bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of the training program for workers at construction sites of the high‐speed railway line between Torino and Novara: Impact on injury rates
Authors: Bena A. , Berchialla P. , Coffano M.E. , Debernardi M.L. , Icardi L.G.
Published: October 2009

Background

There are very few published studies evaluating the impact of safety and health training on injury outcomes in the construction industry. The aim of this study was to assess the impact of the training program on injury rates at a major railway construction project.

Methods

The population consisted of 2,795 workers involved in a safety training program at the construction sites of the high‐speed railway line Torino–Novara. Two types of analyses were carried out in order to assess the effectiveness of the training program in reducing the number of injuries: (i) a pre–post analysis, which took into account the fact that workers were enrolled at different times and the training intervention did not occur at the same time for all subjects; (ii) an interrupted time‐series model, which corrected for the time trend and considered the autocorrelation between individual observations.

Results

Twenty‐nine percent of workers who spent at least 1 day at the construction sites attended at least one training module. Pre–post analysis: At the end of the training program, the incidence of occupational injuries had fallen by 16% after the basic training module and by 25% following the specific modules. Time‐series model: Training led to a 6% reduction in injury rates, which was not statistically significant.

Conclusions

The training program that was implemented had a moderately positive impact on the health of workers. Further studies are being conducted to obtain a more complete assessment of the actual effectiveness of the program in reducing the incidence of injuries. Am. J. Ind. Med. 52:965–972, 2009. © 2009 Wiley‐Liss, Inc.
Screening of DNA methylation at the H19 promoter or the distal region of its ICR1 ensures efficient detection of chromosome 11p15 epimutations in Russell–Silver syndrome
Authors: Horike Shin‐Ichi , Ferreira Jose Carlos P. , Meguro‐Horike Makiko , Choufani Sanaa , Smith Adam C. , Shuman Cheryl , Meschino Wendy , Chitayat David , Zackai Elaine , Scherer Stephen W. , Weksberg Rosanna
Published: October 2009

Over a 10‐year period blood samples were collected from 57 individuals with growth restriction and RSS‐like features. Our goal was to identify epigenetic abnormalities in this cohort, including uniparental disomy of chromosome 7 (UPD7), methylation changes at chromosome11p15, as well as new epigenomic alterations. We evaluated the methylation status of 7 imprinting control regions on chromosomes 7, 11, 14, and 15. UPD7 and chromosome 7 structural abnormalities had been previously identified in five patients. Epigenetic alterations on chromosome 11p15 were identified in 11 patients. Of interest, in 3 of these 11 patients, the epigenetic alterations were limited to the H19 promoter and the distal region of its associated imprinting center, ICR1. In addition, in one patient, we detected methylation changes consistent with maternal UPD at all tested imprinted regions. This patient series suggests that epimutations on chromosome 11p15 can be most efficiently detected in RSS patients by screening for DNA methylation defects at the H19 promoter or the distal region of ICR. © 2009 Wiley‐Liss, Inc.
Clinical problems and everyday abilities of a group of Italian adolescent and young adults with Cornelia de Lange syndrome
Authors: Olioso Giovanna , Passarini Alice , Atzeri Francesca , Milani Donatella , Cereda Anna , Cerutti Marta , Maitz Silvia , Menni Francesca , Selicorni Angelo
Published: October 2009

Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental retardation syndrome, characterized by distinctive facial features, generalized hirsutism, growth and cognitive dysfunction, microcephaly and limb abnormalities. Currently mutations of three different genes, NIPBL, SMC1A, and SMC3, are known to be related to the CdLS phenotype with an overall detection rate of about 50%. Few data are available regarding the level of autonomy in everyday life of CdLS patients. Due to the collaboration of the Italian parents' support group, we collected information regarding clinical and behavioral problems and everyday abilities of 45 CdLS patients between 13 and 39 years, using a specific multi‐item questionnaire. To better analyze clinical information we divided our patients into three groups according to age: 13–20, 21–29, and over 30 years. Data from clinical, malformative and behavioral problems were not significantly different from those described for CdLS patients. Regarding personal autonomies this study showed the significant limitations of these individuals. It is interesting to observe that patients between 21 and 29 years, showed the best performance, while those over 30 had more severe difficulties. We suggest that these data be interpretated as a minimum level of autonomy achievable for CdLS adolescent/young adults, as the level of care, rehabilitation and stimulation of these patients has increased in the last 30 years. © 2009 Wiley‐Liss, Inc.
Cytogenetic and molecular characterization of a partial trisomy 2p arising from inverted duplication of 2p with terminal deletion of 2pter
Authors: Tirado Carlos A. , Henderson Samuel , Uddin Naseem , Stewart Ewa , Iyer Santha , Ratner Ian M. , Matthews Erin , Doolittle Jeffrey , Garcia Rolando , Valdez Federico , Dallaire Stephanie , Appleberry Taylor , Payne Deborah , Collins Robert
Published: October 2009

Partial trisomy 2p is typically associated with partial monosomy of another chromosomal segment and results from a balanced translocation in one of the parents. Inverted duplications with terminal deletions have been reported in an increasing number of chromosomes. Several cases initially interpreted as terminal duplications have instead been documented to represent inverted duplications with terminal deletions. Inv dup del(2p) has been reported in patients who manifest the clinical findings of trisomy 2p syndrome. Here we report on a 2‐month‐old girl with inv dup del(2p) and clinical manifestations that overlap those found commonly in partial 2p trisomy, as previously reported in the literature. Her clinical picture helps delineate the phenotype of 2p duplication disorders. © 2009 Wiley‐Liss, Inc.
Compound heterozygosity for mutations in PAX6 in a patient with complex brain anomaly, neonatal diabetes mellitus, and microophthalmia
Authors: Solomon Benjamin D. , Pineda‐Alvarez Daniel E. , Balog Joan Z. , Hadley Donald , Gropman Andrea L. , Nandagopal Radha , Han Joan C. , Hahn Jin S. , Blain Delphine , Brooks Brian , Muenke Maximilian
Published: October 2009

We report on a patient with trisomy 21, microophthalmia, neonatal diabetes mellitus, hypopituitarism, and a complex structural brain anomaly who was a member of a large bilineal family with eye anomalies. The patient inherited a different mutation in PAX6 from each parent and is the only known living and second reported patient with compound heterozygosity for mutations in PAX6. PAX6 is a transcription factor involved in eye and brain development and has roles in pancreatic and pituitary development. Clinical evaluation of the propositus and his parents demonstrated the effects of mutations of differing severity in multiple individuals. Published 2009 Wiley‐Liss, Inc.
Array‐based comparative genomic hybridization (aCGH) in the genetic evaluation of stillbirth
Authors: Raca Gordana , Artzer Amber , Thorson Laura , Huber Suzanne , Modaff Peggy , Laffin Jennifer , Pauli Richard M.
Published: October 2009

This study examined the utility of array‐based comparative genomic hybridization (aCGH) in detecting genetic abnormalities associated with late pregnancy loss. Comparisons were made with classic cytogenetics to test whether aCGH represents a superior methodology for the clinical evaluation of stillbirth. Stillborn infants were selected for aCGH testing from the Wisconsin Stillbirth Service Program (WiSSP) database and tissue bank, based on abnormal clinical findings (presence of at least two abnormalities of two different organs or parts of the body). aCGH analysis was successfully completed in 15 cases which met the clinical criteria and for which sufficient amount of high quality DNA was recovered from archival material. The testing was performed using commercially available 1 Mb BAC arrays. Among 15 tested stillborns, aCGH detected two abnormalities (trisomy 21 and an unbalanced translocation between chromosomes 3 and 10), for an overall detection rate of 13% in stillborns with malformations who had normal or unobtainable cytogenetic results. This preliminary study supports the clinical value of aCGH testing in diagnostic evaluation of stillborns with congenital anomalies. © 2009 Wiley‐Liss, Inc.
The molecular basis of oral‐facial‐digital syndrome, type 1
Authors: Macca Marina , Franco Brunella
Published: October 2009

Oral–facial–digital syndrome type 1 (OFDI; OFD1; OMIM 311200) is a rare developmental disorder transmitted as an X‐linked dominant condition with embryonic male lethality. OFD1 is characterized by malformation of the oral cavity, face, and digits. Central nervous system (CNS) abnormalities and cystic kidney disease can also be part of this condition. This disorder is due to mutations in theOFD1gene that encodes a centrosomal protein localized at the basal bodies at the origin of primary cilia. Characterization of in vitro and in vivo models demonstrated that, similarly to what described for other ciliary proteins, Ofd1 inactivation is associated to defective sonic hedgehog (Shh) and canonical Wnt signaling pathways. Functional studies have demonstrated that OFD1 has a crucial role in the biology of primary cilia thus ascribing this pleiotropic disease to the growing number of disorders associated to dysfunction of primary cilia. OFD1 shares phenotypic similarities with this latter group of disorders, such as cystic kidneys, skeletal, and CNS abnormalities. Future studies will address whether all clinical manifestations of these diseases can be entirely explained by cilia dysfunction or may also be due to direct roles of the proteins involved. © 2009 Wiley‐Liss, Inc.
Liver and kidney disease in ciliopathies
Authors: Gunay‐Aygun Meral
Published: October 2009

Hepatorenal fibrocystic diseases (HRFCDs) are among the most common inherited human disorders. The discovery that proteins defective in the autosomal dominant and recessive polycystic kidney diseases (ADPKD and ARPKD) localize to the primary cilia and the recognition of the role these organelles play in the pathogenesis of HRFCDs led to the term “ciliopathies.” While ADPKD and ARPKD are the most common ciliopathies associated with both liver and kidney disease, variable degrees of renal and/or hepatic involvement occur in many other ciliopathies, including Joubert, Bardet–Biedl, Meckel–Gruber, and oral–facial–digital syndromes. The ductal plate malformation (DPM), a developmental abnormality of the portobiliary system, is the basis of the liver disease in ciliopathies that manifest congenital hepatic fibrosis (CHF), Caroli syndrome (CS), and polycystic liver disease (PLD). Hepatocellular function remains relatively preserved in ciliopathy‐associated liver diseases. The major morbidity associated with CHF is portal hypertension (PH), often leading to esophageal varices and hypersplenism. In addition, CD predisposes to recurrent cholangitis. PLD is not typically associated with PH, but may result in complications due to mass effects. The kidney pathology in ciliopathies ranges from non‐functional cystic dysplastic kidneys to an isolated urinary concentration defect; the disorders contributing to this pathology, in addition to ADPKD and ARPKD, include nephronophithisis (NPHP), glomerulocystic kidney disease and medullary sponge kidneys. Decreased urinary concentration ability, resulting in polyuria and polydypsia, is the first and most common renal symptom in ciliopathies. While the majority of ADPKD, ARPKD, and NPHP patients require renal transplantation, the frequency and rate of progression to renal failure varies considerably in other ciliopathies. This review focuses on the kidney and liver disease found in the different ciliopathies. Published 2009 Wiley‐Liss, Inc.
Ciliary biology: Understanding the cellular and genetic basis of human ciliopathies
Authors: Cardenas‐Rodriguez Magdalena , Badano Jose L.
Published: October 2009

