Comparison of the effectiveness of three manual physical therapy techniques in a subgroup of patients with low back pain who satisfy a clinical prediction rule: Study protocol of a randomized clinical trial [NCT00257998]

BACKGROUND: Recently a clinical prediction rule (CPR) has been developed and validated that accurately identifies patients with low back pain (LBP) that are likely to benefit from a lumbo-pelvic thrust manipulation. The studies that developed and validated the rule used the identical manipulation procedure. However, recent evidence suggests that different manual therapy techniques may result similar outcomes. The purpose of this study is to investigate the effectiveness of three different manual therapy techniques in a subgroup of patient with low back pain that satisfy the CPR. METHODS/DESIGN: Consecutive patients with LBP referred to physical therapy clinics in one of four geographical locations who satisfy the CPR will be invited to participate in this randomized clinical trial. Subjects who agree to participate will undergo a standard evaluation and complete a number of patient self-report questionnaires including the Oswestry Disability Index (OSW), which will serve as the primary outcome measure. Following the baseline examination patients will be randomly assigned to receive the lumbopelvic manipulation used in the development of the CPR, an alternative lumbar manipulation technique, or non-thrust lumbar mobilization technique for the first 2 visits. Beginning on visit 3, all 3 groups will receive an identical standard exercise program for 3 visits (visits 3,4,5). Outcomes of interest will be captured by a therapist blind to group assignment at 1 week (3(rd )visit), 4 weeks (6(th )visit) and at a 6-month follow-up. The primary aim of the study will be tested with analysis of variance (ANOVA) using the change in OSW score from baseline to 4-weeks (OSW(Baseline )– OSW(4-weeks)) as the dependent variable. The independent variable will be treatment with three levels (lumbo-pelvic manipulation, alternative lumbar manipulation, lumbar mobilization). DISCUSSION: This trial will be the first to investigate the effectiveness of various manual therapy techniques for patients with LBP who satisfy a CPR

Screening for pre-clinical disability in different residential settings

<p>Abstract</p> <p>Background</p> <p>Preventing disability and offering effective interventions to older people during early decline in function is most likely to be effective if those most at risk of progressive disablement are able to be identified. Similarly the ability to easily identify a group with similar functional profile from disparate sectors of the community is of significant benefit to researchers. This study aimed to (1) describe the use of a pre-clinical disability screening tool to select a functionally comparable group of older men and women with early functional limitation from different settings, and (2) explore factors associated with function and disability.</p> <p>Methods</p> <p>Self-reported function and disability measured with the Late-Life Function and Disability Instrument along with a range of physical performance measurements were compared across residential settings and gender in a sample of 471 trial participants identified as pre-clinically disabled after being screened with the Fried pre-clinical disability tool. Factors that might lie on the pathway to progressive disablement were identified using multiple linear regression analysis.</p> <p>Results</p> <p>We found that a sample population, screened for pre-clinical disability, had a functional status and disability profile reflecting early functional limitation, regardless of residential setting or gender. Statistical models identified a range of factors associated with function and disability which explained a greater degree of the variation in function, than disability.</p> <p>Conclusions</p> <p>We selected a group of people with a comparable function and disability profile, consistent with the pre-clinical stage of disability, from a sample of older Australian men and women from different residential settings using the Fried pre-clinical disability screening tool. The results suggest that the screening tool can be used with greater confidence for research, clinical and population health purposes. Further research is required to examine the validity of the tool. These findings offer insight into the type of impairment factors characterising early functional loss that could be addressed through disability prevention initiatives.</p> <p>Trial Registration</p> <p>ACTRN01206000431527</p

Feasibility of a multidimensional home-based exercise programme for the elderly with structured support given by the general practitioner's surgery: Study protocol of a single arm trial preparing an RCT [ISRCTN58562962]

