We present the results of a recent re-reduction of the data from the Very Large Array (VLA) Low-frequency Sky Survey (VLSS). We used the VLSS catalogue as a sky model to correct the ionospheric ...distortions in the data and create a new set of sky maps and corresponding catalogue at 73.8 MHz. The VLSS Redux (VLSSr) has a resolution of 75 arcsec, and an average map rms noise level of σ ∼ 0.1 Jy beam−1. The clean bias is 0.66 × σ and the theoretical largest angular size is 36 arcmin. Six previously unimaged fields are included in the VLSSr, which has an unbroken sky coverage over 9.3 sr above an irregular southern boundary. The final catalogue includes 92 964 sources. The VLSSr improves upon the original VLSS in a number of areas including imaging of large sources, image sensitivity, and clean bias; however the most critical improvement is the replacement of an inaccurate primary beam correction which caused source flux errors which vary as a function of radius to nearest pointing centre in the VLSS.
Summary
Osteoporosis causes an elevated fracture risk. We propose the continued use of T-scores as one means for diagnosis but recommend that, alternatively, hip fracture; osteopenia-associated ...vertebral, proximal humerus, pelvis, or some wrist fractures; or FRAX scores with ≥3 % (hip) or 20 % (major) 10-year fracture risk also confer an osteoporosis diagnosis.
Introduction
Osteoporosis is a common disorder of reduced bone strength that predisposes to an increased risk for fractures in older individuals. In the USA, the standard criterion for the diagnosis of osteoporosis in postmenopausal women and older men is a T-score of ≤ −2.5 at the lumbar spine, femur neck, or total hip by bone mineral density testing.
Methods
Under the direction of the National Bone Health Alliance, 17 clinicians and clinical scientists were appointed to a working group charged to determine the appropriate expansion of the criteria by which osteoporosis can be diagnosed.
Results
The group recommends that postmenopausal women and men aged 50 years should be diagnosed with osteoporosis if they have a demonstrable elevated risk for future fractures. This includes having a T-score of less than or equal to −2.5 at the spine or hip as one method for diagnosis but also permits a diagnosis for individuals in this population who have experienced a hip fracture with or without bone mineral density (BMD) testing and for those who have osteopenia by BMD who sustain a vertebral, proximal humeral, pelvic, or, in some cases, distal forearm fracture. Finally, the term osteoporosis should be used to diagnose individuals with an elevated fracture risk based on the World Health Organization Fracture Risk Algorithm, FRAX.
Conclusions
As new ICD-10 codes become available, it is our hope that this new understanding of what osteoporosis represents will allow for an appropriate diagnosis when older individuals are recognized as being at an elevated risk for fracture.
Summary Both epidemiologic and clinical research continues to be performed in osteoarthritis (OA). While epidemiologic studies identify risk factors for incident and progressive disease, clinical ...studies explore the role of both non-pharmacologic and pharmacologic treatments, including oral and intra-articular therapies. We performed a systematic review of the literature using PubMed for the time period between April 1, 2015 to February 22, 2016. Selected publications in the areas of both epidemiology and treatment are reviewed in this article.
To assess the safety, pharmacokinetics, and exploratory efficacy of SM04690, a novel Wnt pathway inhibitor, as a potential disease modifying treatment for knee osteoarthritis (OA).
Subjects with ...Kellgren-Lawrence grade 2–3 knee OA were randomized in successive dose-escalation cohorts to receive a knee intra-articular (IA) injection with 0.03, 0.07, or 0.23 mg SM04690, or placebo (PBO) (4:1 ratio). Safety, pharmacokinetics, efficacy (WOMAC Total/Function/Pain, Pain VAS, Physician Global Assessment MDGA, and OMERACT-OARSI Response), OA-related biomarker (P1NP, ß-CTX, and cartilage oligomeric matrix protein COMP), and radiographic/imaging data were collected at baseline and during 24-week follow-up.
61 subjects (SM04690 n = 50; PBO n = 11) enrolled. Two dose limiting toxicities (DLTs), increased pain following injection and paroxysmal tachycardia (also the single serious AE), were reported in the 0.07 mg cohort. A total of 72 AEs were reported; Sixteen (occurring in eight subjects) were considered related to study medication. There were three discontinuations; one due to an AE (0.03 mg cohort). Bone marrow edema (BME) remained constant for most subjects. No doses were excluded from further study due to DLT criteria. Plasma levels of SM04690 were below the limit of detection at all time points. At Week 24, improvements from baseline were seen in all cohorts for the exploratory measures WOMAC Total, WOMAC Function, WOMAC Pain, MDGA, Pain VAS, and OMERACT-OARSI response. Joint space width (JSW) improvement was observed in the 0.07 mg cohort (P = 0.02 vs PBO).