Motile cilia have long been known to play a role in processes such as cell locomotion and fluid movement whereas the functions of primary cilia have remained obscure until recent years. To date, ciliary dysfunction has been shown to be causally linked to a number of clinical manifestations that characterize the group of human disorders known as ciliopathies. This classification reflects a common or shared cellular basis and implies that it is possible to associate a series of different human conditions with ciliary dysfunction, which allows gaining insight into the cellular defect in disorders of unknown etiology solely based on phenotypic observations. Furthermore, to date we know that the cilium participates in a number of biological processes ranging from chemo‐ and mechanosensation to the transduction of a growing list of paracrine signaling cascades that are critical for the development and maintenance of different tissues and organs. Consequently, the primary cilium has been identified as a key structure necessary to regulate and maintain cellular and tissue homeostasis and thus its study is providing significant information to understand the pathogenesis of the different phenotypes that characterize these human conditions. Finally, the similarities between different ciliopathies at the phenotypic level are proving to be due to their shared cellular defect and also their common genetic basis. To this end, recent studies are showing that mutations in a given ciliary gene often appear involved in the pathogenesis of more than one clinical entity, complicating their genetic dissection, and hindering our ability to generate accurate genotype–phenotype correlations. © 2009 Wiley‐Liss, Inc.
Making sense of cilia in disease: The human ciliopathies
Authors: Baker Kate , Beales Philip L.
Published: October 2009

Ubiquitous in nature, cilia and flagella comprise nearly identical structures with similar functions. The most obvious example of the latter is motility: driving movement of the organism or particle flow across the epithelial surface in fixed structures. In vertebrates, such motile cilia are evident in the respiratory epithelia, ependyma, and oviducts. For over a century, non‐motile cilia have been observed on the surface of most vertebrate cells but until recently their function has eluded us. Gathering evidence now points to critical roles for the mono‐cilium in sensing the extracellular environment, and perturbation of this function gives rise to a predictable panoply of clinical problems. We review the common clinical phenotypes associated with ciliopathies and interrogate Online Mendelian Inheritance in Man (OMIM) to compile a comprehensive list of putative disorders in which ciliary dysfunction may play a role. © 2009 Wiley‐Liss, Inc.
Glycosphingolipide – Natur, Funktion und pharmakologische Modulierung
Authors: Wennekes Tom , van den Berg Richard J. B. H. N. , Boot Rolf G. , van der Marel Gijsbert A. , Overkleeft Herman S. , Aerts Johannes M. F. G.
Published: October 2009

Die Entdeckung der Glycosphingolipide wird im Allgemeinen Johan L. W. Thudichum zugeschrieben, der 1884 über die chemische Zusammensetzung des Gehirns publizierte. In seinen Studien isolierte er aus ethanolischen Hirnextrakten mehrere Verbindungen, die er als Cerebroside bezeichnete. Eine dieser Verbindungen, Phrenosin (heute als Galactosylceramid bekannt), unterwarf er einer sauren Hydrolyse, aus der drei Komponenten hervorgingen. Eine Komponente identifizierte er als Fettsäure, eine andere als Isomer zur D‐Glucose, heute als D‐Galactose bekannt. Die dritte Komponente mit “alkaloidaler Natur” gab Thudichum “viele Rätsel” auf, weshalb er sie Sphingosin nannte, nach dem mythologischen Rätsel der Sphinx. Derzeit sind Sphingolipide und ihre glycosidierten Derivate Gegenstand intensiver Forschung mit dem Ziel, ihre Funktion für die strukturelle Integrität der Zellmembran, ihre Teilnahme in Erkennungs‐ und Signalübertragungsvorgängen und besonders ihre Beteiligung an pathologischen Prozessen, die als Ursache menschlicher Krankheiten (z. B. von Sphingolipidosen und Typ‐2‐Diabetes) gelten, aufzuklären. Dieser Aufsatz wird auf neuere Befunde zur Biosynthese, Funktion und zum Abbau von Glycosphingolipiden im Menschen eingehen, mit Fokus auf das Glycosphingolipidglucosylceramid. Besondere Aufmerksamkeit richtet sich auf die klinische Bedeutung von Verbindungen, die mit den Faktoren des Glycosphingolipid‐Metabolismus wechselwirken.
Hyoid Skeleton, Its Related Muscles, and Morphological Novelties in the Frog Lepidobatrachus (Anura, Ceratophryidae)
Authors: Fabrezi Marissa , Lobo Fernando
Published: October 2009

Many traits of the skull of ceratophryines are related to the capture of large prey independently of aquatic or terrestrial feeding. Herein, detailed descriptions of the development of hyoid skeleton and the anatomy of muscles responsible for hyoid and tongue movements in Lepidobatrachus laevis and L. llanensis are provided and compared with those of other neobatrachians. The aquatic Lepidobatrachus has special features in its hyoid skeleton that integrates a set of derived features convergent with the conditions observed in non‐neobatrachian anurans and morphological novelties (e.g., dorsal dermal hyoid ossification) that deviate from the generalized pattern found in most frogs. Further, reduction of fibers of muscles of buccal floor, reduction or loss of hyoid muscles (m. geniohyoideus rama lateralis, anterior pair of m. petrohyoideus posteriores), small tongue, and simplified tongue muscles are also morphological deviations from the pattern of terrestrial ceratophryines, and other aquatic ceratophryids (e.g., Telmatobius) that seem to be related to feeding underwater. The historical derived features shared with Chacophrys and Ceratophrys involved in megalophagy are conserved in Lepidobatrachus and morphological changes in the hyoglossal apparatus define a unique functional complex among anurans. Anat Rec, 292:1700–1712, 2009. © 2009 Wiley‐Liss, Inc.
Three‐Dimensional Serial Section Computer Reconstruction of the Arrangement of the Structural Components of the Parabronchus of the Ostrich, Struthio Camelus Lung
Authors: Maina John N. , Woodward Jeremy D.
Published: October 2009

