Economic evidence for nonpharmacological asthma management interventions: A systematic review

Asthma management, education and environmental interventions have been reported as cost‐effective in a previous review (Pharm Pract (Granada), 2014;12:493), but methods used to estimate costs and outcomes were not discussed in detail. This review updates the previous review by providing economic evidence on the cost‐effectiveness of studies identified after 2012, and a detailed assessment of the methods used in all identified studies. Twelve databases were searched from 1990 to January 2016, and studies included economic evaluations, asthma subjects and nonpharmacological interventions written in English. Sixty‐four studies were included. Of these, 15 were found in addition to the earlier review; 53% were rated fair in quality and 47% high. Education and self‐management interventions were the most cost‐effective, in line with the earlier review. Self‐reporting was the most common method used to gather resource‐use data, accompanied by bottom‐up approaches to estimate costs. Main outcome measures were asthma‐related hospitalizations (69%), quality of life (41%) and utility (38%), with AQLQ and the EQ‐5D being the most common questionnaires measured prospectively at fixed time points. More rigorous costing methods are needed with a more common quality of life tool to aid greater replicability and comparability amongst asthma studies

Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation

Background: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. Methods: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. Results: There were 70 participants (age 41.7614.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p,0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiveroperating- characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. Conclusions: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients

Effect of antiandrogen flutamide on measures of hepatic regeneration in rats

Male rat liver undergoes a process of demasculinization during hepatic regeneration following partial hepatectomy. The possibility that antiandrogens might potentiate this demasculinization process and in so doing augment the hepatic regenerative response was investigated. Adult male Wistar rats were treated with the antiandrogen flutamide (2 mg/rat/day or 5 mg/rat/day subcutaneously) or vehicle for three days prior to and daily after a 70% partial hepatectomy. At various times after hepatectomy, the liver remnants were removed and weighed. Rates of DNA and polyamine synthesis were assessed by measuring thymidine kinase and ornithine decarboxylase activities, respectively. Hepatic estrogen receptor status and the activity of alcohol dehydrogenase, an androgen-sensitive protein, were measured. Prior to surgery, the administration of 5 mg/day flutamide reduced the hepatic cytosolic androgen receptor activity by 98% and hepatic cytosolic estrogen receptor content by 92% compared to that present in vehicle-treated controls. After hepatectomy, however, all differences in sex hormone receptor activity between the treatment groups were abolished. The rate of liver growth after partial hepatectomy in the three groups was identical. Moreover, hepatectomy-induced increases in ornithine decarboxylase activity and thymidine kinase activity were comparable. These data demonstrate that, although flutamide administration initially alters the sex hormone receptor status of the liver, these affects have no effect on the hepatic regenerative response following a partial hepatectomy. © 1989 Plenum Publishing Corporation

Sodium bicarbonate and high-intensity-cycling capacity: variability in responses

Purpose: The aim of this study was to determine whether gastrointestinal (GI) distress affects the ergogenicity of sodium bicarbonate and whether the degree of alkalaemia or other metabolic responses are different between individuals who improve exercise capacity and those who do not. Methods: Twenty-one males completed two cycling capacity tests at 110% of maximum power output. Participants were supplemented with 0.3 g∙kg-1BM of either placebo (maltodextrin) or sodium bicarbonate (SB). Blood pH, bicarbonate, base excess and lactate were determined at baseline, pre-exercise, immediately post-exercise and 5 minutes post-exercise. Results: SB supplementation did not significantly increase total work done (TWD) (P = 0.16, 46.8 ± 9.1 vs. 45.6 ± 8.4 kJ, d = 0.14), although magnitude based inferences suggested a 63% likelihood of a positive effect. When data were analysed without four participants who experienced GI discomfort, TWD (P = 0.01) was significantly improved with SB. Immediately post-exercise blood lactate was higher in SB for the individuals who improved but not for those who didn’t. There were also differences in the pre to post-exercise change in blood pH, bicarbonate and base excess between individuals who improved and individuals who did not. Conclusions: SB improved high intensity cycling capacity, but only with the exclusion of participants experiencing GI discomfort. Differences in blood responses suggest that sodium bicarbonate may not be beneficial to all individuals. Magnitude based inferences suggested that the exercise effects are unlikely to be negative; therefore individuals should determine whether they respond well to sodium bicarbonate supplementation prior to competition

PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis

The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Prevalence of Borderline Personality Disorder in University Samples: Systematic Review, Meta-Analysis and Meta-Regression.

OBJECTIVE: To determine pooled prevalence of clinically significant traits or features of Borderline Personality Disorder among college students, and explore the influence of methodological factors on reported prevalence figures, and temporal trends. DATA SOURCES: Electronic databases (1994-2014: AMED; Biological Abstracts; Embase; MEDLINE; PsycARTICLES; CINAHL Plus; Current Contents Connect; EBM Reviews; Google Scholar; Ovid Medline; Proquest central; PsychINFO; PubMed; Scopus; Taylor & Francis; Web of Science (1998-2014), and hand searches. STUDY SELECTION: Forty-three college-based studies reporting estimates of clinically significant BPD symptoms were identified (5.7% of original search). DATA EXTRACTION: One author (RM) extracted clinically relevant BPD prevalence estimates, year of publication, demographic variables, and method from each publication or through correspondence with the authors. RESULTS: The prevalence of BPD in college samples ranged from 0.5% to 32.1%, with lifetime prevalence of 9.7% (95% CI, 7.7-12.0; p < .005). Methodological factors contributing considerable between-study heterogeneity in univariate meta-analyses were participant anonymity, incentive type, research focus and participant type. Study and sample characteristics related to between study heterogeneity were sample size, and self-identifying as Asian or "other" race. The prevalence of BPD varied over time: 7.8% (95% CI 4.2-13.9) between 1994 and 2000; 6.5% (95% CI 4.0-10.5) during 2001 to 2007; and 11.6% (95% CI 8.8-15.1) from 2008 to 2014, yet was not a source of heterogeneity (p = .09). CONCLUSIONS: BPD prevalence estimates are influenced by the methodological or study sample factors measured. There is a need for consistency in measurement across studies to increase reliability in establishing the scope and characteristics of those with BPD engaged in tertiary study

Evolutionary relationships among barley and <i>Arabidopsis</i> core circadian clock and clock-associated genes

The circadian clock regulates a multitude of plant developmental and metabolic processes. In crop species, it contributes significantly to plant performance and productivity and to the adaptation and geographical range over which crops can be grown. To understand the clock in barley and how it relates to the components in the Arabidopsis thaliana clock, we have performed a systematic analysis of core circadian clock and clock-associated genes in barley, Arabidopsis and another eight species including tomato, potato, a range of monocotyledonous species and the moss, Physcomitrella patens. We have identified orthologues and paralogues of Arabidopsis genes which are conserved in all species, monocot/dicot differences, species-specific differences and variation in gene copy number (e.g. gene duplications among the various species). We propose that the common ancestor of barley and Arabidopsis had two-thirds of the key clock components identified in Arabidopsis prior to the separation of the monocot/dicot groups. After this separation, multiple independent gene duplication events took place in both monocot and dicot ancestors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00239-015-9665-0) contains supplementary material, which is available to authorized users