<p>Abstract</p> <p>Background</p> <p>Physical activity programmes can help to prevent functional decline in the elderly. Until now, such programmes use to target either on healthy community-dwelling seniors or on elderly living in special residences or care institutions. Sedentary or frail people, however, are difficult to reach when they live in their own homes. The general practitioner's (GP) practice offers a unique opportunity to acquire these people for participation in activity programmes. We conceptualised a multidimensional home-based exercise programme that shall be delivered to the target group through cooperation between GPs and exercise therapists. In order to prepare a randomised controlled trial (RCT), a feasibility study is being conducted.</p> <p>Methods</p> <p>The study is designed as a single arm interventional trial. We plan to recruit 90 patients aged 70 years and above through their GPs. The intervention lasts 12 weeks and consists of physical activity counselling, a home-exercise programme, and exercise consultations provided by an exercise therapist in the GP's practice and via telephone. The exercise programme consists of two main components: 1. a combination of home-exercises to improve strength, flexibility and balance, 2. walking for exercise to improve aerobic capacity. Primary outcome measures are: appraisal by GP, undesirable events, drop-outs, adherence. Secondary outcome measures are: effects (a. motor tests: timed-up-and-go, chair rising, grip strength, tandem stand, tandem walk, sit-and-reach; b. telephone interview: PRISCUS-Physical Activity Questionnaire, Short Form-8 Health Survey, three month recall of frequency of falls, Falls Efficacy Scale), appraisal by participant, exercise performance, focus group discussion. Data analyses will focus on: 1. decision-making concerning the conduction of a RCT, 2. estimation of the effects of the programme, detection of shortcomings and identification of subgroups with contrary results, 3. feedback to participants and to GPs.</p> <p>Conclusion</p> <p>A new cooperation between GPs and exercise therapists to approach community-dwelling seniors and to deliver a home-exercise programme is object of research with regard to feasibility and acceptance. In case of success, an RCT should examine the effects of the programme. A future implementation within primary medical care may take advantage from the flexibility of the programme.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN58562962.</p

Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.

Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights

Responsiveness and minimal clinically important difference for pain and disability instruments in low back pain patients

BACKGROUND: The choice of an evaluative instrument has been hampered by the lack of head-to-head comparisons of responsiveness and the minimal clinically important difference (MCID) in subpopulations of low back pain (LBP). The objective of this study was to concurrently compare responsiveness and MCID for commonly used pain scales and functional instruments in four subpopulations of LBP patients. METHODS: The Danish versions of the Oswestry Disability Index (ODI), the 23-item Roland Morris Disability Questionnaire (RMQ), the physical function and bodily pain subscales of the SF36, the Low Back Pain Rating Scale (LBPRS) and a numerical rating scale for pain (0–10) were completed by 191 patients from the primary and secondary sectors of the Danish health care system. Clinical change was estimated using a 7-point transition question and a numeric rating scale for importance. Responsiveness was operationalised using standardardised response mean (SRM), area under the receiver operating characteristic curve (ROC), and cut-point analysis. Subpopulation analyses were carried out on primary and secondary sector patients with LBP only or leg pain +/- LBP. RESULTS: RMQ was the most responsive instrument in primary and secondary sector patients with LBP only (SRM = 0.5–1.4; ROC = 0.75–0.94) whereas ODI and RMQ showed almost similar responsiveness in primary and secondary sector patients with leg pain (ODI: SRM = 0.4–0.9; ROC = 0.76–0.89; RMQ: SRM = 0.3–0.9; ROC = 0.72–0.88). In improved patients, the RMQ was more responsive in primary and secondary sector patients and LBP only patients (SRM = 1.3–1.7) while the RMQ and ODI were equally responsive in leg pain patients (SRM = 1.3 and 1.2 respectively). All pain measures demonstrated almost equal responsiveness. The MCID increased with increasing baseline score in primary sector and LBP only patients but was only marginally affected by patient entry point and pain location. The MCID of the percentage change score remained constant for the ODI (51%) and RMQ (38%) specifically and differed in the subpopulations. CONCLUSION: RMQ is suitable for measuring change in LBP only patients and both ODI and RMQ are suitable for leg pain patients irrespectively of patient entry point. The MCID is baseline score dependent but only in certain subpopulations. Relative change measured using the ODI and RMQ was not affected by baseline score when patients quantified an important improvement

The Polygenic and Monogenic Basis of Blood Traits and Diseases

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation. Analysis of blood cell traits in the UK Biobank and other cohorts illuminates the full genetic architecture of hematopoietic phenotypes, with evidence supporting the omnigenic model for complex traits and linking polygenic burden with monogenic blood diseases

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways