA‐strand‐displacement reactions between these complexes offers new opportunities to deterministically tune the number of dyes that are coupled to individual antibodies in order both to increase and controllably balance marker reporting levels within fixed cells.
Stepwise Degradation of Trifluoromethyl Platinum(II) Compounds
Authors: Martínez‐Salvador Sonia , Forniés Juan , Martín Antonio , Menjón Babil , Usón Isabel
Published: November 2012

The action of moisture on the homoleptic organoplatinum(II) compound [NBu4]2[Pt(CF3)4] (1) gives rise to the carbonyl derivative [NBu4][Pt(CF3)3(CO)] (2), which is itself moisture stable. However, treatment of compound 2 with HCl(aq) results in the formation of [NBu4][cis‐Pt(CF3)2Cl(CO)] (3), which undergoes degradation of an additional CF3 group by further treatment with HCl(aq) in large excess, affording [NBu4][cis‐Pt(CF3)Cl2(CO)] (4). The carbonyl derivatives 2–4 are fairly stable species, in which the CO ligand, however, can be readily extruded by reaction with trimethylamine N‐oxide (ONMe3). Thus, compound 2 reacts with ONMe3 in the presence of a number of neutral or anionic ligands affording a series of singly or doubly charged derivatives with the general formulae [NBu4][Pt(CF3)3(L)] [L=CNtBu (5), PPh3 (6), P(o‐tolyl)3 (7), tht (8; tht=tetrahydrothiophene)] and [NBu4]2[Pt(CF3)3X] [X=Cl (9), Br (10), I (11)], respectively. Compound 2 also reacts with ONMe3 and pyridin‐2‐thiol (C5H5NS) giving rise to the five‐membered metallacyclic derivative [NBu4][Pt(CF3)2(CF2NC5H4S‐κC,κS)] (12), which can be viewed as a difluorocarbene species stabilized by intramolecular base coordination. On the other hand, treatment of compound 3 with ONMe3 in the presence of C5H5NS yields the four‐membered metallacyclic compound [NBu4][Pt(CF3)2(NC5H4S‐κN,κS)] (13). The geometries of the metallacycles in compounds 12 and 13 are compared. In the absence of any additional ligand, compound 3 undergoes dimerization producing the dinuclear species [NBu4]2[{Pt(CF3)2}2(μ‐Cl)2] (14). Halide abstraction in the latter compound with AgClO4 in THF yields the solvento compound cis‐[Pt(CF3)2(thf)2] (15). The highly labile character of the THF ligands in compound 15 makes this species a convenient synthon of the “cis‐Pt(CF3)2” unit.
Energy/Hole Transfer Phenomena in Hybrid α‐Sexithiophene (α‐STH) Nanoparticle–CdTe Quantum‐Dot Nanocomposites
Authors: Bhattacharyya Santanu , Paramanik Bipattaran , Kundu Simanta , Patra Amitava
Published: November 2012

Considerable attention has been paid to hybrid organic–inorganic nanocomposites for designing new optical materials. Herein, we demonstrate the energy and hole transfer of hybrid hole‐transporting α‐sexithiophene (α‐STH) nanoparticle–CdTe quantum dot (QD) nanocomposites using steady‐state and time‐resolved spectroscopy. Absorption and photoluminescence studies confirm the loss of planarity of the α‐sexithiophene molecule due to the formation of polymer nanoparticles. Upon photoexcitation at 370 nm, a nonradiative energy transfer (73 %) occurs from the hole‐transporting α‐STH nanoparticles to the CdTe nanoparticles with a rate of energy transfer of 6.13×109 s−1. However, photoluminescence quenching of the CdTe QDs in the presence of the hole‐transporting α‐STH nanoparticles is observed at 490 nm excitation, which is due to both static‐quenching and hole‐transfer‐based dynamic‐quenching phenomena. The calculated hole‐transporting rate is 7.13×107 s−1 in the presence of 42×10−8 M α‐STH nanoparticles. Our findings suggest that the interest in α‐sexithiophene (α‐STH) nanoparticle–CdTe QD hybrid nanocomposites might grow in the coming years because of various potential applications, such as solar cells, optoelectronic devices, and so on.
Emotion Coupling and Regulation in Anorexia Nervosa
Authors: Fox John R. E. , Smithson Emily , Baillie Sarah , Ferreira Nuno , Mayr Ingrid , Power Michael J.
Published: November 2012

Objective

The present study sought to investigate emotion regulation strategies in people with anorexia nervosa (AN) and whether the theoretical concept of ‘emotion coupling’ between anger and disgust could help to explain some of the specific eating disorder symptomatology in people with AN.

Method

This ‘emotion coupling’ hypothesis was tested using a mood induction procedure within laboratory conditions, where individuals with AN (n = 22) were matched with control participants (n = 19). Participants completed a bank of different measures prior to the study, and these included measures of eating pathology, core beliefs about the self and others, and emotion regulation strategies. Within the experimental part of this study, anger, disgust and body size estimation were measured prior to and after an anger induction procedure (i.e., a repeated measures design).

Results

People with AN demonstrated a significantly more internal‐dysfunctional way to regulate their emotional states, when compared with matched controls. Within the ‘emotional coupling’ part of the study, participants showed a significant increase in levels of disgust and body size estimation following an anger induction when compared with matched controls.

Discussion

The significance of these results was considered in the light of the new Schematic, Propositional, Analogical and Associative Representation Systems in eating disorders model. Copyright © 2012 John Wiley & Sons, Ltd.

Key Practitioner Message

Emotions and emotion processing are problematic for people with anorexia nervosa.

Overestimation in body size for people with anorexia nervosa may be due to the coupling of anger and disgust.

Clinicians need to consider the importance of automatic cognitive routes of emotion elicitation that may maintain certain eating disorder symptoms, such as poor body image.
Type 2 diabetes patients educated by other patients perform at least as well as patients trained by professionals
Authors: Gagliardino Juan José , Arrechea Viviana , Assad Daniel , Gagliardino Gabriel G. , González Lorena , Lucero Soledad , Rizzuti Liliana , Zufriategui Zulma , Clark Charles
Published: November 2012

Background

Diabetes education can improve the quality of care of people with diabetes, but many organizations are not equipped to manage its implementation. Involving people with diabetes in the education process can overcome the problem. Thus, we compared clinical, metabolic and psychological outcomes in people with type 2 diabetes 1 year after attending a structured diabetes education programme implemented by professional educators versus the same programme implemented by trained peers with diabetes that also provided ongoing peer support.

Methods

People with type 2 diabetes (25–75 years) were randomly assigned to attend a 4‐week structured diabetes education course delivered by professional educators (control) or previously trained peers (peer). Peers also received continuing psychological support, including examples on how to apply diabetes knowledge in daily life via weekly peer cellular phone calls and bimonthly face‐to‐face interviews in small groups (ten patients), using a structured questionnaire related to the patient's clinical, metabolic and psychological progress. Identical outcome data from both groups were used for follow‐up.

Results

Both groups had a comparable positive effect on clinical, metabolic and psychological indicators immediately following the programme. Over the following year, peer‐educated subjects had lower A1C and systolic blood pressure and showed higher adherence to physical activity and better control of hypoglycaemic episodes.

Conclusion

The non‐inferiority of the peer outcomes and the mentioned improvements in this group suggest that volunteer trained peer educators and ongoing support can be successful. This approach provides an effective alternative method of education, especially in areas with limited availability of professionals and economic resources. Copyright © 2012 John Wiley & Sons, Ltd.