‘Cubed’ three‐dimensional computer reconstruction (from serial sections) of the exchange tissue (parenchyma) of the lung of the ostrich, Struthio camelus showing the profuse anastomoses of the air capillaries (shown in cyan) and the blood capillaries (shown in red). While the two terminal respiratory units interdigitate very copiously as they interface intimately, thereby optimizing the respiratory surface area, regarding their size and shape, they are not mirror images as has previously been reported nor do they spatially form a counter‐current arrangement, as they have been commonly modelled. See Maina et al., “Three‐Dimensional Serial Section Computer Reconstruction of the Arrangement of the Structural Components of the Parabronchus of the Ostrich, Struthio Camelus Lung,” on page 1685, in this issue.
Impaired sexual function in women with systemic sclerosis: A cross‐sectional study
Authors: Schouffoer A. A. , van der Marel J. , ter Kuile M. M. , Weijenborg P. T. M. , Voskuyl A. , Vliet Vlieland C. W. , van Laar J. M. , Vliet Vlieland T. P. M.
Published: October 2009

Objective

To compare sexual functioning and distress in women with systemic sclerosis (SSc) with that in healthy controls and determine the association between disease characteristics and sexual function.

Methods

We conducted a cross‐sectional study of 69 women with SSc (ages 18–60 years) and 58 healthy, age‐matched controls. Assessment included the Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), Hospital Anxiety and Depression Scale, Short Form 36 health survey, sociodemographic characteristics, and in patients only, the Health Assessment Questionnaire.

Results

Of 69 eligible patients with SSc, 37 (54%) responded, in addition to 37 (64%) of 58 controls. The FSFI total score and the subscale scores for lubrication, orgasm, arousal, and pain were significantly lower and the FSDS scores were significantly higher in patients with SSc. Longer disease duration and higher levels of marital dissatisfaction were significantly associated with low sexual function in patients with SSc. Longer disease duration, more depressive symptoms, and the use of antidepressants were significantly associated with sexual distress. Multivariate analyses indicated that marital distress was the only variable significantly associated with low sexual function in patients with SSc (β = 0.40, P < 0.05), whereas depression was the only variable significantly associated with sexual distress (β = 0.32, P < 0.05). The same pattern of associations was found in the healthy control group.

Conclusion

Women with SSc reported significantly impaired sexual functioning and more sexual distress then healthy controls. Impaired sexual functioning and sexual distress were associated with marital distress and depressive symptoms. These results indicate that in daily practice, inquiring about sexuality and screening for depressive symptoms is indicated in every patient with SSc, irrespective of their clinical characteristics.
Predictors of depression in a multiethnic cohort of patients with rheumatoid arthritis
Authors: Margaretten M. , Yelin E. , Imboden J. , Graf J. , Barton J. , Katz P. , Julian L.
Published: October 2009

Objective

Patients with rheumatoid arthritis (RA) who experience depression have worse health outcomes. This study identifies predictors of depression in an ethnically and racially diverse population of patients with RA.

Methods

Patients with RA in a prospective cohort at the San Francisco General Hospital outpatient rheumatology clinic were included if they were age ≥18 years, met the American College of Rheumatology classification criteria for RA, had a Health Assessment Questionnaire (HAQ) score collected, and had the RA‐specific Disease Activity Score performed by a rheumatologist. The outcome variable was a depression score measured by the Patient Health Questionnaire 9 (PHQ‐9), a self‐report questionnaire validated to correlate with a diagnosis of major depression.

Results

Three hundred forty‐nine clinical visits for 172 patients were included in the analysis. Forty percent of patients scored ≥10 on the PHQ‐9 during at least one clinic visit, which corresponds to a symptom severity of at least moderate depression. The mean PHQ‐9 score was 7, corresponding to a symptom severity of mild depression. In the multivariate analysis, higher HAQ scores were associated with depression, and Asians had lower depression scores compared with Hispanic, white, and African American subjects.

Conclusion

Identifying associated predictors of depression in a diverse population of patients with RA can help guide treatment, which should include preventing disability and decreased function as well as targeting depressive symptoms more specifically in patients with RA.
Comparison of clinical versus ultrasound‐determined synovitis in juvenile idiopathic arthritis
Authors: Magni‐Manzoni Silvia , Epis Oscar , Ravelli Angelo , Klersy Catherine , Veisconti Chiara , Lanni Stefano , Muratore Valentina , Sciré Carlo Alberto , Rossi Silvia , Montecucco Carlomaurizio
Published: October 2009

Objective

To compare clinical evaluation and ultrasonography (US) in the assessment of joint synovitis in children with juvenile idiopathic arthritis (JIA).

Methods

Thirty‐two patients underwent clinical evaluation of 52 joints by 2 pediatric rheumatologists. Joints were assessed for swelling, tenderness/pain on motion, and restricted motion. The same joints were scanned independently by an experienced sonographer for synovial hyperplasia, joint effusion, and power Doppler (PD) signal.

Results

In total, 1,664 joints were assessed both clinically and with US. On clinical examination, 98 joints (5.9%) were swollen, 59 joints (3.5%) were tender, and 40 joints (2.4%) had restricted motion. On US evaluation, 125 joints (7.5%) had synovial hyperplasia, 153 joints (9.2%) had joint effusion, and 53 joints (3.2%) had PD signal. A total of 104 (6.3%) and 167 (10%) joints had clinical and US synovitis, respectively. Of the 1,560 clinically normal joints, 86 (5.5%) had subclinical synovitis (i.e., had synovitis on US). US led to classifying 5 patients as having polyarthritis who were classified as having oligoarthritis or were found to have no synovitis on clinical evaluation. US variables were moderately correlated with clinical measures of joint swelling, but poorly correlated with those of joint tenderness/pain on motion and restricted motion. Overall, correlations were lower for PD signal than for synovial hyperplasia and joint effusion.

Conclusion

We found that subclinical synovitis as detected by US is common in children with JIA. This finding may have important implications for patient classification and may affect the choice of the optimal therapeutic strategy in individual patients.
Cartilage loss occurs in the same subregions as subchondral bone attrition: A within‐knee subregion‐matched approach from the multicenter osteoarthritis study
Authors: Neogi T. , Felson D. , Niu J. , Lynch J. , Nevitt M. , Guermazi A. , Roemer F. , Lewis C. E. , Wallace B. , Zhang Y.
Published: October 2009

Objective

By magnetic resonance imaging (MRI), subchondral bone attrition (SBA) can be seen in early osteoarthritis (OA), but the significance of this is unknown. We therefore evaluated whether SBA was associated with cartilage loss within the same subregion of the knee.

Methods

The Multicenter Osteoarthritis Study is a cohort of individuals who have or are at high risk for knee OA. At baseline and 30 months, participants' knee MRIs were graded using the Whole‐Organ Magnetic Resonance Imaging Score in the 10 subregions of the tibiofemoral joint for cartilage morphology and SBA. We conducted analyses within a knee to eliminate between‐person confounding, using an M:N (cases:controls) matched case–control approach with the 10 subregions of a person's knee forming a matched set. Cases within a knee were defined as subregions with cartilage loss, while controls were subregions in that same knee without cartilage loss. We evaluated the association of cartilage loss over 30 months with the presence of baseline SBA in the same subregion within that knee using conditional logistic regression.

Results

SBA was associated with an odds ratio of 7.5 (95% confidence interval 5.6–9.9, P < 0.0001) for cartilage loss in the same subregion compared with subregions without any baseline SBA in our sample of 459 knees from participants, 64% of whom were women, with a mean age of 63 years and a mean body mass index of 30.5 kg/m2.

Conclusion

SBA is strongly associated with cartilage loss within the same subregion of a knee. SBA may directly influence overlying cartilage loss or serve as a marker of an area undergoing great compressive stress and in which cartilage loss is inevitable.
UK‐based physical therapists' attitudes and beliefs regarding exercise and knee osteoarthritis: Findings from a mixed‐methods study
Authors: Holden Melanie A. , Nicholls Elaine E. , Young Julie , Hay Elaine M. , Foster Nadine E.
Published: October 2009

Objective

Within the UK, differences exist between physical therapists' use of exercise for patients with knee osteoarthritis (OA) and recent exercise recommendations. This may be explained by their underlying attitudes and beliefs. We aimed to describe UK physical therapists' attitudes and beliefs regarding exercise and knee OA, and understand and explain them.

Methods

A survey was mailed to 2,000 UK‐based chartered physical therapists that included 23 attitude statements derived from recently published recommendations. Semistructured telephone interviews were conducted with a purposeful sample of questionnaire respondents (n = 24), and were recorded and analyzed thematically.

Results

The questionnaire response rate was 58% (n = 1,152); 538 respondents reported treating a patient with knee OA in the last 6 months. The survey highlighted uncertainty about potential benefits of exercise for knee OA: only 56% largely/totally agreed that knee problems are improved by local exercise. Although exercise adherence was deemed important, it was seen as the patient's, not the therapist's, responsibility. Interviews revealed an underlying biomedical model of care of knee pain, with knee OA viewed as a progressive degenerative condition. A paternalistic treatment approach was evident. Health care systems presented a number of barriers to best practice, including limited opportunity to provide followup.

Conclusion

Although the attitudes and beliefs of physical therapists may help to explain differences between current practice and recent exercise recommendations, the wider health care system also plays a part. Further research is needed to support meaningful shifts in physical therapy care in line with the best practice recommendations.
Arthritic pain among Latinos: Results from a community‐based survey
Authors: Cheriel Chad , Huguet Nathalie , Gupta Shalini , McClure Heather , Leman Richard F. , Ngo Duyen L.
Published: October 2009

Objective

To examine factors associated with pain among Latinos with arthritis, identify common coping strategies and potentially effective interventions, and determine whether pain levels affect the level of interest in potentially useful programs.

Methods

Using a convenience sampling approach and a combination of face‐to‐face and telephone surveys, 588 Latino adults in Oregon with arthritis were interviewed. The intensity of pain during a typical day was assessed using a scale ranging from 0 (no pain) to 10 (worst pain). A score of ≥7 was defined as severe pain.

Results

More than 60% of Latinos reported severe pain. Results from an ordinary least square regression indicated that among Latinos with arthritis, women, those with lower levels of education, and those reporting poor or fair self‐rated health and functional limitations had higher levels of pain, after controlling for confounders. Those with severe pain were more likely than those with lower levels of pain to use over the counter medicine and home remedies to manage their arthritis. In addition, Latinos with greater pain were more likely to be interested in arthritis management programs.

Conclusion

These findings have important implications for public health policy. The strong interest of Latinos in various arthritis and joint pain management programs could prove to be an important avenue for supporting a population with high levels of arthritic pain and lack of health insurance. These pain management programs are all the more appealing, given the availability of a number of evidence‐based, low‐cost interventions.
Tai Chi is effective in treating knee osteoarthritis: A randomized controlled trial
Authors: Wang Chenchen , Schmid Christopher H. , Hibberd Patricia L. , Kalish Robert , Roubenoff Ronenn , Rones Ramel , McAlindon Timothy
Published: October 2009

Objective

To evaluate the effectiveness of Tai Chi in the treatment of knee osteoarthritis (OA) symptoms.

Methods

We conducted a prospective, single‐blind, randomized controlled trial of 40 individuals with symptomatic tibiofemoral OA. Patients were randomly assigned to 60 minutes of Tai Chi (10 modified forms from classic Yang style) or attention control (wellness education and stretching) twice weekly for 12 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 12 weeks. Secondary outcomes included WOMAC function, patient and physician global assessments, timed chair stand, depression index, self‐efficacy scale, and quality of life. We repeated these assessments at 24 and 48 weeks. Analyses were compared by intent‐to‐treat principles.

Results

The 40 patients had a mean age of 65 years and a mean body mass index of 30.0 kg/m2. Compared with the controls, patients assigned to Tai Chi exhibited significantly greater improvement in WOMAC pain (mean difference at 12 weeks −118.80 mm [95% confidence interval (95% CI) −183.66, −53.94; P = 0.0005]), WOMAC physical function (−324.60 mm [95% CI −513.98, −135.22; P = 0.001]), patient global visual analog scale (VAS; −2.15 cm [95% CI −3.82, −0.49; P = 0.01]), physician global VAS (−1.71 cm [95% CI −2.75, −0.66; P = 0.002]), chair stand time (−10.88 seconds [95% CI −15.91, −5.84; P = 0.00005]), Center for Epidemiologic Studies Depression Scale (−6.70 [95% CI −11.63, −1.77; P = 0.009]), self‐efficacy score (0.71 [95% CI 0.03, 1.39; P = 0.04]), and Short Form 36 physical component summary (7.43 [95% CI 2.50, 12.36; P = 0.004]). No severe adverse events were observed.

Conclusion

Tai Chi reduces pain and improves physical function, self‐efficacy, depression, and health‐related quality of life for knee OA.
Erythrocyte sedimentation rate, C‐reactive protein level, and serum amyloid A protein for patient selection and monitoring of anti–tumor necrosis factor treatment in ankylosing spondylitis
Authors: de Vries Mirjam K. , van Eijk Izhar C. , van der Horst‐bruinsma Irene E. , Peters Mike J. L. , Nurmohamed Michael T. , Dijkmans Ben A. C. , Hazenberg Bouke P. C. , Wolbink Gerrit J.
Published: October 2009

Objective

To study the usefulness of erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), and serum amyloid A (SAA) for response prediction and monitoring of anti–tumor necrosis factor (anti‐TNF) treatment in ankylosing spondylitis (AS) patients.

Methods

Patients were included consecutively before starting etanercept or infliximab treatment. ASsessment in Ankylosing Spondylitis (ASAS) response, defined as a 50% improvement or an absolute improvement of 2 points of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; 0–10 scale), was assessed at 3 months. Inflammatory markers and the BASDAI were collected at baseline and 1 and 3 months. Longitudinal data analysis was performed to compare associations between inflammatory markers and the BASDAI over time by calculating standardized betas. Predictive values of baseline levels of inflammatory markers for ASAS response were calculated.

Results

In total, 155 patients were included, of whom, after 3 months of treatment, 70% in the etanercept cohort and 71% in the infliximab cohort responded. All markers, notably SAA, decreased significantly (P < 0.0001). Standardized betas were 0.49 for ESR, 0.43 for CRP, and 0.39 for SAA. Normal baseline levels of CRP and SAA were significantly associated with nonresponse. A combination of elevated CRP and SAA levels at baseline revealed the highest predictive value (81%) for ASAS response.

Conclusion

ESR, CRP, and SAA were significantly associated with the BASDAI over 3 months, and the association with ESR was the strongest. Elevated baseline CRP and SAA levels revealed the highest predictive value for response. Together, this study demonstrates that inflammatory markers, and notably CRP and SAA, may facilitate patient selection and monitoring of efficacy of anti‐TNF treatment in AS, and could be added to response criteria.
Whole‐body bone scintigraphy provides a measure of the total‐body burden of osteoarthritis for the purpose of systemic biomarker validation
Authors: Addison Shelby , Coleman R. Edward , Feng Sheng , McDaniel Gary , Kraus Virginia Byers
Published: October 2009

Objective

To evaluate the association of serum and synovial fluid cartilage oligomeric matrix protein (COMP) with systemic and local measures of osteoarthritis (OA) activity by bone scintigraphy.

Methods

Samples of serum and knee joint synovial fluid (275 knees) were obtained from 159 patients with symptomatic OA of at least 1 knee. Bone scintigraphy using99mTc‐labeled methylene diphosphonate was performed, and early‐phase knee scans and late‐phase whole‐body bone scans of 15 additional joint sites were scored semiquantitatively. To control for within‐subject correlations of knee data, generalized linear modeling was used in the correlation of the bone scan scores with the COMP levels. Principal components analysis was used to explore the contribution of each joint site to the variance in serum COMP levels.