SM04690 appeared safe and well tolerated, with no evidence of systemic exposure. Exploratory efficacy analyses suggested positive trends for measurements of OA pain, function and disease-modifying osteoarthritis drug (DMOAD) properties.
NCT02095548.
Postmenopausal women with severe osteoporosis may require treatment with the bone anabolic drug teriparatide. While changes in bone mineral density (BMD) are one measure of response, BMD changes ...often require a minimum of one year to observe measureable changes. Biochemical markers of bone turnover change within 1 to 3 months of initiating osteoporosis therapy. Monitoring with a marker such as procollagen type I N propeptide (PINP), an osteoblast-derived protein, during teriparatide treatment may provide clinically useful information for managing patients with osteoporosis. Clinical trials have shown consistent increases in PINP within 3 months of initiating teriparatide, increases that are significantly greater than placebo and significantly different from baseline. Increases in PINP concentrations during teriparatide treatment correlate well with increases in skeletal activity assessed by radioisotope bone scans and quantitative bone histomorphometry parameters. Individuals treated with teriparatide in clinical trials usually experienced an increase in PINP > 10 mcg/L from baseline, while those given placebo usually did not. In the clinical setting, patients experiencing a significant increase in PINP > 10 mcg/L after initiating teriparatide therapy may receive an earlier confirmation of anabolic effect, while those who do not may be assessed for adherence, proper injection technique, or undetected secondary conditions that might mitigate an anabolic response. PINP monitoring may provide information supplemental to BMD monitoring and be a useful aid in managing patients receiving anabolic osteoporosis treatment in the same way that biochemical markers of bone resorption are useful in monitoring antiresorptive therapy. This review examines PINP as a biological response marker during teriparatide treatment for osteoporosis.
Summary Objective To respond to a pre-specified set of questions posed by the United States Food and Drug Administration (FDA) on defining the disease state to inform the clinical development of ...drugs, biological products, and medical devices for the prevention and treatment of osteoarthritis (OA). Methods An Osteoarthritis Research Society International (OARSI) Disease State working group was established, comprised of representatives from academia and industry. The Working Group met in person and by teleconference on several occasions from the Spring of 2008 through the Autumn of 2009 to develop consensus-based, evidence-informed responses to these questions. A report was presented at a public forum in December 2009 and accepted by the OARSI Board of Directors in the Summer of 2010. Results An operational definition of OA was developed incorporating current understanding of the condition. The structural changes that characterize OA at the joint level were distinguished from the patients’ experience of OA as the ‘disease’ and ‘illness’, respectively. Recommendations were made regarding the evaluation of both in future OA clinical trials. The current poor understanding of the phenotypes that characterize OA was identified as an important area for future research. Conclusions The design and conduct of clinical trials for new OA treatments should address the heterogeneity of the disease, treatment-associated structural changes in target joints and patient-reported outcomes.
Summary
A 6-month randomized controlled trial of spine-strengthening exercise and posture training reduced both radiographic and clinical measures of kyphosis. Participants receiving the intervention ...improved self-image and satisfaction with their appearance. Results suggest that spine-strengthening exercise and postural training may be an effective treatment option for older adults with hyperkyphosis.
Introduction
The purpose of the present study is to determine in a randomized controlled trial whether spine-strengthening exercises improve Cobb angle of kyphosis in community-dwelling older adults.
Methods
We recruited adults ≥60 years with kyphosis ≥40° and enrolled 99 participants (71 women, 28 men), mean age 70.6 ± 0.6 years, range 60–88, with baseline Cobb angle 57.4 ± 12.5°. The intervention included group spine-strengthening exercise and postural training, delivered by a physical therapist, 1-h, three times weekly for 6 months. Controls received four group health education meetings. The primary outcome was change in the gold standard Cobb angle of kyphosis measured from standing lateral spine radiographs. Secondary outcomes included change in kyphometer-measured kyphosis, physical function (modified Physical Performance Test, gait speed, Timed Up and Go, Timed Loaded Standing, 6-Min Walk), and health-related quality of life (HRQoL) (PROMIS global health and physical function indexes, SRS-30 self-image domain). ANCOVA was used to assess treatment effects on change from baseline to 6 months in all outcomes.
Results
There was a −3.0° (95% CI −5.2, −0.8) between-group difference in change in Cobb angle,
p
= 0.009, favoring the intervention and approximating the magnitude of change from an incident vertebral fracture. Kyphometer-measured kyphosis (
p
= 0.03) and SRS-30 self-esteem (
p
< 0.001) showed favorable between-group differences in change, with no group differences in physical function or additional HRQoL outcomes,
p
> 0.05.
Conclusions
Spine-strengthening exercise and posture training over 6 months reduced kyphosis compared to control. Our randomized controlled trial results suggest that a targeted kyphosis-specific exercise program may be an effective treatment option for older adults with hyperkyphosis.
Trial registration number and name of trial register
ClinicalTrials.gov; identifier NCT01751685
In this 24-week trial, glucosamine and chondroitin sulfate were not more effective, alone or in combination, than placebo in controlling pain in patients with osteoarthritis of the knee. In secondary ...analyses, however, in the subgroup of patients with moderate-to-severe osteoarthritis, those given both glucosamine and chondroitin sulfate were more likely than those given placebo to have a decrease in pain (79 percent vs. 54 percent).
In this trial, glucosamine and chondroitin sulfate were not more effective, alone or in combination, than placebo in controlling pain in patients with osteoarthritis of the knee.
Osteoarthritis is the most common of the arthritides, affecting at least 20 million Americans, a number that is expected to double over the next two decades.
1
,
2
Currently available medical therapies primarily address the treatment of joint pain in patients with osteoarthritis.
3
Analgesics as well as traditional and cyclooxygenase-2–selective nonsteroidal antiinflammatory drugs (NSAIDs) have suboptimal effectiveness,
4
,
5
and there is some question about their safety, especially in the light of recent reports of increased cardiovascular risk.
6
–
8
The dietary supplements glucosamine and chondroitin sulfate have been advocated, especially in the lay media, as safe and effective options for the management . . .
Introduction
Rheumatoid arthritis (RA) is a common systemic autoimmune disease of unknown cause, characterized by a chronic, symmetric, and progressive inflammatory polyarthritis. One of the most ...deleterious effects induced by the chronic inflammation of RA is bone loss. During the last 15 years, the better knowledge of the cytokine network involved in RA allowed the development of potent inhibitors of the inflammatory process classified as biological DMARDs. These new drugs are very effective in the inhibition of inflammation, but there are only few studies regarding their role in bone protection. The principal aim of this review was to show the evidence of the principal biologic therapies and bone loss in RA, focusing on their effects on bone mineral density, bone turnover markers, and fragility fractures.
Methods
Using the PICOST methodology, two coauthors (PC, LM-S) conducted the search using the following MESH terms: rheumatoid arthritis, osteoporosis, clinical trials, TNF- antagonists, infliximab, adalimumab, etanercept, certolizumab, golimumab, IL-6 antagonists, IL-1 antagonists, abatacept, tocilizumab, rituximab, bone mineral density, bone markers, and fractures. The search was conducted electronically and manually from the following databases: Medline and Science Direct. The search period included articles from 2003 to 2015. The selection included only original adult human research written in English. Titles were retrieved and the same two authors independently selected the relevant studies for a full text. The retrieved selected studies were also reviewed completing the search for relevant articles. The first search included 904 titles from which 253 titles were selected. The agreement on the selection among researchers resulted in a Kappa statistic of 0.95 (p < 0.000). Only 248 abstracts evaluated were included in the acronym PICOST. The final selection included only 28 studies, derived from the systematic search. Additionally, a manual search in the bibliography of the selected articles was made and included into the text and into the section of “small molecules of new agents.”
Conclusion
Treatment with biologic drugs is associated with the decrease in bone loss. Studies with anti-TNF blocking agents show preservation or increase in spine and hip BMD and also a better profile of bone markers. Most of these studies were performed with infliximab. Only three epidemiological studies analyzed the effect on fractures after anti-TNF blocking agent’s treatment. IL-6 blocking agents also showed improvement in localized bone loss not seen with anti-TNF agents. There are a few studies with rituximab and abatacept. Although several studies reported favorable actions of biologic therapies on bone protection, there are still unmet needs for studies regarding their actions on the risk of bone fractures.
Benzodiazepine withdrawal is a widespread problem with potentially severe and deadly consequences. Currently, the only medications available for treating benzodiazepine withdrawal are short-acting ...and long-acting benzodiazepines. Identifying other drugs to help in treating benzodiazepine withdrawal is necessary. Gabapentin, an anxiolytic drug that is also used off-label to treat alcohol withdrawal, is a potential candidate for modulating benzodiazepine withdrawal. Using electronic records from a large inpatient psychiatric facility, a retrospective study of 172 patients presenting with benzodiazepine withdrawal was conducted to determine if the coincidental use of gabapentin for other medical conditions was associated with better outcomes of benzodiazepine withdrawal (N=57 gabapentin, N=115 no gabapentin). The primary outcomes were hospital length of stay and total amount of benzodiazepines given (lorazepam milligram equivalent). In this retrospective analysis of electronic medical record data, the patients experiencing benzodiazepine withdrawal who received gabapentin as an adjunct to the use of benzodiazepines were administered a smaller amount of benzodiazepines and had a shorter length of hospital stay relative to the comparison group who did not receive adjunctive gabapentin. These results suggest the potential use of gabapentin as an adjunct to the use of benzodiazepines for treating benzodiazepine withdrawal. The limitations of this study included a small sample size and variability in medication management strategies across the sample.
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