Applying psychological theories to evidence-based clinical practice: identifying factors predictive of lumbar spine x-ray for low back pain in UK primary care practice

Background

Effectiveness of combined physician and patient-level interventions for blood pressure (BP) control in low-income, hypertensive African Americans with multiple co-morbid conditions remains largely untested in community-based primary care practices. Demographic, clinical, psychosocial, and behavioral characteristics of participants in the Counseling African American to Control Hypertension (CAATCH) Trial are described. CAATCH evaluates the effectiveness of a multi-level, multi-component, evidence-based intervention compared with usual care (UC) in improving BP control among poorly controlled hypertensive African Americans who receive primary care in Community Health Centers (CHCs).

Methods

Participants included 1,039 hypertensive African Americans receiving care in 30 CHCs in the New York Metropolitan area. Baseline data on participant demographic, clinical (e.g., BP, anti-hypertensive medications), psychosocial (e.g., depression, medication adherence, self-efficacy), and behavioral (e.g., exercise, diet) characteristics were gathered through direct observation, chart review, and interview.

Results

The sample was primarily female (71.6%), middle-aged (mean age = 56.9 ± 12.1 years), high school educated (62.4%), low-income (72.4% reporting less than $20,000/year income), and received Medicaid (35.9%) or Medicare (12.6%). Mean systolic and diastolic BP were 150.7 ± 16.7 mm Hg and 91.0 ± 10.6 mm Hg, respectively. Participants were prescribed an average of 2.5 ± 1.9 antihypertensive medications; 54.8% were on a diuretic; 33.8% were on a beta blocker; 41.9% were on calcium channel blockers; 64.8% were on angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs). One-quarter (25.6%) of the sample had resistant hypertension; one-half (55.7%) reported medication non-adherence. Most (79.7%) reported one or more co-morbid medical conditions. The majority of the patients had a Charlson Co-morbidity score ≥ 2. Diabetes mellitus was common (35.8%), and moderate/severe depression was present in 16% of participants. Participants were sedentary (835.3 ± 1,644.2 Kcal burned per week), obese (59.7%), and had poor global physical health, poor eating habits, high health literacy, and good overall mental health.

Conclusions

A majority of patients in the CAATCH trial exhibited adverse lifestyle behaviors, and had significant medical and psychosocial barriers to adequate BP control. Trial outcomes will shed light on the effectiveness of evidence-based interventions for BP control when implemented in real-world medical settings that serve high numbers of low-income hypertensive African-Americans with multiple co-morbidity and significant barriers to behavior change.     

Parkinson Symptoms and Health Related Quality of Life as Predictors of Costs: A Longitudinal Observational Study with Linear Mixed Model Analysis

Objective

To estimate the magnitude in which Parkinson’s disease (PD) symptoms and health- related quality of life (HRQoL) determined PD costs over a 4-year period.

Materials and Methods

Data collected during 3-month, each year, for 4 years, from the ELEP study, included sociodemographic, clinical and use of resources information. Costs were calculated yearly, as mean 3-month costs/patient and updated to Spanish €, 2012. Mixed linear models were performed to analyze total, direct and indirect costs based on symptoms and HRQoL.

Results

One-hundred and seventy four patients were included. Mean (SD) age: 63 (11) years, mean (SD) disease duration: 8 (6) years. Ninety-three percent were HY I, II or III (mild or moderate disease). Forty-nine percent remained in the same stage during the study period. Clinical evaluation and HRQoL scales showed relatively slight changes over time, demonstrating a stable group overall. Mean (SD) PD total costs augmented 92.5%, from €2,082.17 (€2,889.86) in year 1 to €4,008.6 (€7,757.35) in year 4. Total, direct and indirect cost incremented 45.96%, 35.63%, and 69.69% for mild disease, respectively, whereas increased 166.52% for total, 55.68% for direct and 347.85% for indirect cost in patients with moderate PD. For severe patients, cost remained almost the same throughout the study. For each additional point in the SCOPA-Motor scale total costs increased €75.72 (p = 0.0174); for each additional point on SCOPA-Motor and the SCOPA-COG, direct costs incremented €49.21 (p = 0.0094) and €44.81 (p = 0.0404), respectively; and for each extra point on the pain scale, indirect costs increased €16.31 (p = 0.0228).

Conclusions

PD is an expensive disease in Spain. Disease progression and severity as well as motor and cognitive dysfunctions are major drivers of costs increments. Therapeutic measures aimed at controlling progression and symptoms could help contain disease expenses.     

Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence

The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly ¹⁵N-labeled Ras as well as [¹³C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions.     

Predicting the timing of cherry blossoms in Washington, DC and Mid-Atlantic States in response to climate change

Cherry blossoms, an icon of spring, are celebrated in many cultures of the temperate region. For its sensitivity to winter and early spring temperatures, the timing of cherry blossoms is an ideal indicator of the impacts of climate change on tree phenology. Here, we applied a process-based phenology model for temperate deciduous trees to predict peak bloom dates (PBD) of flowering cherry trees (Prunus×yedoensis ‘Yoshino’ and Prunus serrulata ‘Kwanzan’) in the Tidal Basin, Washington, DC and the surrounding Mid-Atlantic States in response to climate change. We parameterized the model with observed PBD data from 1991 to 2010. The calibrated model was tested against independent datasets of the past PBD data from 1951 to 1970 in the Tidal Basin and more recent PBD data from other locations (e.g., Seattle, WA). The model performance against these independent data was satisfactory (Yoshino: r² = 0.57, RMSE = 6.6 days, bias = 0.9 days and Kwanzan: r² = 0.76, RMSE = 5.5 days, bias = −2.0 days). We then applied the model to forecast future PBD for the region using downscaled climate projections based on IPCC''s A1B and A2 emissions scenarios. Our results indicate that PBD at the Tidal Basin are likely to be accelerated by an average of five days by 2050 s and 10 days by 2080 s for these cultivars under a mid-range (A1B) emissions scenario projected by ECHAM5 general circulation model. The acceleration is likely to be much greater (13 days for 2050 s and 29 days for 2080s ) under a higher (A2) emissions scenario projected by CGCM2 general circulation model. Our results demonstrate the potential impacts of climate change on the timing of cherry blossoms and illustrate the utility of a simple process-based phenology model for developing adaptation strategies to climate change in horticulture, conservation planning, restoration and other related disciplines.     

Creatine supplementation and performance in 6 consecutive 60 meter sprints

Creatine is an ergogenic aid used in individual and team sports. The aim of this study is to analyze the effect of monohydrate creatine supplementation on physical performance during 6 consecutive maximal speed 60 meter races, and the changes induced in some characteristic biochemical and ventilatory parameters. The study was carried out on nineteen healthy and physically active male volunteers, and randomly distributed into two groups: Group C received a supplement of creatine monohydrate (20 g/day for 5 days) and group P received placebo. Tests were performed before and after supplementation. No significant changes were observed in weight or body water measured by bioimpedance or the sum of 7 skinfold or performance during the 60 meter races. Group C showed a statistically significant increase in plasma creatinine from 69.8 +/- 12.4 to 89.3 +/- 12.4 micromol x L(-1) (p<0.05). In group C in the second control day (after creatine supplementation), expiratory volume V(E), O2 uptake and CO2 production were lower after 2 minutes of active recovery period. These results indicate that creatine monohydrate supplementation does not appear to improve the performance in 6 consecutive 60 meter repeated races but may modify ventilatory dynamics during the recovery after maximal effort.     

Ciclosporin A proof of concept study in patients with active, progressive HTLV-1 associated myelopathy/tropical spastic paraparesis

Introduction

Patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) become progressively impaired, with chronic pain, immobility and bladder, bowel and sexual dysfunction. Tested antiretroviral therapies have not been effective and most patients are offered a short course of corticosteroids or interferon-α, physiotherapy and symptomatic management. Pathogenesis studies implicate activated T-lymphocytes and cytokines in tissue damage. We therefore tested the hypothesis that inhibition of T-cell activation with ciclosporin A would be safe and clinically beneficial in patients with early and/or clinically progressing HAM/TSP.

Materials and Methods

Open label, proof of concept, pilot study of 48 weeks therapy with the calcineurin antagonist, ciclosporin A (CsA), in seven patients with ‘early’ (50% deterioration in timed walk during the preceding three months) HAM/TSP. Primary outcomes were incidence of clinical failure at 48 weeks and time to clinical failure.

Results

All patients completed 72 weeks study participation and five showed objective evidence of clinical improvement after 3 months treatment with CsA. Two patients exhibited clinical failure over 6.4 person-years of follow-up to week 48. One patient had a >2 point deterioration in IPEC (Insituto de Pesquisa Clinica Evandro Chagas) disability score at weeks 8 and 12, and then stopped treatment. The other stopped treatment at week 4 because of headache and tremor and deterioration in timed walk, which occurred at week 45. Overall pain, mobility, spasticity and bladder function improved by 48 weeks. Two patients recommenced CsA during follow-up due to relapse.

Conclusions

These data provide initial evidence that treatment with CsA is safe and may partially reverse the clinical deterioration seen in patients with early/progressive HAM/TSP. This trial supports further investigation of this agent''s safety and effectiveness in larger, randomised controlled studies in carefully selected patients with disease progression.     

Genome-Wide Association Study Identifies a Novel Canine Glaucoma Locus

Glaucoma is an optic neuropathy and one of the leading causes of blindness. Its hereditary forms are classified into primary closed-angle (PCAG), primary open-angle (POAG) and primary congenital glaucoma (PCG). Although many loci have been mapped in human, only a few genes have been identified that are associated with the development of glaucoma and the genetic basis of the disease remains poorly understood. Glaucoma has also been described in many dog breeds, including Dandie Dinmont Terriers (DDT) in which it is a late-onset (>7 years) disease. We designed clinical and genetic studies to better define the clinical features of glaucoma in the DDT and to identify the genetic cause. Clinical diagnosis was based on ophthalmic examinations of the affected dogs and 18 additionally investigated unaffected DDTs. We collected DNA from over 400 DTTs and a genome wide association study was performed in a cohort of 23 affected and 23 controls, followed by a fine mapping, a replication study and candidate gene sequencing. The clinical study suggested that ocular abnormalities including abnormal iridocorneal angles and pectinate ligament dysplasia are common (50% and 72%, respectively) in the breed and the disease resembles human PCAG. The genetic study identified a novel 9.5 Mb locus on canine chromosome 8 including the 1.6 Mb best associated region (p = 1.63×10⁻¹⁰, OR = 32 for homozygosity). Mutation screening in five candidate genes did not reveal any causative variants. This study indicates that although ocular abnormalities are common in DDTs, the genetic risk for glaucoma is conferred by a novel locus on CFA8. The canine locus shares synteny to a region in human chromosome 14q, which harbors several loci associated with POAG and PCG. Our study reveals a new locus for canine glaucoma and ongoing molecular studies will likely help to understand the genetic etiology of the disease.