Results

The correlation between synovial fluid and serum COMP levels was significant (r = 0.206,P= 0.006). Synovial fluid COMP levels correlated most strongly with the early‐phase knee bone scan scores (P= 0.0003), even after adjustment for OA severity according to the late‐phase bone scan scores (P= 0.015), as well as synovial fluid volumes (P< 0.0001). Serum COMP levels correlated with the total‐body bone scan scores (r = 0.188,P= 0.018) and with a factor composed of the bone scan scores in the shoulders, spine, lateral knees, and sacroiliac joints (P= 0.0004).

Conclusion

Synovial fluid COMP levels correlated strongly with 2 indicators of knee joint inflammation: early‐phase bone scintigraphic findings and synovial fluid volume. Serum COMP levels correlated with total‐body joint disease severity as determined by late‐phase bone scintigraphy, supporting the hypothesis that whole‐body bone scintigraphy is a means of quantifying the total‐body burden of OA for systemic biomarker validation.
The robust association between childhood physical abuse and osteoarthritis in adulthood: Findings from a representative community sample
Authors: Fuller‐Thomson Esme , Stefanyk Maria , Brennenstuhl Sarah
Published: October 2009

Objective

Research suggests a role of early‐life trauma in the development of arthritis. This study investigated the relationship between childhood physical abuse and osteoarthritis (OA) while controlling for age, sex, race, and socioeconomic status (SES), in addition to the following types of risk factors for OA: 1) concurrent childhood stressors, 2) adult health behaviors, and 3) depression.

Methods

Data from the provinces of Manitoba and Saskatchewan were selected from the 2005 Canadian Community Health Survey (n = 13,093). Respondents with missing arthritis data or with arthritis types other than OA were excluded (n = 1,985). Of the 11,108 remaining respondents, 6.9% (n = 854) reported childhood physical abuse by someone close to them, and 10.1% (n = 1,452) reported that they had been diagnosed with OA by a health professional. The regional‐level response rate was 84%.

Results

When adjusting for all 3 types of risk factors, a significant association between childhood physical abuse and OA was found (odds ratio [OR] 1.56, 95% confidence interval [95% CI] 1.21–2.00). In contrast, when adjusting for age, sex, race, and SES only, the OR was 1.99 (95% CI 1.57–2.52).

Conclusion

The association between childhood physical abuse and OA remained significant, even after controlling for many risk factors that may mediate the relationship. Further research is needed to investigate potential pathways through which arthritis develops as a consequence of childhood physical abuse.
Improved influenza and pneumococcal vaccination in rheumatology patients taking immunosuppressants using an electronic health record best practice alert
Authors: Ledwich Lindsay J. , Harrington Thomas M. , Ayoub William T. , Sartorius Jennifer A. , Newman Eric D.
Published: October 2009

Objective

To examine whether an electronic health record (EHR) best practice alert (BPA), a clinical reminder to help guideline adherence, improved vaccination rates in rheumatology patients receiving immunosuppressants. Guidelines recommend yearly influenza and pneumococcal vaccination with revaccination for patients age >65 years who are taking immunosuppressive medications.

Methods

A vaccination BPA was developed based on immunosuppressant treatment, age, and prior vaccinations. At site 1, a hospital‐based academic practice, physicians ordered vaccinations. At site 2, a community‐based practice, physicians signed orders placed by nurses. Demographics, vaccination rates, and documentation (vaccination or no administration) were obtained. Chi‐square and Fisher's exact test analysis compared vaccination and documentation rates for October 1 through December 31, 2006 (preBPA), and October 1 through December 31, 2007 (postBPA). Breslow‐Day statistics tested the odds ratio of improvement across the years between the sites.

Results

PostBPA influenza vaccination rates significantly increased (47% to 65%;P< 0.001), with significant improvement at both sites. PostBPA pneumococcal vaccination rates likewise significantly increased (19% to 41%;P< 0.001). PostBPA documentation rates for influenza and pneumococcal vaccinations also increased significantly. Site 2 (nurse‐driven) had significantly higher preBPA vaccination rates for influenza (69% versus 43%;P< 0.001) than pneumococcal (47% versus 15%;P< 0.001).

Conclusion

The use of a BPA significantly increased influenza and pneumococcal vaccination and documentation rates in rheumatology patients taking immunosuppressants. A nurse‐driven process offered higher efficacy. An EHR programmed to alert providers is an effective tool for improving quality of care for patients receiving immunosuppressants.
A novel T cell cytokine, secreted osteoclastogenic factor of activated T cells, induces osteoclast formation in a RANKL‐independent manner
Authors: Rifas Leonard , Weitzmann M. Neale
Published: October 2009

Objective

Chronic T cell activation is central to the etiology of rheumatoid arthritis (RA), an inflammatory autoimmune disease that leads to severe focal bone erosions and generalized systemic osteoporosis. Previous studies have shown novel cytokine‐like activities in medium containing activated T cells, characterized by potent induction of the osteoblastic production of interleukin‐6 (IL‐6), an inflammatory cytokine and stimulator of osteoclastogenesis, as well as induction of an activity that directly stimulates osteoclast formation in a manner independent of the key osteoclastogenic cytokine RANKL. This study was undertaken to identify the factors secreted by T cells that are responsible for these activities.

Methods

Human T cells were activated using anti‐human CD3 and anti‐human CD28 antibodies for 72 hours in AIM V serum‐free medium to obtain T cell–conditioned medium, followed by concentration and fractionation of the medium by fast‐protein liquid chromatography. Biologically active fractions were resolved using sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Major bands were analyzed by mass spectrometry, and a major candidate protein was identified. This novel cytokine was cloned, and its expression was analyzed using recombinant DNA technologies.

Results

A single novel cytokine that could induce both osteoblastic IL‐6 production and functional osteoclast formation in the absence of osteoblasts or RANKL and that was insensitive to the effects of the RANKL inhibitor osteoprotegerin was identified in the activated T cell–conditioned medium; this cytokine was designated secreted osteoclastogenic factor of activated T cells (SOFAT). Further analysis of SOFAT revealed that it was derived from an unusual messenger RNA splice variant coded by the threonine synthase–like 2 gene homolog, which is a conserved gene remnant coding for threonine synthase, an enzyme that functions only in microorganisms and plants.

Conclusion

SOFAT may act to exacerbate inflammation and/or bone turnover under inflammatory conditions such as RA or periodontitis and in conditions of estrogen deficiency.
Effects of teriparatide versus alendronate for treating glucocorticoid‐induced osteoporosis: Thirty‐six–month results of a randomized, double‐blind, controlled trial
Authors: Saag Kenneth G. , Zanchetta Jose R. , Devogelaer Jean‐Pierre , Adler Robert A. , Eastell Richard , See Kyoungah , Krege John H. , Krohn Kelly , Warner Margaret R.
Published: October 2009

Objective

To compare the bone anabolic drug teriparatide (20 μg/day) with the antiresorptive drug alendronate (10 mg/day) for treating glucocorticoid‐induced osteoporosis (OP).

Methods

This was a 36‐month, randomized, double‐blind, controlled trial in 428 subjects with OP (ages 22–89 years) who had received ≥5 mg/day of prednisone equivalent for ≥3 months preceding screening. Measures included changes in lumbar spine and hip bone mineral density (BMD), changes in bone biomarkers, fracture incidence, and safety.

Results

Increases in BMD from baseline were significantly greater in the teriparatide group than in the alendronate group, and at 36 months were 11.0% versus 5.3% for lumbar spine, 5.2% versus 2.7% for total hip, and 6.3% versus 3.4% for femoral neck (P < 0.001 for all). In the teriparatide group, median percent increases from baseline in N‐terminal type I procollagen propeptide (PINP) and osteocalcin (OC) levels were significant from 1 to 36 months (P < 0.01), and increases in levels of C‐terminal telopeptide of type I collagen (CTX) were significant from 1 to 6 months (P < 0.01). In the alendronate group, median percent decreases in PINP, OC, and CTX were significant by 6 months and remained below baseline through 36 months (P < 0.001). Fewer subjects had vertebral fractures in the teriparatide group than in the alendronate group (3 [1.7%] of 173 versus 13 [7.7%] of 169; P = 0.007), with most occurring during the first 18 months. There was no significant difference between groups in the incidence of nonvertebral fractures (16 [7.5%] of 214 subjects taking teriparatide versus 15 [7.0%] of 214 subjects taking alendronate; P = 0.843). More subjects in the teriparatide group (21%) versus the alendronate group (7%) had elevated predose serum calcium concentrations (P < 0.001).

Conclusion

Our findings indicate that subjects with glucocorticoid‐induced OP treated with teriparatide for 36 months had greater increases in BMD and fewer new vertebral fractures than subjects treated with alendronate.
Gadd45β deficiency in rheumatoid arthritis: Enhanced synovitis through JNK signaling
Authors: Svensson Camilla I. , Inoue Tomoyuki , Hammaker Deepa , Fukushima Akihisa , Papa Salvatore , Franzoso Guido , Schett Georg , Corr Maripat , Boyle David L. , Firestein Gary S.
Published: October 2009

Objective

JNK‐mediated cell signaling plays a critical role in matrix metalloproteinase (MMP) expression and joint destruction in rheumatoid arthritis (RA). Gadd45β, which is an NF‐κB–regulated gene, was recently identified as an endogenous negative regulator of the JNK pathway, since it could block the upstream kinase MKK‐7. This study was carried out to evaluate whether low Gadd45β expression in RA enhances JNK activation and overproduction of MMPs in RA, and whether Gadd45β deficiency increases arthritis severity in passive K/BxN murine arthritis.

Methods

Activation of the NF‐κB and JNK pathways and Gadd45β expression were analyzed in human synovium and fibroblast‐like synoviocytes (FLS) using quantitative polymerase chain reaction, immunoblotting, immunohistochemistry, electrophoretic mobility shift assay, and luciferase reporter constructs. Gadd45β−/−and wild‐type mice were evaluated in the K/BxN serum transfer model of inflammatory arthritis, and clinical signs of arthritis, osteoclast formation, and bone erosion were assessed.

Results

Expression levels of the Gadd45β gene and protein were unexpectedly low in human RA synovium despite abundant NF‐κB activity. Forced Gadd45β expression in human FLS attenuated tumor necrosis factor–induced signaling through the JNK pathway, reduced the activation of activator protein 1, and decreased the expression of MMP genes. Furthermore, Gadd45β deficiency exacerbated K/BxN serum–induced arthritis in mice, dramatically increased signaling through the JNK pathway, elevatedMMP3andMMP13gene expression in the mouse joints, and increased the synovial inflammation and number of osteoclasts.

Conclusion

Deficient Gadd45β expression in RA can contribute to activation of JNK, exacerbate clinical arthritis, and augment joint destruction. This process can be mitigated by enhancing Gadd45β expression or by inhibiting the activity of JNK or its upstream regulator, MKK‐7.